Targets Associated with Immuno Processes - B cell (activation)
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| B cell (activation) | Download as CSV | |||
Targets Associated to Immuno Processes
Full documentation can be found in the GtoImmuPdb immuno cell type data documentation (PDF). ✖ |
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| GPCRs | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| ADGRG3 (Adhesion Class GPCRs) |
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ADGRG3 is expressed by immune cells. It is required for proper B cell development in the spleen [346] ... | ||
| C3a receptor (Complement peptide receptors) |
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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 [316,354] ... |
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| CCR2 (Chemokine receptors) |
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CCR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CCR2 is discussed in relation to immuno-oncology in [2] ... | ||
| CCR6 (Chemokine receptors) |
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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 [164,191] ... | ||
| CCR7 (Chemokine receptors) |
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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. | ||
| CXCR5 (Chemokine receptors) |
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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. | ||
| GPR183 (Class A Orphans) |
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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 [157,248] ... | ||
| Ion Channels | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| nicotinic acetylcholine receptor α7 subunit (Nicotinic acetylcholine receptors (nACh)) |
Included in Guide to Immunopharmacology as CHRNA7 knockout aggravates rheumatoid arthritis in mice [336] ... | |||
| Orai1 (Orai channels) |
ORAI1 is the gene that encodes the essential pore-forming subunit of CRAC store-operated Ca2+ entry (SOCE) channels [258] ... | |||
| P2X7 (P2X receptors) |
The P2X7 receptor is involved in NLRP3-type inflammasome formation, and subsequent maturation of IL-1β [194,260] ... | |||
| TRPM4 (Transient Receptor Potential channels (TRP)) |
TRPM4 is expressed on human T cells, mouse dendritic cells, human and mouse monocytes/macrophages, and mouse mast cells [243] ... | |||
| Nuclear Hormone Receptors | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| RAR-related orphan receptor-γ (1F. Retinoic acid-related orphans) |
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) [76,110,234,300] ... | |||
| Enzymes | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| ABL proto-oncogene 1, non-receptor tyrosine kinase (Abl family) |
Included in GtoImmuPdb based on its association with leukemia. | |||
| ADAM17 (M12: Astacin/Adamalysin) |
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 [59] ... | |||
| Adenosine deaminase (Adenosine turnover) |
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 ... | |||
| Arginase I (Arginase) |
The role of ARG1 in immuno-oncology is reviewed in [2] ... | |||
| Arginase II (Arginase) |
The role of ARG2 in immuno-oncology is reviewed in [2] ... | |||
| BMX non-receptor tyrosine kinase (Tec family) |
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 [30] ... | |||
| Bruton tyrosine kinase (Tec family) |
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 [30] ... | |||
| calcium/calmodulin dependent protein kinase IV (CAMK1 family) |
CAMKIV has been implicated in the differentiation of Th17 cells, suggesting CAMKIV as a target for therapeutic intervention in Th17-driven autoimmune diseases [165] ... | |||
| Caspase 3 (C14: Caspase) |
Defective caspase 3 expression in immune effector cells may influence susceptibility to Kawasaki disease, an acute vasculitis syndrome affecting small- and medium-sized arteries of infants and children [239] ... | |||
| Caspase 8 (C14: Caspase) |
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 [199] ... | |||
| cathepsin C (C1: Papain) |
