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Targets Associated to Immuno Processes - Immune regulation

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Immune regulation
GPCRs
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
ADGRE2
(Adhesion Class GPCRs)
  • regulation of mast cell degranulation (GO:0043304) IMP
ADGRE2 is included in GtoImmuPdb because its tissue expression profile and its ability to activate secretion of inflammatory cytokines (IL-8, TNF) by monocytes and macrophages [255] ...
A1 receptor
(Adenosine receptors)
  • negative regulation of inflammatory response (GO:0050728) IGI
  • negative regulation of acute inflammatory response (GO:0002674) IEA
  • negative regulation of leukocyte migration (GO:0002686) IEA
Adenosine exerts anti-inflammatory effects on a number of immune cells types. These effects are mediated by the adenosine G portein-coupled receptors. All four adenosine receptors are expressed on the surface of mouse invariant NKT (iNKT) cells. The specific role of the A1 receptor in ade ...
A2A receptor
(Adenosine receptors)
  • negative regulation of alpha-beta T cell activation (GO:0046636) IEA
  • negative regulation of inflammatory response (GO:0050728) IEA
Agonist stimulation of the A2A and A3 receptors down-regulates production of the pro-inflammatory mediators TNF-α and IL-8 in human synoviocytes [610] ...
A2B receptor
(Adenosine receptors)
  • positive regulation of chronic inflammatory response to non-antigenic stimulus (GO:0002882) IEA
  • positive regulation of mast cell degranulation (GO:0043306) IEA
A2B receptor is discussed in this immuno-oncology review [2] ...
A3 receptor
(Adenosine receptors)
  • positive regulation of leukocyte migration (GO:0002687) IMP
  • positive regulation of mast cell degranulation (GO:0043306) IDA
  • positive regulation of inflammatory response (GO:0050729) IMP
Agonist stimulation of the A2A and A3 receptors down-regulates production of the pro-inflammatory mediators TNF-α and IL-8 in human synoviocytes [610] ...
AT1 receptor
(Angiotensin receptors)
  • regulation of inflammatory response (GO:0050727) IC
  • positive regulation of inflammatory response (GO:0050729) TAS
Accumulating evidence suggests that regulation of the mutually antagonistic angiotensin receptors AT1 and AT2 is essential for maintaining control of inflammation and that an imbalance between these two receptors has pathophysiological potential [545] ...
β2-adrenoceptor
(Adrenoceptors)
  • negative regulation of inflammatory response (GO:0050728) IDA
β2-ARs are expressed on innate and adaptive immune cells of humans and rodents, and are reported to have an immuno-modulating effect [175] ...
B1 receptor
(Bradykinin receptors)
  • positive regulation of leukocyte migration (GO:0002687) IEA
Bradykinin ...
C3a receptor
(Complement peptide receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IDA
  • complement component C3a receptor activity (GO:0004876) IDA
  • regulation of complement activation (GO:0030449) TAS
  • positive regulation of macrophage chemotaxis (GO:0010759) IEA
  • positive regulation of neutrophil chemotaxis (GO:0090023) IEA
Complement C3a receptor 1 is the receptor for complement factor C3a, a component of the alternative complement cascade. It can have pro-inflammatory actions, but can also counteract the proinflammatory effects of C5a.
The complement system plays a critical role intestinal immune homeostasis. In particular, C3 and the C3aR have been identified as being involved in regulating the intestinal immune response during chronic colitis [575,635] ...
C5a1 receptor
(Complement peptide receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • complement component C5a receptor activity (GO:0004878) IDA
  • regulation of complement activation (GO:0030449) TAS
  • complement component C5a signaling pathway (GO:0038178) IDA
  • regulation of astrocyte activation (GO:0061888) ISS
  • regulation of microglial cell activation (GO:1903978) ISS
  • positive regulation of macrophage chemotaxis (GO:0010759) IEA
  • positive regulation of neutrophil chemotaxis (GO:0090023) IEA
C5aR is typically associated with the compement cascade and innate immunity.
MorphoSys have an anti-C5aR monoclonal antibody (MOR210) in preclinical development as an immuno-oncology agent. The goal of anti-C5aR therapy is to reduce the effects that activation of the C5a/C5aR axis has on promoting cancer cell migration and invasiveness [252,374,430-431] ...
C5a2 receptor
(Complement peptide receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • complement component C5a receptor activity (GO:0004878) IBA
  • regulation of complement activation (GO:0030449) TAS
  • negative regulation of neutrophil chemotaxis (GO:0090024) IMP
C5aR is typically associated with the compement cascade and innate immunity. However, the complement C5a receptor 2 may act as a decoy receptor for C5a, as it has no reported G protein signalling capacity.
CB1 receptor
(Cannabinoid receptors)
  • positive regulation of acute inflammatory response to antigenic stimulus (GO:0002866) IEA
  • positive regulation of fever generation (GO:0031622) IEA
  • negative regulation of mast cell activation (GO:0033004) IEA
CB1 receptor is involved in controlling mast cell degranulation and maturation [566] ...
CB2 receptor
(Cannabinoid receptors)
  • negative regulation of mast cell activation (GO:0033004) IEA
  • negative regulation of inflammatory response (GO:0050728) IEA
CB2 receptor on eosinophils mainly mediates anti-inflammatory and immunomodulatory actions e.g. downregulation of pro-inflammatory mediator release. Pharmacological targeting with the CB2 receptor selective antagonist SR144528 attenuates the recruitment of eosinophils and ear swelling in a murine chronic contact dermatitis model [445] ...
CCR1
(Chemokine receptors)
  • positive regulation of osteoclast differentiation (GO:0045672) IMP
  • positive regulation of monocyte chemotaxis (GO:0090026) IDA
  • negative regulation of innate immune response (GO:0045824) IEA
CCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR2
(Chemokine receptors)
  • regulation of T cell cytokine production (GO:0002724) ISS
  • positive regulation of T-helper 1 type immune response (GO:0002827) ISS
  • negative regulation of type 2 immune response (GO:0002829) ISS
  • positive regulation of T cell chemotaxis (GO:0010820) ISS
  • negative regulation of eosinophil degranulation (GO:0043310) ISS
  • regulation of T cell differentiation (GO:0045580) ISS
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) IC
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) ISS
  • regulation of inflammatory response (GO:0050727) ISS
  • positive regulation of inflammatory response (GO:0050729) ISS
  • positive regulation of T cell activation (GO:0050870) ISS
  • positive regulation of monocyte chemotaxis (GO:0090026) IDA
  • positive regulation of immune complex clearance by monocytes and macrophages (GO:0090265) ISS
  • positive regulation of thymocyte migration (GO:2000412) ISS
  • positive regulation of monocyte extravasation (GO:2000439) ISS
  • positive regulation of CD8-positive, alpha-beta T cell extravasation (GO:2000451) ISS
  • neutrophil clearance (GO:0097350) IEA
  • positive regulation of leukocyte tethering or rolling (GO:1903238) IEA
CCR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CCR2 is discussed in relation to immuno-oncology in [2] ...
CCR5
(Chemokine receptors)
  • positive regulation of fever generation (GO:0031622) IMP
  • positive regulation of inflammatory response (GO:0050729) IMP
CCR5 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CCR5 is discussed in relation to immuno-oncology in [2] ...
CCR6
(Chemokine receptors)
  • regulation of T cell migration (GO:2000404) ISS
  • positive regulation of dendritic cell chemotaxis (GO:2000510) IBA
CCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. CCR6 is expressed on a variety of immune cells including memory and regulatory T-cells [310,357] ...
CCR7
(Chemokine receptors)
  • positive regulation of dendritic cell antigen processing and presentation (GO:0002606) ISS
  • regulation of tolerance induction to self antigen (GO:0002649) TAS
  • positive regulation of hypersensitivity (GO:0002885) ISS
  • positive regulation of humoral immune response (GO:0002922) ISS
  • positive regulation of macrophage chemotaxis (GO:0010759) NAS
  • positive regulation of T cell chemotaxis (GO:0010820) TAS
  • positive regulation of T cell proliferation (GO:0042102) IC
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) IC
  • positive regulation of neutrophil chemotaxis (GO:0090023) IDA
  • positive regulation of thymocyte migration (GO:2000412) TAS
  • positive regulation of dendritic cell chemotaxis (GO:2000510) ISS
  • positive regulation of immunological synapse formation (GO:2000522) ISS
  • positive regulation of T cell costimulation (GO:2000525) ISS
  • positive regulation of T cell receptor signaling pathway (GO:0050862) IEA
CCR7 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
chemerin receptor 1
(Chemerin receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • positive regulation of macrophage chemotaxis (GO:0010759) IMP
Studies in CMKLR1 (chemerin receptor 1) knockout mice highlight the role of this receptor in inflammation and obesity. Chemerin receptor 1 is activated by the lipid-derived, anti-inflammatory autacoid ligand resolvin E1. As its name suggests, reslovin E1 is involved in resolving physiological inflammatory responses. The metabolically stable resolvin E1 analogue, RX-10045 (navamepent) has completed Phase 2 clinical trials in several occular inflammation indications. In relation to multiple sclerosis (MS), clinical EAE is significantly reduced in CMKLR1 KO mice. Taking this in to consideration with data that confirm CMKLR1 expression by the main effector cells in MS, this protein is judged to be a novel and tractable target for therapeutic intervention in MS. CMKLR1 antagonists are being pursued as anti-inflammatory agents. The selective CMKLR1 antagonist CCX832 was developed by ChemoCentryx and GlaxoSmithKline as a potential anti-psoriatic medication, but development appears to have halted at Phase 1. is a CMKLR1 antagonist that has shown efficacious effects applicable to MS in vitro and in vivo [217] ...
CXCR2
(Chemokine receptors)
  • positive regulation of leukocyte chemotaxis (GO:0002690) IMP
  • negative regulation of neutrophil apoptotic process (GO:0033030) IEA
  • positive regulation of neutrophil chemotaxis (GO:0090023) IEA
CXCR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR2 is discussed in relation to immuno-oncology in [2] ...
CXCR3
(Chemokine receptors)
  • regulation of leukocyte migration (GO:0002685) IEA
CXCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR3 is the receptor for CXCL9, -10 and -11, three CXC chemokines that are preferentially expressed on Th1 lymphocytes.
CX3CR1
(Chemokine receptors)
  • negative regulation of chronic inflammatory response to non-antigenic stimulus (GO:0002881) ISO
  • regulation of microglial cell migration (GO:1904139) TAS
  • positive regulation of microglial cell migration (GO:1904141) IMP
CX3CR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
D2 receptor
(Dopamine receptors)
  • negative regulation of innate immune response (GO:0045824) IEA
D2 receptor-mediated anti-inflammatory effects in the kidney have a protective effect. In contrast, impaired D2 receptor function results in renal inflammation and organ damage [686] ...
EP3 receptor
(Prostanoid receptors)
  • positive regulation of fever generation (GO:0031622) ISS
  • positive regulation of neutrophil extravasation (GO:2000391) IMP
Foudi et al. (2012) [189] ...
EP4 receptor
(Prostanoid receptors)
  • negative regulation of inflammatory response (GO:0050728) IDA
  • positive regulation of inflammatory response (GO:0050729) ISS
  • positive regulation of neutrophil extravasation (GO:2000391) IMP
  • negative regulation of eosinophil extravasation (GO:2000420) IDA
The EP4 prostanoid receptor is one of four receptor subtypes for prostaglandin PGE2. The anti- and pro-inflammatory (and non-inflammatory) activities of this receptor are reviewed in [668] ...
FFA2 receptor
(Free fatty acid receptors)
  • regulation of acute inflammatory response (GO:0002673) ISS
  • positive regulation of cytokine production involved in immune response (GO:0002720) ISS
  • cell surface pattern recognition receptor signaling pathway (GO:0002752) IMP
  • positive regulation of acute inflammatory response to non-antigenic stimulus (GO:0002879) ISS
FFAR2 is a GPCR activated by short-chain fatty acids, and evidence suggests that FFAR2 (and FFAR3) mediate beneficial effects associated with a fiber-rich diet. These GPCRs are of interest as targets for the treatment of inflammatory and metabolic diseases. FFAR2 is included in GtoImmuPdb as it is highly expressed on immune cells, in particular neutrophils, and evidence points to a role in diseases with dysfunctional neutrophil responses, such as inflammatory bowel disease (IBD). A Phase 2 trial of the clinical candidate GLPG0974 in ulcerative colitis has been completed (see NCT0182932).
In vitro and in vivo studies suggest that the short-chain fatty acid/FFAR2 axis is modulated by metabolites of cholera toxin, that are produced by gut microbiota, which leads to enhanced mucosal antibody responses against enteric pathogen infection [662] ...
FFA3 receptor
(Free fatty acid receptors)
  • positive regulation of cytokine production involved in immune response (GO:0002720) ISS
  • positive regulation of acute inflammatory response to non-antigenic stimulus (GO:0002879) ISS
FFA3 has been included in GtoImmuPdb as its expression has been detected in immune cells [76] ...
FPR1
(Formylpeptide receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IBA
The primary function of FPR1 is recognition of formylpeptides. Detection of bacterial N-formylpeptides via FPR1 activates immune-cell chemotaxis and cytokine release, making this GPCR an important component of the host defense mechanism.

Osei-Owusu et al. (2019) demonstrated that FPR1 on immune cells is the target of the needle cap protein (LcrV; Uniprot accession P0C7U7) of Yersinia pestis (the plague bacterium), via which the bacteria destroy host immune cells [453] ...
FPR2/ALX
(Formylpeptide receptors, Leukotriene receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) IDA
  • positive regulation of innate immune response (GO:0045089) IDA
  • negative regulation of inflammatory response (GO:0050728) IDA
  • positive regulation of monocyte chemotaxis (GO:0090026) IGI
Formyl peptide receptor type 2 (FPR2/ALX) activation by lipoxin A4 and annexin 1 has been linked to resolution of inflammation, via upregulation of anti-inflammatory cytokines including IL-10. Resolvin D1-mediated activation of FPR2/ALX appears to resolve salivary gland inflammation in a mouse model of Sjögren syndrome [618] ...
GPR183
(Class A Orphans)
  • positive regulation of B cell proliferation (GO:0030890) IDA
  • dendritic cell homeostasis (GO:0036145) ISS
Gpr183-deficient mice show a reduction in the early antibody response to a T-dependent antigen. GPR183-deficient B cells fail to migrate to the outer follicle and instead stay in the follicle centre [298,467] ...
GPR55
(GPR18, GPR55 and GPR119, Class A Orphans)
  • negative regulation of osteoclast differentiation (GO:0045671) IDA
(LPI)-activated GPR55 has been shown to negatively regulate migration to, and accumulation of γδ T cells (a type of intraepithelial lymphocytes or IELs) in the small intestine [568] ...
MAS1
(Class A Orphans)
  • regulation of inflammatory response (GO:0050727) IEA
Experimental evidence from animal studies suggest a role for MAS1 in the anti-inflammatory pathway mediated by angiotensin-(1-7) [140,174] ...
NK1 receptor
(Tachykinin receptors)
  • positive regulation of leukocyte migration (GO:0002687) IEA
  • positive regulation of lymphocyte proliferation (GO:0050671) IEA
Expression in monocytes, macrophages and T helper cells suggests a role in inflammation/immunity.
