Targets Associated to Immuno Processes - Immune system development

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Immune system development
GPCRs
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
CCR1
(Chemokine receptors)
  • positive regulation of osteoclast differentiation (GO:0045672) IMP
CCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR4
(Chemokine receptors)
  • tolerance induction (GO:0002507) IEA
CCR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR6
(Chemokine receptors)
  • isotype switching to IgA isotypes (GO:0048290) ISS
  • DN2 thymocyte differentiation (GO:1904155) ISS
  • DN3 thymocyte differentiation (GO:1904156) ISS
CCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR7
(Chemokine receptors)
  • negative thymic T cell selection (GO:0045060) IEA
  • mature conventional dendritic cell differentiation (GO:0097029) ISS
CCR7 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR9
(Chemokine receptors)
  • CD8-positive, gamma-delta intraepithelial T cell differentiation (GO:0002305) IEA
CCR9 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. Activation of CCR9 by CCL25 plays a key role in leukocyte recruitment to the gut and CCR9 antagonists are being pursued as therapeutic agents for inflammatory bowel disease [125] ...
CXCR5
(Chemokine receptors)
  • lymph node development (GO:0048535) 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.
EP4 receptor
(Prostanoid receptors)
  • T-helper cell differentiation (GO:0042093) ISS
The EP4 prostanoid receptor is one of four receptor subtypes for prostaglandin PGE2. The anti- and pro-inflammatory (and non-inflammatory) activities of this receptor are reviewed in [134] ...
GPR183
(Class A Orphans)
  • mature B cell differentiation involved in immune response (GO:0002313) ISS
  • osteoclast differentiation (GO:0030316) ISS
  • T follicular helper cell differentiation (GO:0061470) ISS
Gpr183-deficient mice show a reduction in the early antibody response to a T-dependent antigen. GPR183-deficient B cells fail to migrate to the outer follicle and instead stay in the follicle centre [54,92] ...
PAR2
(Proteinase-activated receptors)
  • mature conventional dendritic cell differentiation (GO:0097029) IDA
PAR2 receptors have been reported to elicit pain and inflammation through a neurogenic mechanism of action, causing release of substance P, activation of NK1 receptors, and sensitization of TRPV1 voltage-gated ion channels. This action can be negated using a selective NK1 receptor antagonist (L732,138) or a TRPV1 receptor antagonist (capsazepine) [34] ...
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 cell differentiation (GO:0042093) ISS
  • lymph node development (GO:0048535) ISS
  • Peyer's patch development (GO:0048541) ISS
  • 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 [46] ...
Enzymes
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
ABL proto-oncogene 1, non-receptor tyrosine kinase
(Abl family)
  • transitional one stage B cell differentiation (GO:0002333) IEA
  • alpha-beta T cell differentiation (GO:0046632) IEA
  • spleen development (GO:0048536) IEA
  • thymus development (GO:0048538) IEA
Included in GtoImmuPdb based on its association with leukemia.
ADAM17
(M12: Astacin/Adamalysin)
  • B cell differentiation (GO:0030183) ISS
  • T cell differentiation in thymus (GO:0033077) ISS
  • spleen development (GO:0048536) 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 [18] ...
ADAM8
(M12: Astacin/Adamalysin)
  • positive regulation of T cell differentiation in thymus (GO:0033089) ISS
ADAM8 is reported to drive acute allergen-induced airway inflammation in a mouse model, and effect negated by ADAM8-deficiency (antibody-induced or gene knockout) [91] ...
Adenosine deaminase
(Adenosine turnover)
  • germinal center B cell differentiation (GO:0002314) IEA
  • positive regulation of T cell differentiation in thymus (GO:0033089) IEA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
  • Peyer's patch development (GO:0048541) 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 ...
BMX non-receptor tyrosine kinase
(Tec family)
  • NK T cell differentiation (GO:0001865) IBA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [11] ...
