Top ▲

Top ▲

Targets Associated to Immuno Processes - Inflammation

Jump to: GPCR | Ion Channels | NHRs | Enzymes | Catalytic Receptors | Transporters | Other Protein Targets |

Inflammation
GPCRs
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
ACKR1
(Chemokine receptors)
  • inflammatory response (GO:0006954) IBA
ACKR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. Studies in ACKR1 null mice, and analysis of ACKR1 SNPs in asthmatic patients with poorly controlled symptoms, suggest a role for this cytokine receptor in the temporal regulation of asthma pathophysiology and symptoms [107] ...
ACKR2
(Chemokine receptors)
  • inflammatory response (GO:0006954) IEA
ACKR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
ADGRE2
(Adhesion Class GPCRs)
  • regulation of mast cell degranulation (GO:0043304) IMP
  • granulocyte chemotaxis (GO:0071621) IMP
  • inflammatory response (GO:0006954) IEA
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 [250] ...
ADGRE5
(Adhesion Class GPCRs)
  • inflammatory response (GO:0006954) TAS
  • neutrophil degranulation (GO:0043312) TAS
ADGRE5 is included in GtoImmuPdb because its tissue expression profile and the phenotypes expressed by mouse ADGRE5 knockouts suggest an involvement in inflammation.
A1 receptor
(Adenosine receptors)
  • phagocytosis (GO:0006909) TAS
  • inflammatory response (GO:0006954) TAS
  • 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)
  • phagocytosis (GO:0006909) TAS
  • inflammatory response (GO:0006954) TAS
  • astrocyte activation (GO:0048143) 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 [600] ...
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 [3] ...
A3 receptor
(Adenosine receptors)
  • inflammatory response (GO:0006954) TAS
Agonist stimulation of the A2A and A3 receptors down-regulates production of the pro-inflammatory mediators TNF-α and IL-8 in human synoviocytes [600] ...
AT1 receptor
(Angiotensin receptors)
  • inflammatory response (GO:0006954) IBA
  • 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 [535] ...
AT2 receptor
(Angiotensin receptors)
  • inflammatory response (GO:0006954) IEA
AT2 receptors have been have been identified on human immunocompetent cells, and selective AT2 receptor activation stimulates an anti-inflammatory effect (reduces production of pro-inflammatory cytokines TNFα, IL-6, and IL-10 after LPS challenge) in human monocytes [393] ...
BLT1 receptor
(Leukotriene receptors)
  • inflammatory response (GO:0006954) IBA
The human BLT1 receptor is the high affinity leukotriene B4 receptor, involved in mediating chemotaxis and immunomodulation in several leukocyte populations.
BLT2 receptor
(Leukotriene receptors)
  • inflammatory response (GO:0006954) IBA
The human BLT2 receptor is the low affinity leukotriene B4 receptor, and may be involved in maintaining intestinal barrier function (leading to colitis) and eosinophilic airway inflammation. BLT2 receptor is considered to be the principal mediator of leukotriene B4 effects in synovial tissues from patients with rheumatoid arthritis [228] ...
B1 receptor
(Bradykinin receptors)
  • positive regulation of leukocyte migration (GO:0002687) IEA
  • inflammatory response (GO:0006954) IEA
Bradykinin ...
B2 receptor
(Bradykinin receptors)
  • inflammatory response (GO:0006954) IC
Bradykinin is a vasoactive, pain inducing and pro-inflammatory (phlogistic) kinin released during acute inflammation, and its receptors, B1 and B2, are expressed on eosinophils, and neutrophils. The B2 receptor antagonist icatibant was evaluated in a Phase 2 trial for osteoarthritis [146] ...
C3a receptor
(Complement peptide receptors)
  • inflammatory response (GO:0006954) IBA
  • neutrophil degranulation (GO:0043312) 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 [568,625] ...
C5a1 receptor
(Complement peptide receptors)
  • inflammatory response (GO:0006954) IBA
  • neutrophil degranulation (GO:0043312) TAS
  • regulation of astrocyte activation (GO:0061888) ISS
  • regulation of microglial cell activation (GO:1903978) ISS
  • positive regulation of macrophage chemotaxis (GO:0010759) IEA
  • neutrophil chemotaxis (GO:0030593) 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 [246,366,424-425] ...
C5a2 receptor
(Complement peptide receptors)
  • inflammatory response (GO:0006954) IBA
  • 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 [561] ...
CB2 receptor
(Cannabinoid receptors)
  • inflammatory response (GO:0006954) IEA
  • leukocyte chemotaxis (GO:0030595) IEA
  • 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 [442] ...
CCR1
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • inflammatory response (GO:0006954) IBA
  • positive regulation of monocyte chemotaxis (GO:0090026) IDA
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)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • regulation of T cell cytokine production (GO:0002724) ISS
  • inflammatory response (GO:0006954) IBA
  • positive regulation of T cell chemotaxis (GO:0010820) ISS
  • monocyte extravasation (GO:0035696) ISS
  • T-helper 17 cell chemotaxis (GO:0035705) ISS
  • negative regulation of eosinophil degranulation (GO:0043310) ISS
  • regulation of inflammatory response (GO:0050727) ISS
  • positive regulation of inflammatory response (GO:0050729) ISS
  • positive regulation of monocyte chemotaxis (GO:0090026) IDA
  • inflammatory response to wounding (GO:0090594) ISS
  • macrophage migration (GO:1905517) 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
  • monocyte chemotaxis (GO:0002548) IEA
  • 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 [3] ...
CCR3
(Chemokine receptors)
  • inflammatory response (GO:0006954) IBA
CCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR4
(Chemokine receptors)
  • inflammatory response (GO:0006954) TAS
CCR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
In disease states CCR4 is involved in recruiting T helper type 2 cell (Th2) subsets in autoimmune disorders such as asthma, allergic rhinitis, and atopic dermatitis [538] ...
CCR5
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • inflammatory response (GO:0006954) IBA
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 [3] ...
CCR6
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • leukocyte migration involved in inflammatory response (GO:0002523) ISS
  • isotype switching to IgA isotypes (GO:0048290) ISS
  • lymphocyte migration (GO:0072676) ISS
  • T cell migration (GO:0072678) ISS
  • thymocyte migration (GO:0072679) ISS
  • 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 [304,344] ...
CCR7
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) IC
  • myeloid dendritic cell chemotaxis (GO:0002408) IDA
  • positive regulation of hypersensitivity (GO:0002885) ISS
  • inflammatory response (GO:0006954) NAS
  • positive regulation of neutrophil chemotaxis (GO:0090023) IDA
  • lymphocyte migration into lymph node (GO:0097022) TAS
  • positive regulation of dendritic cell chemotaxis (GO:2000510) ISS
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.
CCRL2
(Chemokine receptors)
  • inflammatory response (GO:0006954) ISS
CCRL2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. However, the nomenclature of CCLR2 for this receptor and its classification as a member of the chemokine receptor family is prov ...
chemerin receptor 1
(Chemerin receptors)
  • inflammatory response (GO:0006954) 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 [210] ...
CXCR1
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • neutrophil chemotaxis (GO:0030593) IBA
  • neutrophil degranulation (GO:0043312) TAS
CXCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR1 is discussed in relation to immuno-oncology in [3] ...
CXCR2
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • inflammatory response (GO:0006954) TAS
  • neutrophil chemotaxis (GO:0030593) IDA
  • neutrophil activation (GO:0042119) IDA
  • neutrophil degranulation (GO:0043312) TAS
  • acute inflammatory response to antigenic stimulus (GO:0002438) 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 [3] ...
CXCR3
(Chemokine receptors)
  • regulation of leukocyte migration (GO:0002685) IEA
  • inflammatory response (GO:0006954) IEA
  • T cell chemotaxis (GO:0010818) 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.
CXCR4
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • inflammatory response (GO:0006954) TAS
CXCR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. Due to its role in cancer cell homing and metastasis the CXCR4-CXCL12 axis is a potential target for cancer therapy [483,510,608,618] ...