PAF receptor
(Platelet-activating factor receptor)
  • positive regulation of cellular extravasation (GO:0002693) IMP
  • lipopolysaccharide receptor activity (GO:0001875) IEA
  • positive regulation of neutrophil degranulation (GO:0043315) IEA
  • positive regulation of leukocyte tethering or rolling (GO:1903238) IEA
PAF deficiency results in defective inflammatory response to infection in mice.
PAR2
(Proteinase-activated receptors)
  • positive regulation of leukocyte chemotaxis (GO:0002690) IDA
  • positive regulation of cytokine secretion involved in immune response (GO:0002741) IDA
  • positive regulation of toll-like receptor 2 signaling pathway (GO:0034137) IMP
  • negative regulation of toll-like receptor 3 signaling pathway (GO:0034140) IMP
  • positive regulation of toll-like receptor 3 signaling pathway (GO:0034141) IMP
  • positive regulation of toll-like receptor 4 signaling pathway (GO:0034145) IDA
  • positive regulation of eosinophil degranulation (GO:0043311) IDA
  • positive regulation of neutrophil mediated killing of gram-negative bacterium (GO:0070963) IDA
PAR2 receptors have been reported to elicit pain and inflammation through a neurogenic mechanism of action, causing release of substance P, activation of NK1 receptors, and sensitization of TRPV1 voltage-gated ion channels. This action can be negated using a selective NK1 receptor antagonist (L732,138) or a TRPV1 receptor antagonist (capsazepine) [200] ...
succinate receptor
(Succinate receptor)
  • positive regulation of inflammatory response (GO:0050729) IEA
Succinate acts an an alarmin that triggers the initiation and propagation of danger signals resulting from tissue injury or inflammatory stimuli. It acts through the succinate receptor, SUCNR1. SUCNR1-expressing macrophages release succinate that acts in an autocrine and paracrine feed-forward loop that elevates SUCNR1 expression and leads to enhanced IL-1β production [361] ...
Ion Channels
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
Cav1.4
(Voltage-gated calcium channels)
  • T cell homeostasis (GO:0043029) IEA
  • regulation of T cell receptor signaling pathway (GO:0050856) IEA
Cav1.4 and Cav1.3 are involved in CD8+ T cell survival and cytokine production [450,600] ...
KCa3.1
(Calcium- and sodium-activated potassium channels)
  • positive regulation of T cell receptor signaling pathway (GO:0050862) IDA
KCa3.1 and KV1.3 are the predominant potassium channels involved in regulating the hyperpolarized (negative) membrane potential which is critical for immune cell activation [153,184,393] ...
nicotinic acetylcholine receptor α7 subunit
(Nicotinic acetylcholine receptors)
  • regulation of inflammatory response (GO:0050727) IMP
  • negative regulation of inflammatory response (GO:0050728) IMP
Included in Guide to Immunopharmacology as CHRNA7 knockout aggravates rheumatoid arthritis in mice [606] ...
P2X4
(P2X receptors)
  • positive regulation of microglial cell migration (GO:1904141) ISS
P2X ligand-gated ion channels elicit pro-inflammatory immune responses upon activation by extracellular ATP that acts as a DAMP when released from damaged or infected cells [81,97] ...
P2X7
(P2X receptors)
  • positive regulation of T cell mediated cytotoxicity (GO:0001916) IEA
  • T cell homeostasis (GO:0043029) IEA
The P2X7 receptor is involved in NLRP3-type inflammasome formation, and subsequent maturation of IL-1β [360,492] ...
TRPM4
(Transient Receptor Potential channels)
  • regulation of T cell cytokine production (GO:0002724) IDA
TRPM4 is expressed on human T cells, mouse dendritic cells, human and mouse monocytes/macrophages, and mouse mast cells [458] ...
TRPV4
(Transient Receptor Potential channels)
  • positive regulation of macrophage chemotaxis (GO:0010759) IEA
  • positive regulation of inflammatory response (GO:0050729) IEA
Expressed on mouse neutrophils [458] ...
Nuclear Hormone Receptors
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
Farnesoid X receptor
(1H. Liver X receptor-like receptors)
  • toll-like receptor 4 signaling pathway (GO:0034142) IDA
  • negative regulation of inflammatory response (GO:0050728) IBA
  • toll-like receptor 9 signaling pathway (GO:0034162) IEA
FXR is predominantly expressed in liver, intestine, kidney and adipose tissue, but has also been detected in immune cells (CD4+, CD8+, CD19+ and CD14+ cells) [524] ...
Liver X receptor-α
(1H. Liver X receptor-like receptors)
  • positive regulation of toll-like receptor 4 signaling pathway (GO:0034145) IDA
  • negative regulation of macrophage activation (GO:0043031) ISS
  • negative regulation of inflammatory response (GO:0050728) ISS
  • negative regulation of interferon-gamma-mediated signaling pathway (GO:0060336) NAS
Liver X receptors (LXR) are involved in the regulation of lipid metabolism and inflammatory responses. As such they are novel drug targets for cholesterol homeostasis (hypercholesterolaemia), inflammation, and with potential therapeutic effects in neurodegenerative diseases [653] ...
Liver X receptor-β
(1H. Liver X receptor-like receptors)
  • negative regulation of interferon-gamma-mediated signaling pathway (GO:0060336) NAS
Liver X receptors are involved in the regulation of lipid metabolism and inflammatory responses. LXRs are drug targets for cholesterol homeostasis (hypercholesterolaemia), inflammation, and with therapeutic potential in neurodegenerative diseases [653] ...
Peroxisome proliferator-activated receptor-γ
(1C. Peroxisome proliferator-activated receptors)
  • negative regulation of interferon-gamma-mediated signaling pathway (GO:0060336) IMP
  • negative regulation of neuroinflammatory response (GO:0150079) IGI
  • negative regulation of microglial cell activation (GO:1903979) IGI
  • negative regulation of acute inflammatory response (GO:0002674) IEA
PPARγ agonists have anti-inflammatory effects. Full PPARγ agonists can cause undesireable weight gain, but partial agonists are devoid of this adverse effect and retain the anti-inflammatory effects of PPARγ modulation.
The PPARγ agonist boosts the inflammatory phenotype of microglia and enhances their phagocytic capacity [336] ...
RAR-related orphan receptor-γ
(1F. Retinoic acid-related orphans)
  • regulation of gamma-delta T cell differentiation (GO:0045586) IDA
RORγ is a nuclear receptor transcription factor that acts as an immune cell master control switch (most likely associated with expression of the RORγt isoform). This receptor is an essential regulator of type 17 effector T cell differentiation and function. RORγt inhibitors (antagonists and inverse agonists) [141,204,433,552] ...
Retinoic acid receptor-γ
(1B. Retinoic acid receptors)
  • regulation of myeloid cell differentiation (GO:0045637) IEA
Retinoid drugs reduce the proinflammatory factors and disrupt the immunoinflammatory cascade associated with acne vulgaris. RARγ is one of the molecular targets of anti-acne retinoid family drugs. RARγ-selective retinoid derivatives are being investigated as topical agents, which are exp ...
Enzymes
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
3-phosphoinositide dependent protein kinase 1
(PDK1 family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) IEA
  • regulation of mast cell degranulation (GO:0043304) IEA
In addition to its role in oncology, in mouse studies, PDK1 is reported to play a part in regulating insulin sensitivity (and inhibiting adipose tissue inflammation), via the Pdk1/Foxo1 pathway and expression of Ccr2 [294] ...
ABL proto-oncogene 1, non-receptor tyrosine kinase
(Abl family)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • regulation of T cell differentiation (GO:0045580) ISS
  • regulation of hematopoietic stem cell differentiation (GO:1902036) TAS
  • B-1 B cell homeostasis (GO:0001922) IEA
  • T cell receptor signaling pathway (GO:0050852) IEA
  • B cell receptor signaling pathway (GO:0050853) IEA
Included in GtoImmuPdb based on its association with leukemia.
aconitate decarboxylase 1
(Itaconate biosynthesis)
  • positive regulation of antimicrobial humoral response (GO:0002760) IDA
  • negative regulation of toll-like receptor 2 signaling pathway (GO:0034136) ISS
  • negative regulation of toll-like receptor 4 signaling pathway (GO:0034144) ISS
  • negative regulation of innate immune response (GO:0045824) ISS
  • negative regulation of inflammatory response (GO:0050728) ISS
Itaconate (itaconic acid) is generated from the citric acid (TCA) cycle intermediate cis-aconitic acid which is produced by mitochondria. Itaconate is synthesised by the enzyme aconitate decarboxylase 1 (referred to as immunoresponsive gene 1 or IRG1). Its synthesis links metabolism to immunity and it plays an important role in the macrophage-based immune response [123,162] ...
ADAM10
(M12: Astacin/Adamalysin)
  • positive regulation of T cell chemotaxis (GO:0010820) IMP
  • regulation of osteoclast differentiation (GO:0045670) NAS
ADAM10 has been identified as the primary physiologically relevant sheddase responsible for cleavage of , and regulation of ICOS/ICOSL-dependent immune responses [370] ...
ADAM17
(M12: Astacin/Adamalysin)
  • positive regulation of leukocyte chemotaxis (GO:0002690) IC
  • positive regulation of T cell chemotaxis (GO:0010820) IMP
  • regulation of mast cell apoptotic process (GO:0033025) ISS
The proteolytic activity of ADAM17 (a type I transmembrane metalloproteinase; a.k.a.TNF-alpha converting enzyme or TACE) is involved in the shedding of the extracellular domains of several transmembrane proteins e.g. cytokines (TNFα), growth factors, receptors (IL-6R and TNF-R for example) and adhesion molecules. Cleavage of substrates, including TNFα, IL-6R and L-selectin, produce pro-inflammatory effects stimulating both innate and acquired immune responses. ADAM17 activity is crucial during development (ADAM17 knockout is embryonic lethal), and it has been shown that the soluble IL-6R/IL-6 complex generates agonist-like signals in a process termed IL-6 trans-signaling. The generation and maintenance of several inflammatory and autoimmune diseases is driven by IL-6 trans-signaling [100] ...
ADAM8
(M12: Astacin/Adamalysin)
  • positive regulation of acute inflammatory response (GO:0002675) ISS
  • positive regulation of cellular extravasation (GO:0002693) IMP
  • positive regulation of T cell differentiation in thymus (GO:0033089) ISS
  • positive regulation of innate immune response (GO:0045089) ISS
  • regulation of osteoclast differentiation (GO:0045670) NAS
  • positive regulation of inflammatory response (GO:0050729) IDA
  • positive regulation of neutrophil extravasation (GO:2000391) IDA
  • positive regulation of T cell migration (GO:2000406) IMP
  • positive regulation of fibronectin-dependent thymocyte migration (GO:2000415) ISS
  • positive regulation of eosinophil migration (GO:2000418) ISS
ADAM8 is reported to drive acute allergen-induced airway inflammation in a mouse model, and effect negated by ADAM8-deficiency (antibody-induced or gene knockout) [464] ...
Adenosine deaminase
(Adenosine turnover)
  • regulation of T cell differentiation (GO:0045580) IMP
  • positive regulation of T cell differentiation (GO:0045582) IMP
  • positive regulation of T cell activation (GO:0050870) IMP
  • positive regulation of germinal center formation (GO:0002636) IEA
  • negative regulation of leukocyte migration (GO:0002686) IEA
  • negative regulation of mature B cell apoptotic process (GO:0002906) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • positive regulation of T cell differentiation in thymus (GO:0033089) IEA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
  • negative regulation of inflammatory response (GO:0050728) IEA
  • positive regulation of T cell receptor signaling pathway (GO:0050862) IEA
Adenosine deaminase deficiency causes immunodeficiency (ADA deficiency or ADA-SCID). Around 30 known genotypes are associated with this autosomal recessive metabolic disorder. Mitotically active cells such as developing T cells and B cells are susceptible to this deficiency, expaining the resulting ...
αβ-Hydrolase 12
(2-Acylglycerol ester turnover)
  • regulation of inflammatory response (GO:0050727) IEA
The lysophosphatidylserine (lyso-PSs) and lysophosphatidylinositol (lyso-PI) class lipide are immunomodulators that regulate immunological and neurological processes. ABHD12 is one of a number of lyso-PS lipases that are implicated in lyso-PS-induced cytokine production. Pharmacological inhibition of ABHD12 augments inflammatory cytokine production in human macrophages, which suggests a role for this enzyme in (lyso)-PS/PI metabolism and signalling, and downstream immunological functions [440-441] ...
amine oxidase copper containing 3
(1.-.-.- Oxidoreductases)
  • positive regulation of acute inflammatory response (GO:0002675) IMP
  • positive regulation of leukocyte migration (GO:0002687) IMP
As a membrane-bound glycoprotein AOC3 (a.k.a. SSAO, VAP-1) is expressed on the surface of endothelial cells when exposed to inflammatory conditions. It has been noted to mediate binding of lymphocytes to peripheral lymph node vascular endothelial cells, a process required for the recirculation of lymphocytes between blood and tissue. This activity profile has suggested AOC3 as a potential drug target for inflammatory and vascular diseases [516] ...
Arginase I
(Arginase)
  • negative regulation of T cell proliferation (GO:0042130) IDA
  • negative regulation of interferon-gamma-mediated signaling pathway (GO:0060336) IMP
  • positive regulation of neutrophil mediated killing of fungus (GO:0070965) IMP
  • negative regulation of activated T cell proliferation (GO:0046007) IEA
  • negative regulation of T-helper 2 cell cytokine production (GO:2000552) IEA
The role of ARG1 in immuno-oncology is reviewed in [2] ...
Arginase II
(Arginase)
  • negative regulation of type 2 immune response (GO:0002829) IEA
  • negative regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000562) IEA
The role of ARG2 in immuno-oncology is reviewed in [2] ...
BLK proto-oncogene, Src family tyrosine kinase
(Src family)
  • B cell receptor signaling pathway (GO:0050853) IDA
  • regulation of B cell receptor signaling pathway (GO:0050855) TAS
BLK is a B cell-specific kinase. In Blk knockout mice B cells develop normally and show unaltered in vitro activation and humoral immune responses to T cell-dependent and -independent antigens, a result which is indicative of functional redundancy of Blk in B cell development and immune responses [584] ...
BMX non-receptor tyrosine kinase
(Tec family)
  • B cell receptor signaling pathway (GO:0050853) IBA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [49] ...
B-Raf proto-oncogene, serine/threonine kinase
(RAF family)
  • regulation of T cell differentiation (GO:0045580) IEA
  • T cell receptor signaling pathway (GO:0050852) IEA
BRAFV600E- immuno-oncology [2] ...
Bruton tyrosine kinase
(Tec family)
  • regulation of B cell cytokine production (GO:0002721) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • positive regulation of B cell differentiation (GO:0045579) TAS
  • T cell receptor signaling pathway (GO:0050852) IBA
  • B cell receptor signaling pathway (GO:0050853) IBA
  • positive regulation of type III hypersensitivity (GO:0001805) IEA
  • positive regulation of type I hypersensitivity (GO:0001812) IEA
  • negative regulation of B cell proliferation (GO:0030889) IEA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [49] ...
calcium/calmodulin dependent protein kinase IV
(CAMK1 family)
  • regulation of T cell differentiation in thymus (GO:0033081) TAS
  • regulation of osteoclast differentiation (GO:0045670) TAS
CAMKIV has been implicated in the differentiation of Th17 cells, suggesting CAMKIV as a target for therapeutic intervention in Th17-driven autoimmune diseases [312] ...
