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Targets Associated to Immuno Processes - B cell (activation)

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B cell (activation)
GPCRs
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
CCR2
(Chemokine receptors)
  • positive regulation of T-helper 1 type immune response (GO:0002827) ISS
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)
  • isotype switching to IgA isotypes (GO:0048290) ISS
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 [79,90] ...
CXCR5
(Chemokine receptors)
  • B cell activation (GO:0042113) 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.
GPR183
(Class A Orphans)
  • adaptive immune response (GO:0002250) ISS
  • B cell activation involved in immune response (GO:0002312) IBA
  • mature B cell differentiation involved in immune response (GO:0002313) ISS
  • positive regulation of B cell proliferation (GO:0030890) IDA
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 [73,118] ...
Ion Channels
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
P2X7
(P2X receptors)
  • positive regulation of T cell mediated cytotoxicity (GO:0001916) IEA
The P2X7 receptor is involved in NLRP3-type inflammasome formation, and subsequent maturation of IL-1β [91,124] ...
TRPM4
(Transient Receptor Potential channels)
  • adaptive immune response (GO:0002250) IEA
  • regulation of T cell cytokine production (GO:0002724) IDA
Expressed on human T cells, mouse dendritic cells, human and mouse monocytes/macrophages, and mouse mast cells [115] ...
Nuclear Hormone Receptors
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
RAR-related orphan receptor-γ
(1F. Retinoic acid-related orphans)
  • T-helper 17 cell differentiation (GO:0072539) ISS
RORγ inhibitors are under development for the treatment of autoimmune diseases such as psoriasis and rheumatoid arthritis [63] ...
Enzymes
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
ABL proto-oncogene 1, non-receptor tyrosine kinase
(Abl family)
  • B cell proliferation involved in immune response (GO:0002322) IEA
  • transitional one stage B cell differentiation (GO:0002333) IEA
Included in GtoImmuPdb based on its association with leukemia.
ADAM17
(M12: Astacin/Adamalysin)
  • germinal center formation (GO:0002467) ISS
  • B cell differentiation (GO:0030183) ISS
The proteolytic activity of ADAM17 (a type I transmembrane metalloproteinase; a.k.a.TNF-alpha converting enzyme or TACE) is involved in the shedding of the extracellular domains of several transmembrane proteins e.g. cytokines (TNFα), growth factors, receptors (IL-6R and TNF-R for example) and adhesion molecules. Cleavage of substrates, including TNFα, IL-6R and L-selectin, produce pro-inflammatory effects stimulating both innate and acquired immune responses. ADAM17 activity is crucial during development (ADAM17 knockout is embryonic lethal), and it has been shown that the soluble IL-6R/IL-6 complex generates agonist-like signals in a process termed IL-6 trans-signaling. The generation and maintenance of several inflammatory and autoimmune diseases is driven by IL-6 trans-signaling [30] ...
Adenosine deaminase
(Adenosine turnover)
  • germinal center B cell differentiation (GO:0002314) IEA
  • positive regulation of germinal center formation (GO:0002636) IEA
  • negative regulation of mature B cell apoptotic process (GO:0002906) IEA
  • positive regulation of B cell proliferation (GO:0030890) 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 ...
Bruton tyrosine kinase
(Tec family)
  • positive regulation of type III hypersensitivity (GO:0001805) IEA
  • positive regulation of type I hypersensitivity (GO:0001812) IEA
  • adaptive immune response (GO:0002250) TAS
  • B cell affinity maturation (GO:0002344) IEA
  • regulation of B cell cytokine production (GO:0002721) TAS
  • regulation of B cell apoptotic process (GO:0002902) TAS
  • negative regulation of B cell proliferation (GO:0030889) IEA
  • B cell activation (GO:0042113) TAS
  • positive regulation of B cell differentiation (GO:0045579) TAS
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 [18] ...
calcium/calmodulin dependent protein kinase IV
(CAMK1 family)
  • adaptive immune response (GO:0002250) IEA
CAMKIV has been implicated in the differentiation of Th17 cells, suggesting CAMKIV as a target for therapeutic intervention in Th17-driven autoimmune diseases [80] ...