Cathepsin C (CatC) is a lysosomal cysteine protease that is constitutively expressed at high levels in lung, kidney, liver and spleen. As well as activity in lysosomal protein degradation, cathepsin C also plays a key role in the activation of granule serine proteases in cytotoxic T cells, natural killer cells (granzymes A and B), mast cells (chymase and tryptase) and neutrophils (cathepsin G, neutrophil elastase, proteinase 3). Dysregulated activation of neutrophil elastase at inflammatory sites induces the release of pro-inflammatoy mediators and can lead to acute tissue injury. This mechanism is recognised as causing lung damage in neutrophil driven conditions such as asthma and COPD, and has driven the pharmaceutical industry to search for cathepsin C inhibitors with clinical utility (e.g. brensocatib; formerly AZD7986 and INS1007). SARS-CoV-2 and COVID-19: CatC has been proposed as a drug target to combat ARDS-associated inflammatory lung damage in patients with severe COVID-19. In this setting CatC inhibitors would be expected to protect the lungs from ARDS by reducing the observed virally-induced hyperinflammation that leads to diffuse alveolar collapse and pulmonary tissue damage [169] ... |
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| cathepsin H (C1: Papain) |
Cathepsin H may act as a pro-granzyme B convertase [75] ... | |||
| cathepsin L (C1: Papain) |
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) |
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 [323] ... | |||
| complement C1r (S1: Chymotrypsin) |
A protease component of the C1-complex of the classical complement pathway. | |||
| complement C1s (S1: Chymotrypsin) |
A protease component of the C1-complex of the classical complement pathway. | |||
| C-terminal Src kinase (Csk family) |
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 [339] ... | |||
| eukaryotic translation initiation factor 2 alpha kinase 4 (GCN2 subfamily) |
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 [333] ... |
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| FYN proto-oncogene, Src family tyrosine kinase (Src family) |
Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [242] ... | |||
| IL2 inducible T cell kinase (Tec family) |
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 [30] ... | |||
| INPP5D (Inositol polyphosphate phosphatases) |
SHIP1 activators are proposed as novel anti-inflammatory agents e.g. rosiptor (AQX-1125) which is in Phase 2 and 3 clinical trials [232,312] ... | |||
| Janus kinase 2 (Janus kinase (JakA) family) |
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 [33,35,308] ... | |||
| Janus kinase 3 (Janus kinase (JakA) family) |
Psoriatic skin samples show elevated JAK3 (and JAK1) expression, with signalling predominantly through STAT3 [9] ... | |||
| LYN proto-oncogene, Src family tyrosine kinase (Src family) |
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 [105,108,328] ... | |||
| mitogen-activated protein kinase kinase kinase 7 (TAK1 subfamily) |
TAK1 (MAP3K7) mediates signaling downstream of multiple cytokine receptors and is functionally important in mitogen, immune, and inflammatory signaling pathways [77,278] ... | |||
| MMP14 (M10: Matrix metallopeptidase) |
MMP14 is included in GtoImmuPdb based on its contribution to degradation of collagenous cartilage matrix in rheumatoid arthritis. An anti-MMP14 antibody, DX-2400 [86] ... | |||
| phosphatase and tensin homolog (Lipid phosphate phosphatases) |
Accumulating evidence suggests that loss-of-function mutations or deletion of PTEN is an immune evasion mechanism exploited by tumour cells [309] ... | |||
| phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases) |
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 [123] ... | |||
| phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases) |
The role of PI3Kγ in immuno-oncology is reviewed in [2] ... | |||
| phosphoinositide-3-kinase regulatory subunit 1 (Phosphatidylinositol kinases) |
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 [195] ... | |||
| PLCγ2 (Phosphoinositide-specific phospholipase C) |
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 [113,277] ... | |||
| protein kinase C beta (Alpha subfamily) |
PKCβ is included in GtoImmuPdb based on its GO immune process associations. | |||
| protein kinase C delta (Delta subfamily) |
PKCδ is included in GtoImmuPdb based on its GO immune process associations. | |||
| protein kinase C theta (Delta subfamily) |
PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [18] ... | |||
| protein kinase C zeta (Iota subfamily) |
PKCζ is included in GtoImmuPdb based on its GO process associations. | |||
| protein kinase, DNA-activated, catalytic subunit (Other PIKK family kinases) |