Caspase 1
(C14: Caspase)
  • regulation of inflammatory response (GO:0050727) IBA
Caspase 1 is also known as interleukin-1beta (IL-1α) converting enzyme (ICE). Amongst its substrates are the precursors of the inflammatory cytokines IL-1β and IL-18, which it proteolytically cleaves into active mature peptides.
Caspase 3
(C14: Caspase)
  • erythrocyte differentiation (GO:0030218) IDA
  • B cell homeostasis (GO:0001782) IEA
  • negative regulation of B cell proliferation (GO:0030889) IEA
  • T cell homeostasis (GO:0043029) IEA
  • negative regulation of activated T cell proliferation (GO:0046007) IEA
Defective caspase 3 expression in immune effector cells may influence susceptibility to Kawasaki disease, an acute vasculitis syndrome affecting small- and medium-sized arteries of infants and children [451] ...
Caspase 4
(C14: Caspase)
  • regulation of inflammatory response (GO:0050727) IBA
Recognition of cytoplasmic lipopolysaccharide (LPS) by Inflammatory caspases including caspases-4 and -5 leads to pyroptosis and secretion of inflammatory mediators [536-537] ...
Caspase 5
(C14: Caspase)
  • regulation of inflammatory response (GO:0050727) IBA
Recognition of cytoplasmic lipopolysaccharide (LPS) by Inflammatory caspases including caspases-4 and -5 leads to pyroptosis and secretion of inflammatory mediators [536-537] ...
Caspase 8
(C14: Caspase)
  • toll-like receptor 3 signaling pathway (GO:0034138) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • positive regulation of macrophage differentiation (GO:0045651) IMP
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
Roles of apoptotic caspases extending beyond cell death, for example, mediating cellular immune processes such as inflammasome modulation, necroptosis and pro-inflammatory cytokine processing have been reported [379] ...
cathepsin B
(C1: Papain)
  • toll-like receptor signaling pathway (GO:0002224) TAS
Cathepsins B, H and L have become important therapeutic targets as their proteolytic activity has been implicated in several pathological inflammatory conditions, such as arthritis and periodontitis. Therefore, pharmacological inhibitors of these enzymes are in development as novel therapeutics.
cathepsin C
(C1: Papain)
  • positive regulation of microglial cell activation (GO:1903980) IEA
Cathepsin C is a lysosomal cysteine protease constitutively expressed at high levels in lung, kidney, liver and spleen. As well as activity in lysosomal protein degradation, catheposin C also plays a key role in the activation of granule serine proteases in cytotoxic T cells, natural killer cells (g ...
cathepsin G
(S1: Chymotrypsin)
  • positive regulation of immune response (GO:0050778) IEA
Cathepsin G is a leukocyte serine protease of the chymotrypsin family, related to neutrophil elastase and the granzymes. It is stored in azurophil granules and acts intracellularly to degrade ingested host pathogens and axtracellularly to breakdown ECM components at sites of inflammation. Cathepsin ...
cathepsin H
(C1: Papain)
  • immune response-regulating signaling pathway (GO:0002764) IDA
Cathepsin H may act as a pro-granzyme B convertase [139] ...
cathepsin L
(C1: Papain)
  • toll-like receptor signaling pathway (GO:0002224) TAS
Cathepsins B, H and L have become important therapeutic targets as their proteolytic activity has been implicated in several pathological inflammatory conditions, such as arthritis and periodontitis. Therefore, pharmacological inhibitors of these enzymes are in development as novel therapeutics.
cathepsin S
(C1: Papain)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • positive regulation of inflammatory response (GO:0050729) IGI
Cathepsin S is expressed in the lysosome of antigen presenting cells (dendritic cells, B-cells and macrophages) where it processes the invariant chain-MHC-II complex (a chaperone protein that prevents premature peptide loading) inside antigen presenting cells and in this way controls antigen presentation. Due to this role in antigen presentation, inhibition of cathepsin S is expected to cause immunosuppression [587] ...
chymase 1
(S1: Chymotrypsin)
  • regulation of inflammatory response (GO:0050727) IC
Chymase is a chymotrypsin-like serine protease that is expressed by mast cells. Amongst its activities, chymase is involved in the conversion of angiotensin (AT) I to ATII, its protease activity cleaves latent TGFβ1 and IL-1β in the cellular environment to generate the active cytokines, and it can further stimulate mast cell degranulation in a self-amplification loop. The potential of chymase as a drug target for inflammatory and gastrointestinal disorders is reviewed by Heuston and Hyland (2012) [241] ...
complement C1r
(S1: Chymotrypsin)
  • complement activation (GO:0006956) TAS
  • complement activation, classical pathway (GO:0006958) TAS
  • regulation of complement activation (GO:0030449) TAS
A protease component of the C1-complex of the classical complement pathway.
complement C1s
(S1: Chymotrypsin)
  • complement activation (GO:0006956) TAS
  • complement activation, classical pathway (GO:0006958) TAS
  • regulation of complement activation (GO:0030449) TAS
A protease component of the C1-complex of the classical complement pathway.
complement factor B
(S1: Chymotrypsin)
  • complement activation (GO:0006956) TAS
  • complement activation, alternative pathway (GO:0006957) TAS
  • regulation of complement activation (GO:0030449) TAS
A protease component of the alternative complement pathway. Cleaved by complement factor D ...
complement factor D
(3.4.21.46 Complement factor D)
  • complement activation (GO:0006956) TAS
  • complement activation, alternative pathway (GO:0006957) TAS
A protease component of the alternative complement pathway; responsible for cleaving complement factor B ...
component of inhibitor of nuclear factor kappa B kinase complex
(IKK family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
Ikkα is one of the catalytic subunits of the IκB kinase (IKK) complex, an upstream component of the NF-κB signal transduction cascade; NF-κB signaling being involved in propagating the cellular response to inflammation. IKK frees NF-κB from its inhibitory interaction with IκBα (inhibitor of kappa B), allowing NF-κB translocation to the nucleus where it modulates transcriptional activity. Additional functions of Ikkα beyond NF-κB activation are reviewed in [254] ...
COX-2
(Cyclooxygenase)
  • positive regulation of fever generation (GO:0031622) ISS
  • regulation of inflammatory response (GO:0050727) NAS
  • regulation of neuroinflammatory response (GO:0150077) ISS
The cyclooxygenase enzymes are included in GtoImmuPdb as they are involved in the production of inflammatory mediators, and are long-standing anti-inflammatory drug targets. The role of COX-2 in immuno-oncology is reviewed in [2] ...
C-terminal Src kinase
(Csk family)
  • T cell costimulation (GO:0031295) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • regulation of T cell activation (GO:0050863) TAS
  • regulation of Fc receptor mediated stimulatory signaling pathway (GO:0060368) IBA
CSK is an inhibitory regulator of Src family kinases, a family of protein tyrosine kinases indispensable to the initiation of signal transduction via ITAM-bearing immunoreceptors, and cytokine, growth factor, and pattern recognition receptor signalling. CSK phosphorylates an inhibitory tyrosine residue at the C terminus of Src kinases, leading to autoinhibition. CSK-induced Src kinase inhibition can also be mediated by binding to PEST family receptor tyrosine phosphatases [611] ...
cyclin dependent kinase 6
(CDK4 subfamily)
  • negative regulation of myeloid cell differentiation (GO:0045638) IDA
  • regulation of erythrocyte differentiation (GO:0045646) IMP
  • negative regulation of monocyte differentiation (GO:0045656) IDA
  • regulation of hematopoietic stem cell differentiation (GO:1902036) IEA
Phenotypic abnormalities in CDK6 knockout mice suggest biological roles in addition to mitotic cell cycle regulation. Alternate roles include involvement in hematopoietic function and inhibition of T cell differentiation [219,461] ...
death associated protein kinase 2
(Death-associated kinase (DAPK) family)
  • positive regulation of neutrophil chemotaxis (GO:0090023) IMP
  • positive regulation of eosinophil chemotaxis (GO:2000424) IMP
DAPk2 is recognised as a regulator of apoptosis, autophagy and inflammation [203] ...
Ecto-5'-Nucleotidase
(Adenosine turnover)
  • negative regulation of inflammatory response (GO:0050728) IEA
Via the conversion of ADP/ATP to AMP (CD39; ENTPD1) and AMP to adenosine (CD73; NT5E) these ectonucleotidase enzymes are crucial to the regulation of purinergic signals delivered to immune cells [18] ...
elastase, neutrophil expressed
(S1: Chymotrypsin)
  • negative regulation of inflammatory response (GO:0050728) NAS
  • positive regulation of immune response (GO:0050778) IEA
  • positive regulation of leukocyte tethering or rolling (GO:1903238) IEA
Neutrophil elastase (NE) is a serine proteinase with broad substrate specificity. It is stored in azurophil granules within neutrophils and is involved primarily in host defence. However, in addition to attacking proteins on invading microorganisms, secreted NE also hydrolyzes proteins of the host extracellular matrix, such as collagen-IV and elastin, hence its role in degenerative and inflammatory diseases. NE functions as a promoter of γδ T cell activation via a protease-activated receptor (PAR1)-dependent mechanism [594] ...
eukaryotic translation initiation factor 2 alpha kinase 2
(Other PEK family kinases)
  • regulation of hematopoietic progenitor cell differentiation (GO:1901532) ISS
  • regulation of hematopoietic stem cell proliferation (GO:1902033) ISS
  • regulation of hematopoietic stem cell differentiation (GO:1902036) ISS
Protein kinase-R (EIF2AK2) is activated by virally-introduced double-stranded RNA (dsRNA), and is therefore involved in protection against viral infection. Protein activator of the interferon-induced protein kinase EIF2AK2 (PACT; PRKRA) also activates protein kinase-R. Activated protein kinase-R phosphorylates the eukaryotic translation initiation factor eIF2α inhibiting viral protein synthesis [199] ...
eukaryotic translation initiation factor 2 alpha kinase 4
(GCN2 subfamily)
  • positive regulation of defense response to virus by host (GO:0002230) ISS
  • positive regulation of adaptive immune response (GO:0002821) ISS
GCN2 is a so-called 'stress kinase'. It phosphorylates serine 51 on the global transcription factor eIF2α upon activation by uncharged tRNA; tRNAs accumulate when amino acid levels are depleted. Phospho-eIF2α blocks translation to cause proliferative arrest.

GCN2 plays several roles in the immune system. It is required for dendritic cell activation and antigen presentation. The GCN2 stress response is required for both optimal proliferation of CD8+ T cells after antigen stimulation, and trafficking to lymphoid organs, i.e. for normal cytotoxic T cell function [601] ...
FER tyrosine kinase
(Fer family)
  • negative regulation of mast cell activation involved in immune response (GO:0033007) ISS
  • Fc-epsilon receptor signaling pathway (GO:0038095) ISS
  • regulation of mast cell degranulation (GO:0043304) IBA
FER acts downstream of the activated high affinity immunoglobulin epsilon receptor (FCεR1) and plays a role in FCεR1-mediated signaling in mast cells, regulation of mast cell degranulation, leukocyte recruitment, and leukocyte extravasation following bacterial lipopolysaccharide (LPS ...
FGR proto-oncogene, Src family tyrosine kinase
(Src family)
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • positive regulation of mast cell degranulation (GO:0043306) ISS
  • regulation of innate immune response (GO:0045088) ISS
  • negative regulation of natural killer cell activation (GO:0032815) IEA
Fgr may be involved in neutrophil migration, potentially via binding to intergrins [40] ...
FYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) IDA
Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [457] ...
glycogen synthase kinase 3 beta
(GSK subfamily)
  • positive regulation of osteoclast differentiation (GO:0045672) IMP
GSK3β plays an essential function in T cell differentiation and proliferation, and its activity is inhibited following antigen-driven T cell activation [58-59,368,444] ...
Haem oxygenase 1
(Haem oxygenase)
  • negative regulation of leukocyte migration (GO:0002686) TAS
  • erythrocyte homeostasis (GO:0034101) IMP
  • negative regulation of mast cell cytokine production (GO:0032764) IEA
  • negative regulation of mast cell degranulation (GO:0043305) IEA
Heme oxygenase (HO) is a rate-limiting enzyme in the catabolism of heme, catalyzing the oxidative cleavage of heme (Fe-protoporphyrin-IX) to render equimolar amounts of biliverdin, ferrous iron (Fe2+), and carbon monoxide (CO).

Heme oxygenase 1 (HO1) is a Nrf2-regulated gene, whose expression is upregulated as a cytoprotective mechanism in response to cellular stresses including inflammation, ischemia, hypoxia, hyperoxia, hyperthermia, or radiation.

HO1 has antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, playing an important role in the prevention of vascular inflammation and atherogenesis (reviewed in [20] ...
HCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • innate immune response-activating signal transduction (GO:0002758) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • regulation of inflammatory response (GO:0050727) TAS
Hck is thought to be involved in neutrophil migration, potentially via binding to intergrins [40] ...
IL2 inducible T cell kinase
(Tec family)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) ISS
  • B cell receptor signaling pathway (GO:0050853) IBA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [49] ...
indoleamine 2,3-dioxygenase 1
(1.13.11.- Dioxygenases)
  • negative regulation of activated T cell proliferation (GO:0046007) IMP
  • positive regulation of T cell tolerance induction (GO:0002666) IEA
  • positive regulation of chronic inflammatory response (GO:0002678) IEA
  • positive regulation of type 2 immune response (GO:0002830) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
The indoleamine 2,3 dioxygenase (IDO) branch of the kynurenine (KYN) pathway of tryptophan metabolism has been intensely studied in relation to immune tolerance and allergy. IDO is generally considered to be a tolerogenic, immunosuppressive enzyme, that is induced by IFN-γ. It provides a negative feedback pathway that limits uncontrolled immune responses. Its immunosuppressive actions arise from its promotion of tryptophan depletion, and elevation of KYN metabolite levels. The aryl hydrocarbon receptor serves as a receptor for KYN and should be considered when evaluating the IDO-KYN pathway in immune homeostasis and its potential to modulate innate and adaptive immune responses [311] ...
Inducible NOS
(Nitric oxide synthases)
  • regulation of cytokine production involved in inflammatory response (GO:1900015) IDA
The role of iNOS in immuno-oncology is reviewed in [2] ...
inhibitor of nuclear factor kappa B kinase subunit beta
(IKK family)
  • B cell homeostasis (GO:0001782) IMP
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
Iκβ kinase β (IKK-2) is the pivotal enzyme component of the Iκβ kinase (IKK) complex, a complex crucial in regulating expression and activation of inflammatory mediators in airway epithelium. IKK-2 is an attractive target for development of pharmaceutical inhibitors with antiinflammatory action as treatments for asthma and chronic obstructive pulmonary disease (COPD) [45,64,550] ...
inhibitor of nuclear factor kappa B kinase subunit epsilon
(IKK family)
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • positive regulation of type I interferon-mediated signaling pathway (GO:0060340) IEA
IKKε is the only inducible IKK family member. Expression is induced in response to LPS, viral infection and several cytokines. IKKε expression is restricted to pancreas, thymus, spleen and peripheral blood leukocytes. This is in contrast to all other IKK family kinases which are cons ...