B-Raf proto-oncogene, serine/threonine kinase
(RAF family)
  • myeloid progenitor cell differentiation (GO:0002318) IEA
  • CD4-positive, alpha-beta T cell differentiation (GO:0043367) IEA
  • CD4-positive or CD8-positive, alpha-beta T cell lineage commitment (GO:0043369) IEA
  • regulation of T cell differentiation (GO:0045580) IEA
  • thymus development (GO:0048538) IEA
BRAFV600E- immuno-oncology [1] ...
Bruton tyrosine kinase
(Tec family)
  • B cell affinity maturation (GO:0002344) IEA
  • 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 [11] ...
calcium/calmodulin dependent protein kinase IV
(CAMK1 family)
  • regulation of T cell differentiation in thymus (GO:0033081) TAS
  • myeloid dendritic cell differentiation (GO:0043011) IMP
  • regulation of osteoclast differentiation (GO:0045670) TAS
CAMKIV has been implicated in the differentiation of Th17 cells, suggesting CAMKIV as a target for therapeutic intervention in Th17-driven autoimmune diseases [58] ...
Caspase 3
(C14: Caspase)
  • erythrocyte differentiation (GO:0030218) IDA
  • platelet formation (GO:0030220) TAS
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 [84] ...
Caspase 8
(C14: Caspase)
  • macrophage differentiation (GO:0030225) TAS
  • positive regulation of macrophage differentiation (GO:0045651) IMP
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 [72] ...
cyclin dependent kinase 6
(CDK4 subfamily)
  • negative regulation of myeloid cell differentiation (GO:0045638) IDA
  • regulation of erythrocyte differentiation (GO:0045646) IMP
  • negative regulation of monocyte differentiation (GO:0045656) IDA
Phenotypic abnormalities in CDK6 knockout mice suggest biological roles in addition to mitotic cell cycle regulation. Alternate roles include involvement in hematopoietic function and inhibition of T cell differentiation [38,89] ...
DNA-dependent protein kinase catalytic subunit
(Other PIKK family kinases)
  • B cell lineage commitment (GO:0002326) IEA
  • pro-B cell differentiation (GO:0002328) IEA
  • T cell lineage commitment (GO:0002360) IEA
  • T cell differentiation in thymus (GO:0033077) IEA
  • immunoglobulin V(D)J recombination (GO:0033152) IEA
  • T cell receptor V(D)J recombination (GO:0033153) IEA
  • spleen development (GO:0048536) IEA
  • thymus development (GO:0048538) 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 2
(Other PEK family kinases)
  • regulation of hematopoietic progenitor cell differentiation (GO:1901532) ISS
  • regulation of hematopoietic stem cell proliferation (GO:1902033) ISS
  • regulation of hematopoietic stem cell differentiation (GO:1902036) ISS
Protein kinase-R (EIF2AK2) is activated by virally-introduced double-stranded RNA (dsRNA), and is therefore involved in protection against viral infection. Protein activator of the interferon-induced protein kinase EIF2AK2 (PACT; PRKRA) also activates protein kinase-R. Activated protein kinase-R phosphorylates the eukaryotic translation initiation factor eIF2α inhibiting viral protein synthesis [33] ...
IL2 inducible T-cell kinase
(Tec family)
  • NK T cell differentiation (GO:0001865) IBA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [11] ...
indoleamine 2,3-dioxygenase 1
(1.13.11.- Dioxygenases)
  • positive regulation of T cell tolerance induction (GO:0002666) IEA
Depletion of tryptophan (catalyzed by IDO1) promotes Treg cell differentiation, suppresses the immune response and decreases DC function, creating a tolerogenic environment. IDO1 inhibitors reverse this response. ID01 has emerged as a promising molecular target for the development of novel agents as cancer immunotherapeutics, and for the treatment of other diseases characterized by the reduction of local tryptophan levels. The applicability of ID01 inhibition has been shown preclinical models of many diseases, including arthritis, ischemia-reperfusion injury, endotoxin shock, human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection, airway inflammation, and cancer [44,119] ...