Caspase 3
(C14: Caspase)
  • negative regulation of B cell proliferation (GO:0030889) IEA
Defective caspase 3 expression in immune effector cells my influence susceptibility to Kawasaki disease, an acute vasculitis syndrome affecting small- and medium-sized arteries of infants and children [112] ...
Caspase 8
(C14: Caspase)
  • B cell activation (GO:0042113) 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 [95] ...
cathepsin C
(C1: Papain)
  • T cell mediated cytotoxicity (GO:0001913) 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 H
(C1: Papain)
  • T cell mediated cytotoxicity (GO:0001913) ISS
  • adaptive immune response (GO:0002250) IEP
Cathepsin H may act as a pro-granzyme B convertase [39] ...
cathepsin L
(C1: Papain)
  • adaptive immune response (GO:0002250) IEP
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)
  • adaptive immune response (GO:0002250) IEP
Due to its role in antigen presentation, inhibition of cathepsin S is expected to cause immunosuppression. Cathepsin S inhibitors are being investigated for clinical efficacy in inflammatory conditions- e.g. RG7625 (Roche) in celiac disease (Phase 1) and Sjogren's syndrome (Phase 2).
complement C1r
(S1: Chymotrypsin)
  • complement activation, classical pathway (GO:0006958) TAS
A protease component of the C1-complex of the classical complement pathway.
complement C1s
(S1: Chymotrypsin)
  • complement activation, classical pathway (GO:0006958) TAS
A protease component of the C1-complex of the classical complement pathway.
C-terminal Src kinase
(Csk family)
  • adaptive immune response (GO:0002250) 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 [155] ...
DNA-dependent protein kinase catalytic subunit
(Other PIKK family kinases)
  • B cell lineage commitment (GO:0002326) 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 ...
eukaryotic translation initiation factor 2 alpha kinase 4
(GCN2 subfamily)
  • adaptive immune response (GO:0002250) IEA
  • positive regulation of adaptive immune response (GO:0002821) ISS
GCN2 is a so-called 'stress kinase'. It phosphorylates serine 51 on the global transcription factor eIF2α upon activation by uncharged tRNA; tRNAs accumulate when amino acid levels are depleted. Phospho-eIF2α blocks translation to cause proliferative arrest.

GCN2 plays several roles in the immune system. It is required for dendritic cell activation and antigen presentation. The GCN2 stress response is required for both optimal proliferation of CD8+ T cells after antigen stimulation, and trafficking to lymphoid organs, i.e. for normal cytotoxic T cell function [154] ...
FYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • adaptive immune response (GO:0002250) IEA
Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [114] ...
IL2 inducible T-cell kinase
(Tec family)
  • adaptive immune response (GO:0002250) ISS
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 [18] ...
INPP5D
(Inositol polyphosphate phosphatases)
  • immunoglobulin mediated immune response (GO:0016064) IEA
  • negative regulation of B cell proliferation (GO:0030889) IEA
  • positive regulation of B cell differentiation (GO:0045579) IEA
SHIP1 activators are proposed as novel anti-inflammatory agents e.g. rosiptor (AQX-1125) which is in Phase 2 and 3 clinical trials [109,144] ...
Janus kinase 2
(Janus kinase (JakA) family)
  • adaptive immune response (GO:0002250) IEA
CEP-33779, a selective JAK2 inhibitor has demonstrated efficacy in mouse models of rheumatoid arthritis [145] ...
Janus kinase 3
(Janus kinase (JakA) family)
  • adaptive immune response (GO:0002250) IEA
  • B cell differentiation (GO:0030183) ISS
  • negative regulation of T-helper 1 cell differentiation (GO:0045626) ISS
Psoriatic skin samples show elevated JAK3 (and JAK1) expression, with signalling predominantly through STAT3 [5] ...
LYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • adaptive immune response (GO:0002250) IEA
  • regulation of B cell apoptotic process (GO:0002902) IBA
  • negative regulation of B cell proliferation (GO:0030889) IBA
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 [48,50,151] ...
mitogen-activated protein kinase kinase kinase 7
(TAK1 subfamily)
  • positive regulation of T cell cytokine production (GO:0002726) IMP
TAK1 (MAP3K7) mediates signaling downstream of multiple cytokine receptors and is functionally important in mitogen, immune, and inflammatory signaling pathways [40,133] ...