INPP5D
(Inositol polyphosphate phosphatases)
  • negative regulation of granulocyte differentiation (GO:0030853) IMP
  • positive regulation of lymphocyte differentiation (GO:0045621) IMP
  • T cell receptor signaling pathway (GO:0050852) TAS
  • negative regulation of B cell activation (GO:0050869) IMP
  • negative regulation of B cell proliferation (GO:0030889) IEA
  • positive regulation of B cell differentiation (GO:0045579) IEA
  • positive regulation of erythrocyte differentiation (GO:0045648) IEA
  • negative regulation of monocyte differentiation (GO:0045656) IEA
  • negative regulation of neutrophil differentiation (GO:0045659) IEA
  • negative regulation of osteoclast differentiation (GO:0045671) IEA
  • negative regulation of immune response (GO:0050777) IEA
SHIP1 activators are proposed as novel anti-inflammatory agents e.g. rosiptor (AQX-1125) which is in Phase 2 and 3 clinical trials [429,560] ...
interleukin 1 receptor associated kinase 1
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 2 signaling pathway (GO:0034134) IMP
  • toll-like receptor 4 signaling pathway (GO:0034142) IBA
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
One of the two proximal mediators of IL-1 signaling via the IL-1 receptor, plays a part in IL-1-induced upregulation of the transcription factor NF-κB, the other being IRAK2. Interacts with other proteins including TRAF6, Myd88, CHUK, IKK2 and TLR4.
interleukin 1 receptor associated kinase 2
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
IRAK2 is one of the proximal mediators of IL-1 signalling via the IL-1 receptor, the other being IRAK1. It plays a part in IL-1-induced upregulation of the transcription factor NF-κB. IRAK2 interacts with TRAF6 and Myd88.
interleukin 1 receptor associated kinase 3
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • positive regulation of macrophage tolerance induction (GO:0010933) ISS
  • negative regulation of macrophage cytokine production (GO:0010936) ISS
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) ISS
  • negative regulation of innate immune response (GO:0045824) ISS
IRAK3 expression is restricted to monocytes and macrophages.
interleukin 1 receptor associated kinase 4
(Interleukin-1 receptor-associated kinase (IRAK) family)
IRAK4 is involved in Myddosome formation which regulates transcription factor activation and drives cytokine production to effect anti-pathogen responses and inflammation [172,421].
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
IRAK4 is essential for most innate immune responses to bacteria and viruses, and IRAK4 deficiency (caused by mutations) has been shown to result in recurrent invasive pneumococcal disease [401] ...
IP3 kinase B
(Inositol 1,4,5-trisphosphate 3-kinases)
  • myeloid cell homeostasis (GO:0002262) IEA
  • negative regulation of neutrophil apoptotic process (GO:0033030) IEA
  • negative regulation of myeloid cell differentiation (GO:0045638) IEA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
IP3 kinase B (ITPKB) as an essential mediator of T cell activation, whose inhibition is considered a novel approach to treat autoimmune disease [405] ...
Janus kinase 1
(Janus kinase (JakA) family)
JAK1 is crucial for mediating the intracellular signals for a range of type I and type II cytokines, and for type I and type II interferons (IFN-α/β and IFN-γ respectively) following ligand-receptor interaction.
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
The JAK1 tyrosine kinase is crucial for signaling of certain type I and type II cytokines, via receptors belonging to the IL-2, IL-4 and IL-6 receptor families as well as neurotrophin-1 and leptin receptors (all type I cytokine receptors). JAK1 is also involved in signalling via type I ...
Janus kinase 2
(Janus kinase (JakA) family)
  • erythrocyte differentiation (GO:0030218) ISS
  • regulation of inflammatory response (GO:0050727) IDA
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
  • positive regulation of inflammatory response (GO:0050729) IEA
JAK2 signal transduction is a critical mediator of the immune response and is implicated in autoimmune conditions and in graft-versus-host disease (GvHD). The pro-inflammatory effects of IL-6, IL-12, and IL-23 on T cells are mediated via JAK2 [55,57,556] ...
Janus kinase 3
(Janus kinase (JakA) family)
  • negative regulation of dendritic cell cytokine production (GO:0002731) ISS
  • erythrocyte differentiation (GO:0030218) IBA
  • positive regulation of T cell proliferation (GO:0042102) IBA
  • positive regulation of activated T cell proliferation (GO:0042104) ISS
  • T cell homeostasis (GO:0043029) ISS
  • negative regulation of T-helper 1 cell differentiation (GO:0045626) ISS
  • negative regulation of T cell activation (GO:0050868) ISS
Psoriatic skin samples show elevated JAK3 (and JAK1) expression, with signalling predominantly through STAT3 [13] ...
LCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • T cell costimulation (GO:0031295) TAS
  • positive regulation of gamma-delta T cell differentiation (GO:0045588) IMP
  • regulation of regulatory T cell differentiation (GO:0045589) IGI
  • T cell receptor signaling pathway (GO:0050852) TAS
  • B cell receptor signaling pathway (GO:0050853) IBA
  • regulation of T cell receptor signaling pathway (GO:0050856) IDA
  • positive regulation of T cell receptor signaling pathway (GO:0050862) NAS
  • positive regulation of T cell activation (GO:0050870) IDA
  • regulation of lymphocyte activation (GO:0051249) NAS
Phosphorylation and activation of Lck is an early and critical step in pre-TCR (T cell receptor) and TCR signalling. Activated Lck phosphorylates immunoreceptor tyrosine-based activation motifs of the ζ chain of the TCR leading to recruitment and activation of ZAP-70 tyrosine kinase, and activation of downstream MAPKs and NF-κB. TCR-based signals are required at several stages of T-cell development and it is thought that Lck is the major contributor to TCR signal transduction (with the related Src tyrosine kinase Fyn also playing a role) [457] ...
LYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • B cell homeostasis (GO:0001782) ISS
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc receptor mediated stimulatory signaling pathway (GO:0002431) ISS
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) ISS
  • Fc receptor mediated inhibitory signaling pathway (GO:0002774) ISS
  • erythrocyte differentiation (GO:0030218) ISS
  • negative regulation of B cell proliferation (GO:0030889) IBA
  • T cell costimulation (GO:0031295) TAS
  • regulation of mast cell activation (GO:0033003) ISS
  • negative regulation of toll-like receptor 2 signaling pathway (GO:0034136) ISS
  • negative regulation of toll-like receptor 4 signaling pathway (GO:0034144) ISS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • regulation of mast cell degranulation (GO:0043304) ISS
  • regulation of erythrocyte differentiation (GO:0045646) ISS
  • negative regulation of immune response (GO:0050777) TAS
  • regulation of B cell receptor signaling pathway (GO:0050855) ISS
  • regulation of monocyte chemotaxis (GO:0090025) IMP
  • negative regulation of myeloid leukocyte differentiation (GO:0002762) IEA
  • toll-like receptor 4 signaling pathway (GO:0034142) IEA
  • regulation of inflammatory response (GO:0050727) IEA
  • B cell receptor signaling pathway (GO:0050853) IEA
  • positive regulation of B cell receptor signaling pathway (GO:0050861) IEA
  • positive regulation of Fc receptor mediated stimulatory signaling pathway (GO:0060369) IEA
LYN is a Src family tyrosine kinase, expressed predominantly in hematopoietic cells, but also in neural, liver, and adipose tissues. LYN appears to function as a rheostat to modulate B cell signaling, and can be activating or inhibitory in action, depending on the B cell receptor and interacting protein complement present in particular cells [190,197,593] ...
mitogen-activated protein kinase 1
(ERK subfamily)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) IEA
  • B cell receptor signaling pathway (GO:0050853) IEA
In endothelial cells of the vasculature, and in activated human mast cells, ERK serves as an anti-inflammatory signal that suppresses production of pro-inflammatory mediators [303,375] ...
mitogen-activated protein kinase 13
(p38 subfamily)
  • positive regulation of inflammatory response (GO:0050729) IC
p38 MAP kinases are ubiquitous, highly conserved enzymes which regulate the production of proinflammatory mediators (such as TNFα and IL-1) in response to inflammatory cytokines or environmental stress [225-226,338,465,488,625] ...
mitogen-activated protein kinase 14
(p38 subfamily)
  • positive regulation of erythrocyte differentiation (GO:0045648) IMP
  • regulation of cytokine production involved in inflammatory response (GO:1900015) IDA
  • positive regulation of cytokine secretion involved in immune response (GO:0002741) IEA
  • positive regulation of macrophage chemotaxis (GO:0010759) IEA
p38 MAP kinases are ubiquitous, highly conserved enzymes which regulate the production of proinflammatory mediators (such as TNFα and IL-1) in response to inflammatory cytokines or environmental stress [225-226,338,465,488,625] ...
mitogen-activated protein kinase 8
(JNK subfamily)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
By regulating AP-1 transcriptional activity in response to cytokine activation, JNK1 contributes to the production of immunomodulators such as RANTES, IL-8 and GM-CSF .
mitogen-activated protein kinase 9
(JNK subfamily)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
Experimental evidence suggests that JNK2 is important in T-cell differentiation [270,511,564,659] ...
mitogen-activated protein kinase kinase kinase 7
(TAK1 subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • positive regulation of T cell cytokine production (GO:0002726) IMP
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
TAK1 (MAP3K7) mediates signaling downstream of multiple cytokine receptors and is functionally important in mitogen, immune, and inflammatory signaling pathways [142,514] ...
MMP12
(M10: Matrix metallopeptidase)
  • regulation of defense response to virus by host (GO:0050691) IEA
  • negative regulation of type I interferon-mediated signaling pathway (GO:0060339) IEA
  • positive regulation of type I interferon-mediated signaling pathway (GO:0060340) IEA
MMP12 is included in GtoImmuPdb based on its reported involvement in asthma and potential as a asthma therapeutic target.
MMP14
(M10: Matrix metallopeptidase)
  • positive regulation of B cell differentiation (GO:0045579) ISS
  • positive regulation of macrophage migration (GO:1905523) IEA
MMP14 is included in GtoImmuPdb based on its contribution to degradation of collagenous cartilage matrix in rheumatoid arthritis. An anti-MMP14 antibody, DX-2400 [157] ...
MMP2
(M10: Matrix metallopeptidase)
  • positive regulation of innate immune response (GO:0045089) IDA
MMP2 is included in GtoImmuPdb based on its potential involvement in asthma.
MMP3
(M10: Matrix metallopeptidase)
  • regulation of neuroinflammatory response (GO:0150077) TAS
MMP3 is included in GtoImmuPdb based on its reported involvement in inflammatory diseases.
MMP8
(M10: Matrix metallopeptidase)
  • regulation of neuroinflammatory response (GO:0150077) TAS
  • positive regulation of neuroinflammatory response (GO:0150078) ISS
  • regulation of microglial cell activation (GO:1903978) TAS
  • positive regulation of microglial cell activation (GO:1903980) ISS
MMP8 is included in GtoImmuPdb based on its potential protective role in asthma.
MMP9
(M10: Matrix metallopeptidase)
  • positive regulation of leukocyte migration (GO:0002687) ISO
  • regulation of neuroinflammatory response (GO:0150077) TAS
Mucosal up-regulation of MMP-9 correlates with the severity of inflammation in ulcerative colitis, and may be responsible for the mucosal damage in active ulcerative colitis [330] ...
otulin
(C101: OTULIN peptidase)
  • negative regulation of inflammatory response (GO:0050728) IMP
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IMP
Otulin is reported as a negative regulator of inflammation and autoimmunity [144] ...
p21 (RAC1) activated kinase 1
(PAKA subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
PAK1 is reported to modulate a pro-inflammatory PPARγ/NF-κB cascade in intestinal inflammation, that may be relevant in inflammatory bowel disease and colitis-associated cancer [145] ...
p21 (RAC1) activated kinase 2
(PAKA subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
Pharmacological inhibition of PAK2 has immunosuppressive effects [442] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases)
  • T cell costimulation (GO:0031295) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
PI3Kα is primarily recognised for its oncogenic function. We have included it in GtoImmuPdb based on its numerous GO immune process associations.
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases)
  • B cell homeostasis (GO:0001782) IMP
  • positive regulation of neutrophil apoptotic process (GO:0033031) IMP
  • T cell receptor signaling pathway (GO:0050852) TAS
  • B cell receptor signaling pathway (GO:0050853) TAS
PI3Kδ is preferentially expressed in cells of hemopoietic lineage and is involved in neutrophil chemotaxis. It is the only PI3K isoform with expression restricted to leukocytes. Genetic and pharmacological inactivation of PI3Kδ indicates its importantance for the function of T cells, B cell, mast cells and neutrophils. PI3kδ is a promising target for drugs for preventing or treating inflammation, autoimmunity and transplant rejection [235] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases)
  • positive regulation of acute inflammatory response (GO:0002675) IEA
The role of PI3Kγ in immuno-oncology is reviewed in [2] ...
phosphodiesterase 4B
(Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs))
  • neutrophil homeostasis (GO:0001780) ISS
  • T cell receptor signaling pathway (GO:0050852) IMP
PDE4 is a drug target, whose inhibition has anti-inflammatory action. PDE4 inhibitors have already entered clinical use, being employed in the treatment of inflammatory skin conditions such as psoriatic arthritis () and atopic dermatitis (). PDE4B is the predominant phosphodiesterase subtype in monocytes and neutrophils and this is thought to be the sub-type central to inflammatory action of phosphodiesterases [622] ...
phosphodiesterase 4D
(Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs))
  • T cell receptor signaling pathway (GO:0050852) IMP
The selective PDE4 inhibitor (OPA-15406) has been shown to inhibit PDE4D3 [446] ...
phosphodiesterase 5A
(Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs))
  • positive regulation of chronic inflammatory response (GO:0002678) ISO
  • negative regulation of T cell proliferation (GO:0042130) IEA
The role of PDE5A in immuno-oncology is reviewed in [2] ...
phosphoinositide-3-kinase regulatory subunit 1
(Phosphatidylinositol kinases)
  • T cell costimulation (GO:0031295) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • negative regulation of osteoclast differentiation (GO:0045671) IEA
p85α is included in GtoImmuPdb as it is the regulatory subunit of several PI3Ks (e.g. PI3Kδ and PI3Kγ) with roles in leukocyte biology and therefore important for immunity [371] ...
PLA2-G7
(Phospholipase A2, Hydrolases)
  • positive regulation of inflammatory response (GO:0050729) TAS
  • positive regulation of monocyte chemotaxis (GO:0090026) IDA
PLA2-G7 (also referred to as Lp-PLA2) is a pro-inflammatory enzyme. It cleaves oxidatively damaged phospholipid substrates to generate pro-inflammatory mediators including lysophosphatidylcholine and oxidized nonesterified fatty acids [373] ...
PLCγ1
(Phosphoinositide-specific phospholipase C)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [209,513] ...