INPP5D
(Inositol polyphosphate phosphatases)
  • positive regulation of B cell differentiation (GO:0045579) IEA
  • positive regulation of erythrocyte differentiation (GO:0045648) IEA
  • negative regulation of monocyte differentiation (GO:0045656) IEA
  • negative regulation of neutrophil differentiation (GO:0045659) IEA
  • negative regulation of osteoclast differentiation (GO:0045671) IEA
SHIP1 activators are proposed as novel anti-inflammatory agents e.g. rosiptor (AQX-1125) which is in Phase 2 and 3 clinical trials [81,110] ...
interleukin 1 receptor associated kinase 3
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • positive regulation of macrophage tolerance induction (GO:0010933) ISS
IRAK3 expression is restricted to monocytes and macrophages.
IP3 kinase B
(Inositol 1,4,5-trisphosphate 3-kinases)
  • positive thymic T cell selection (GO:0045059) IEA
  • negative regulation of myeloid cell differentiation (GO:0045638) IEA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
IP3 kinase B (ITPKB) as an essential mediator of T cell activation, whose inhibition is considered a novel approach to treat autoimmune disease [76] ...
Janus kinase 2
(Janus kinase (JakA) family)
  • erythrocyte differentiation (GO:0030218) ISS
CEP-33779, a selective JAK2 inhibitor has demonstrated efficacy in mouse models of rheumatoid arthritis [111] ...
Janus kinase 3
(Janus kinase (JakA) family)
  • B cell differentiation (GO:0030183) ISS
  • erythrocyte differentiation (GO:0030218) IBA
  • 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 [3] ...
LCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • hemopoiesis (GO:0030097) NAS
  • T cell differentiation (GO:0030217) IMP
Phosphorylation and activation of Lck is an early and critical step in pre-TCR (T cell receptor) and TCR signalling. Activated Lck phosphorylates immunoreceptor tyrosine-based activation motifs of the ζ chain of the TCR leading to recruitment and activation of ZAP-70 tyrosine kinase, and activation of downstream MAPKs and NF-κB. TCR-based signals are required at several stages of T-cell development and it is thought that Lck is the major contributor to TCR signal transduction (with the related Src tyrosine kinase Fyn also playing a role) [86] ...
LYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • tolerance induction to self antigen (GO:0002513) ISS
  • negative regulation of myeloid leukocyte differentiation (GO:0002762) IEA
  • erythrocyte differentiation (GO:0030218) ISS
  • regulation of erythrocyte differentiation (GO:0045646) ISS
  • dendritic cell differentiation (GO:0097028) ISS
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 [31-32,117] ...
mitogen-activated protein kinase 1
(ERK subfamily)
  • thymus development (GO:0048538) IEA
In endothelial cells of the vasculature, and in activated human mast cells, ERK serves as an anti-inflammatory signal that suppresses production of pro-inflammatory mediators [55,70] ...
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.
MMP9
(M10: Matrix metallopeptidase)
  • macrophage differentiation (GO:0030225) TAS
Mucosal up-regulation of MMP-9 correlates with the severity of inflammation in ulcerative colitis, and may be responsible for the mucosal damage in active ulcerative colitis [61] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • natural killer cell differentiation (GO:0001779) TAS
  • T cell differentiation (GO:0030217) TAS
  • mast cell differentiation (GO:0060374) TAS
The potential for PI3kδ as ta arget in immuno-oncology is discussed in [1] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • natural killer cell differentiation (GO:0001779) TAS
  • T cell differentiation (GO:0030217) TAS
  • mast cell differentiation (GO:0060374) TAS
The potential for PI3kδ as ta arget in immuno-oncology is discussed in [1] ...
phosphoinositide-3-kinase regulatory subunit 1
(Phosphatidylinositol kinases)
  • B cell differentiation (GO:0030183) IEA
  • negative regulation of osteoclast differentiation (GO:0045671) IEA
p85α is included in GtoImmuPdb as it is the regulatory subunit of several PI3Ks (e.g. PI3Kδ and PI3Kγ) with roles in leukocyte biology and therefore important for immunity [68] ...