CXCR5
(Chemokine receptors)
  • leukocyte chemotaxis (GO:0030595) IEA
CXCR5 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CXCR6
(Chemokine receptors)
  • inflammatory response (GO:0006954) IEA
CXCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR6 is upregulated by IL-2 and IL-15 [591] ...
CX3CR1
(Chemokine receptors)
  • innate immune response (GO:0045087) IC
  • leukocyte tethering or rolling (GO:0050901) ISS
  • regulation of microglial cell migration (GO:1904139) TAS
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.
CysLT1 receptor
(Leukotriene receptors)
  • inflammatory response to antigenic stimulus (GO:0002437) IEA
CysLT1 is a receptor for cysteinyl-leukotrienes. Both CysLT1 and CysLT2 mediate cysteinyl-leukotriene-induced modulation of smooth muscle cell contraction, regulation of vascular permeability, and leukocyte activation.
DP1 receptor
(Prostanoid receptors)
  • inflammatory response (GO:0006954) IBA
DP1 receptor activation by prostaglandins mediates chemotaxis of pro-inflammatory cells such as basophils, eosinophils, and T cells. DP2 and DP1 may function to counteract each other's inflammatory action [236] ...
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 [669] ...
EP1 receptor
(Prostanoid receptors)
  • inflammatory response (GO:0006954) IBA
Foudi et al. (2012) [180] ...
EP2 receptor
(Prostanoid receptors)
  • inflammatory response (GO:0006954) IBA
Foudi et al. (2012) [180] ...
EP3 receptor
(Prostanoid receptors)
  • inflammatory response (GO:0006954) IBA
  • positive regulation of fever generation (GO:0031622) ISS
Foudi et al. (2012) [180] ...
EP4 receptor
(Prostanoid receptors)
  • inflammatory response (GO:0006954) IBA
  • T-helper cell differentiation (GO:0042093) ISS
  • negative regulation of inflammatory response (GO:0050728) IDA
  • positive regulation of inflammatory response (GO:0050729) ISS
  • 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 [653] ...
FFA2 receptor
(Free fatty acid receptors)
  • leukocyte chemotaxis involved in inflammatory response (GO:0002232) ISS
  • regulation of acute inflammatory response (GO:0002673) 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 [648] ...
FFA3 receptor
(Free fatty acid receptors)
  • positive regulation of acute inflammatory response to non-antigenic stimulus (GO:0002879) ISS
  • inflammatory response (GO:0006954) IEA
FFA3 has been included in GtoImmuPdb as its expression has been detected in immune cells [74] ...
FPR1
(Formylpeptide receptors)
  • inflammatory response (GO:0006954) IBA
  • neutrophil degranulation (GO:0043312) TAS
The primary function of FPR1 is recognition of formylpeptides including bacterial formylpeptides, so it is therefore a component of the host defense mechanism.
FPR2/ALX
(Formylpeptide receptors, Leukotriene receptors)
  • microglial cell activation (GO:0001774) ISS
  • inflammatory response (GO:0006954) IBA
  • neutrophil degranulation (GO:0043312) TAS
  • positive regulation of innate immune response (GO:0045089) IDA
  • astrocyte activation (GO:0048143) ISS
  • negative regulation of inflammatory response (GO:0050728) IDA
  • positive regulation of phagocytosis (GO:0050766) 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. FPR2/ALX receptor agonism is a new therapeutic concept that is being investigated for the development of novel non-steroidal anti-inflammatory agents as modulators of pathological dysregulated inflammation [68] ...
H1 receptor
(Histamine receptors)
  • inflammatory response (GO:0006954) TAS
  • eosinophil chemotaxis (GO:0048245) IEA
The H1 receptor was the first of the family to be targeted for clinical use, with antagonists (anti-histamines) developed that are still used widely to treat allergic inflammation such as rhinitis, allergic conjunctivitis, urticaria and even anaphylaxis.
H4 receptor
(Histamine receptors)
  • inflammatory response (GO:0006954) IBA
H4 receptor is primarily expressed in mast cells and eosinophils, but is also found on human neutrophils and basophils, and plays an important role in modulating eosinophil chemotaxis [433,661] ...
GPR15
(Class A Orphans)
  • T cell migration (GO:0072678) IEA
Several lines of evidence suggest that GPR15 is a chemoattractant receptor supporting the trafficking of T effector cells to the colon [215,421,435,564] ...
GPR183
(Class A Orphans)
  • mature B cell differentiation involved in immune response (GO:0002313) ISS
  • dendritic cell chemotaxis (GO:0002407) ISS
  • T cell chemotaxis (GO:0010818) ISS
  • leukocyte chemotaxis (GO:0030595) IMP
  • T follicular helper cell differentiation (GO:0061470) 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 [292,463] ...
GPR84
(Class A Orphans)
  • neutrophil degranulation (GO:0043312) TAS
GPR84 is proposed as a receptor for free fatty acids. It is predominantly expressed in immune system-related tissues and cells [259] ...
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) [138,162] ...
MRGPRX2
(Class A Orphans)
  • mast cell degranulation (GO:0043303) IDA
  • mast cell activation (GO:0045576) IDA
Expression of MRGPRX2 was initially reported predominantly in sensory neurons of the dorsal root ganglion. More recently expression has been detected in human mast cells. In these cells the receptor is activated by the antimicrobial peptide LL-37, resulting in calcium mobilisation and degranulation [390,559] ...
IP receptor
(Prostanoid receptors)
  • inflammatory response (GO:0006954) IBA
Although primarily recognised for vasodilatory and antihypertensive action in pulmonary arterial hypertension (PAH) the importance of PGI2 as an immunomodulatory agent has been investigated more recently. PGI2 regulates both the innate and adaptive immune systems and its effects are thought to be mainly anti-inflammatory or immunosuppressive, which may have implications for clinical use. Note also that the prostacyclin analog, cicaprost, exhibits potent anti-inflammatory activity in human primary immune cells [611] ...
NK1 receptor
(Tachykinin receptors)
  • inflammatory response (GO:0006954) TAS
  • acute inflammatory response (GO:0002526) IEA
  • positive regulation of leukocyte migration (GO:0002687) IEA
Expression in monocytes, macrophages and T helper cells suggests a role in inflammation/immunity.
P2Y6 receptor
(P2Y receptors)
  • phagocytosis (GO:0006909) ISS
P2Y6R expression on airway epithelial cells is up-regulated during acute and chronic allergic airway inflammation, and selective antagonism of P2Y6R reduces typical features of experimental asthma [604] ...
PAF receptor
(Platelet-activating factor receptor)
  • inflammatory response (GO:0006954) TAS
  • neutrophil degranulation (GO:0043312) TAS
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • 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.
PAR1
(Proteinase-activated receptors)
  • connective tissue replacement involved in inflammatory response wound healing (GO:0002248) IDA
  • inflammatory response (GO:0006954) ISS
PAR1 has been found to mediate the effects of neutrophil elastase (NE) on γδ T cell activation, as the PAR1 inhibitor abrogates NE (from neutrophils)-induced activation of these T cells [587] ...
PAR2
(Proteinase-activated receptors)
  • T cell activation involved in immune response (GO:0002286) ISS
  • positive regulation of leukocyte chemotaxis (GO:0002690) 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
  • neutrophil activation (GO:0042119) IDA
  • positive regulation of eosinophil degranulation (GO:0043311) IDA
  • leukocyte migration (GO:0050900) IDA
  • positive regulation of phagocytosis, engulfment (GO:0060100) IDA
  • inflammatory response (GO:0006954) IEA
  • innate immune response (GO:0045087) IEA
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) [192] ...
S1P1 receptor
(Lysophospholipid (S1P) receptors)
  • T cell migration (GO:0072678) ISS
  • leukocyte chemotaxis (GO:0030595) IEA
S1P1R activation by agonists downregulates allergic inflammation (i.e. it has an inhibitory effect) [256,260,509] ...