Protein kinase, DNA-activated, catalytic polypeptide (DNA-PKcs) principally acts to repair DNA in a process called non-homologous end joining (NHEJ). NHEJ is required for V(D)J recombination (somatic recombination) in developing lymphocytes during the early stages of T and B cell maturation. DNA-PKc ... | |||
| protein kinase N1 (Protein kinase N (PKN) family) |
Evidence suggests that PKN1 plays a role in modulation of the NF-κB signalling pathway. Specifically, in Salmonella infection, PKN1 is hijacked by a bacterial effector protein which results in inhibition of NF-κB-dependent gene expression (i.e. inhibition of production of the proinflammatory cytokines that would normally effect bacterial destruction and removal) [122] ... | |||
| protein tyrosine kinase 2 beta (Fak family) |
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 [62] ... | |||
| RAB27A, member RAS oncogene family (RAB subfamily) |
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 [147] ... | |||
| receptor interacting serine/threonine kinase 2 (Receptor interacting protein kinase (RIPK) family) |
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) [236] ... | |||
| receptor interacting serine/threonine kinase 3 (Receptor interacting protein kinase (RIPK) family) |
RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [230,264,296,343] ... | |||
| sirtuin 1 (3.5.1.- Histone deacetylases (HDACs)) |
Sirtuin 1 has been suggested as a molecular target for host-directed therapy against Mycobacterium tuberculosis infection by research that shows that activation of sirtuin 1 decreases lung pathology, reduces inflammation, and enhances drug efficacy against Mycobacterium tuberculosis [67] ... | |||
| spleen associated tyrosine kinase (Syk family) |
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 [111,263] ... | |||
| tec protein tyrosine kinase (Tec family) |
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 [30] ... | |||
| TXK tyrosine kinase (Tec family) |
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 [30] ... | |||
| zeta chain of T cell receptor associated protein kinase 70 (Syk family) |
ZAP-70 has much lower intrinsic enzyme activity than SYK, and expression is restricted to T cells and NK cells [13] ... | |||
| Catalytic Receptors | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| BAFF receptor (Tumour necrosis factor (TNF) receptor family) |
This is a type III membrane bound receptor for B cell activating factor (BAFF). BAFF enhances B cell survival and hence regulates the peripheral B cell population. It is suggested that overproduction of BAFF may enhance the survival of autoreactive B cells, an effect which may contribute in the path ... | |||
| B cell maturation antigen (Tumour necrosis factor (TNF) receptor family) |
B-cell maturation antigen (BCMA) is a cell surface receptor for B-cell activating factor (BAFF). It interacts with various TRAF family adaptor proteins to modulate cell survival and proliferation, via NF-κB and MAPK8/JNK signal transduction pathways. BCMA is highly plasma cell-selective for malignant plasma cells from multiple myeloma (MM) patients, and is being investigated as a target for therapies to tackle relapsed/refractory MM [125,181] ... | |||
| CD27 (Tumour necrosis factor (TNF) receptor family) |
CD27 (TNFRSF7) is a co-stimulatory immune checkpoint molecule that is expressed on various immune cells, including T cells and NK (natural killer) cells. The endogenous ligand for CD27 is CD70. CD27 interacts with various TRAF adaptor proteins and apoptosis regulatory protein SIVA (SIVA1). It has been recognized as playing an important role in priming, enhancing and sustaining a productive anti-cancer (CD8 T cell) adaptive immune response. CD27 is an immuno-oncology target [48,334] ... | |||
| CD40 (Immune checkpoint catalytic receptors, Tumour necrosis factor (TNF) receptor family) |
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 ... | |||
| Cytokine receptor-like factor 2 (IL-2 receptor family) |
Cytokine receptor-like factor 2 is the signal transducing subunit of the functional heterodimeric receptor for thymic stromal lymphopoietin (TSLP). Ligand binding is attributed to the interleukin-7 receptor subunit α. | |||
| death receptor 6 (Tumour necrosis factor (TNF) receptor family) |
Expressed predominantly in the thymus, spleen and white blood cells. May play a role in T helper cell activation, inflammation and immune regulation. Signals via the TRADD adaptor protein to the NF-κB and MAPK8/JNK pathways. | |||