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 [36,102] ...
proteinase 3
(S1: Chymotrypsin)
  • mature conventional dendritic cell differentiation (GO:0097029) IDA
Proteinase 3 (PR3), called myeloblastin when it was first identified, is an abundant serine protease found principally in neutrophil granules (but is also found on the surface of quiescent human neutrophils from peripheral blood). It is stored in the primary granules of circulating neutrophils alongside other cathepsin C-activated neutrophil serine proteases (NSPs), such as human neutrophil elastase (HNE), CatG, and NSP4. In pathological conditions it is thought that PR3 behaves to accelerate inflammation, by enhancing cytokine bioactivity, inactivating anti-inflammatory mediators and by promoting tissue injury (potentially by degrading extra-cellular matrix components like elastin, collagen, fibronectin, and laminins). In addition, imbalances between NSPs and their endogenous inhibitors can contribute towards pathological tissue damage, such as the damage associated with inflammatory lung diseases like chronic obstructive pulmonary disease (COPD), emphysema, and cystic fibrosis. PR3 inhibitors are considered to be useful clinical candidates for anti-inflammatory drug development [60] ...
protein kinase C alpha
(Delta subfamily)
  • positive regulation of macrophage differentiation (GO:0045651) ISS
PKCα is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C zeta
(Iota subfamily)
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) ISS
PKCζ is included in GtoImmuPdb based on its GO process associations.
protein kinase N1
(Protein kinase N (PKN) family)
  • spleen development (GO:0048536) 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) [41] ...
protein tyrosine kinase 2 beta
(Fak family)
  • marginal zone B cell differentiation (GO:0002315) ISS
  • negative regulation of myeloid cell differentiation (GO:0045638) IMP
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 [21] ...
receptor interacting serine/threonine kinase 1
(Receptor interacting protein kinase (RIPK) family)
  • positive regulation of macrophage differentiation (GO:0045651) IMP
RIPK1 and RIPK3 are involved in necroptosis [99,107,121] ...
receptor interacting serine/threonine kinase 2
(Receptor interacting protein kinase (RIPK) family)
  • 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) [82] ...
receptor interacting serine/threonine kinase 3
(Receptor interacting protein kinase (RIPK) family)
  • T cell differentiation in thymus (GO:0033077) ISS
  • lymph node development (GO:0048535) ISS
  • spleen development (GO:0048536) ISS
  • thymus development (GO:0048538) ISS
RIPK1 and RIPK3 are involved in necroptosis [99,107,121] ...
sirtuin 1
(3.5.1.- Histone deacetylases (HDACs))
  • macrophage differentiation (GO:0030225) ISS
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 [22] ...
spleen associated tyrosine kinase
(Syk family)
  • beta selection (GO:0043366) IEA
  • positive regulation of B cell differentiation (GO:0045579) IMP
  • positive regulation of gamma-delta T cell differentiation (GO:0045588) IEA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
SYK plays a key role in coupling activated immunoreceptors to downstream cellular responses such as proliferation, differentiation, and phagocytosis. Mast cell, macrophage and B-cell activation (and release of inflammatory modulators) is disrupted by inhibition of SYK-mediated immunoreceptor signalling. Selective SYK inhibitors are being sought for a number of inflammatory conditions including rheumatoid arthritis, B-cell lymphoma and asthma/rhinitis [35,98] ...