PLCγ2
(Phosphoinositide-specific phospholipase C)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) ISS
  • B cell receptor signaling pathway (GO:0050853) ISS
Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [209,513] ...
proteasome 20S subunit beta 8
(T1: Proteasome)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • regulation of hematopoietic stem cell differentiation (GO:1902036) TAS
PSMB8 is a component of the immunoproteasome [183] ...
protein kinase C alpha
(Delta subfamily)
  • positive regulation of macrophage differentiation (GO:0045651) ISS
  • positive regulation of inflammatory response (GO:0050729) IMP
PKCα is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C beta
(Alpha subfamily)
  • regulation of myeloid cell differentiation (GO:0045637) TAS
  • B cell receptor signaling pathway (GO:0050853) ISS
  • positive regulation of B cell receptor signaling pathway (GO:0050861) ISS
PKCβ is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C delta
(Delta subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • negative regulation of inflammatory response (GO:0050728) IC
PKCδ is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C epsilon
(Eta subfamily)
  • TRAM-dependent toll-like receptor 4 signaling pathway (GO:0035669) ISS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
PKCε is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C eta
(Eta subfamily)
  • positive regulation of B cell receptor signaling pathway (GO:0050861) IMP
PKCη is included in GtoImmuPdb based on the involvement of other PKC isozymes in immune processes.
protein kinase C theta
(Delta subfamily)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • regulation of megakaryocyte differentiation (GO:0045652) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • positive regulation of T cell activation (GO:0050870) ISS
  • positive regulation of T-helper 17 type immune response (GO:2000318) ISS
  • positive regulation of T-helper 2 cell activation (GO:2000570) ISS
  • positive regulation of T cell proliferation (GO:0042102) IEA
PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [27] ...
protein kinase C zeta
(Iota subfamily)
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) ISS
  • positive regulation of T-helper 2 cell cytokine production (GO:2000553) ISS
PKCζ is included in GtoImmuPdb based on its GO process associations.
protein kinase, DNA-activated, catalytic subunit
(Other PIKK family kinases)
  • activation of innate immune response (GO:0002218) IDA
  • positive regulation of immune system process (GO:0002684) ISO
  • negative regulation of immunoglobulin production (GO:0002638) IEA
Protein kinase, DNA-activated, catalytic polypeptide (DNA-PKcs) principally acts to repair DNA in a process called non-homologous end joining (NHEJ). NHEJ is required for V(D)J recombination (somatic recombination) in developing lymphocytes during the early stages of T and B cell maturation. DNA-PKc ...
protein kinase N1
(Protein kinase N (PKN) family)
  • B cell homeostasis (GO:0001782) IEA
  • regulation of germinal center formation (GO:0002634) IEA
  • regulation of immunoglobulin production (GO:0002637) IEA
  • negative regulation of B cell proliferation (GO:0030889) IEA
Evidence suggests that PKN1 plays a role in modulation of the NF-κB signalling pathway. Specifically, in Salmonella infection, PKN1 is hijacked by a bacterial effector protein which results in inhibition of NF-κB-dependent gene expression (i.e. inhibition of production of the proinflammatory cytokines that would normally effect bacterial destruction and removal) [233] ...
protein tyrosine kinase 2
(Fak family)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
FAK and Pyk2 are phosphorylated downstream of the T cell antigen receptor (TCR) to bring about receptor-specific T cell development and activation [104] ...
protein tyrosine kinase 2 beta
(Fak family)
  • regulation of macrophage chemotaxis (GO:0010758) ISS
  • negative regulation of myeloid cell differentiation (GO:0045638) IMP
  • positive regulation of B cell chemotaxis (GO:2000538) ISS
FAK and Pyk2 are phosphorylated downstream of the T cell antigen receptor (TCR) to bring about receptor-specific (e.g. chemokine and integrin receptors) T cell development and activation [104] ...
protein tyrosine phosphatase non-receptor type 22
(Protein tyrosine phosphatases non-receptor type (PTPN))
  • positive regulation of defense response to virus by host (GO:0002230) IMP
  • regulation of leukocyte migration (GO:0002685) IMP
  • regulation of natural killer cell proliferation (GO:0032817) IDA
  • positive regulation of toll-like receptor 3 signaling pathway (GO:0034141) IMP
  • positive regulation of toll-like receptor 4 signaling pathway (GO:0034145) IMP
  • positive regulation of toll-like receptor 7 signaling pathway (GO:0034157) IMP
  • positive regulation of toll-like receptor 9 signaling pathway (GO:0034165) IMP
  • regulation of innate immune response (GO:0045088) IC
  • T cell receptor signaling pathway (GO:0050852) TAS
  • regulation of B cell receptor signaling pathway (GO:0050855) NAS
  • negative regulation of T cell receptor signaling pathway (GO:0050860) IDA
  • negative regulation of T cell activation (GO:0050868) IMP
  • negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070433) IMP
  • positive regulation of granzyme B production (GO:0071663) IMP
  • positive regulation of CD8-positive, alpha-beta T cell proliferation (GO:2000566) IMP
PTPN22 is a lymphoid-specific, inducible protein tyrosine phosphatase [121] ...
RAB27A, member RAS oncogene family
(RAB subfamily)
  • complement-dependent cytotoxicity (GO:0097278) IMP
Small molecule inhibitors of Rab27a-JFC1 binding, termed Nexinhibs (neutrophil exocytosis inhibitors) demonstrate the druggability of Rab GTPases and inhibition of exocytosis of azurophilic granules in human neutrophils without affecting other important innate immune responses, including phagocytosis and neutrophil extracellular trap production. These thus have potential use as an inhibitor of systemic inflammation [280] ...
receptor interacting serine/threonine kinase 1
(Receptor interacting protein kinase (RIPK) family)
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • toll-like receptor 3 signaling pathway (GO:0034138) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • positive regulation of macrophage differentiation (GO:0045651) IMP
RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [427,497,540,615] ...
receptor interacting serine/threonine kinase 2
(Receptor interacting protein kinase (RIPK) family)
  • positive regulation of T-helper 1 type immune response (GO:0002827) IMP
  • toll-like receptor 2 signaling pathway (GO:0034134) IDA
  • T cell receptor signaling pathway (GO:0050852) ISS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IDA
  • positive regulation of immature T cell proliferation (GO:0033091) IEA
  • toll-like receptor 4 signaling pathway (GO:0034142) IEA
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) IEA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
  • nucleotide-binding oligomerization domain containing 1 signaling pathway (GO:0070427) IEA
RIPK2 is involved in innate immune responses, mediating pro-inflammatory signaling from the bacterial peptidoglycan-sensing NOD1/NOD2 subfamily of innate immune pattern recognition receptors (PRRs) and signalling downstream from the Toll-like receptor (TLR) family of PRRs. Further evidence suggesting an inflammatory role is the targeting of RIPK2 (along with RIPK1/3) by the IAP family E3 ubiquitin ligases (enzymes playing a critical role in innate immunity) [438] ...
receptor interacting serine/threonine kinase 3
(Receptor interacting protein kinase (RIPK) family)
  • regulation of T cell mediated cytotoxicity (GO:0001914) ISS
  • regulation of adaptive immune response (GO:0002819) ISS
  • T cell homeostasis (GO:0043029) ISS
  • regulation of activated T cell proliferation (GO:0046006) ISS
  • regulation of activation-induced cell death of T cells (GO:0070235) ISS
  • regulation of CD8-positive, alpha-beta cytotoxic T cell extravasation (GO:2000452) ISS
RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [427,497,540,615] ...
serine/threonine kinase 11
(LKB subfamily)
  • T cell receptor signaling pathway (GO:0050852) IEA
Development of fatal TH2-dominant inflammatory symptoms in mice with a specific Stk11 knockout in their Treg cells, and experiments showing Stk11's role in the coordination of metabolic and functional fitness of Treg cells, suggest that this kinase acts as a crucial checkpoint that actively maintains Treg cell survival and homeostatic function [237,661] ...
sirtuin 1
(3.5.1.- Histone deacetylases (HDACs))
  • positive regulation of adaptive immune response (GO:0002821) IDA
Sirtuin 1 has been suggested as a molecular target for host-directed therapy against Mycobacterium tuberculosis infection by research that shows that activation of sirtuin 1 decreases lung pathology, reduces inflammation, and enhances drug efficacy against Mycobacterium tuberculosis [113] ...
sphingosine kinase 2
(Sphingosine kinase)
  • positive regulation of mast cell activation involved in immune response (GO:0033008) ISS
  • positive regulation of mast cell degranulation (GO:0043306) ISS
SK2 is involved in regulating interleukin (IL)-12/interferon gamma (IFN-γ) and histone deacetylase-1/2 (HDAC-1/2) signalling, and is considered to be an anti-inflammatory enzyme with potential druggability for the treatment of autoimmune and inflammatory diseases [485] ...
sPLA2-1B
(Phospholipase A2)
  • positive regulation of immune response (GO:0050778) ISS
sPLA2 enzymes catalyze the first step of the arachidonic acid pathway, so are inextricably involved in the production of arachadonic acid for inflammatory mediator synthesis. Excess sPLA2 activity is suggested to contribute to several inflammatory diseases. The sPLA2-1B isozyme has been reported to induce leukotriene B4 (LTB4) production in human neutrophils, using a mechanism independent of arachadonic acid generation [337] ...
spleen associated tyrosine kinase
(Syk family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • positive regulation of mast cell degranulation (GO:0043306) IBA
  • regulation of neutrophil degranulation (GO:0043313) ISS
  • positive regulation of B cell differentiation (GO:0045579) IMP
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IBA
  • regulation of immune response (GO:0050776) ISO
  • B cell receptor signaling pathway (GO:0050853) ISS
  • positive regulation of gamma-delta T cell differentiation (GO:0045588) IEA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
SYK plays a key role in coupling activated immunoreceptors to downstream cellular responses such as proliferation, differentiation, and phagocytosis. Mast cell, macrophage and B-cell activation (and release of inflammatory modulators) is disrupted by inhibition of SYK-mediated immunoreceptor signalling. Selective SYK inhibitors are being sought for a number of inflammatory conditions including rheumatoid arthritis, B-cell lymphoma and asthma/rhinitis [207,496] ...
SRC proto-oncogene, non-receptor tyrosine kinase
(Src family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
Src family tyrosine kinases act as general modulators of immune cell signaling, playing diverse signaling functions, both inhibitory and stimulatory, in immunoreceptor and integrin signaling pathways [369] ...
TANK binding kinase 1
(IKK family)
  • activation of innate immune response (GO:0002218) IMP
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • positive regulation of type I interferon-mediated signaling pathway (GO:0060340) IEA
TBK1 belongs to the IKK-kinase family of enzymes. It is a ubiquitously expressed serine/threonine protein kinase, and constitutes a key regulatory node for several signaling pathways involved in the innate immune response that lead to induction of type I interferons. Several classes of innate sensors including the TLRs and retinoic acid-inducible gene 1 (RIG-I)-like helicases engage TBK1-IRF3 signaling pathways to regulate transcription of type I IFNs. In neuroinflammation TBK1 is involved in TLR-dependent [292] ...
tec protein tyrosine kinase
(Tec family)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) IBA
  • B cell receptor signaling pathway (GO:0050853) IDA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [49] ...
transglutaminase 2
(2.3.2.13 Transglutaminases)
  • positive regulation of inflammatory response (GO:0050729) IEA
TGM2 upregulation by amyloid β (Aβ)1-42 in THP-1 monocytes increases pro-inflammatory mediators, including IL-1β and IL-6. A transglutaminase inhibitor can blunt this activation, suggesting that TGM2 up-regulation is involved in the pro-inflammatory effect of Aβ1-42 on monocytes [134] ...
tripartite motif containing 38
(2.3.2.27 RING-type E3 ubiquitin transferase)
  • negative regulation of defense response to virus (GO:0050687) IEA
TRIM38 catalyses the ubiquitination of Lys48 of the Toll-like receptor (TLR) adaptor protein TICAM1 (commonly referred to as TRIF) which mediates its proteosomal degradation. This action has been shown to inhibit TLR3-driven type I interferon signaling of the innate immune response [654] ...
TXK tyrosine kinase
(Tec family)
  • T cell receptor signaling pathway (GO:0050852) ISS
  • positive regulation of interferon-gamma-mediated signaling pathway (GO:0060335) IDA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [49] ...
vanin 1
(Hydrolases)
  • positive regulation of T cell differentiation in thymus (GO:0033089) ISS
Mounting evidence indicates that vanin 1 is involved in inflammation associated with diseases including systemic lupus erythematosus [573] ...
YES proto-oncogene 1, Src family tyrosine kinase
(Src family)
  • T cell costimulation (GO:0031295) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
Although primarily recognised for its oncogenic activity, we have iincluded YES1 in GtoImmuPdb based on its expression in cells of the immune system.
zeta chain of T cell receptor associated protein kinase 70
(Syk family)
  • positive regulation of T cell differentiation (GO:0045582) IDA
  • T cell receptor signaling pathway (GO:0050852) TAS
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
ZAP-70 has much lower intrinsic enzyme activity than SYK, and expression is restricted to T cells and NK cells [22] ...
Catalytic Receptors
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
AXL receptor tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • positive regulation of natural killer cell differentiation (GO:0032825) IDA
  • erythrocyte homeostasis (GO:0034101) IEA
  • negative regulation of lymphocyte activation (GO:0051250) IEA
  • neutrophil clearance (GO:0097350) IEA
All three TAM family receptor tyrosine kinases are involved in regulating inflammatory responses through a negative feedback loop. Specifically, AXL-Gas6 signalling is reported to induce autophagy in murine macrophages via inhibition of the NLRP3 inflammasome, an effect which reduces hepatic inflammation in a mouse model [224] ...
BAFF receptor
(Tumour necrosis factor (TNF) receptor family)
  • regulation of immune response (GO:0050776) IMP
  • B cell homeostasis (GO:0001782) IEA
  • positive regulation of germinal center formation (GO:0002636) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • T cell costimulation (GO:0031295) IEA
  • B cell costimulation (GO:0031296) IEA
  • positive regulation of T cell proliferation (GO:0042102) IEA
A type III membrane bound receptor for B-cell activating factor (BAFF). BAFF enhances B-cell survival and hence regulates the peripheral B-cell population. It is suggested that overproduction of BAFF may enhance the survival of autoreactive B cells, an effect which may contribute in the pathogenesis ...
B cell maturation antigen
(Tumour necrosis factor (TNF) receptor family)
  • lymphocyte homeostasis (GO:0002260) IEA
B-cell maturation antigen (BCMA) is a cell surface receptor for B-cell activating factor (BAFF). It interacts with various TRAF family adaptor proteins to modulate cell survival and proliferation, via NF-κB and MAPK8/JNK signal transduction pathways. BCMA is highly plasma cell-selective for malignant plasma cells from multiple myeloma (MM) patients, and is being investigated as a target for T-cell redirecting therapies to tackle relapsed/refractory MM [239,340] ...
CD27
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of B cell differentiation (GO:0045579) NAS
  • positive regulation of T cell differentiation (GO:0045582) IEA
CD27 (TNFRSF7) is a co-stimulatory immune checkpoint molecule that is expressed on various immune cells, including T cells and NK (natural killer) cells. The endogenous ligand for CD27 is CD70. CD27 interacts with various TRAF adaptor proteins and apoptosis regulatory protein SIVA (SIVA1). It has been recognized as playing an important role in priming, enhancing and sustaining a productive anti-cancer (CD8 T cell) adaptive immune response. CD27 is an immuno-oncology target [79,602] ...