| Fas (Tumour necrosis factor (TNF) receptor family) |
Fas receptor (CD95) is a cell surface protein that belongs to the tumor necrosis factor receptor family, that along with its ligand CD95L (or FasL), generates a death receptor/death ligand system that mediates apoptosis induction to maintain immune homeostasis. This system is also important in the immune elimination of virus-infected cells, cancer cells and autoreactive T cells. Mouse strains with mutations in Fas or FasL develop lymphoproliferative conditions, indicating the importance of these proteins to immune cell homeostasis [318] ... | |||
| Fc fragment of IgE receptor Ia (Fc epsilon receptors) |
The product of the FCεR1A gene is a single-pass type I membrane protein that is a high-affinity receptor for immunoglobulin E (IgE). It is the ligand binding subunit of the tetrameric FCεRI, exhibiting a Kd of ~0.1nM. | |||
| Fc fragment of IgE receptor Ig (Fc epsilon receptors) |
The FCER1G protein is a gamma subunit that is utilised as part of the high affinity IgE receptor (a key complex involved in mediating allergic reactions) and other Fc receptors. | |||
| Fc fragment of IgE receptor II (Fc epsilon receptors) |
FcεRII (CD23) is the low-affinity receptor for immunoglobulin E (IgE) with a Kd > 100nM. This protein is a C-type lectin found on mature B cells, activated macrophages, eosinophils, follicular dendritic cells, and platelets. It has no structural similarities with other Fc receptors. FcεRII has functions as both a membrane-bound and as a soluble receptor [159,369] ... | |||
| fms related receptor tyrosine kinase 3 (Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family) |
FLT3 is the receptor for the cytokine Flt3 ligand (FLT3LG). Flt3 ligand is a growth factor akin to stem cell factor and colony stimulating factor 1, and is essential for hematopoietic progenitor cell development and expansion of both myeloid and lymphoid lineages. It is one of the growth factor receptors targeted by the chemotherapeutic tyrosine kinase inhibitor sorafenib. Results from mouse experiments suggest that Flt3 ligand is effective in treating sepsis, by potentiating innate immune functions of dendritic cells and neutrophils and improving T cell function [246] ... |
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| herpes virus entry mediator (Immune checkpoint catalytic receptors, Tumour necrosis factor (TNF) receptor family) |
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) |
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 [121] ... | |||
| Interleukin-12 receptor, β1 subunit (IL-12 receptor family) |
This protein is a subunit of both the IL-12 and IL-23 cytokine receptors. | |||
| Interleukin 13 receptor, α2 (IL-2 receptor family) |
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 [362] ... | |||
| Interleukin-18 receptor 1 (Immunoglobulin-like family of IL-1 receptors) |
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) |
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 [106] ... | |||
| Interleukin 1 receptor, type I (Immunoglobulin-like family of IL-1 receptors) |
This is one of the subunits of the functional IL-1 receptor type I heterodimer. | |||
| Interleukin 20 receptor, β subunit (IL-10 receptor family) |
Interleukin 20 receptor, β subunit is a component of the functional receptor heterodimers for interleukins 19, 20 and 24. | |||
| Interleukin 23 receptor (IL-12 receptor family) |
This is one of the subunits of the functional IL-23 receptor heterodimer. | |||
| Interleukin 27 receptor, alpha (IL-6 receptor family) |
This is the ligand binding subunit of the IL-27 receptor heterodimer, a complex with IL6ST (signal transducing subunit). | |||
| Interleukin-2 receptor subunit γ (IL-2 receptor family) |
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) |
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| Interleukin-4 receptor subunit α (IL-2 receptor family) |
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 [126] ... | |||
| Interleukin-6 receptor, α subunit (IL-6 receptor family) |
IL6R polymorphisms are associated with asthma risk [99] ... | |||
| Interleukin-6 receptor, β subunit (IL-6 receptor family) |
This is the common signal transducing subunit shared by members of the IL-6 family of cytokine receptors [271] ... | |||
| Interleukin-7 receptor subunit α (IL-2 receptor family) |