SRC proto-oncogene, non-receptor tyrosine kinase
(Src family)
  • osteoclast development (GO:0036035) IBA
Src family tyrosine kinases act as general modulators of immune cell signaling, playing diverse signaling functions, both inhibitory and stimulatory, in immunoreceptor and integrin signaling pathways [67] ...
zeta chain of T-cell receptor associated protein kinase 70
(Syk family)
  • T cell differentiation (GO:0030217) NAS
  • beta selection (GO:0043366) IEA
  • positive thymic T cell selection (GO:0045059) IDA
  • negative thymic T cell selection (GO:0045060) IEA
  • positive regulation of T cell differentiation (GO:0045582) IDA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
ZAP-70 has much lower intrinsic enzyme activity than SYK, and expression is restricted to T cells and NK cells [4] ...
Catalytic Receptors
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
AXL receptor tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • natural killer cell differentiation (GO:0001779) IEA
  • positive regulation of natural killer cell differentiation (GO:0032825) IDA
  • dendritic cell differentiation (GO:0097028) IEP
All three TAM family receptor tyrosine kinases are involved in regulating inflammatory responses through a negative feedback loop. Specifically, AXL-Gas6 signalling is reported to induce autophagy in murine macrophages via inhibition of the NLRP3 inflammasome, an effect which reduces hepatic inflammation in a mouse model [39] ...
CD27
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of B cell differentiation (GO:0045579) NAS
  • positive regulation of T cell differentiation (GO:0045582) IEA
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 isotype switching to IgG isotypes (GO:0048304) IEA
A costimulatory protein found on antigen presenting cells, required for their activation. Endogenous ligand is CD154 (CD40L) on TH cells.
colony stimulating factor 1 receptor
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • hemopoiesis (GO:0030097) IMP
  • monocyte differentiation (GO:0030224) TAS
  • macrophage differentiation (GO:0030225) TAS
  • osteoclast differentiation (GO:0030316) ISS
Activation of the CSF1R induces myeloid proliferation, and in the tumour microenvironment this promotes M1 to M2 polarization and accumulation of tumour-associated macrophages (TAMs). The CSF1R is therefore being investigated as an immuno-oncology drug target [1] ...
Fas
(Tumour necrosis factor (TNF) receptor family)
  • negative thymic T cell selection (GO:0045060) IEA
  • regulation of lymphocyte differentiation (GO:0045619) IEA
  • regulation of myeloid cell differentiation (GO:0045637) IEA
  • spleen development (GO:0048536) 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 [114] ...
fms related tyrosine kinase 3
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • myeloid progenitor cell differentiation (GO:0002318) ISS
  • pro-B cell differentiation (GO:0002328) ISS
  • hemopoiesis (GO:0030097) IDA
  • B cell differentiation (GO:0030183) ISS
  • dendritic cell differentiation (GO:0097028) 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 [90] ...
Granulocyte colony-stimulating factor receptor
(Prolactin receptor family)
  • regulation of myeloid cell differentiation (GO:0045637) IEA
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 [40] ...
Interleukin-12 receptor, β1 subunit
(IL-12 receptor family)
  • positive regulation of memory T cell differentiation (GO:0043382) 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-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 2
(Immunoglobulin-like family of IL-1 receptors)
  • positive regulation of T cell differentiation (GO:0045582) IEA
Interleukin-1 receptor-like 2 is one of the subunits of the functional receptor for IL-36.
Interleukin 23 receptor
(IL-12 receptor family)
  • positive regulation of memory T cell differentiation (GO:0043382) ISS
  • positive regulation of osteoclast differentiation (GO:0045672) IC
  • 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)
  • 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-2 receptor subunit α
(IL-2 receptor family)
  • regulation of T cell tolerance induction (GO:0002664) IMP
  • positive regulation of T cell differentiation (GO:0045582) IEA
IL2RA is a ligand binding component of the IL-2R complex. This subunit is the molecular target of the approved biologics daclizumab (including daclizumab beta) and basiliximab.