S1P3 receptor
(Lysophospholipid (S1P) receptors)
  • inflammatory response (GO:0006954) TAS
In the immune system S1P receptors regulate immune cell trafficking and mitogenesis, are involved in immune-modulation, and suppression of innate immune T cell responses.
succinate receptor
(Succinate receptor)
  • macrophage activation involved in immune response (GO:0002281) IEA
  • 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 [347] ...
XCR1
(Chemokine receptors)
  • inflammatory response (GO:0006954) TAS
XCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. XCR1 is expressed by a subset of dendritic cells [332] ...
Ion Channels
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
Hv1
(Voltage-gated proton channel)
  • neutrophil degranulation (GO:0043312) TAS
Detection of low intracellular pH by the Hv1 ion channel impacts upon the function of B cells, macrophages, neutrophils and microglia [88,593] ...
P2X1
(P2X receptors)
  • neutrophil degranulation (GO:0043312) TAS
  • serotonin secretion by platelet (GO:0002554) IEA
Functional P2X1 receptors are expressed by healthy human eosinophils [636] ...
P2X4
(P2X receptors)
  • microglial cell migration (GO:1904124) TAS
  • 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 [79,94] ...
P2X7
(P2X receptors)
  • phagolysosome assembly (GO:0001845) IEA
  • inflammatory response (GO:0006954) IEA
The P2X7 receptor is involved in NLRP3-type inflammasome formation, and subsequent maturation of IL-1β [346,486] ...
TRPM2
(Transient Receptor Potential channels)
  • dendritic cell chemotaxis (GO:0002407) ISS
  • neutrophil degranulation (GO:0043312) TAS
Expressed on human T cells, mouse dendritic cells, human and mouse neutrophils and monocytes/macrophages, and mouse mast cells [457] ...
TRPM4
(Transient Receptor Potential channels)
  • dendritic cell chemotaxis (GO:0002407) ISS
  • 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 [457] ...
TRPV1
(Transient Receptor Potential channels)
  • fever generation (GO:0001660) IEA
  • microglial cell activation (GO:0001774) IEA
Several lines of evidence suggest that TRPV1 is implicated in some inflammatory processes [26,55,358,369,507] ...
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 [457] ...
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
  • inflammatory response (GO:0006954) IEA
  • toll-like receptor 9 signaling pathway (GO:0034162) IEA
  • innate immune response (GO:0045087) 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) [515] ...
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
  • apoptotic cell clearance (GO:0043277) IMP
  • 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 [641] ...
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 [641] ...
Peroxisome proliferator-activated receptor-γ
(1C. Peroxisome proliferator-activated receptors)
  • innate immune response (GO:0045087) TAS
  • negative regulation of interferon-gamma-mediated signaling pathway (GO:0060336) IMP
  • negative regulation of acute inflammatory response (GO:0002674) IEA
  • positive regulation of phagocytosis, engulfment (GO:0060100) 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 [324] ...
RAR-related orphan receptor-γ
(1F. Retinoic acid-related orphans)
  • T-helper cell differentiation (GO:0042093) ISS
  • T-helper 17 cell differentiation (GO:0072539) ISS
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) [139,196,427,544] ...
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
  • 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 [288] ...
5-LOX
(Lipoxygenases)
  • neutrophil degranulation (GO:0043312) TAS
  • leukotriene production involved in inflammatory response (GO:0002540) IEA
5-LOX is included in GtoImmuPdb because of its involvement in eicosanoid turnover and because it is being actively pursued as a molecular target for the development of novel anti-inflammatory therapeutics [532] ...
8-oxoguanine DNA glycosylase
(DNA glycosylases)
  • acute inflammatory response (GO:0002526) IEA
OGG1 has recognised roles in processes that are associated with innate and adaptive immunity [7,29] ...
ABL proto-oncogene 1, non-receptor tyrosine kinase
(Abl family)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • B cell proliferation involved in immune response (GO:0002322) IEA
Included in GtoImmuPdb based on its association with leukemia.
aconitate decarboxylase 1
(Itaconate biosynthesis)
  • 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
  • cellular response to interferon-gamma (GO:0071346) ISS
  • inflammatory response (GO:0006954) IEA
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 [123,157] ...
ADAM10
(M12: Astacin/Adamalysin)
  • positive regulation of T cell chemotaxis (GO:0010820) IMP
  • monocyte activation (GO:0042117) IMP
  • neutrophil degranulation (GO:0043312) TAS
ADAM10 has been identified as the primary physiologically relevant sheddase responsible for cleavage of , and regulation of ICOS/ICOSL-dependent immune responses [359] ...
ADAM17
(M12: Astacin/Adamalysin)
  • positive regulation of leukocyte chemotaxis (GO:0002690) IC
  • positive regulation of T cell chemotaxis (GO:0010820) IMP
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)
  • leukocyte migration involved in inflammatory response (GO:0002523) ISS
  • positive regulation of acute inflammatory response (GO:0002675) ISS
  • inflammatory response (GO:0006954) IDA
  • neutrophil degranulation (GO:0043312) TAS
  • positive regulation of innate immune response (GO:0045089) ISS
  • lymphocyte chemotaxis (GO:0048247) ISS
  • positive regulation of neutrophil extravasation (GO:2000391) IDA
  • 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) [461] ...
Adenosine deaminase
(Adenosine turnover)
  • germinal center B cell differentiation (GO:0002314) IEA
  • negative regulation of leukocyte migration (GO:0002686) IEA
  • negative regulation of inflammatory response (GO:0050728) 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 ...
alkaline ceramidase 3
(Alkaline ceramidases)
  • inflammatory response (GO:0006954) IEA
ACER3 may play a role in inflammation, since it is reported that loss of Acer3 in mice aggravates colitis and colitis-associated colorectal cancer [612] ...
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 [438-439] ...
amine oxidase copper containing 3
(1.-.-.- Oxidoreductases)
  • inflammatory response (GO:0006954) TAS
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 [506] ...
Aminopeptidase N
(M1: Aminopeptidase N)
  • neutrophil degranulation (GO:0043312) TAS
Pharmacological inhibitors of APN are being investigated to counter the dysregulated APN expression that has been associated with inflammatory diseases [47,360] ...
Arginase I
(Arginase)
  • neutrophil degranulation (GO:0043312) TAS
  • negative regulation of interferon-gamma-mediated signaling pathway (GO:0060336) IMP
  • innate immune response (GO:0045087) IEA
  • negative regulation of T-helper 2 cell cytokine production (GO:2000552) IEA
The role of ARG1 in immuno-oncology is reviewed in [3] ...
Arginase II
(Arginase)
  • innate immune response (GO:0045087) IEA
The role of ARG2 in immuno-oncology is reviewed in [3] ...
Bruton tyrosine kinase
(Tec family)
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • innate immune response (GO:0045087) TAS
  • positive regulation of type III hypersensitivity (GO:0001805) IEA
  • positive regulation of type I hypersensitivity (GO:0001812) IEA
  • histamine secretion by mast cell (GO:0002553) 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 [51] ...
calcium/calmodulin dependent protein kinase IV
(CAMK1 family)
  • myeloid dendritic cell differentiation (GO:0043011) IMP
  • inflammatory response (GO:0006954) IEA
CAMKIV has been implicated in the differentiation of Th17 cells, suggesting CAMKIV as a target for therapeutic intervention in Th17-driven autoimmune diseases [306] ...
casein kinase 2, beta polypeptide subunit
(Casein kinase 2 (CK2) family)
  • neutrophil degranulation (GO:0043312) TAS
CSNK2B is included in Guide to IMMUNOPHARMACOLOGY as it is a subunit of the casein kinase 2 complex.
Caspase 1
(C14: Caspase)
  • cellular response to interferon-gamma (GO:0071346) IMP
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 4
(C14: Caspase)
  • inflammatory response (GO:0006954) IEA
  • innate immune response (GO:0045087) IEA
Recognition of cytoplasmic lipopolysaccharide (LPS) by Inflammatory caspases including caspases-4 and -5 leads to pyroptosis and secretion of inflammatory mediators [526-527] ...