CD40
(Immune checkpoint catalytic receptors, Tumour necrosis factor (TNF) receptor family)
  • regulation of immune response (GO:0050776) TAS
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
  • regulation of immunoglobulin secretion (GO:0051023) IEA
CD40 is a stimulatory receptor and a member of the tumor necrosis factor receptor superfamily (TNFRSF). It is expressed on a variety of immune cells, including macrophages, B cells, and dendritic cells (DCs). CD40 plays a key role in the activation of the immune system. Endogenous ligand is CD154 (C ...
colony stimulating factor 1 receptor
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • positive regulation of osteoclast differentiation (GO:0045672) ISO
Activation of the CSF1R induces myeloid proliferation, and in the tumour microenvironment this promotes M1 to M2 polarization and accumulation of tumour-associated macrophages (TAMs). The CSF1R is therefore being investigated as an immuno-oncology drug target [2] ...
Cytokine receptor-like factor 2
(IL-2 receptor family)
  • positive regulation of mast cell activation (GO:0033005) IMP
Cytokine receptor-like factor 2 is the signal transducing subunit of the functional heterodimeric receptor for thymic stromal lymphopoietin (TSLP). Ligand binding is attributed to the interleukin-7 receptor subunit α.
death receptor 6
(Tumour necrosis factor (TNF) receptor family)
  • negative regulation of B cell proliferation (GO:0030889) ISS
  • negative regulation of T cell proliferation (GO:0042130) ISS
  • T cell receptor signaling pathway (GO:0050852) ISS
Expressed predominantly in the thymus, spleen and white blood cells. May play a role in T helper cell activation, inflammation and immune regulation. Signals via the TRADD adaptor protein to the NF-κB and MAPK8/JNK pathways.
DExD/H-box helicase 58
(RIG-I-like receptor family)
  • positive regulation of defense response to virus by host (GO:0002230) IMP
  • positive regulation of myeloid dendritic cell cytokine production (GO:0002735) ISS
  • cytoplasmic pattern recognition receptor signaling pathway in response to virus (GO:0039528) TAS
  • RIG-I signaling pathway (GO:0039529) IMP
RIG-I is an intracellular sensor that responds to viral nucleic acids and activates downstream signaling, resulting in the induction of the type I interferon response [391] ...
DExH-box helicase 58
(RIG-I-like receptor family)
  • negative regulation of MDA-5 signaling pathway (GO:0039534) IMP
  • negative regulation of RIG-I signaling pathway (GO:0039536) IDA
  • regulation of innate immune response (GO:0045088) IDA
  • negative regulation of innate immune response (GO:0045824) IDA
  • positive regulation of MDA-5 signaling pathway (GO:1900245) ISS
  • positive regulation of RIG-I signaling pathway (GO:1900246) ISS
LGP2 binds RNA but does not participate in the signaling pathway that RIG-1 and MDA5 are part of, and is assumed to provide a negative feedback for IFNβ induction by sequestering pathogen-derived RNA.
Fas
(Tumour necrosis factor (TNF) receptor family)
  • activation-induced cell death of T cells (GO:0006924) IDA
  • T cell homeostasis (GO:0043029) IMP
  • regulation of lymphocyte differentiation (GO:0045619) IMP
  • regulation of myeloid cell differentiation (GO:0045637) IMP
  • negative regulation of B cell activation (GO:0050869) IMP
Fas receptor (CD95) is a cell surface protein that belongs to the tumor necrosis factor receptor family, that along with its ligand CD95L, generates a death receptor/death ligand system that mediates apoptosis induction to maintain immune homeostasis. This system is also important in the immune elimination of virus-infected cells, cancer cells and autoreactive T cells. Mouse strains with mutations in Fas or CD95L develop lymphoproliferative conditions, indicating the importance of these proteins to immune cell homeostasis [577] ...
fms related tyrosine kinase 3
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • leukocyte homeostasis (GO:0001776) ISS
  • dendritic cell homeostasis (GO:0036145) IMP
  • negative regulation of B cell differentiation (GO:0045578) IDA
FLT3 is the receptor for the cytokine Flt3 ligand (FLT3LG). Flt3 ligand is a growth factor akin to stem cell factor and colony stimulating factor 1, and is essential for hematopoietic progenitor cell development and expansion of both myeloid and lymphoid lineages. It is one of the growth factor receptors targeted by the chemotherapeutic tyrosine kinase inhibitor sorafenib.
Results from mouse experiments suggest that Flt3 ligand is effective in treating sepsis, by potentiating innate immune functions of dendritic cells and neutrophils and improving T cell function [462] ...
glucocorticoid-induced TNF receptor
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of leukocyte migration (GO:0002687) IMP
  • regulation of regulatory T cell differentiation (GO:0045589) TAS
GITR appears to act as a co-stimulatory immune checkpoint molecule. T cell activation induces GITR expression. GITR inhibits the suppressive activity of Treg cells and promotes survival of Teff cells.
Granulocyte colony-stimulating factor receptor
(Prolactin receptor family)
  • regulation of myeloid cell differentiation (GO:0045637) IEA
This nuclear receptor mediates the effects of the cytokine, colony stimulating factor 3 (CSF3). CSF3 regulates the production, differentiation, and function of granulocytes.
herpes virus entry mediator
(Immune checkpoint catalytic receptors, Tumour necrosis factor (TNF) receptor family)
  • positive regulation of cytokine secretion involved in immune response (GO:0002741) IBA
  • T cell costimulation (GO:0031295) TAS
  • negative regulation of alpha-beta T cell proliferation (GO:0046642) IBA
  • negative regulation of adaptive immune memory response (GO:1905675) IDA
  • positive regulation of T cell migration (GO:2000406) IBA
HSV viral envelope glycoprotein D (gD) binds to this protein and thereby gains entry to the cell. HVEM binds to several TRAFadaptor proteins to mediate intracellular signalling and activation of the immune response.
integrin, alpha 4 subunit (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
(Integrins)
  • positive regulation of leukocyte migration (GO:0002687) ISO
  • regulation of immune response (GO:0050776) TAS
  • positive regulation of leukocyte tethering or rolling (GO:1903238) IEA
  • positive regulation of T cell migration (GO:2000406) IEA
Integrin subunit alpha 4 is the alpha subunit of the α4β1 lymphocyte homing receptor. The cytoplasmic domain of α4 binds tightly to paxillin, a signaling adaptor protein, and this interaction promotes increased cell migration and inhibits cell spreading [227] ...
integrin, alpha L subunit (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide)
(Integrins)
  • positive regulation of T cell proliferation (GO:0042102) IMP
  • regulation of immune response (GO:0050776) TAS
ITGAL associates with the beta 2 chain (ITGB2) integrin and CD18 to form the lymphocyte function-associated antigen-1 (LFA-1) complex. LFA-1 is crucial for leukocyte intercellular adhesion and costimulatory signaling in the immune system. Ligands for LFA-1 are the intercellular adhesion molecules (ICAMs) 1-3. ITGAL is the target of the withdrawn psoriasis monoclonal antibody drug efalizumab ...
integrin, beta 2 subunit (complement component 3 receptor 3 and 4 subunit)
(Integrins)
  • toll-like receptor 4 signaling pathway (GO:0034142) TAS
  • positive regulation of neutrophil degranulation (GO:0043315) IGI
  • regulation of immune response (GO:0050776) TAS
  • positive regulation of microglial cell activation (GO:1903980) NAS
ITGB2 is the beta component of the β2 integrins. It forms αβ heterodimers with the CD11 alpha subunits ITGAL (αL aka CD11a forming integrin LFA-1), ITGAM (αM aka CD11b, forming integrin Mac-1) and ITGAX (αX aka CD11c, forming integrin p150/95). Beta2-integrins are essential for leukocyte extravasation to sites of infection (i.e. leukocyte trafficking), and other immunological processes including neutrophil phagocytosis and ROS production, and T cell activation. Their absence causes a leukocyte adhesion deficiency, which manifests clinically as recurrent severe infections, defective wound healing and neutrophilia [308] ...
Interferon α/β receptor 2
(Interferon receptor family)
  • regulation of type I interferon-mediated signaling pathway (GO:0060338) TAS
A subunit of the functional receptor for various interferons (NOT interferon γ).
Interferon γ receptor 1
(Interferon receptor family)
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
A subunit of the functional receptor for interferon γ.
Interferon γ receptor 2
(Interferon receptor family)
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
A subunit of the functional receptor for interferon γ.
interferon induced with helicase C domain 1
(RIG-I-like receptor family)
  • cytoplasmic pattern recognition receptor signaling pathway in response to virus (GO:0039528) TAS
  • MDA-5 signaling pathway (GO:0039530) IDA
MDA5 is an intracellualar RNA sensor. It recognizes longer double-stranded RNA sequences than RIG-1. In autoimmunity, MDA5 has been specifically linked with type I diabetes and anti-MDA5 autoantibodies can be detected in patients with certain connective tissue autoimmune conditions [5,249,404] ...
Interferon-λ receptor subunit 1
(IL-10 receptor family)
  • regulation of defense response to virus by host (GO:0050691) IDA
Interferon-λ receptor subunit 1 is the ligand binding component of the functional heterodimeric receptor for interferons λ1, λ2 and λ3
Interleukin-12 receptor, β1 subunit
(IL-12 receptor family)
  • positive regulation of T cell mediated cytotoxicity (GO:0001916) ISS
  • positive regulation of defense response to virus by host (GO:0002230) IDA
  • positive regulation of T-helper 1 type immune response (GO:0002827) IDA
  • positive regulation of activated T cell proliferation (GO:0042104) IDA
  • positive regulation of memory T cell differentiation (GO:0043382) ISS
  • positive regulation of T-helper 17 type immune response (GO:2000318) ISS
  • positive regulation of T-helper 17 cell lineage commitment (GO:2000330) ISS
This protein is a subunit of both the IL-12 and IL-23 cytokine receptors.
Interleukin 13 receptor, α2
(IL-2 receptor family)
  • negative regulation of immunoglobulin production (GO:0002638) IEA
  • negative regulation of mast cell degranulation (GO:0043305) IEA
Interleukin 13 receptor, α2 acts as a high affinity decoy receptor for interleukin 13 that sequesters the ligand away from IL13Rα1 and is involved in down-regulating IL-13 responses in vivo. IL13ra2 null mice exhibit enhanced IL-13 responses [646] ...
Interleukin-15 receptor subunit α
(IL-2 receptor family)
  • positive regulation of natural killer cell differentiation (GO:0032825) IMP
This is the ligand binding subunit of the functional IL-15 receptor complex.
Interleukin 17 receptor A
(IL-17 receptor family)
  • positive regulation of inflammatory response (GO:0050729) IMP
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) IEA
This protein is a common subunit shared by the heterodimeric receptors for interleukins 17 (A, B , C and F) and 25.
Interleukin 17 receptor B
(IL-17 receptor family)
  • positive regulation of inflammatory response (GO:0050729) IEA
IL17RB is a subunit of the heterodimeric interleukin-25 receptor.
interleukin 17 receptor C
(IL-17 receptor family)
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) IEA
This is a subunit of the heterodimeric interleukin-17 receptor.
Interleukin-18 receptor 1
(Immunoglobulin-like family of IL-1 receptors)
  • positive regulation of T-helper 1 cell cytokine production (GO:2000556) IDA
Interleukin-18 1 protein (IL18R1) is the ligand binding subunit of the functional IL-18 receptor heterodimer.
Interleukin-1 receptor-like 1
(Immunoglobulin-like family of IL-1 receptors)
  • negative regulation of T-helper 1 type immune response (GO:0002826) IEA
  • positive regulation of macrophage activation (GO:0043032) IEA
  • positive regulation of inflammatory response (GO:0050729) IEA
IL1RL1 (ST2) is the ligand binding subunit of the functional receptor for IL-33. It is mainly expressed on mast cells, eosinophils and other immune cells [195] ...
Interleukin-1 receptor-like 2
(Immunoglobulin-like family of IL-1 receptors)
  • positive regulation of T cell differentiation (GO:0045582) IEA
  • regulation of inflammatory response (GO:0050727) IEA
Interleukin-1 receptor-like 2 is one of the subunits of the functional receptor for IL-36.

An antibody that mimics IL-36RA's antagonist activity at the IL-36 receptor (MAB92) has been described [194] ...
Interleukin 1 receptor, type I
(Immunoglobulin-like family of IL-1 receptors)
  • positive regulation of T-helper 1 cell cytokine production (GO:2000556) IDA
  • regulation of inflammatory response (GO:0050727) IEA
  • positive regulation of neutrophil extravasation (GO:2000391) IEA
This is one of the subunits of the functional IL-1 receptor type I heterodimer.
Interleukin 1 receptor, type II
(Immunoglobulin-like family of IL-1 receptors)
  • negative regulation of cytokine production involved in inflammatory response (GO:1900016) IEA
IL-1R2 acts as a decoy receptor for IL-1β, thus reducing IL-1β binding/activation of IL-1R1. IL-1R2 thereby acts to down-regulate IL-1 responses [210,425] ...
Interleukin 20 receptor, β subunit
(IL-10 receptor family)
  • negative regulation of type IV hypersensitivity (GO:0001808) IEA
  • immune response-inhibiting signal transduction (GO:0002765) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
Interleukin 20 receptor, β subunit is a component of the functional receptor heterodimers for interleukins 19, 20 and 24.
Interleukin-22 receptor α2
(IL-10 receptor family)
  • negative regulation of inflammatory response (GO:0050728) IEA
IL22RA2 (a.k.a. IL-22 binding protein) appears to act as a high affinity, soluble monomeric decoy receptor for IL-22 capable of neutralizeing the potent antimicrobial activity of IL-22 [147,181] ...
Interleukin 23 receptor
(IL-12 receptor family)
  • positive regulation of T cell mediated cytotoxicity (GO:0001916) ISS
  • positive regulation of defense response to virus by host (GO:0002230) IDA
  • positive regulation of T-helper 1 type immune response (GO:0002827) IDA
  • positive regulation of natural killer cell proliferation (GO:0032819) IC
  • positive regulation of T cell proliferation (GO:0042102) IC
  • positive regulation of activated T cell proliferation (GO:0042104) IC
  • positive regulation of memory T cell differentiation (GO:0043382) ISS
  • positive regulation of osteoclast differentiation (GO:0045672) IC
  • positive regulation of NK T cell activation (GO:0051135) IC
  • positive regulation of T-helper 17 type immune response (GO:2000318) ISS
  • positive regulation of T-helper 17 cell lineage commitment (GO:2000330) ISS
This is one of the subunits of the functional IL-23 receptor heterodimer.
Interleukin 27 receptor, alpha
(IL-6 receptor family)
  • negative regulation of cellular extravasation (GO:0002692) IGI
  • positive regulation of T-helper 1 type immune response (GO:0002827) IEA
  • negative regulation of type 2 immune response (GO:0002829) IEA
  • regulation of isotype switching to IgG isotypes (GO:0048302) IEA
  • negative regulation of T-helper 17 type immune response (GO:2000317) IEA
  • negative regulation of T cell extravasation (GO:2000408) IEA
This is the ligand binding subunit of the IL-27 receptor heterodimer, a complex with IL6ST (signal transducing subunit).