This is the ligand binding subunit of the functional IL-7 receptor complex. Effimmune are developing anti-IL7Rα monoclonal antibodies (e.g. OSE-127 [255] ... |
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| KIT proto-oncogene, receptor tyrosine kinase (Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family) |
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 [116] ... | |||
| NLRP10 (NOD-like receptor family) |
NLRP10 is an intracellular pattern recognition receptor (PRR) that has apoptotic and anti-inflammatory functions [138] ... | |||
| NLRP3 (NOD-like receptor family) |
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 |
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| nucleotide binding oligomerization domain containing 2 (NOD-like receptor family) |
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 ... |
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| OX40 (Tumour necrosis factor (TNF) receptor family) |
The OX40/OX40L axis is involved in late T cell costimulatory signalling and both partners are transiently expressed following antigen recognition. This checkpoint is particularly important for sustaining the effector function of Th1 and Th2 T cells. Blocking OX40/OX40L is reported to prevent the development of disease in in vivo autoimmune and inflammatory disease models [352] ... | |||
| receptor activator of NF-kappa B (Tumour necrosis factor (TNF) receptor family) |
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) |
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 [78] ... | |||
| TACI (Tumour necrosis factor (TNF) receptor family) |
TACI is a lymphocyte-specific TNF superfamily receptor expressed on B cells. Endogenous ligands include APRIL, BAFF and CAML. Defects in the function of TACI can underlie immunodeficiencies and autoimmune diseases. TACI ligands are molecular targets of approved and investigational biologics that are ... | |||
| TLR4 (Toll-like receptor family) |
TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [36,256] ... | |||
| TLR8 (Toll-like receptor family) |
TLR8 is an endosomal receptor detecting ssRNA [332] ... | |||
| TLR9 (Toll-like receptor family) |
TLR9 is an endosomal receptor detecting viral and bacterial CpG DNA and genomic DNA from some protozoan species [332] ... | |||
| tumor necrosis factor receptor 2 (Tumour necrosis factor (TNF) receptor family) |
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 [117,231] ... | |||
| Transporters | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| ABCB3 (ABCB subfamily) |
TAP1 (ABCB2) and TAP2 (ABCB3) form a transporter that plays an important role in antigen presentation by major histocompatibility complex class I (MHCI) molecules in the adaptive immune response [288] ... | |||
| NRAMP1 (SLC11 family of proton-coupled metal ion transporters) |
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 [45,299,301] ... | |||
| Other Protein Targets | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| advanced glycosylation end-product specific receptor (Immunoglobulin like domain containing proteins) |
RAGE is a single chain, membrane bound immunoglobulin type protein [228,282,367] ... | |||
| amyloid P component, serum (Serum pentraxins) |
Serum amyloid P or pentraxin 2 is a multi-function circulating plasma protein. It exhibits activity as a soluble pattern recognition receptor of the innate immune system, that can bind DNA and histones when these are released from damaged cells. A recombinant form of human pentraxin 2 (PRM-151; Promedior) has been reported as an anti-fibrotic immunomodulator [94] ... |
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| Aryl hydrocarbon receptor (Aryl hydrocarbon receptor) |
The AhR is activated by small signalling molecules derived from the diet, microorganisms and environmental agents, and when expressed by immune cells, it integrates the effects of the environment and metabolism on the immune response [274] ... | |||
| BCL2 apoptosis regulator (B-cell lymphoma 2 (Bcl-2) protein family) |
The role of Bcl-2 family members in immunity and disease is reviewed in [92] ... | |||
| BCL6 transcription repressor (BTB (POZ) domain containing TFs) |
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 [54,58] ... | |||
| butyrophilin like 8 (Butyrophilin and butyrophilin-like proteins) |
BTNL3 and BTNL8 are two proteins expressed on the surface of human gut epithelial cells that are involved in shaping the constitution of gut resident dendritic γδ T cells [88] ... | |||