MMP14
(M10: Matrix metallopeptidase)
  • positive regulation of B cell differentiation (GO:0045579) ISS
MMP14 is included in GtoImmuPdb based on its contribution to degradation of collagenous cartilage matrix in rheumatoid arthritis.
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • adaptive immune response (GO:0002250) IBA
PI3Kα is priomarily 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 alpha
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • adaptive immune response (GO:0002250) IBA
PI3Kα is priomarily 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)
  • adaptive immune response (GO:0002250) TAS
  • B cell activation (GO:0042113) TAS
The potential for PI3kδ as ta arget in immuno-oncology is discussed in [2] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • adaptive immune response (GO:0002250) TAS
  • B cell activation (GO:0042113) TAS
The potential for PI3kδ as ta arget in immuno-oncology is discussed in [2] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • adaptive immune response (GO:0002250) TAS
The role of PIK3CG in immuno-oncology is reviewed in [2] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • adaptive immune response (GO:0002250) TAS
The role of PIK3CG in immuno-oncology is reviewed in [2] ...
phosphoinositide-3-kinase regulatory subunit 1
(Phosphatidylinositol kinases)
  • B cell differentiation (GO:0030183) IEA
p85α is included in GtoImmuPdb as it is the regulatory subunit of several PI3Ks (e.g. PI3Kδ and PI3Kγ) with roles in leukocyte biology and therefore important for immunity [92] ...
PLCγ2
(Phosphoinositide-specific phospholipase C)
  • follicular B cell differentiation (GO:0002316) IEA
  • B cell differentiation (GO:0030183) ISS
Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [52,132] ...
protein kinase C beta
(Alpha subfamily)
  • adaptive immune response (GO:0002250) IEA
  • B cell activation (GO:0042113) ISS
PKCβ is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C delta
(Delta subfamily)
  • immunoglobulin mediated immune response (GO:0016064) IEA
  • B cell proliferation (GO:0042100) IEA
PKCδ is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C theta
(Delta subfamily)
  • positive regulation of T-helper 17 type immune response (GO:2000318) ISS
PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [12] ...
protein kinase C zeta
(Iota subfamily)
  • positive regulation of T-helper 2 cell cytokine production (GO:2000553) ISS
PKCζ is included in GtoImmuPdb based on its GO process associations.
protein kinase N1
(Protein kinase N (PKN) family)
  • B cell apoptotic process (GO:0001783) IEA
  • regulation of germinal center formation (GO:0002634) IEA
  • negative regulation of B cell proliferation (GO:0030889) IEA
Evidence suggests that PKN1 plays a role in modulation of the NF-κB signalling pathway. Specifically, in Salmonella infection, PKN1 is hijacked by a bacterial effector protein which results in inhibition of NF-κB-dependent gene expression (i.e. inhibition of production of the proinflammatory cytokines that would normally effect bacterial destruction and removal) [56] ...
protein tyrosine kinase 2 beta
(Fak family)
  • adaptive immune response (GO:0002250) IEA
  • marginal zone B cell differentiation (GO:0002315) 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 [32] ...
RAB27A, member RAS oncogene family
(RAB subfamily)
  • cytotoxic T cell degranulation (GO:0043316) 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 [68] ...
receptor interacting serine/threonine kinase 2
(Receptor interacting protein kinase (RIPK) family)
  • adaptive immune response (GO:0002250) ISS
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) 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) [111] ...
receptor interacting serine/threonine kinase 3
(Receptor interacting protein kinase (RIPK) family)
  • regulation of T cell mediated cytotoxicity (GO:0001914) ISS
  • regulation of adaptive immune response (GO:0002819) ISS
RIPK1 and RIPK3 are involved in necroptosis [127,140,157] ...
sirtuin 1
(3.5.1.- Histone deacetylases (HDACs))
  • positive regulation of adaptive immune response (GO:0002821) IDA
Sirtuin 1 has been suggested as a molecular target for host-directed therapy against Mycobacterium tuberculosis infection by research that shows that activation of sirtuin 1 decreases lung pathology, reduces inflammation, and enhances drug efficacy against Mycobacterium tuberculosis [33] ...
spleen associated tyrosine kinase
(Syk family)
  • adaptive immune response (GO:0002250) ISS
  • positive regulation of B cell differentiation (GO:0045579) IMP
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 [51,126] ...
tec protein tyrosine kinase
(Tec family)
  • adaptive immune response (GO:0002250) 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 [18] ...