Interleukin-2 receptor subunit α
(IL-2 receptor family)
  • regulation of T cell tolerance induction (GO:0002664) IMP
  • positive regulation of T cell proliferation (GO:0042102) ISO
  • T cell homeostasis (GO:0043029) IMP
  • regulation of regulatory T cell differentiation (GO:0045589) TAS
  • negative regulation of lymphocyte proliferation (GO:0050672) IMP
  • activation-induced cell death of T cells (GO:0006924) IEA
  • positive regulation of activated T cell proliferation (GO:0042104) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
  • positive regulation of T cell differentiation (GO:0045582) IEA
  • regulation of T cell homeostatic proliferation (GO:0046013) IEA
  • negative regulation of defense response to virus (GO:0050687) IEA
  • negative regulation of inflammatory response (GO:0050728) IEA
  • negative regulation of immune response (GO:0050777) IEA
IL2RA is a ligand binding component of the IL-2R complex. This subunit is the molecular target of the approved biologics daclizumab (including daclizumab beta) and basiliximab. Another anti-CD25 mAb, inolimomab, has received orphan drug designation from the EMA, for the treatment of graft-versus-host disease. Phase 3 findings for this drug and indication are reported in [548] ...
Interleukin-2 receptor subunit γ
(IL-2 receptor family)
  • positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation (GO:0032831) IMP
  • positive regulation of T cell differentiation in thymus (GO:0033089) IMP
  • positive regulation of B cell differentiation (GO:0045579) IMP
  • positive regulation of lymphocyte differentiation (GO:0045621) IMP
IL2RG is a common signal transducing subunit shared by the receptors for several different cytokines, namely the IL-2 receptor heterotrimer, the IL-4 receptor type I, the IL-7 receptor, the IL-9 receptor, the IL-15 receptor and the IL-21 receptor.
Interleukin-31 receptor, α subunit
(IL-6 receptor family)
  • negative regulation of macrophage activation (GO:0043031) NAS
Interleukin-4 receptor subunit α
(IL-2 receptor family)
  • positive regulation of immunoglobulin production (GO:0002639) IEA
  • positive regulation of macrophage activation (GO:0043032) IEA
  • positive regulation of mast cell degranulation (GO:0043306) IEA
  • negative regulation of T-helper 1 cell differentiation (GO:0045626) IEA
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) IEA
IL4R is the common ligand binding subunit shared by the IL-4 receptors type I (receptor for IL-4) and type II (receptor for IL-4 and IL-13). A gain-of-function mutation in IL4R has been associated with atopy, enhanced B cell isotype switching from mu to epsilon and therefore elevated IgE levels [240] ...
Interleukin-6 receptor, α subunit
(IL-6 receptor family)
  • positive regulation of leukocyte chemotaxis (GO:0002690) TAS
  • positive regulation of T-helper 1 type immune response (GO:0002827) IBA
  • positive regulation of natural killer cell activation (GO:0032816) IBA
  • positive regulation of activated T cell proliferation (GO:0042104) IBA
  • positive regulation of lymphocyte proliferation (GO:0050671) IBA
  • positive regulation of NK T cell activation (GO:0051135) IBA
IL6R polymorphisms are associated with asthma risk [182] ...
Interleukin-6 receptor, β subunit
(IL-6 receptor family)
  • positive regulation of acute inflammatory response (GO:0002675) IC
  • positive regulation of adaptive immune response (GO:0002821) IC
  • positive regulation of T cell proliferation (GO:0042102) IMP
This is the common signal transducing subunit shared by members of the IL-6 family of cytokine receptors [505] ...
Interleukin-7 receptor subunit α
(IL-2 receptor family)
  • negative regulation of T cell mediated cytotoxicity (GO:0001915) IEA
  • positive regulation of T cell differentiation in thymus (GO:0033089) IEA
This is the ligand binding subunit of the functional IL-7 receptor complex.
Effimmune are developing anti-IL7Rα monoclonal antibodies (e.g. OSE-127 [479] ...
KIT proto-oncogene, receptor tyrosine kinase
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • erythrocyte differentiation (GO:0030218) ISS
  • Fc receptor signaling pathway (GO:0038093) IDA
Stem cell factor (SCF) and its receptor KIT (c-KIT) play an essential part in mast cell biology. In addition to CSF/KIT-mediated regulation of mast cell development, proliferation and survival, KIT is also reported to be involved in the adhesion of mast cells to human airway epithelial cells (a homing and adhesion role), suggesting a mechanism that could be targeted for anti-asthmatic potential [216] ...
MER proto-oncogene, tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • negative regulation of lymphocyte activation (GO:0051250) IEA
  • neutrophil clearance (GO:0097350) IEA
Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [46,617] ...
NLRC3
(NOD-like receptor family)
  • negative regulation of innate immune response (GO:0045824) ISS
  • negative regulation of inflammatory response (GO:0050728) IDA
  • negative regulation of cytokine production involved in inflammatory response (GO:1900016) ISS
NLRC3 is an intracellular pattern recognition receptor of the innate immune system. It has been shown to directly interact with and inhibit the type I interferon response of the intracellular DNA sensor STING to cytosolic DNA, cyclic di-GMP (c-di-GMP), and DNA viruses [381,684] ...
NLRC4
(NOD-like receptor family)
  • activation of innate immune response (GO:0002218) ISS
As part of the innate inflammatory response to invading mobile bacteria, NLRC4 (Ipaf) in macrophages induces a pro-inflammatory response upon detection of cytosolic bacterial flagellin. In contrast, extracellular bacterial flagellin is detected by TLR5 [403] ...
NLRC5
(NOD-like receptor family)
  • positive regulation of interferon-gamma-mediated signaling pathway (GO:0060335) IDA
  • negative regulation of type I interferon-mediated signaling pathway (GO:0060339) IDA
  • positive regulation of type I interferon-mediated signaling pathway (GO:0060340) IDA
NLRC5 is an intracellular pattern recognition receptor mediating an innate immune response to viral infection [424] ...
NLRP1
(NOD-like receptor family)
  • regulation of inflammatory response (GO:0050727) IC
NLRP1 is a cytosolic sensor of bacterial infection and regulator of the resulting innate immune response [101] ...
NLRP10
(NOD-like receptor family)
  • positive regulation of T-helper 1 type immune response (GO:0002827) ISS
  • positive regulation of inflammatory response (GO:0050729) ISS
  • positive regulation of T-helper 17 type immune response (GO:2000318) ISS
NLRP10 is an intracellular pattern recognition receptor (PRR) that has apoptotic and anti-inflammatory functions [264] ...
NLRP3
(NOD-like receptor family)
  • negative regulation of acute inflammatory response (GO:0002674) IMP
  • positive regulation of type 2 immune response (GO:0002830) ISS
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) ISS
  • regulation of inflammatory response (GO:0050727) IMP
  • negative regulation of inflammatory response (GO:0050728) IMP
  • positive regulation of T-helper 2 cell cytokine production (GO:2000553) ISS
  • positive regulation of T-helper 17 cell differentiation (GO:2000321) IEA
NLRP3 is a component of the NLRP3 inflammasome, a protein complex which activates caspase-1, and plays an important role in the regulation of inflammation and apoptosis (pyroptosis). Drug-like NLRP3 inhibitors are under investigation as novel therapeutics for the treatment of autoinflammatory diseases and neuroinflammation, as an alternative to anti-IL-1 therapies such as , and [29,382] ...
NLRP6
(NOD-like receptor family)
  • regulation of inflammatory response (GO:0050727) ISS
  • negative regulation of immune response (GO:0050777) IMP
  • negative regulation of inflammatory response to antigenic stimulus (GO:0002862) IEA
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) IEA
NLRP6 is an intracellular pattern recognition receptor (PRR). It is a member of the NACHT, LRR and PYD domains-containing protein (NALP) subfamily of PRRs. The presence of NALPs in inflammasomes underlies their involvement in regulating proinflammatory caspases (esp. caspase 1) ...
NLRP7
(NOD-like receptor family)
  • negative regulation of cytokine production involved in inflammatory response (GO:1900016) IMP
NLRP7 is an intracellular pattern recognition receptor (PRR). It is a member of the NACHT, LRR and PYD domains-containing protein (NALP) subfamily of PRRs. The presence of NALPs in inflammasomes underlies their involvement in regulating proinflammatory caspases (esp. caspase 1) ...
NLRX1
(NOD-like receptor family)
  • negative regulation of RIG-I signaling pathway (GO:0039536) IEA
  • negative regulation of innate immune response (GO:0045824) IEA
  • negative regulation of inflammatory response (GO:0050728) IEA
NLRX1 is an intracellular pattern recognition receptor that plays a role in host immunity to certain bacterial infections.
nucleotide binding oligomerization domain containing 1
(NOD-like receptor family)
  • positive regulation of dendritic cell antigen processing and presentation (GO:0002606) ISS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
NOD1 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing a D-glutamyl-meso-diaminopimelic acid (iE-DAP) moiety.

Mutations in NOD proteins are implicated in various inflammatory diseases associated with aberrant NF-κB activ ...
nucleotide binding oligomerization domain containing 2
(NOD-like receptor family)
  • activation of immune response (GO:0002253) IMP
  • positive regulation of dendritic cell antigen processing and presentation (GO:0002606) ISS
  • negative regulation of T cell mediated immunity (GO:0002710) IMP
  • positive regulation of type 2 immune response (GO:0002830) IMP
  • negative regulation of inflammatory response to antigenic stimulus (GO:0002862) IMP
  • positive regulation of humoral immune response mediated by circulating immunoglobulin (GO:0002925) IMP
  • positive regulation of antibacterial peptide biosynthetic process (GO:0006963) IDA
  • positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria (GO:0006965) IMP
  • negative regulation of toll-like receptor 2 signaling pathway (GO:0034136) IMP
  • positive regulation of innate immune response (GO:0045089) IDA
  • positive regulation of gamma-delta T cell activation (GO:0046645) ISS
  • regulation of inflammatory response (GO:0050727) IC
  • positive regulation of B cell activation (GO:0050871) IDA
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IDA
  • regulation of neutrophil chemotaxis (GO:0090022) IMP
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) IDA
  • positive regulation of dendritic cell cytokine production (GO:0002732) IEA
NOD2 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing muramyl dipeptide (MDP).

Mutations in NOD proteins are implicated in various inflammatory diseases associated with aberrant NF-κB activity; NF-κB being a major ...
Oncostatin M-specific receptor, β subunit
(IL-6 receptor family)
  • positive regulation of acute inflammatory response (GO:0002675) IC
Oncostatin M-specific receptor, β subunit (OSMR) is a component of two functional heterodimeric receptor complexes:
1. OSMR+ interleukin-6 receptor, β subunit (IL6ST) forms the receptor for oncostatin M
2. OSMR+ interleukin-31 receptor, α subunit forms the recept ...
OX40
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of B cell proliferation (GO:0030890) ISS
  • positive regulation of immunoglobulin secretion (GO:0051024) ISS
  • negative regulation of activation-induced cell death of T cells (GO:0070236) IBA
The OX40/OX40L pair is involved in late T-cell costimulatory signaling and both are transiently expressed following antigen recognition, and blocking OX40/OX40L is reported to prevent the development of disease in in vivo autoimmune and inflammatory disease models [632] ...
receptor activator of NF-kappa B
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of fever generation by positive regulation of prostaglandin secretion (GO:0071812) ISS
RANK is the receptor for RANK-ligand (RANKL). It is associated with immune cell function and lymph node development, in addition to bone remodeling and repair, thermal regulation, and mammary gland development. Signals to NF-κB and JNK via TRAF adaptor proteins.
RTP Type C
(Receptor tyrosine phosphatase (RTP) family)
  • negative regulation of T cell mediated cytotoxicity (GO:0001915) ISS
  • positive regulation of T cell mediated immunity (GO:0002711) IMP
  • regulation of humoral immune response mediated by circulating immunoglobulin (GO:0002923) IMP
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • positive regulation of T cell proliferation (GO:0042102) ISS
  • positive regulation of T cell differentiation (GO:0045582) IMP
  • T cell receptor signaling pathway (GO:0050852) IDA
  • B cell receptor signaling pathway (GO:0050853) ISS
  • positive regulation of antigen receptor-mediated signaling pathway (GO:0050857) ISS
  • negative regulation of microglial cell activation (GO:1903979) TAS
  • positive regulation of Fc-gamma receptor signaling pathway involved in phagocytosis (GO:1905451) ISS
  • positive regulation of T cell mediated cytotoxicity (GO:0001916) IEA
  • positive regulation of humoral immune response mediated by circulating immunoglobulin (GO:0002925) IEA
  • regulation of B cell differentiation (GO:0045577) IEA
  • positive regulation of gamma-delta T cell differentiation (GO:0045588) IEA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
  • regulation of B cell receptor signaling pathway (GO:0050855) IEA
CD45 is a high molecular weight cell surface glycoprotein expressed by cells of hematopoietic origin. Alternate transcripts lead to expression of isoforms that differ in their extracellular (ligand binding) domain (potentially facilitating differential and/or cell type specific biological functions [143] ...
TACI
(Tumour necrosis factor (TNF) receptor family)
  • B cell homeostasis (GO:0001782) IBA
  • negative regulation of B cell proliferation (GO:0030889) IBA
TACI is a lymphocyte-specific TNF superfamily receptor expressed on B cells. Endogenous ligands include APRIL, BAFF and CAML. Defects in the function of TACI can underlie immunodeficiencies and autoimmune diseases. A TACI-IgG Fc fusion protein named RC18 will be evaluated in Phase 3 clinical trials ...
TEK receptor tyrosine kinase
(Type XII RTKs: TIE family of angiopoietin receptors)
  • positive regulation of cytokine secretion involved in immune response (GO:0002741) IDA
  • negative regulation of inflammatory response (GO:0050728) TAS
In inflammation, angiopoietin-2 (ANG2) antagonism of TIE2 initiates a positive feedback loop via forkhead box O1 (FOXO1) activation, which drives further ANG2 expression and enhances vascular remodeling and leakage [305] ...
TLR1
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • positive regulation of toll-like receptor 2 signaling pathway (GO:0034137) IGI
  • toll-like receptor TLR1:TLR2 signaling pathway (GO:0038123) TAS
  • toll-like receptor 1 signaling pathway (GO:0034130) IEA
TLR1/2 heterodimers detect and respond to bacterial triacyl lipopeptides [598] ...
TLR10
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 10 signaling pathway (GO:0034166) TAS
  • positive regulation of inflammatory response (GO:0050729) IEA
To date, ligands and biological functions of human TLR10 remain unclear. However, evidence suggests it plays a modulatory role with predominantly inhibitory (anti-inflammatory) effects [452] ...
TLR2
(Toll-like receptor family)
  • lipopolysaccharide receptor activity (GO:0001875) TAS
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • positive regulation of leukocyte migration (GO:0002687) IMP
  • regulation of dendritic cell cytokine production (GO:0002730) IDA
  • cell surface pattern recognition receptor signaling pathway (GO:0002752) IMP
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • signaling pattern recognition receptor activity (GO:0008329) IDA
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • toll-like receptor TLR1:TLR2 signaling pathway (GO:0038123) TAS
  • toll-like receptor TLR6:TLR2 signaling pathway (GO:0038124) TAS
  • positive regulation of inflammatory response (GO:0050729) IC
  • induction by symbiont of defense-related host nitric oxide production (GO:0052063) IMP
  • positive regulation of macrophage cytokine production (GO:0060907) IMP
  • toll-like receptor 2 signaling pathway (GO:0034134) IEA
TLR1/2 and 2/6 heterodimers detect and initiate an immune response to triacylated and diacylated [419] ...