Caspase 8
(C14: Caspase)
  • toll-like receptor 3 signaling pathway (GO:0034138) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • 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 [371] ...
cathepsin B
(C1: Papain)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • neutrophil degranulation (GO:0043312) 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)
  • neutrophil degranulation (GO:0043312) TAS
  • 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)
  • neutrophil degranulation (GO:0043312) TAS
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)
  • neutrophil degranulation (GO:0043312) TAS
Cathepsin H may act as a pro-granzyme B convertase [137] ...
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
  • neutrophil degranulation (GO:0043312) TAS
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 [578] ...
chitinase acidic
(Chitinases)
  • production of molecular mediator involved in inflammatory response (GO:0002532) IDA
AMCase has been shown to be produced during type 2 inflammatory responses [676] ...
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) [234] ...
complement C1r
(S1: Chymotrypsin)
  • innate immune response (GO:0045087) IEA
A protease component of the C1-complex of the classical complement pathway.
complement C1s
(S1: Chymotrypsin)
  • innate immune response (GO:0045087) IEA
A protease component of the C1-complex of the classical complement pathway.
complement factor B
(S1: Chymotrypsin)
  • complement activation, alternative pathway (GO:0006957) 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, alternative pathway (GO:0006957) TAS
  • neutrophil degranulation (GO:0043312) 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
  • inflammatory response (GO:0006954) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • innate immune response (GO:0045087) 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 [249] ...
COX-1
(Cyclooxygenase)
  • inflammatory response (GO:0006954) IEA
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.
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
  • inflammatory response (GO:0006954) IEA
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 [3] ...
C-terminal Src kinase
(Csk family)
  • negative regulation of phagocytosis (GO:0050765) IEA
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 [601] ...
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
  • neutrophil migration (GO:1990266) IEA
DAPk2 is recognised as a regulator of apoptosis, autophagy and inflammation [195] ...
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 [22] ...
elastase, neutrophil expressed
(S1: Chymotrypsin)
  • acute inflammatory response to antigenic stimulus (GO:0002438) IBA
  • phagocytosis (GO:0006909) IBA
  • neutrophil degranulation (GO:0043312) TAS
  • negative regulation of inflammatory response (GO:0050728) NAS
  • leukocyte migration involved in inflammatory response (GO:0002523) 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 [587] ...
epoxide hydrolase 2
(Hydrolases)
  • inflammatory response (GO:0006954) NAS
Its role in metabolism of arachadonic acid EET metabolites, means that sEH participates in the regulation of prostaglandin and leukotriene production and therefore in immune homeostasis. Small molecule sEH inhibitors can be used as chemical probes to investigate EET (immuno)biology [401] ...
eukaryotic translation initiation factor 2 alpha kinase 2
(Other PEK family kinases)
  • innate immune response (GO:0045087) IEA
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 [191] ...
eukaryotic translation initiation factor 2 alpha kinase 4
(GCN2 subfamily)
  • T cell activation involved in immune response (GO:0002286) 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 [594] ...
FER tyrosine kinase
(Fer family)
  • negative regulation of mast cell activation involved in immune response (GO:0033007) ISS
  • regulation of mast cell degranulation (GO:0043304) IBA
  • diapedesis (GO:0050904) ISS
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)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • positive regulation of mast cell degranulation (GO:0043306) ISS
  • neutrophil degranulation (GO:0043312) TAS
  • regulation of innate immune response (GO:0045088) ISS
  • regulation of phagocytosis (GO:0050764) ISS
  • innate immune response (GO:0045087) IEA
Fgr may be involved in neutrophil migration, potentially via binding to intergrins [43] ...
FYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • leukocyte migration (GO:0050900) TAS
Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [455] ...
Haem oxygenase 1
(Haem oxygenase)
  • wound healing involved in inflammatory response (GO:0002246) IMP
  • negative regulation of leukocyte migration (GO:0002686) TAS
  • 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 [24] ...
HCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • leukocyte migration involved in immune response (GO:0002522) TAS
  • 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
  • regulation of phagocytosis (GO:0050764) IMP
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • inflammatory response (GO:0006954) IEA
Hck is thought to be involved in neutrophil migration, potentially via binding to intergrins [43] ...
heparanase
(3.2.1.- Glycosidases)
  • neutrophil degranulation (GO:0043312) TAS
Heparanase has been studied as a novel drug target associated with the immune response and inflammation [105-106] ...
indoleamine 2,3-dioxygenase 1
(1.13.11.- Dioxygenases)
  • cytokine production involved in inflammatory response (GO:0002534) IEA
  • positive regulation of chronic inflammatory response (GO:0002678) 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 [305] ...
Inducible NOS
(Nitric oxide synthases)
  • innate immune response in mucosa (GO:0002227) NAS
  • regulation of cytokine production involved in inflammatory response (GO:1900015) IDA
  • cellular response to interferon-gamma (GO:0071346) IEA
The role of iNOS in immuno-oncology is reviewed in [3] ...
inhibitor of nuclear factor kappa B kinase subunit beta
(IKK family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • inflammatory response (GO:0006954) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • innate immune response (GO:0045087) 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) [48,64,540] ...
inhibitor of nuclear factor kappa B kinase subunit epsilon
(IKK family)
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • response to type I interferon (GO:0034340) IEA
  • 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)
  • leukocyte migration (GO:0050900) TAS
SHIP1 activators are proposed as novel anti-inflammatory agents e.g. rosiptor (AQX-1125) which is in Phase 2 and 3 clinical trials [422,554] ...
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
  • innate immune response (GO:0045087) IBA
  • type I interferon signaling pathway (GO:0060337) IMP
  • 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
  • inflammatory response (GO:0006954) 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
  • 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 [161,412].
  • 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
  • innate immune response (GO:0045087) TAS
  • neutrophil migration (GO:1990266) IMP
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 [392] ...
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.
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
  • type I interferon signaling pathway (GO:0060337) 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)
  • regulation of inflammatory response (GO:0050727) IDA
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • 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 [56,58,547] ...
Janus kinase 3
(Janus kinase (JakA) family)
  • negative regulation of T-helper 1 cell differentiation (GO:0045626) ISS
  • innate immune response (GO:0045087) IEA
Psoriatic skin samples show elevated JAK3 (and JAK1) expression, with signalling predominantly through STAT3 [16] ...
LCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • leukocyte migration (GO:0050900) TAS
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) [455] ...
Leukotriene A4 hydrolase
(Leukotriene and lipoxin metabolism, M1: Aminopeptidase N, Hydrolases)
  • neutrophil degranulation (GO:0043312) TAS
LTA4H is an established anti-inflammatory target. Expression has been identified in some cancer cells, where it may play a role in the development and progression of cancers associated with chronic inflammation, suggesting that LTA4H inhibitors may have efficacy as anti-cancer therapeutics [111] ...
LYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) 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-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • regulation of mast cell degranulation (GO:0043304) ISS
  • leukocyte migration (GO:0050900) TAS
  • regulation of monocyte chemotaxis (GO:0090025) IMP
  • histamine secretion by mast cell (GO:0002553) IEA
  • innate immune response (GO:0045087) IEA
  • regulation of inflammatory response (GO:0050727) 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 [181,189,586] ...
lysine demethylase 6B
(1.14.11.- Histone demethylases)
  • inflammatory response to antigenic stimulus (GO:0002437) IEA
In relation to the immune system, overexpression of JMJD3 is associated with inflammation [149-150] ...
mitogen-activated protein kinase 1
(ERK subfamily)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • neutrophil degranulation (GO:0043312) TAS
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 [297,367] ...
mitogen-activated protein kinase kinase kinase 5
(STE11 family)
  • innate immune response (GO:0045087) IEA
ASK1 is included in the GToImmuP as it is a molecular target for anti-fibrotic drug development. This kinase acts upstream of p38 MAPK and JNK kinases [258] ...