TXK tyrosine kinase
(Tec family)
  • adaptive immune response (GO:0002250) ISS
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 [18] ...
zeta chain of T-cell receptor associated protein kinase 70
(Syk family)
  • adaptive immune response (GO:0002250) TAS
  • B cell activation (GO:0042113) TAS
ZAP-70 has much lower intrinsic enzyme activity than SYK, and expression is restricted to T cells and NK cells [8] ...
Catalytic Receptors
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
BAFF receptor
(Tumour necrosis factor (TNF) receptor family)
  • adaptive immune response (GO:0002250) IEA
  • positive regulation of germinal center formation (GO:0002636) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • B cell costimulation (GO:0031296) IEA
A type III membrane bound receptor for B-cell activating factor (BAFF). BAFF enhances B-cell survival and hence regulates the peripheral B-cell population. It is suggested that overproduction of BAFF may enhance the survival of autoreactive B cells, an effect which may contribute in the pathogenesis ...
B cell maturation antigen
(Tumour necrosis factor (TNF) receptor family)
  • adaptive immune response (GO:0002250) IEA
B-cell maturation antigen (BCMA) is a cell surface receptor for B-cell activating factor (BAFF). It interacts with various TRAF family adaptor proteins to modulate cell survival and proliferation, via NF-κB and MAPK8/JNK signal transduction pathways. BCMA is highly plasma cell-selective for malignant plasma cells from multiple myeloma (MM) patients, and is being investigated as a target for for T-cell redirecting therapies to tackle relapsed/refractory MM. Novel anti-BCMA pharmacological agents in early stage development for MM include monoclonal antibodies and CAR-T cells [59,121,176] ...
CD27
(Tumour necrosis factor (TNF) receptor family)
  • immunoglobulin mediated immune response (GO:0016064) NAS
  • positive regulation of B cell differentiation (GO:0045579) NAS
A co-stimulatory immune checkpoint molecule. Endogenous ligand is CD70. Interacts with various TRAF adaptor proteins and apoptosis regulatory protein SIVA (SIVA1).
CD40
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • B cell proliferation (GO:0042100) NAS
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
  • regulation of immunoglobulin secretion (GO:0051023) IEA
A costimulatory protein found on antigen presenting cells, required for their activation. Endogenous ligand is CD154 (CD40L) on TH cells.
CD40
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • B cell proliferation (GO:0042100) NAS
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
  • regulation of immunoglobulin secretion (GO:0051023) IEA
A costimulatory protein found on antigen presenting cells, required for their activation. Endogenous ligand is CD154 (CD40L) on TH cells.
death receptor 6
(Tumour necrosis factor (TNF) receptor family)
  • B cell apoptotic process (GO:0001783) ISS
  • adaptive immune response (GO:0002250) ISS
  • negative regulation of B cell proliferation (GO:0030889) ISS
Expressed predominantly in the thymus, spleen and white blood cells. May play a role in T helper cell activation, inflammation and immune regulation. Signals via the TRADD adaptor protein to the NF-κB and MAPK8/JNK pathways.
Fas
(Tumour necrosis factor (TNF) receptor family)
  • B cell mediated immunity (GO:0019724) IEA
  • negative regulation of B cell activation (GO:0050869) IEA
Fas receptor (CD95) is a cell surface protein that belongs to the tumor necrosis factor receptor family, that along with its ligand CD95L, generates a death receptor/death ligand system that mediates apoptosis induction to maintain immune homeostasis. This system is also important in the immune elimination of virus-infected cells, cancer cells and autoreactive T cells. Mouse strains with mutations in Fas or CD95L develop lymphoproliferative conditions, indicating the importance of these proteins to immune cell homeostasis [148] ...
fms related tyrosine kinase 3
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • B cell differentiation (GO:0030183) ISS
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 [117] ...
integrin, alpha 4 subunit (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
(Integrins)
  • B cell differentiation (GO:0030183) IC
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 [55] ...