TLR3
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • negative regulation of MyD88-independent toll-like receptor signaling pathway (GO:0034128) TAS
  • toll-like receptor 3 signaling pathway (GO:0034138) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • negative regulation of osteoclast differentiation (GO:0045671) NAS
  • positive regulation of inflammatory response (GO:0050729) IC
  • regulation of dendritic cell cytokine production (GO:0002730) IEA
TLR3 is an endosomal anti-viral receptor [598] ...
TLR4
(Toll-like receptor family)
  • lipopolysaccharide receptor activity (GO:0001875) IDA
  • activation of innate immune response (GO:0002218) IMP
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) ISS
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • innate immune response-activating signal transduction (GO:0002758) ISO
  • negative regulation of MyD88-independent toll-like receptor signaling pathway (GO:0034128) TAS
  • toll-like receptor 4 signaling pathway (GO:0034142) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) ISS
  • positive regulation of macrophage activation (GO:0043032) ISS
  • negative regulation of osteoclast differentiation (GO:0045671) NAS
  • positive regulation of lymphocyte proliferation (GO:0050671) IMP
  • regulation of inflammatory response (GO:0050727) IMP
  • positive regulation of inflammatory response (GO:0050729) IC
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) ISS
  • regulation of dendritic cell cytokine production (GO:0002730) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • positive regulation of macrophage cytokine production (GO:0060907) IEA
  • positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway (GO:0070430) IEA
  • positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070434) IEA
TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [60,480] ...
TLR5
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • toll-like receptor 5 signaling pathway (GO:0034146) TAS
TLR5 induces a pro-inflammatory response upon detection of extracellular bacterial flagellin from invading mobile bacteria [403] ...
TLR6
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) ISS
  • negative regulation of toll-like receptor 2 signaling pathway (GO:0034136) IGI
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) ISS
  • toll-like receptor TLR6:TLR2 signaling pathway (GO:0038124) TAS
  • positive regulation of macrophage activation (GO:0043032) ISS
  • positive regulation of inflammatory response (GO:0050729) IGI
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) ISS
  • toll-like receptor 6 signaling pathway (GO:0034150) IEA
TLR6 forms heterodimers with TLR2 to detect a wide range of bacterial lipopeptides (LP) from bacterial cell membranes, and effect an immune response [178] ...
TLR7
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • signaling pattern recognition receptor activity (GO:0008329) IBA
  • toll-like receptor 7 signaling pathway (GO:0034154) IBA
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
  • positive regulation of inflammatory response (GO:0050729) IC
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
TLR7 is an endosomal receptor detecting ssRNA [598] ...
TLR8
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • signaling pattern recognition receptor activity (GO:0008329) IBA
  • toll-like receptor 8 signaling pathway (GO:0034158) IDA
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
  • positive regulation of innate immune response (GO:0045089) IDA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
TLR8 is an endosomal receptor detecting ssRNA [598] ...
TLR9
(Toll-like receptor family)
  • activation of innate immune response (GO:0002218) IDA
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • positive regulation of immunoglobulin production (GO:0002639) IDA
  • regulation of dendritic cell cytokine production (GO:0002730) IDA
  • signaling pattern recognition receptor activity (GO:0008329) IBA
  • positive regulation of B cell proliferation (GO:0030890) IDA
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) IDA
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
  • regulation of toll-like receptor 9 signaling pathway (GO:0034163) IDA
  • positive regulation of toll-like receptor 9 signaling pathway (GO:0034165) IMP
  • regulation of B cell differentiation (GO:0045577) IDA
  • regulation of inflammatory response (GO:0050727) IMP
  • positive regulation of inflammatory response (GO:0050729) IC
  • regulation of B cell activation (GO:0050864) IGI
  • positive regulation of B cell activation (GO:0050871) IDA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
TLR9 is an endosomal receptor detecting viral and bacterial CpG DNA and genomic DNA from some protozoan species [598] ...
tumor necrosis factor receptor 1
(Tumour necrosis factor (TNF) receptor family)
  • negative regulation of inflammatory response (GO:0050728) IMP
  • positive regulation of inflammatory response (GO:0050729) ISS
We have included TNFR1 in GtoImmuPdb based on it being a receptor for lymphotoxin-α, a cytotoxic protein performing a variety of important roles in immune system development and regulation [220,428] ...
tumor necrosis factor receptor 2
(Tumour necrosis factor (TNF) receptor family)
  • regulation of T cell cytokine production (GO:0002724) ISS
  • regulation of cytokine secretion involved in immune response (GO:0002739) ISS
  • regulation of T cell proliferation (GO:0042129) ISS
  • regulation of neuroinflammatory response (GO:0150077) ISS
  • negative regulation of neuroinflammatory response (GO:0150079) ISS
  • negative regulation of inflammatory response (GO:0050728) IEA
TNFR2 is a receptor for lymphotoxin-α, and the membrane form of tumour necrosis factor (TNF). It plays a variety of important roles in immune system development and regulation [220,428] ...
TYRO3 protein tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) ISS
  • negative regulation of innate immune response (GO:0045824) ISS
  • negative regulation of inflammatory response (GO:0050728) ISS
  • negative regulation of lymphocyte activation (GO:0051250) IEA
TYRO3 is a negative regulator of type 2 immunity [102] ...
Transporters
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
ABCB3
(ABCB subfamily)
  • positive regulation of T cell mediated cytotoxicity (GO:0001916) IDA
  • positive regulation of antigen processing and presentation of peptide antigen via MHC class I (GO:0002591) ISO
  • protection from natural killer cell mediated cytotoxicity (GO:0042270) ISO
TAP1 (ABCB2) and TAP2 (ABCB3) form a transporter that plays an important role in antigen presentation by major histocompatibility complex class I (MHCI) molecules in the adaptive immune response [530] ...
NRAMP1
(SLC11 family of proton-coupled metal ion transporters)
  • positive regulation of dendritic cell antigen processing and presentation (GO:0002606) ISS
  • positive regulation of T-helper 1 type immune response (GO:0002827) ISS
NRAMP1 / SLC11A1 appears to be involved in macrophage antimicrobial action against intracellular pathogens, and although its precise mechanism is not fully resolved, evidence indicates its involvement in the activation of phagocytes and synthesis of proinflammatory cytokines. Polymorphisms in the human SLC11A1 gene have been associated with susceptibility to several infections [73,551,554] ...
Other Protein Targets
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
absent in melanoma 2
(Absent in melanoma (AIM)-like receptors (ALRs))
  • activation of innate immune response (GO:0002218) IDA
  • positive regulation of defense response to virus by host (GO:0002230) ISS
AIM2 primarily senses cytosolic DNA and initiates formation of an inflammasome to drive IL-1β cleavage and secretion.
advanced glycosylation end-product specific receptor
(Immunoglobulin like domain containing proteins)
  • regulation of T cell mediated cytotoxicity (GO:0001914) IDA
  • positive regulation of activated T cell proliferation (GO:0042104) IMP
  • regulation of inflammatory response (GO:0050727) IDA
  • positive regulation of inflammatory response (GO:0050729) ISO
  • positive regulation of astrocyte activation (GO:0061890) IGI
  • positive regulation of microglial cell activation (GO:1903980) IGI
  • positive regulation of monocyte extravasation (GO:2000439) IMP
  • regulation of CD4-positive, alpha-beta T cell activation (GO:2000514) IDA
  • positive regulation of dendritic cell differentiation (GO:2001200) IMP
  • negative regulation of connective tissue replacement involved in inflammatory response wound healing (GO:1904597) IEA
RAGE is a single chain, membrane bound immunoglobulin type protein [423,522,658] ...
amyloid P component, serum
(Serum pentaxins)
  • negative regulation of acute inflammatory response (GO:0002674) IC
  • complement activation, classical pathway (GO:0006958) IBA
  • negative regulation of monocyte differentiation (GO:0045656) IDA
Serum amyloid P or pentraxin 2 is a multi-function circulating plasma protein. It exhibits activity as a soluble pattern recognition receptor of the innate immune system, that can bind DNA and histones when these are released from damaged cells.

A recombinant form of human pentraxin 2 (PRM-151) has been reported as an anti-fibrotic immunomodulator [169] ...
Aryl hydrocarbon receptor
(Aryl hydrocarbon receptor complex)
  • B cell homeostasis (GO:0001782) IMP
  • B-1 B cell homeostasis (GO:0001922) TAS
  • lymphocyte homeostasis (GO:0002260) IMP
  • regulation of B cell proliferation (GO:0030888) IDA
  • T cell homeostasis (GO:0043029) IMP
The AhR is activated by small signalling molecules derived from the diet, microorganisms and environmental agents, and when expressed by immune cells, it integrates the effects of the environment and metabolism on the immune response. The AhR is a critical regulator of innate and adaptive immune responses that influences the balance of Th17 and Treg cells [389] ...
B7-H3 (CD276)
(Other immune checkpoint proteins, CD molecules)
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • negative regulation of T cell proliferation (GO:0042130) IDA
  • negative regulation of inflammatory response (GO:0050728) IMP
  • regulation of immune response (GO:0050776) IBA
  • T cell receptor signaling pathway (GO:0050852) IBA
B7-H3 is an immunoregulatory receptor involved in T cell activation and IFN-γ production [105,163] ...
baculoviral IAP repeat containing 2
(Inhibitors of apoptosis (IAP) protein family)
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • regulation of toll-like receptor signaling pathway (GO:0034121) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • regulation of RIG-I signaling pathway (GO:0039535) TAS
  • regulation of innate immune response (GO:0045088) TAS
  • regulation of inflammatory response (GO:0050727) TAS
  • regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
Cellular inhibitors of apoptosis proteins BIRC2 and BIRC3 are required for efficient caspase-1 activation by the inflammasome [329] ...
baculoviral IAP repeat containing 3
(Inhibitors of apoptosis (IAP) protein family)
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • regulation of toll-like receptor signaling pathway (GO:0034121) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • regulation of RIG-I signaling pathway (GO:0039535) TAS
  • regulation of innate immune response (GO:0045088) TAS
  • regulation of inflammatory response (GO:0050727) TAS
  • regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
Cellular inhibitor of apoptosis proteins (cIAPs) suppress apoptosis thereby promoting cell survival, and participate in the immune response (e.g. negative regulation of the necrosome, inflammasome and ripoptosome. In asthma, cIAPs extend the survival of neutrophils, macrophages and eosinophils, prolonging the inflammation. The minor alleles of single nucleotide polymorphisms in BIRC3 are shown to correlate with reduced numbers of circulating eosinophils and neutrophils, suggesting a protective effect against the development of asthma[504] ...
BCL2 apoptosis regulator
(B-cell lymphoma 2 (Bcl-2) protein family)
  • leukocyte homeostasis (GO:0001776) IMP
  • lymphocyte homeostasis (GO:0002260) IMP
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • B cell receptor signaling pathway (GO:0050853) IMP
  • B cell homeostasis (GO:0001782) IEA
  • T cell homeostasis (GO:0043029) IEA
The role of Bcl-2 family members in immunity and disease is reviewed in [166] ...
BCL6 transcription repressor
(BTB (POZ) domain containing TFs)
  • regulation of germinal center formation (GO:0002634) NAS
  • negative regulation of type 2 immune response (GO:0002829) IGI
  • positive regulation of regulatory T cell differentiation (GO:0045591) IMP
  • regulation of inflammatory response (GO:0050727) IBA
  • regulation of immune response (GO:0050776) NAS
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • negative regulation of mast cell cytokine production (GO:0032764) IEA
  • regulation of memory T cell differentiation (GO:0043380) IEA
  • negative regulation of T-helper 2 cell differentiation (GO:0045629) IEA
  • negative regulation of isotype switching to IgE isotypes (GO:0048294) IEA
  • erythrocyte development (GO:0048821) IEA
BCL6/corepressor complexes are important for the formation of germinal centers and differentiation and proliferation of lymphocytes. Oncogenic mutations in BCL6 lead to the development of diffuse large B-cell lymphoma cells from germinal center B cells. Disruption of BCL6/corepressor complex formation by pharmacological inhibitors has therefore been identified as a novel drug mechanism with potential for the treatment of autoimmune diseases and cancer [90,99] ...
butyrophilin like 3
(Butyrophilin and butyrophilin-like proteins)
  • regulation of immune response (GO:0050776) IBA
  • T cell receptor signaling pathway (GO:0050852) IBA
BTNL3 and BTNL8 are two proteins expressed on the surface of human gut epithelial cells that are involved in shaping the constitution of gut resident dendritic γδ T cells [159] ...
butyrophilin like 8
(Butyrophilin and butyrophilin-like proteins)
  • regulation of immune response (GO:0050776) IBA
  • T cell receptor signaling pathway (GO:0050852) IBA
BTNL3 and BTNL8 are two proteins expressed on the surface of human gut epithelial cells that are involved in shaping the constitution of gut resident dendritic γδ T cells [159] ...
butyrophilin subfamily 3 member A1
(Butyrophilin and butyrophilin-like proteins)
  • regulation of immune response (GO:0050776) IBA
  • T cell receptor signaling pathway (GO:0050852) IDA
Vγ2Vδ2 (a.k.a. Vγ9Vδ2) T cells bridge the gap between innate and adaptive immunity and play roles in microbial immunity and tumour immunity [409] ...
CD19
(CD molecules)
  • regulation of complement activation (GO:0030449) TAS
  • regulation of immune response (GO:0050776) TAS
  • antigen receptor-mediated signaling pathway (GO:0050851) IDA
  • B cell receptor signaling pathway (GO:0050853) IBA
  • regulation of B cell receptor signaling pathway (GO:0050855) IMP
  • regulation of B cell activation (GO:0050864) IDA
CD19 is a B cell antigen used as a biomarker for normal and neoplastic B cells, and follicular dendritic cells. Anti-CD19 monoclonal antibodies are being investigated for potential clinical utility in oncology, transplantation and autimmune diseases (e.g. inebilizumab ...
CD1d molecule
(CD molecules)
  • positive regulation of T cell mediated cytotoxicity (GO:0001916) IBA
  • regulation of immature T cell proliferation in thymus (GO:0033084) IMP
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • positive regulation of macrophage activation (GO:0043032) IDA
  • positive regulation of innate immune response (GO:0045089) TAS
  • regulation of immune response (GO:0050776) TAS
  • positive regulation of NK T cell activation (GO:0051135) IDA
  • positive regulation of NK T cell differentiation (GO:0051138) IMP
CD1d is a lipid-binding MHC class I-like protein that is expressed by dendritic cells. CD1d presents self and microbial lipid/glycolipid antigens to unconventional T cells known as invariant natural killer T (iNKT) cells [110,643] ...
CD2
(CD molecules)
  • positive regulation of myeloid dendritic cell activation (GO:0030887) NAS
  • regulation of T cell differentiation (GO:0045580) NAS
CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells [660] ...
CD209 molecule
(C-type lectin-like receptors (CLRs))
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • regulation of T cell proliferation (GO:0042129) IDA
DC-SIGN is a pathogen-recognition receptor involved in initiating the primary immune response to various viral and bacterial pathogens, as well as antigen presentation and initiation of the adaptive immune response.
CD20 (membrane-spanning 4-domains, subfamily A, member 1)
(CD molecules)
  • B cell receptor signaling pathway (GO:0050853) IDA
CD20 is a B cell antigen, involved in B cell development and maturation to antibody-producing plasma cells [125] ...
CD22
(Other immune ch