| butyrophilin subfamily 3 member A1 (Butyrophilin and butyrophilin-like proteins) |
Vγ2Vδ2 (a.k.a. Vγ9Vδ2) T cells bridge the gap between innate and adaptive immunity and play roles in microbial immunity and tumour immunity [216] ... | |||
| CD19 (CD molecules) |
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) |
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 [65,361] ... | |||
| CD209 molecule (C-type lectin-like receptors (CLRs)) |
DC-SIGN is a pathogen-recognition receptor involved in initiating the primary immune response to various viral and bacterial pathogens, as well as antigen presentation and initiation of the adaptive immune response. | |||
| CD20 (membrane-spanning 4-domains, subfamily A, member 1) (CD molecules) |
CD20 is a B cell antigen, involved in B cell development and maturation to antibody-producing plasma cells [72] ... | |||
| CD22 (Other immune checkpoint proteins, CD molecules, SIGLECs (conserved)) |
CD22 (SIGLEC2) is a B cell I-type (Ig-type) lectin that binds glycans containing sialic acids. It is involved in adhesion and activation, mediates B cell-B cell interactions and may be involved in the localisation of B cells in lymphoid tissues. Most SIGLECs inhibit immune cell activation, via | |||
| CD28 (Other immune checkpoint proteins, CD molecules) |
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 [6] ... | |||
| CD300a (CD molecules) |
CD300a is a member of the CD300 family of leucocyte surface receptors [43] ... | |||
| CD38 (Abscisic acid receptor complex, CD molecules) |
CD38 is a type II transmembrane glycoprotein, that is widely expressed on immune cells and is involved in cell adhesion and signal transduction. Its extracellular domain acts as an ectoenzyme, catalyzing the conversion of nicotinamide adenine dinucleotide (NAD+) into nicotinamide, adenosine diphosphate-ribose (ADPR), and cyclic ADPR. Expression of CD38 is tightly regulated during B-cell development and maturation [120] ... | |||
| CD3e (CD molecules) |
CD3e is a subunit of the T cell receptor (TCR)-CD3 complex that mediates T cell receptor signal transduction in response to antigen detection. The TCR complex contains a CD3γ chain (CD3G), a CD3δ chain (CD3D), and two CD3ε chains (CD3E), plus the TCR (that can be α/β, or γ/δ type in the subsets of T cells named after the TCR they express) and the ζ-chain (zeta-chain). CD3e plays a crucial role in T cell development, highlighted by the discovery that defects in CD3e cause severe immunodeficiency [79,302] ... |
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| CD4 (CD molecules) |
CD4 is being targeted for clinical utility in inflammatory diseases like rheumatoid arthritis (RA), neoplasms derived from T helper cells (T cell lymphomas and related malignancies), and for anti-HIV potential. Depending on the design of CD4 targeting antibodies, they can produce immunosuppressive effects via activation of Tregs and induction of tolerance, block HIV binding to CD4 to prevent HIV infection, or induce depletion of CD4+ T cells by apoptosis, ADCC, or CDC [167,341] ... | |||
| CD6 (CD molecules) |
CD6 is a co-stimulatory molecule, predominantly expressed on lymphocytes and associated with autoimmune responses. CD6 interacts with activated leucocyte-cell adhesion molecule (ALCAM/CD166), found on antigen presenting cells. This interaction induces the production of proinflammatory cytokines [223] ... | |||
| CD74 (CD molecules) |
CD74 is a type II transmembrane glycoprotein which associates with the MHC class II α and β chains and directs the transport of class II molecules to lysosomal and endosomal compartments [73] ... | |||
| CD79B (CD molecules) |
CD79B is a component of the multimeric B cell antigen receptor (along with CD79A and a membrane-bound antibody that acts as the antigen recognition moiety). The CD79A/B component is responsible for signal transduction. The B cell antigen receptor complex is reported to be involved in the pathogenesis of various B cell-derived lymphoid cancers [219,285] ... | |||
| CD80 (Other immune checkpoint proteins, CD molecules) |
CD80 (B7-1) is expressed on dendritic cells and activated B cells and monocytes. It is required to provide a costimulatory signal necessary for T cell activation and survival. CD80 works in concert with CD86 to prime T cells. CD80 binds CD28 and CTLA-4 on T cells. It is the interaction with CTLA-4 t ... | |||