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
  • 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 [140,504] ...
mitogen-activated protein kinase kinase kinase kinase 2
(KHS subfamily)
  • innate immune response (GO:0045087) IEA
In vitro analyses suggest that GCK plays important roles in the innate immune response and cell signalling [117] ...
MMP1
(M10: Matrix metallopeptidase)
  • leukocyte migration (GO:0050900) TAS
Overexpression of MMP-1 degrades extracellular matrix causing damage to the colon mucosa in patients with ulcerative colitis. The MMP-1 promotes secretion of TNFα causing futher damage. Levels of MMP-1 and TNFα correlate with disease severity [617] ...
MMP12
(M10: Matrix metallopeptidase)
  • 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 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 [154] ...
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)
  • neutrophil degranulation (GO:0043312) TAS
  • 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)
  • neutrophil degranulation (GO:0043312) TAS
  • regulation of neuroinflammatory response (GO:0150077) TAS
  • leukocyte migration (GO:0050900) IEA
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 [319] ...
mPGES1
(Prostaglandin synthases)
  • acute inflammatory response (GO:0002526) IEA
  • chronic inflammatory response (GO:0002544) IEA
Inhibition of mPGES-1 is proposed as a potentially safer alternative to COX-2 inhibition for the treatment of pain and inflammation, with a reduced risk of cardiovascular side effects [452] ...
myeloperoxidase
(1.-.-.- Oxidoreductases)
  • neutrophil degranulation (GO:0043312) TAS
Myeloperoxidase (MPO) is a leukocyte-derived redox enzyme whose peroxidase enzymatic activity generates hypohalous acids that constitute the major component responsible for neutrophil antimicrobial activity, and as such MPO participates in the innate immune defense mechanism. Since the discovery that MPO-derived oxidants contribute towards the propagation of inflammatory diseases (including cystic fibrosis, chronic obstructive pulmonary disease, Parkinson's disease, rheumatoid arthritis, acute kidney injury, atherosclerosis and cardiovascular disease) [303,431] ...
NADPH oxidase 4
(NADPH oxidases)
  • inflammatory response (GO:0006954) TAS
Nox4 is a known driver of the fibrotic process. We have included Nox4 in GToImmunoPdb based on the association between fibrosis and inflammation.
otulin
(C101: OTULIN peptidase)
  • innate immune response (GO:0045087) IDA
  • 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 [143] ...
p21 (RAC1) activated kinase 1
(PAKA subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) 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 [144] ...
p21 (RAC1) activated kinase 2
(PAKA subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
Pharmacological inhibition of PAK2 has immunosuppressive effects [440] ...
peptidyl arginine deiminase 4
(3.5.3.15 Peptidyl arginine deiminases (PADI))
  • innate immune response (GO:0045087) IEA
PADI4 is essential for neutrophil extracellular trap (NET) formation (NETosis) in pathogen elimination. PADI4-formed NETs containing hypercitrullinated histone H3 are detected in several systemic autoimmune diseases, including lupus and rheumatoid arthritis [182] ...
phosphatase and tensin homolog
(Lipid phosphate phosphatases)
  • negative regulation of phagocytosis (GO:0050765) IEA
Accumulating evidence suggests that loss-of-function mutations or deletion of PTEN is an immune evasion mechanism exploited by tumour cells [548] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • leukocyte migration (GO:0050900) 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)
  • mast cell chemotaxis (GO:0002551) TAS
  • inflammatory response (GO:0006954) TAS
  • T cell chemotaxis (GO:0010818) TAS
  • neutrophil chemotaxis (GO:0030593) TAS
  • natural killer cell chemotaxis (GO:0035747) TAS
  • B cell chemotaxis (GO:0035754) TAS
  • mast cell degranulation (GO:0043303) TAS
  • innate immune response (GO:0045087) TAS
  • neutrophil extravasation (GO:0072672) 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 [224] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • inflammatory response (GO:0006954) TAS
  • T cell chemotaxis (GO:0010818) TAS
  • neutrophil chemotaxis (GO:0030593) TAS
  • natural killer cell chemotaxis (GO:0035747) TAS
  • mast cell degranulation (GO:0043303) TAS
  • innate immune response (GO:0045087) TAS
  • neutrophil extravasation (GO:0072672) TAS
  • positive regulation of acute inflammatory response (GO:0002675) IEA
The role of PI3Kγ in immuno-oncology is reviewed in [3] ...
phosphodiesterase 4B
(Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs))
  • neutrophil chemotaxis (GO:0030593) ISS
  • leukocyte migration (GO:0050900) ISS
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 [614] ...
phosphodiesterase 4D
(Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs))
  • neutrophil chemotaxis (GO:0030593) IEA
The selective PDE4 inhibitor (OPA-15406) has been shown to inhibit PDE4D3 [443] ...
phosphoinositide-3-kinase regulatory subunit 1
(Phosphatidylinositol kinases)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • leukocyte migration (GO:0050900) TAS
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 [361] ...
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 [365] ...
PLCγ1
(Phosphoinositide-specific phospholipase C)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • leukocyte migration (GO:0050900) 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 [201,503] ...
PLCγ2
(Phosphoinositide-specific phospholipase C)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • follicular B cell differentiation (GO:0002316) IEA
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 [201,503] ...
proteasome 20S subunit beta 8
(T1: Proteasome)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • type I interferon signaling pathway (GO:0060337) TAS
PSMB8 is a component of the immunoproteasome [174] ...
proteinase 3
(S1: Chymotrypsin)
  • phagocytosis (GO:0006909) IBA
  • neutrophil degranulation (GO:0043312) TAS
  • negative regulation of phagocytosis (GO:0050765) IDA
  • neutrophil extravasation (GO:0072672) IMP
Proteinase 3 (PR3), called myeloblastin when it was first identified, is an abundant serine protease found principally in neutrophil granules (but is also found on the surface of quiescent human neutrophils from peripheral blood). It is stored in the primary granules of circulating neutrophils alongside other cathepsin C-activated neutrophil serine proteases (NSPs), such as human neutrophil elastase (HNE), CatG, and NSP4. In pathological conditions it is thought that PR3 behaves to accelerate inflammation, by enhancing cytokine bioactivity, inactivating anti-inflammatory mediators and by promoting tissue injury (potentially by degrading extra-cellular matrix components like elastin, collagen, fibronectin, and laminins). In addition, imbalances between NSPs and their endogenous inhibitors can contribute towards pathological tissue damage, such as the damage associated with inflammatory lung diseases like chronic obstructive pulmonary disease (COPD), emphysema, and cystic fibrosis. PR3 inhibitors are considered to be useful clinical candidates for anti-inflammatory drug development [309] ...
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
  • neutrophil activation (GO:0042119) IDA
  • neutrophil degranulation (GO:0043312) TAS
  • negative regulation of inflammatory response (GO:0050728) IC
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
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
  • macrophage activation involved in immune response (GO:0002281) IEA
PKCε is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C gamma
(Alpha subfamily)
  • regulation of phagocytosis (GO:0050764) IEA
PKCγ is included in GtoImmuPdb based on the involvement of other PKC isozymes in immune processes.
protein kinase C theta
(Delta subfamily)
  • inflammatory response (GO:0006954) IEA
PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [33] ...
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
  • inflammatory response (GO:0006954) IEA
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
  • innate immune response (GO:0045087) 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 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 [108] ...
protein tyrosine kinase 2 beta
(Fak family)
  • marginal zone B cell differentiation (GO:0002315) ISS
  • regulation of macrophage chemotaxis (GO:0010758) ISS
  • 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 [108] ...
protein tyrosine phosphatase non-receptor type 22
(Protein tyrosine phosphatases non-receptor type (PTPN))
  • positive regulation of toll-like receptor 3 signaling pathway (GO:0034141) IMP
  • positive regulation of toll-like receptor 4 signaling pathway (GO:0034145) IMP
  • regulation of innate immune response (GO:0045088) IC
  • negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070433) IMP
PTPN22 is a lymphoid-specific, inducible protein tyrosine phosphatase [121] ...
