Targets Associated to Immuno Processes - Cellular signalling

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

Cellular signalling
GPCRs
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
ADGRE5
(Adhesion Class GPCRs)
  • neutrophil degranulation (GO:0043312) TAS
ADGRE5 is included in GtoImmuPdb because its tissue expression profile and the phenotypes expressed by mouse ADGRE5 knockouts suggest an involvement in inflammation.
A2A receptor
(Adenosine receptors)
  • negative regulation of alpha-beta T cell activation (GO:0046636) IEA
A2A receptor is discussed in this immuno-oncology review [2] ...
A2B receptor
(Adenosine receptors)
  • positive regulation of mast cell degranulation (GO:0043306) IEA
A2B receptor is discussed in this immuno-oncology review [2] ...
β2-adrenoceptor
(Adrenoceptors)
  • positive regulation of protein ubiquitination (GO:0031398) IMP
β2-ARs are expressed on innate and adaptive immune cells of humans and rodents, and are reported to have an immuno-modulating effect [77] ...
C3a receptor
(Complement peptide receptors)
  • complement component C3a receptor activity (GO:0004876) IBA
  • neutrophil degranulation (GO:0043312) TAS
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.
C5a1 receptor
(Complement peptide receptors)
  • complement component C5a receptor activity (GO:0004878) IDA
  • neutrophil degranulation (GO:0043312) TAS
C5aR is typically associated with the compement cascade and innate immunity.
C5a2 receptor
(Complement peptide receptors)
  • complement component C5a receptor activity (GO:0004878) IBA
C5aR is typically associated with the compement cascade and innate immunity. However, the complement C5a receptor 2 may act as a decoy receptor for C5a, as it has no reported G protein signalling capacity.
CB1 receptor
(Cannabinoid receptors)
  • negative regulation of mast cell activation (GO:0033004) IEA
CB1 receptor is involved in controlling mast cell degranulation and maturation [234] ...
CB2 receptor
(Cannabinoid receptors)
  • negative regulation of mast cell activation (GO:0033004) IEA
CB2 receptor on eosinophils mainly mediates anti-inflammatory and immunomodulatory actions e.g. downregulation of pro-inflammatory mediator release. Pharmacological targeting with the CB2 receptor selective antagonist SR144528 attenuates the recruitment of eosinophils and ear swelling in a murine chronic contact dermatitis model [187] ...
CCR2
(Chemokine receptors)
  • negative regulation of eosinophil degranulation (GO:0043310) ISS
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) ISS
  • positive regulation of T cell activation (GO:0050870) 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
  • 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)
  • establishment of T cell polarity (GO:0001768) IC
  • negative thymic T cell selection (GO:0045060) IEA
  • positive regulation of T cell receptor signaling pathway (GO:0050862) IEA
  • positive regulation of immunological synapse formation (GO:2000522) ISS
  • positive regulation of T cell costimulation (GO:2000525) ISS
  • positive regulation of glycoprotein biosynthetic process involved in immunological synapse formation (GO:2000526) 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 [260] ...
CXCR1
(Chemokine receptors)
  • neutrophil degranulation (GO:0043312) TAS
CXCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR1 is discussed in relation to immuno-oncology in [2] ...
CXCR2
(Chemokine receptors)
  • neutrophil activation (GO:0042119) IDA
  • neutrophil degranulation (GO:0043312) TAS
CXCR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR2 is discussed in relation to immuno-oncology in [2] ...
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.
CX3CR1
(Chemokine receptors)
  • microglial cell activation (GO:0001774) IEA
CX3CR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
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 [276] ...
FFA2 receptor
(Free fatty acid receptors)
  • cell surface pattern recognition receptor signaling pathway (GO:0002752) IMP
FFA2 is a GPCR activated by short-chain fatty acids, and evidence suggests that FFA2 (and FFA3) mediate beneficial effects associated with a fiber-rich diet. These GPCRs are of interest as targets for the treatment of inflammatory and metabolic diseases. FFA2 is included in GtoImmuPdb as it is highly expressed on immune cells, in particular neutrophils, and evidence points to a role in diseases with dysfunctional neutrophil responses, such as inflammatory bowel disease (IBD). A Phase 2 trial of the clinical candidate GLPG0974 ...