Interleukin-12 receptor, β1 subunit
(IL-12 receptor family)
  • positive regulation of T cell mediated cytotoxicity (GO:0001916) ISS
  • positive regulation of T-helper 1 type immune response (GO:0002827) IDA
  • positive regulation of T-helper 17 type immune response (GO:2000318) ISS
  • positive regulation of T-helper 17 cell lineage commitment (GO:2000330) ISS
This protein is a subunit of both the IL-12 and IL-23 cytokine receptors.
Interleukin 13 receptor, α2
(IL-2 receptor family)
  • immunoglobulin mediated immune response (GO:0016064) 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 [167] ...
Interleukin-18 1
(Immunoglobulin-like family of IL-1 receptors)
  • 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)
  • negative regulation of T-helper 1 type immune response (GO:0002826) 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 [49] ...
Interleukin 20 receptor, β subunit
(IL-10 receptor family)
  • negative regulation of type IV hypersensitivity (GO:0001808) IEA
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)
  • positive regulation of T cell mediated cytotoxicity (GO:0001916) ISS
  • positive regulation of T-helper 1 type immune response (GO:0002827) IDA
  • positive regulation of T-helper 17 type immune response (GO:2000318) ISS
  • positive regulation of T-helper 17 cell lineage commitment (GO:2000330) ISS
This is one of the subunits of the functional IL-23 receptor heterodimer.
Interleukin 27 receptor, alpha
(IL-6 receptor family)
  • positive regulation of T-helper 1 type immune response (GO:0002827) IEA
  • regulation of isotype switching to IgG isotypes (GO:0048302) IEA
This is the ligand binding subunit of the IL-27 receptor heterodimer, a complex with IL6ST (signal transducing subunit).
Interleukin-31 receptor, α subunit
(IL-6 receptor family)
  • T-helper 2 cell cytokine production (GO:0035745) IEA
Interleukin-4 receptor subunit α
(IL-2 receptor family)
  • immunoglobulin mediated immune response (GO:0016064) IEA
  • negative regulation of T-helper 1 cell differentiation (GO:0045626) 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 [58] ...
Interleukin-6 receptor, β subunit
(IL-6 receptor family)
  • positive regulation of adaptive immune response (GO:0002821) IC
This is the common signal transducing subunit shared by members of the IL-6 family of cytokine receptors.
Interleukin-7 receptor subunit α
(IL-2 receptor family)
  • negative regulation of T cell mediated cytotoxicity (GO:0001915) IEA
  • B cell proliferation (GO:0042100) IEA
This is the ligand binding subunit of the functional IL-7 receptor complex.
KIT proto-oncogene receptor tyrosine kinase
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • immature B cell differentiation (GO:0002327) ISS
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 [53] ...
NLRP10
(NOD-like receptor family)
  • adaptive immune response (GO:0002250) IEA
  • positive regulation of T-helper 1 type immune response (GO:0002827) ISS
  • helper T cell enhancement of adaptive immune response (GO:0035397) ISS
  • positive regulation of T-helper 17 type immune response (GO:2000318) ISS
NLRP10 is an intracellular pattern recognition receptor (PRR) that has apoptotic and anti-inflammatory functions [64] ...
NLRP3
(NOD-like receptor family)
  • positive regulation of T-helper 17 cell differentiation (GO:2000321) IEA
  • positive regulation of T-helper 2 cell cytokine production (GO:2000553) ISS
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. 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 rilonacept, anakinra and canakinumab [13] ...
nucleotide binding oligomerization domain containing 2
(NOD-like receptor family)
  • positive regulation of B cell activation (GO:0050871) IDA
NOD2 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing muramyl dipeptide (MDP).