RAB27A, member RAS oncogene family
(RAB subfamily)
  • neutrophil degranulation (GO:0043312) TAS
  • positive regulation of phagocytosis (GO:0050766) IMP
  • cytotoxic T cell degranulation (GO:0043316) IEA
  • natural killer cell degranulation (GO:0043320) IEA
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 [279] ...
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
RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [418,490,530,606] ...
receptor interacting serine/threonine kinase 2
(Receptor interacting protein kinase (RIPK) family)
  • inflammatory response (GO:0006954) TAS
  • toll-like receptor 2 signaling pathway (GO:0034134) IDA
  • innate immune response (GO:0045087) IDA
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IDA
  • toll-like receptor 4 signaling pathway (GO:0034142) IEA
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) 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) [434] ...
receptor interacting serine/threonine kinase 3
(Receptor interacting protein kinase (RIPK) family)
  • 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 [418,490,530,606] ...
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 [479] ...
sPLA2-1B
(Phospholipase A2)
  • innate immune response in mucosa (GO:0002227) IDA
  • neutrophil chemotaxis (GO:0030593) 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 [326] ...
spleen associated tyrosine kinase
(Syk family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • macrophage activation involved in immune response (GO:0002281) ISS
  • neutrophil activation involved in immune response (GO:0002283) ISS
  • leukocyte activation involved in immune response (GO:0002366) ISS
  • serotonin secretion by platelet (GO:0002554) ISS
  • neutrophil chemotaxis (GO:0030593) IDA
  • 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
  • innate immune response (GO:0045087) ISS
  • regulation of phagocytosis (GO:0050764) ISS
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 [199,489] ...
SRC proto-oncogene, non-receptor tyrosine kinase
(Src family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • leukocyte migration (GO:0050900) 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 [357] ...
TANK binding kinase 1
(IKK family)
  • inflammatory response (GO:0006954) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • innate immune response (GO:0045087) 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 [287] ...
transglutaminase 2
(2.3.2.13 Transglutaminases)
  • apoptotic cell clearance (GO:0043277) IDA
  • 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 [132] ...
tripartite motif containing 21
(2.3.2.27 RING-type E3 ubiquitin transferase)
  • response to interferon-gamma (GO:0034341) IDA
  • innate immune response (GO:0045087) IDA
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
Tripartite motif-containing (TRIM) superfamily proteins are critical in a variety of biological processes in innate immunity and are important for eradication of invading pathogens [451,481,603] ...
tripartite motif containing 38
(2.3.2.27 RING-type E3 ubiquitin transferase)
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
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 [642] ...
TXK tyrosine kinase
(Tec family)
  • 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 [51] ...
tyrosine kinase 2
(Janus kinase (JakA) family)
  • type I interferon signaling pathway (GO:0060337) TAS
TYK2 was the first member of the Janus kinase family to be identified. It associates with the cytoplasmic domain of type I and type II cytokine receptors, where it phosphorylates receptor subunits and facilitates signalling downstream of the receptors for the p40-containing cytokines IL-12 and IL-23 via activation of STAT-dependent transcription factors. It also mediates Type I IFN-driven responses [552] ...
vanin 1
(Hydrolases)
  • acute inflammatory response (GO:0002526) ISS
  • chronic inflammatory response (GO:0002544) ISS
  • inflammatory response (GO:0006954) ISS
  • neutrophil degranulation (GO:0043312) TAS
  • innate immune response (GO:0045087) ISS
Mounting evidence indicates that vanin 1 is involved in inflammation associated with diseases including systemic lupus erythematosus [566] ...
YES proto-oncogene 1, Src family tyrosine kinase
(Src family)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • leukocyte migration (GO:0050900) 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)
  • T cell migration (GO:0072678) TAS
ZAP-70 has much lower intrinsic enzyme activity than SYK, and expression is restricted to T cells and NK cells [27] ...
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)
  • phagocytosis (GO:0006909) IDA
  • inflammatory response (GO:0006954) IEA
  • apoptotic cell clearance (GO:0043277) IEA
  • innate immune response (GO:0045087) 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 [216] ...
CD40
(Immune checkpoint catalytic receptors, Tumour necrosis factor (TNF) receptor family)
  • inflammatory response (GO:0006954) TAS
  • response to interferon-gamma (GO:0034341) IEA
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) 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 ...
CIITA
(NOD-like receptor family)
  • inflammatory response (GO:0006954) IBA
  • response to interferon-gamma (GO:0034341) IDA
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
CIITA is a transcriptional coactivator for the transcription factor RFX5 [514] ...
colony stimulating factor 1 receptor
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • inflammatory response (GO:0006954) TAS
  • innate immune response (GO:0045087) IEA
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 [3] ...
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.
DExD/H-box helicase 58
(RIG-I-like receptor family)
  • cytoplasmic pattern recognition receptor signaling pathway in response to virus (GO:0039528) TAS
  • RIG-I signaling pathway (GO:0039529) IMP
  • innate immune response (GO:0045087) 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 [381] ...
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
  • innate immune response (GO:0045087) IEA
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.
glucocorticoid-induced TNF receptor
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of leukocyte migration (GO:0002687) IMP
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)
  • neutrophil chemotaxis (GO:0030593) 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 T cell migration (GO:2000406) IBA
  • innate immune response (GO:0045087) IEA
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)
  • leukocyte migration (GO:0050900) TAS
  • leukocyte tethering or rolling (GO:0050901) IMP
  • diapedesis (GO:0050904) IEA
  • 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 [217] ...
integrin, alpha L subunit (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide)
(Integrins)
  • T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:0002291) IMP
  • inflammatory response (GO:0006954) NAS
  • neutrophil degranulation (GO:0043312) TAS
  • leukocyte migration (GO:0050900) TAS
  • phagocytosis (GO:0006909) IEA
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)
  • microglial cell activation (GO:0001774) NAS
  • phagocytosis, engulfment (GO:0006911) ISS
  • inflammatory response (GO:0006954) NAS
  • neutrophil chemotaxis (GO:0030593) IDA
  • toll-like receptor 4 signaling pathway (GO:0034142) TAS
  • neutrophil degranulation (GO:0043312) TAS
  • positive regulation of neutrophil degranulation (GO:0043315) IGI
  • leukocyte migration (GO:0050900) TAS
  • positive regulation of microglial cell activation (GO:1903980) NAS
  • neutrophil migration (GO:1990266) IMP
  • leukocyte migration involved in inflammatory response (GO:0002523) IEA
  • cellular extravasation (GO:0045123) IEA
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 [301] ...
interferon α/β receptor 1
(Interferon receptor family)
  • type I interferon receptor activity (GO:0004905) IDA
  • type I interferon signaling pathway (GO:0060337) IDA
IFNAR1 is a subunit of the functional receptor for type I interferons (NOT interferon γ). Type I interferons (IFN) exhibit an established anti-viral action. However, type I IFN signalling also appears to play a role in impaired resistance to a range of other pathogens (e.g. bacterial infection) [90,419] ...
Interferon α/β receptor 2
(Interferon receptor family)
  • type I interferon receptor activity (GO:0004905) IDA
  • type I interferon signaling pathway (GO:0060337) IDA
  • 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)
  • interferon-gamma receptor activity (GO:0004906) TAS
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • 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)
  • interferon-gamma receptor activity (GO:0004906) TAS
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • 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
  • innate immune response (GO:0045087) TAS
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 [8,243,395] ...
Interferon-λ receptor subunit 1
(IL-10 receptor family)
  • response to type III interferon (GO:0034342) ISS
Interferon-λ receptor subunit 1 is the ligand binding component of the functional heterodimeric receptor for interferons λ1, λ2 and λ3
Interleukin 10 receptor, β subunit
(IL-10 receptor family)
  • inflammatory response (GO:0006954) TAS
Interleukin 10 receptor, β subunit is a component of the functional receptor heterodimers for interleukins 10 and 22 and for interferons λ1, λ2 and λ3.