| CD86 (Other immune checkpoint proteins, CD molecules) |
CD86 (B7-2) is a type I membrane immunoglobulin. It is expressed on antigen-presenting cells and in association with CD80 provides the costimulatory signal necessary for T cell activation and survival. CD86 interacts with CD28 or CTLA-4 on T cells. It is the interaction with CTLA-4 that is targeted ... | |||
| CS1 (CD319) (CD molecules) |
CS1 is a member of the signalling lymphocyte activation molecule (SLAM) receptor family. CS1 is a membrane glycoprotein primarily expressed on plasma cells. Homophilic interaction (i.e. interaction with itself) of CS1 induces B cell proliferation and autocrine cytokine secretion, thus playing a role in various immune functions. CS1 is a validated molecular target for the development of novel immunotherapeutics with the potential to treat MM, a malignant disease of plasma cells which remains incurable despite advances in treatment (such as bortezomib, lenalidomide and immunotherapies in clinical trial). Indeed, a combination therapy containing the anti-CS1 mAb elotuzumab (elotuzumab + lenalidomide + dexamethasone), was FDA approved for MM in 2015. CS1 expression is also elevated in patients with systemic lupus erythematosus (SLE) [161] ... |
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| C-type lectin domain family 4 member A (C-type lectin-like receptors (CLRs)) |
CLEC4A is an pattern recognition receptor and immunoreceptor that functions in cell adhesion, cell-cell signalling, glycoprotein turnover, and plays roles in inflammation and the immune response. It contains a immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain. | |||
| C-type lectin domain family 6 member A (C-type lectin-like receptors (CLRs)) |
Dectin-2 is involved in initiating the innate immune response upon recognition of high mannose structures on fungal cell walls. It associates with the ITAM-containing FcRβ adaptor and signals through the Syk, PKCδ, and CARD9-Bcl10-MALT1 pathways to promote cytokine production in response ... | |||
| cytotoxic T-lymphocyte-associated protein 4 (CD152) (Other immune checkpoint proteins, CD molecules) |
CTLA-4 is expressed almost exclusively on CD4+ and CD8+ T cells. It functions as an immune checkpoint providing an inhibitory signal as a balance to stimulatory signals of the immune response i.e. it plays a crucial role in the maintenance of T cell homeostasis [208] ... | |||
| E1A binding protein p300 (Non-enzymatic BRD containing proteins) |
CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. PMID: 26261308 ... | |||
| immunoglobulin heavy constant epsilon (Immunoglobulins) |
IgE is being investigated as a molecular target in allergic inflammatory conditions such as asthma, allergic rhinitis and chronic spontaneous urticaria. One anti-IgE monoclonal, omalizumab, has already been approved for use in patients with asthma or chronic spontaneous urticaria. Omalizumab binds t ... | |||
| LAG3 (CD223) (Other immune checkpoint proteins, CD molecules) |
Membrane-bound LAG3 (CD223) is a T cell inhibitory co-receptor and immune checkpoint being investigated as a cancer immunotherapeutic target [11,115] ... | |||
| leukocyte associated immunoglobulin like receptor 1 (CD305) (CD molecules) |
LAIR1 has been identified as a potential molecular receptor for Plasmodium falciparum-coded proteins that are expressed by infected host erythrocytes. Interaction of these parasite RIFIN proteins (encoded by rif genes) and inhibitory leucocyte receptors such as LAIR1 may mediate parasite-driven evasion of the host's immune system [276] ... | |||
| leukocyte immunoglobulin like receptor B1 (CD85j) (CD molecules, Other immune checkpoint proteins) |
LILRB1 (CD85j) is a member of the inhibitory leukocyte immunoglobulin like receptor (LILRB) family (HGNC family 1182). It acts as an inhibitory immune checkpoint for B cell function. Ligands identified for LILRB include native MHC class I proteins, some HLA molecules, pathogen-derived ligands (e.g. from CMV, Dengue virus and some bacteria) and host immunomodulatory proteins such as S100 calcium binding protein A9 (S100A9; P06702; which also binds TLR4 and RAGE) [49] ... | |||
| MALT1 paracaspase (Immunoglobulin like domain containing proteins) |
MALT1 inhibition is considered a tractable mechanism for the treatment of severe autoimmune diseases. The MALT1 inhibitory action of |