OX40
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of B cell proliferation (GO:0030890) ISS
  • positive regulation of immunoglobulin secretion (GO:0051024) ISS
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 [162] ...
receptor activator of NF-kappa B
(Tumour necrosis factor (TNF) receptor family)
  • adaptive immune response (GO:0002250) IMP
RANK is the receptor for RANK-ligand (RANKL). It is associated with immune cell function and lymph node development, in addition to bone remodeling and repair, thermal regulation, and mammary gland development. Signals to NF-κB and JNK via TRAF adaptor proteins.
RTP Type C
(Receptor tyrosine phosphatase (RTP) family)
  • negative regulation of T cell mediated cytotoxicity (GO:0001915) ISS
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • B cell proliferation (GO:0042100) ISS
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 [41] ...
TACI
(Tumour necrosis factor (TNF) receptor family)
  • adaptive immune response (GO:0002250) IEA
  • negative regulation of B cell proliferation (GO:0030889) IBA
Lymphocyte-specific TNF superfamily receptor expressed on B cells. Endogenous ligands include APRIL, BAFF and CAML. Defects in the function of TACI can lead to immune system diseases (e.g. immunodeficiency).
TLR4
(Toll-like receptor family)
  • B cell proliferation involved in immune response (GO:0002322) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • T-helper 1 type immune response (GO:0042088) NAS
TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [20,123] ...
TLR6
(Toll-like receptor family)
  • T-helper 1 type immune response (GO:0042088) IC
TLR6 forms heterodimers with TLR2 to detect a wide range of bacterial lipopeptides from bacterial cell membranes, and effect an immune response [47] ...
TLR8
(Toll-like receptor family)
  • immunoglobulin mediated immune response (GO:0016064) TAS
TLR8 is an endosomal receptor detecting ssRNA [153] ...
Transporters
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
ABCB3
(ABCB subfamily)
  • adaptive immune response (GO:0002250) IEA
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 [138] ...
NRAMP1
(SLC11 family of proton-coupled metal ion transporters)
  • T cell cytokine production (GO:0002369) ISS
  • positive regulation of T-helper 1 type immune response (GO:0002827) ISS
NRAMP1 / SLC11A1 appears to be involved in macrophage antimicrobial action against intracellular pathogens, and although its precise mechanism is not fully resolved, evidence indicates its involvement in the activation of phagocytes and synthesis of proinflammatory cytokines. Polymorphisms in the human SLC11A1 gene have been associated with susceptibility to several infections [25,141-142] ...
Other Protein Targets
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
advanced glycosylation end-product specific receptor
(Immunoglobulins)
  • regulation of T cell mediated cytotoxicity (GO:0001914) IDA
RAGE is a single chain, membrane bound immunoglobulin type protein [108,134,170] ...
BCL2, apoptosis regulator
(B-cell lymphoma 2 (Bcl-2) protein family)
  • B cell lineage commitment (GO:0002326) IEA
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • B cell proliferation (GO:0042100) IDA
The role of Bcl-2 family members in immunity and disease is reviewed in [46] ...
butyrophilin like 8
(Butyrophilin and butyrophilin-like proteins)
  • adaptive immune response (GO:0002250) IEA
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 [44] ...
butyrophilin subfamily 3 member A1
(Butyrophilin and butyrophilin-like proteins)
  • adaptive immune response (GO:0002250) IEA
Vγ2Vδ2 (a.k.a. Vγ9Vδ2) T cells bridge the gap between innate and adaptive immunity and play roles in microbial immunity and tumour immunity [100] ...
CD209 molecule
(C-type lectin-like receptors (CLRs))
  • adaptive immune response (GO:0002250) 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.
CD20 (membrane-spanning 4-domains, subfamily A, member 1)
(CD molecules)
  • B cell proliferation (GO:0042100) NAS
CD20 is a B cell antigen, involved in B cell development and maturation to antibody-producing plasma cells [36] ...
CD28
(CD molecules)
  • 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 [4] ...
CD28
(CD molecules)
  • 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 [4] ...
CD300a
(CD molecules)
  • negative regulation of B cell proliferation (GO:0030889) IMP
CD300a is a member of the CD300 family of leucocyte surface receptors [23] ...