Interleukin-12 receptor, β1 subunit
(IL-12 receptor family)
  • positive regulation of memory T cell differentiation (GO:0043382) ISS
  • cellular response to interferon-gamma (GO:0071346) IDA
  • 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 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 [634] ...
Interleukin-15 receptor subunit α
(IL-2 receptor family)
  • positive regulation of phagocytosis (GO:0050766) IMP
This is the ligand binding subunit of the functional IL-15 receptor complex.
Interleukin 17 receptor A
(IL-17 receptor family)
  • granulocyte chemotaxis (GO:0071621) IEA
  • 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)
  • granulocyte chemotaxis (GO:0071621) IEA
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) IEA
This is a subunit of the heterodimeric interleukin-17 receptor.
Interleukin 17 receptor E
(IL-17 receptor family)
  • inflammatory response (GO:0006954) IEA
This is a component of the heterodimeric interleukin-17C receptor.
Interleukin-18 receptor 1
(Immunoglobulin-like family of IL-1 receptors)
  • positive regulation of T-helper 1 cell cytokine production (GO:2000556) IDA
  • inflammatory response (GO:0006954) IEA
  • T-helper 1 cell differentiation (GO:0045063) IEA
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)
  • 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 [188] ...
Interleukin-1 receptor-like 2
(Immunoglobulin-like family of IL-1 receptors)
  • inflammatory response (GO:0006954) IEA
  • innate immune response (GO:0045087) 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 [187] ...
Interleukin 1 receptor, type I
(Immunoglobulin-like family of IL-1 receptors)
  • positive regulation of T-helper 1 cell cytokine production (GO:2000556) IDA
  • inflammatory response (GO:0006954) IEA
  • 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 [202,416] ...
Interleukin 20 receptor, β subunit
(IL-10 receptor family)
  • negative regulation of type IV hypersensitivity (GO:0001808) IEA
  • inflammatory response to antigenic stimulus (GO:0002437) 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 [148,172] ...
Interleukin 23 receptor
(IL-12 receptor family)
  • response to interferon-gamma (GO:0034341) IDA
  • positive regulation of memory T cell differentiation (GO:0043382) ISS
  • positive regulation of T-helper 17 cell lineage commitment (GO:2000330) ISS
  • inflammatory response (GO:0006954) IEA
This is one of the subunits of the functional IL-23 receptor heterodimer.
Interleukin 27 receptor, alpha
(IL-6 receptor family)
  • regulation of isotype switching to IgG isotypes (GO:0048302) 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)
  • inflammatory response to antigenic stimulus (GO:0002437) IEA
  • negative regulation of inflammatory response (GO:0050728) 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 [537] ...
Interleukin-2 receptor subunit β
(IL-2 receptor family)
  • positive regulation of phagocytosis (GO:0050766) IMP
IL2RB is a ligand binding component of the IL-2R and is required to elevate ligand affinity. It also a component of the IL-15R.
Interleukin-2 receptor subunit γ
(IL-2 receptor family)
  • positive regulation of phagocytosis (GO:0050766) 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
  • acute inflammatory response to antigenic stimulus (GO:0002438) IEA
  • T-helper 2 cell cytokine production (GO:0035745) IEA
Interleukin-4 receptor subunit α
(IL-2 receptor family)
  • production of molecular mediator involved in inflammatory response (GO:0002532) 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 [233] ...
Interleukin 5 receptor, α subunit
(IL-3 receptor family)
  • inflammatory response to antigenic stimulus (GO:0002437) IEA
This is the ligand binding subunit of the functional IL-5 receptor complex.
Interleukin-6 receptor, α subunit
(IL-6 receptor family)
  • monocyte chemotaxis (GO:0002548) IC
  • positive regulation of leukocyte chemotaxis (GO:0002690) TAS
  • acute-phase response (GO:0006953) TAS
IL6R polymorphisms are associated with asthma risk [173] ...
Interleukin-6 receptor, β subunit
(IL-6 receptor family)
  • positive regulation of acute inflammatory response (GO:0002675) IC
This is the common signal transducing subunit shared by members of the IL-6 family of cytokine receptors [498] ...
KIT proto-oncogene, receptor tyrosine kinase
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • mast cell chemotaxis (GO:0002551) IDA
  • inflammatory response (GO:0006954) ISS
  • mast cell degranulation (GO:0043303) IMP
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 [209] ...
lymphotoxin β receptor
(Tumour necrosis factor (TNF) receptor family)
  • myeloid dendritic cell differentiation (GO:0043011) IBA
Interaction of the lymphotoxin β receptor (LTBR) with its ligand is required for the development and organization of the secondary lymphoid organs and is involved in chemokine release (reported to induce interleukin 8 gene expression [104] ...
macrophage stimulating 1 receptor
(Type X RTKs: HGF (hepatocyte growth factor) receptor family)
  • innate immune response (GO:0045087) IEA
The role of RON in immuno-oncology is reviewed in [3] ...
MER proto-oncogene, tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • phagocytosis (GO:0006909) IMP
  • positive regulation of phagocytosis (GO:0050766) IDA
  • leukocyte migration (GO:0050900) TAS
  • apoptotic cell clearance (GO:0043277) IEA
  • neutrophil clearance (GO:0097350) IEA
Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [50,610] ...
MET proto-oncogene, receptor tyrosine kinase
(Type X RTKs: HGF (hepatocyte growth factor) receptor family)
  • phagocytosis (GO:0006909) IBA
The leucine-rich repeat (LRR)-containing protein InlB of Listeria monocytogenes is reported to mediate bacterial entry in to non-phagocytic host cells by binding to the MET proto-oncogene, receptor tyrosine kinase (MET, or hepatocyte growth factor receptor, HGFR) [63] ...
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 [373,667] ...
NLRC4
(NOD-like receptor family)
  • activation of innate immune response (GO:0002218) ISS
  • inflammatory response (GO:0006954) ISS
  • innate immune response (GO:0045087) IEA
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 [394] ...
NLRC5
(NOD-like receptor family)
  • innate immune response (GO:0045087) IMP
  • 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 [415] ...
NLRP1
(NOD-like receptor family)
  • regulation of inflammatory response (GO:0050727) IC
  • inflammatory response (GO:0006954) IEA
  • innate immune response (GO:0045087) IEA
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 inflammatory response (GO:0050729) ISS
  • inflammatory response (GO:0006954) IEA
  • innate immune response (GO:0045087) IEA
NLRP10 is an intracellular pattern recognition receptor (PRR) that has apoptotic and anti-inflammatory functions [262] ...
NLRP3
(NOD-like receptor family)
  • negative regulation of acute inflammatory response (GO:0002674) IMP
  • inflammatory response (GO:0006954) IMP
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) ISS
  • negative regulation of inflammatory response (GO:0050728) IMP
  • positive regulation of T-helper 2 cell cytokine production (GO:2000553) ISS
  • innate immune response (GO:0045087) IEA
  • 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 [35,374] ...
NLRP6
(NOD-like receptor family)
  • regulation of inflammatory response (GO:0050727) ISS
  • negative regulation of inflammatory response to antigenic stimulus (GO:0002862) IEA
  • inflammatory response (GO:0006954) IEA
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) IEA
  • innate immune response (GO:0045087) 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
  • innate immune response (GO:0045087) 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)
  • inflammatory response (GO:0006954) TAS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
  • innate immune response (GO:0045087) IEA
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)
  • innate immune response (GO:0045087) IDA
  • regulation of inflammatory response (GO:0050727) IC
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IDA
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) IDA
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)
  • inflammatory response (GO:0006954) 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 [622] ...
receptor activator of NF-kappa B
(Tumour necrosis factor (TNF) receptor family)
  • monocyte chemotaxis (GO:0002548) NAS
  • 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)
  • neutrophil degranulation (GO:0043312) TAS
  • regulation of phagocytosis (GO:0050764) IDA
  • 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 isotype switching to IgG isotypes (GO:0048304) 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 [142] ...
single Ig and TIR domain containing
(Immunoglobulin-like family of IL-1 receptors)
  • acute-phase response (GO:0006953) ISS
IL-1R8 has been identified as a natural killer (NK) cell checkpoint that is involved in regulating NK cells' anti-viral and anti-tumour effector functions [398] ...