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| myeloid cell nuclear differentiation antigen (Absent in melanoma (AIM)-like receptors (ALRs)) |
MNDA can be detected exclusively in nuclei of hematopoietic cells of the monocyte lineage. Expression is induced by interferon α [44] ... | |||
| NFKB inhibitor zeta (Inhibitors of NF-kappaB (IκB) family proteins) |
IκBζ is a key component of the immune response that regulates the transcription of a set of inflamatory genes through its association with the p50 or p52 subunits of NF-κB. IκBζ acts as an inhibitor of primary NF-κB response genes, but may also act as a coactivator of the expression of secondary response genes (through association with the NF-κB p50 subunit). IκBζ is in fact the product of a primary NF-κB reponse gene, being rapidly upregulated by various inflammatory stimuli. Pro-inflammatory gene products that are regulated by IκBζ include CCL2, IL-6, IL12p40, IL-17, IFNγ, and GM-CSF [145,156] ... | |||
| perforin 1 (Cytolytic pore-forming proteins) |
Perforin 1 is expressed only in the secretory granules of cytotoxic T cells and natural killer (NK) cells, and it is an essential component of the immune system. These cell types release perforin 1 close to target cells (e.g. virus-infected and neoplastic cells) in process known as the granule exocytosis pathway [80] ... | |||
| programmed cell death 1 (CD279) (Other immune checkpoint proteins, CD molecules) |
Immune checkpoint blockade in oncology: Many types of cancer cells evolve mechanisms to evade control and elimination by the immune system. Such mechanisms can include inhibition of so-called 'immune checkpoints', which would normally be involved in the maintenance of immune homeostasis. An increasingly important area of clinical oncology research is the development of new agents which impede these evasion techniques, thereby switching immune vigilance back on, and effecting immune destruction of cancer cells. Three molecular targets of checkpoint inhibitors which are being extensively pursued are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). Using antibody-based therapies targeting these pathways, clinical responses have been reported in various tumour types, including melanoma, renal cell carcinoma [241] ... |
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| PVR cell adhesion molecule (Immunoglobulin like domain containing proteins) |
The PVR protein (a.k.a. CD155) is a single-pass immunoglobulin-like adhesion molecule. It plays a role in modulating natural killer and T cell-mediated immunity. PVR expression is upregulated in response to exposure to different stimuli, such as Toll-like receptor activation or T cell receptor stimulation [150,365] ... | |||
| signal transducer and activator of transcription 3 (STAT transcription factors) |
STAT3 regulates the expression of a variety of genes in response to cytokines and growth factors (e.g. IFNs, EGF, IL-5, IL-6, HGF, LIF and BMP2) and plays important roles in several cellular processes, including cell growth and apoptosis. STAT3 is a crucial component of the JAK/STAT signalling pathway that is implicated in cancer and inflammation. STAT3 is frequently activated in cancers, where it downmodulates intrinsic immune surveillance of tumour cells. Phosphorylated (activated) STAT3 (pSTAT3) is a marker of poor cancer prognosis [370,376] ... | |||
| signal transducer and activator of transcription 6 (STAT transcription factors) |
STAT6 plays a central role in exerting IL-4 mediated biological responses. The prosurvival activity of the Th2 cytokine IL-4 is mediated by STAT6-dependent transcription of the anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL). This mechanism explains the resistance to apoptosis that is observed epithelial tumours which produce IL-4 [326] ... | |||
| TIM3 (CD366) (Other immune checkpoint proteins, CD molecules) |
TIM3 is an immunoglobulin type protein expressed exclusively on the surface of differentiated Th1 cells [215] ... | |||
| V-set immunoregulatory receptor (Other immune checkpoint proteins) |
V-set immunoregulatory receptor (VSIR) is commonly referred to as VISTA in the literature corpus. This is an Ig superfamily (B7 family) protein that acts as an inhibitory immune-checkpoint molecule. In common with other T cell co-inhibitory receptors (e.g. CTLA-4, PD-1, TIM3, and LAG3) it is involved in maintaining peripheral tolerance [187] ... | |||