Interleukin-31 receptor, α subunit
(IL-6 receptor family)
  • monocyte differentiation (GO:0030224) IEP
  • macrophage differentiation (GO:0030225) NAS
Interleukin-4 receptor subunit α
(IL-2 receptor family)
  • negative regulation of T-helper 1 cell differentiation (GO:0045626) IEA
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) IEA
IL4R is the common ligand binding subunit shared by the IL-4 receptors type I (receptor for IL-4) and type II (receptor for IL-4 and IL-13). A gain-of-function mutation in IL4R has been associated with atopy, enhanced B cell isotype switching from mu to epsilon and therefore elevated IgE levels [43] ...
Interleukin-7 receptor subunit α
(IL-2 receptor family)
  • T cell differentiation (GO:0030217) IEA
  • positive regulation of T cell differentiation in thymus (GO:0033089) IEA
  • lymph node development (GO:0048535) 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)
  • myeloid progenitor cell differentiation (GO:0002318) IEA
  • lymphoid progenitor cell differentiation (GO:0002320) IEA
  • immature B cell differentiation (GO:0002327) ISS
  • hemopoiesis (GO:0030097) TAS
  • T cell differentiation (GO:0030217) ISS
  • erythrocyte differentiation (GO:0030218) ISS
  • embryonic hemopoiesis (GO:0035162) ISS
  • megakaryocyte development (GO:0035855) ISS
  • mast cell differentiation (GO:0060374) 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 [37] ...
lymphotoxin β receptor
(Tumour necrosis factor (TNF) receptor family)
  • myeloid dendritic cell differentiation (GO:0043011) IEA
Interaction of the lymphotoxin β receptor with its ligand is required for the development and organization of the secondary lymphoid organs and is involved in chemokine release (reported to induce interleukin 8 gene expression [20] ...
MER proto-oncogene, tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • natural killer cell differentiation (GO:0001779) IEA
Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [10,123] ...
NLRP3
(NOD-like receptor family)
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) ISS
  • positive regulation of T-helper 17 cell differentiation (GO:2000321) IEA
NLRP3 is a component of the NLRP3 inflammasome, a protein complex which activates caspase-1, and plays an important role in the regulation of inflammation and apoptosis. 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 [6] ...
receptor activator of NF-kappa B
(Tumour necrosis factor (TNF) receptor family)
  • osteoclast differentiation (GO:0030316) IMP
  • lymph node development (GO:0048535) IEA
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)
  • hematopoietic progenitor cell differentiation (GO:0002244) IMP
  • T cell differentiation (GO:0030217) ISS
  • bone marrow development (GO:0048539) IMP
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 [26] ...
TACI
(Tumour necrosis factor (TNF) receptor family)
  • hematopoietic progenitor cell differentiation (GO:0002244) 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).
TEK receptor tyrosine kinase
(Type XII RTKs: TIE family of angiopoietin receptors)
  • definitive hemopoiesis (GO:0060216) TAS
In inflammation, angiopoietin-2 (ANG2) antagonism of TIE2 initiates a positive feedback loop via forkhead box O1 (FOXO1) activation, which drives further ANG2 expression and enhances vascular remodeling and leakage [56] ...
TLR3
(Toll-like receptor family)
  • negative regulation of osteoclast differentiation (GO:0045671) NAS
TLR3 is an endosomal anti-viral receptor [118] ...
TLR4
(Toll-like receptor family)
  • negative regulation of osteoclast differentiation (GO:0045671) NAS
TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [12,96] ...
transforming growth factor beta receptor 1
(Type I receptor serine/threonine kinases)
  • thymus development (GO:0048538) ISS
The role of TGFBR1 in immuno-oncology is reviewed in [1] ...
TYRO3 protein tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • natural killer cell differentiation (GO:0001779) IEA
TYRO3 is a negative regulator of type 2 immunity [19] ...
Transporters
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
Other Protein Targets
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
advanced glycosylation end-product specific receptor
(Immunoglobulins)
  • positive regulation of dendritic cell differentiation (GO:2001200) IMP
RAGE is a single chain, membrane bound immunoglobulin type protein [80,103,131] ...