TEK receptor tyrosine kinase
(Type XII RTKs: TIE family of angiopoietin receptors)
  • negative regulation of inflammatory response (GO:0050728) TAS
  • leukocyte migration (GO:0050900) 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 [299] ...
TLR1
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • inflammatory response (GO:0006954) IBA
  • positive regulation of toll-like receptor 2 signaling pathway (GO:0034137) IGI
  • toll-like receptor TLR1:TLR2 signaling pathway (GO:0038123) TAS
  • macrophage activation (GO:0042116) NAS
  • toll-like receptor 1 signaling pathway (GO:0034130) IEA
  • innate immune response (GO:0045087) IEA
TLR1/2 heterodimers detect and respond to bacterial triacyl lipopeptides [590] ...
TLR10
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • inflammatory response (GO:0006954) IBA
  • toll-like receptor 10 signaling pathway (GO:0034166) TAS
  • innate immune response (GO:0045087) IEA
  • 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 [450] ...
TLR2
(Toll-like receptor family)
  • lipopolysaccharide receptor activity (GO:0001875) TAS
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • inflammatory response (GO:0006954) IBA
  • 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
  • neutrophil degranulation (GO:0043312) TAS
  • innate immune response (GO:0045087) TAS
  • positive regulation of inflammatory response (GO:0050729) IC
  • negative regulation of phagocytosis (GO:0050765) ISS
  • cellular response to interferon-gamma (GO:0071346) IDA
  • microglial cell activation (GO:0001774) IEA
  • 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 [409] ...
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
  • innate immune response (GO:0045087) TAS
  • positive regulation of inflammatory response (GO:0050729) IC
  • microglial cell activation (GO:0001774) IEA
  • cellular response to interferon-gamma (GO:0071346) IEA
TLR3 is an endosomal anti-viral receptor [590] ...
TLR4
(Toll-like receptor family)
  • lipopolysaccharide receptor activity (GO:0001875) IDA
  • 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
  • phagocytosis (GO:0006909) IDA
  • inflammatory response (GO:0006954) IBA
  • 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
  • macrophage activation (GO:0042116) IMP
  • positive regulation of macrophage activation (GO:0043032) ISS
  • innate immune response (GO:0045087) TAS
  • positive regulation of inflammatory response (GO:0050729) IC
  • cellular response to interferon-gamma (GO:0071346) IDA
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) ISS
  • B cell proliferation involved in immune response (GO:0002322) IEA
  • nitric oxide production involved in inflammatory response (GO:0002537) 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) [59,472] ...
TLR5
(Toll-like receptor family)
  • 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
  • inflammatory response (GO:0006954) IEA
  • innate immune response (GO:0045087) IEA
TLR5 induces a pro-inflammatory response upon detection of extracellular bacterial flagellin from invading mobile bacteria [394] ...
TLR6
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) ISS
  • inflammatory response (GO:0006954) IBA
  • 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 cytokine production involved in inflammatory response (GO:1900017) ISS
  • microglial cell activation (GO:0001774) IEA
  • toll-like receptor 6 signaling pathway (GO:0034150) IEA
  • innate immune response (GO:0045087) IEA
TLR6 forms heterodimers with TLR2 to detect a wide range of bacterial lipopeptides (LP) from bacterial cell membranes, and effect an immune response [169] ...
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
  • microglial cell activation (GO:0001774) IEA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
  • innate immune response (GO:0045087) IEA
TLR7 is an endosomal receptor detecting ssRNA [590] ...
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
  • innate immune response (GO:0045087) NAS
  • positive regulation of innate immune response (GO:0045089) IDA
  • microglial cell activation (GO:0001774) IEA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
TLR8 is an endosomal receptor detecting ssRNA [590] ...
TLR9
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • signaling pattern recognition receptor activity (GO:0008329) IBA
  • 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
  • innate immune response (GO:0045087) TAS
  • positive regulation of inflammatory response (GO:0050729) IC
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
  • inflammatory response (GO:0006954) IEA
TLR9 is an endosomal receptor detecting viral and bacterial CpG DNA and genomic DNA from some protozoan species [590] ...
tumor necrosis factor receptor 1
(Tumour necrosis factor (TNF) receptor family)
  • inflammatory response (GO:0006954) ISS
  • 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 [213,420] ...
tumor necrosis factor receptor 2
(Tumour necrosis factor (TNF) receptor family)
  • regulation of T cell cytokine production (GO:0002724) ISS
  • neutrophil degranulation (GO:0043312) TAS
  • regulation of neuroinflammatory response (GO:0150077) ISS
  • negative regulation of neuroinflammatory response (GO:0150079) ISS
  • inflammatory response (GO:0006954) IEA
  • 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 [213,420] ...
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
  • apoptotic cell clearance (GO:0043277) ISS
  • negative regulation of innate immune response (GO:0045824) ISS
  • negative regulation of inflammatory response (GO:0050728) ISS
TYRO3 is a negative regulator of type 2 immunity [102] ...
Transporters
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
L-type amino acid transporter 1
(SLC7 family)
  • leukocyte migration (GO:0050900) TAS
LAT1 has been identified as being a key transporter of the essential amino acids [230] ...
NRAMP1
(SLC11 family of proton-coupled metal ion transporters)
  • T cell proliferation involved in immune response (GO:0002309) ISS
  • T cell cytokine production (GO:0002369) ISS
  • phagocytosis (GO:0006909) ISS
  • inflammatory response (GO:0006954) ISS
  • response to interferon-gamma (GO:0034341) ISS
  • macrophage activation (GO:0042116) ISS
  • neutrophil degranulation (GO:0043312) TAS
  • positive regulation of phagocytosis (GO:0050766) 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 [71,541,546] ...
Peptide transporter 4
(SLC15 family of peptide transporters)
  • neutrophil degranulation (GO:0043312) TAS
SLC15A4 is an oligopeptide transporter that is expressed in early endosomes, and which is involved in NOD1-dependent NF-κB signaling [327] ...
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
  • inflammatory response (GO:0006954) IEA
  • innate immune response (GO:0045087) IEA
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)
  • inflammatory response (GO:0006954) TAS
  • innate immune response (GO:0045087) TAS
  • 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
  • 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 [414,512,646] ...
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 [318] ...
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[497] ...
BCL6 transcription repressor
(BTB (POZ) domain containing TFs)
  • regulation of inflammatory response (GO:0050727) IBA
  • inflammatory response (GO:0006954) 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
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 [89,96] ...
CD19
(CD molecules)
  • B cell proliferation involved in immune response (GO:0002322) 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 innate immune response (GO:0045089) TAS
  • innate immune response (GO:0045087) IEA
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 [112,631] ...
CD2
(CD molecules)
  • positive regulation of myeloid dendritic cell activation (GO:0030887) NAS
  • leukocyte migration (GO:0050900) TAS
CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells [647] ...
CD209 molecule
(C-type lectin-like receptors (CLRs))
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • innate immune response (GO:0045087) IEA
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.
CD28
(Other immune checkpoint proteins, CD molecules)
  • positive regulation of inflammatory response to antigenic stimulus (GO:0002863) IEA
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
CD28 is expressed on the surface of T cells and is required for the co-stimulatory signal essential for the activation, proliferation and survival of T cells, and Th2 cell development. CD28 acts in concert with the T cell receptor to stimulate cytokine release (promotes IL-2 production). CD28 binds the the B7 proteins CD80 and CD86 on the surface of antigen presenting cells to effect a co-stimulatory signal to T cells. In contrast, CTLA-4 delivers a co-inhibitory signal via CD80/CD86 [12] ...
CD300a
(CD molecules)
  • negative regulation of mast cell activation involved in immune response (GO:0033007) IDA