CD38
(CD molecules)
  • positive regulation of B cell proliferation (GO:0030890) IMP
CD38 is a type II transmembrane glycoprotein, widely expressed on immune cells and 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 [54] ...
CD6
(CD molecules)
  • adaptive immune response (GO:0002250) IEA
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 [105] ...
CD74
(CD molecules)
  • negative regulation of mature B cell apoptotic process (GO:0002906) IEA
  • immunoglobulin mediated immune response (GO:0016064) ISS
  • positive regulation of B cell proliferation (GO:0030890) IMP
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 [37] ...
CD79B
(CD molecules)
  • adaptive immune response (GO:0002250) IEA
  • B cell differentiation (GO:0030183) IBA
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 [103,136] ...
CD80
(CD molecules)
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) NAS
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 ...
CD80
(CD molecules)
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) NAS
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
(CD molecules)
  • adaptive immune response (GO:0002250) IEA
  • B cell activation (GO:0042113) IEA
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 ...
CD86
(CD molecules)
  • adaptive immune response (GO:0002250) IEA
  • B cell activation (GO:0042113) IEA
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)
  • adaptive immune response (GO:0002250) IEA
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) [77] ...
C-type lectin domain family 4 member A
(C-type lectin-like receptors (CLRs))
  • adaptive immune response (GO:0002250) IEA
C-type lectin domain family 6 member A
(C-type lectin-like receptors (CLRs))
  • adaptive immune response (GO:0002250) IEA
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)
(CD molecules)
  • adaptive immune response (GO:0002250) IEA
  • negative regulation of B cell proliferation (GO:0030889) IMP
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 [97] ...
cytotoxic T-lymphocyte-associated protein 4 (CD152)
(CD molecules)
  • adaptive immune response (GO:0002250) IEA
  • negative regulation of B cell proliferation (GO:0030889) IMP
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 [97] ...
E1A binding protein p300
(Non-enzymatic BRD containing proteins)
  • B cell differentiation (GO:0030183) IEA
CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. PMID: 26261308 ...
Fc fragment of IgE receptor Ia
(Fc epsilon receptors)
  • positive regulation of type I hypersensitivity (GO:0001812) IEA
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)
  • positive regulation of type IIa hypersensitivity (GO:0001798) IEA
  • positive regulation of type III hypersensitivity (GO:0001805) IEA
  • positive regulation of type I hypersensitivity (GO:0001812) IEA
  • immunoglobulin mediated immune response (GO:0016064) IBA
Fc fragment of IgE receptor II
(Fc epsilon receptors)
  • positive regulation of humoral immune response mediated by circulating immunoglobulin (GO:0002925) IEA
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 [75,172] ...
immunoglobulin heavy constant epsilon
(Immunoglobulins)
  • complement activation, classical pathway (GO:0006958) IBA
  • positive regulation of B cell activation (GO:0050871) IBA
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 ...
LILRA4 (CD85g)
(CD molecules)
  • adaptive immune response (GO:0002250) IEA
CD85g is involved in activation of eosinophils and homeostatic regulation of the innate immunity of plasmacytoid dendritic cells (pDCs) [28] ...
myeloid cell nuclear differentiation antigen
(Absent in melanoma (AIM)-like receptors (ALRs))
  • negative regulation of B cell proliferation (GO:0030889) IMP
MNDA can be detected exclusively in nuclei of hematopoietic cells of the monocyte lineage. Expression is induced by interferon α [24] ...
TIM3 (CD366)
(CD molecules)
  • adaptive immune response (GO:0002250) IEA
  • regulation of tolerance induction dependent upon immune response (GO:0002652) IEA
  • negative regulation of T-helper 1 type immune response (GO:0002826) IEA
TIM3 is an immunoglobulin type protein expressed exclusively on the surface of differentiated Th1 cells [99] ...
TIM3 (CD366)
(CD molecules)
  • adaptive immune response (GO:0002250) IEA
  • regulation of tolerance induction dependent upon immune response (GO:0002652) IEA
  • negative regulation of T-helper 1 type immune response (GO:0002826) IEA
TIM3 is an immunoglobulin type protein expressed exclusively on the surface of differentiated Th1 cells [99] ...