BCL2, apoptosis regulator
(B-cell lymphoma 2 (Bcl-2) protein family)
  • lymphoid progenitor cell differentiation (GO:0002320) IEA
  • B cell lineage commitment (GO:0002326) IEA
  • T cell differentiation in thymus (GO:0033077) IEA
  • CD8-positive, alpha-beta T cell lineage commitment (GO:0043375) IEA
  • spleen development (GO:0048536) IEA
  • thymus development (GO:0048538) IEA
The role of Bcl-2 family members in immunity and disease is reviewed in [30] ...
CD2
(CD molecules)
  • regulation of T cell differentiation (GO:0045580) NAS
CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells [132] ...
CD28
(CD molecules)
  • negative thymic T cell selection (GO:0045060) IEA
  • regulatory T cell differentiation (GO:0045066) IDA
  • regulation of regulatory T cell differentiation (GO:0045589) IEA
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
CD28 is expressed on the surface of T cells and is required for the co-stimulaory 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). The B7 proteins CD80 and CD86 on the surface of antigen presenting cells bind CD28.
As a drug target, CD28 modulation is being investigated as a treatment for autoimmume conditions. In 2006 an anti-CD28 antbody with superagonist activity (TGN1412) caused catastrophic organ failure in clinical trial participants due to 'cytokine storm' (multiple cytokine-release syndrome) in response to massive systemic T cell activation and inflammatory response [113] ...
CD3e
(CD molecules)
  • positive regulation of T cell anergy (GO:0002669) IEA
  • negative thymic T cell selection (GO:0045060) IEA
CD3e is part of the CD3/TCR complex that mediates T-cell receptor signal transduction. Defects in this gene cause severe immunodeficiency [27,108] ...
CD74
(CD molecules)
  • T cell selection (GO:0045058) NAS
  • positive thymic T cell selection (GO:0045059) IEA
  • negative thymic T cell selection (GO:0045060) IEA
  • negative regulation of T cell differentiation (GO:0045581) IEA
  • positive regulation of T cell differentiation (GO:0045582) IEA
  • positive regulation of monocyte differentiation (GO:0045657) IDA
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 [24] ...
CD79B
(CD molecules)
  • 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 [78,105] ...
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)
  • negative regulation of T cell anergy (GO:0002668) IEA
  • myeloid dendritic cell differentiation (GO:0043011) IEA
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) NAS
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 ...
C-type lectin domain family 4 member E
(C-type lectin-like receptors (CLRs))
  • T cell differentiation involved in immune response (GO:0002292) IEA
Mincle is an FcRγ-associated membrane receptor involved in initiating the innate immune response upon recognition of endogenous and exogenous ligands including Sin3A-associated protein (SAP130), α-mannan on fungal cell walls and mycobacterial cord factor (trehalose-6,6′-dimycolate (TDM)) [15] ...
cytotoxic T-lymphocyte-associated protein 4 (CD152)
(CD molecules)
  • negative regulation of regulatory T cell differentiation (GO:0045590) IDA
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 [75] ...
E1A binding protein p300
(Non-enzymatic BRD containing proteins)
  • B cell differentiation (GO:0030183) IEA
  • platelet formation (GO:0030220) IEA
  • megakaryocyte development (GO:0035855) IEA
CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. PMID: 26261308 ...
Fc fragment of IgE receptor Ig
(Fc epsilon receptors)
  • T cell differentiation involved in immune response (GO:0002292) IBA
interferon gamma inducible protein 16
(Absent in melanoma (AIM)-like receptors (ALRs))
  • hemopoiesis (GO:0030097) NAS
  • myeloid cell differentiation (GO:0030099) NAS
  • monocyte differentiation (GO:0030224) IDA
IFI16 is a sensor for cytosolic DNA which induces type I interferon production via activation of the IRF3/NFκB pathway.
programmed cell death 1 (CD279)
(CD molecules)
  • negative regulation of tolerance induction (GO:0002644) IEA
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 [85] ...