FPR1
(Formylpeptide receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • complement receptor activity (GO:0004875) IBA
  • neutrophil degranulation (GO:0043312) TAS
The primary function of FPR1 is recognition of formylpeptides including bacterial formylpeptides, so it is therefore a component of the host defense mechanism.
FPR2/ALX
(Formylpeptide receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • complement receptor activity (GO:0004875) IBA
  • neutrophil degranulation (GO:0043312) TAS
Formyl peptide receptor type 2 ( (FPR2/ALX) activation by lipoxin A4 and annexin 1 has been linked to resolution of inflammation, via upregulation of anti-inflammatory cytokines including IL-10. FPR2/ALX receptor agonism is a new therapeutic concept to treat inflammatory conditions.
FPR2/ALX
(Formylpeptide receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • complement receptor activity (GO:0004875) IBA
  • neutrophil degranulation (GO:0043312) TAS
Formyl peptide receptor type 2 ( (FPR2/ALX) activation by lipoxin A4 and annexin 1 has been linked to resolution of inflammation, via upregulation of anti-inflammatory cytokines including IL-10. FPR2/ALX receptor agonism is a new therapeutic concept to treat inflammatory conditions.
GPR183
(Class A Orphans)
  • 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
  • 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 [124,198] ...
MRGPRX2
(Class A Orphans)
  • mast cell degranulation (GO:0043303) IDA
  • mast cell activation (GO:0045576) IDA
Expression of MRGPRX2 was initially reported predominantly in sensory neurons of the dorsal root ganglion. More recently expression has been detected in human mast cells. In these cells the receptor is activated by the antimicrobial peptide LL-37, resulting in calcium mobilisation and degranulation [166,232] ...
NK1 receptor
(Tachykinin receptors)
  • positive regulation of lymphocyte proliferation (GO:0050671) IEA
Expression in monocytes, macrophages and T helper cells suggests a role in inflammation/immunity.
PAF receptor
(Platelet-activating factor receptor)
  • lipopolysaccharide receptor activity (GO:0001875) IEA
  • neutrophil degranulation (GO:0043312) TAS
  • positive regulation of neutrophil degranulation (GO:0043315) IEA
PAF deficiency results in defective inflammatory response to infection in mice.
PAR2
(Proteinase-activated receptors)
  • T cell activation involved in immune response (GO:0002286) ISS
  • positive regulation of toll-like receptor 2 signaling pathway (GO:0034137) IMP
  • negative regulation of toll-like receptor 3 signaling pathway (GO:0034140) IMP
  • positive regulation of toll-like receptor 3 signaling pathway (GO:0034141) IMP
  • positive regulation of toll-like receptor 4 signaling pathway (GO:0034145) IDA
  • neutrophil activation (GO:0042119) IDA
  • positive regulation of eosinophil degranulation (GO:0043311) IDA
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) [85] ...
Nuclear Hormone Receptors
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
Farnesoid X receptor
(1H. Liver X receptor-like receptors)
  • toll-like receptor 4 signaling pathway (GO:0034142) IDA
  • toll-like receptor 9 signaling pathway (GO:0034162) IEA
FXR is predominantly expressed in liver, intestine, kidney and adipose tissue, but has also been detected in immune cells (CD4+, CD8+, CD19+ and CD14+ cells) [218] ...
Liver X receptor-α
(1H. Liver X receptor-like receptors)
  • positive regulation of toll-like receptor 4 signaling pathway (GO:0034145) IDA
  • negative regulation of macrophage activation (GO:0043031) ISS
Liver X receptors are involved in the regulation of lipid metabolism and inflammatory responses- drug target for cholesterol homeostasis (hypercholesterolaemia), inflammation, and with potential therapeutic effects in neurodegenerative diseases [270] ...
RAR-related orphan receptor-γ
(1F. Retinoic acid-related orphans)
  • T-helper cell differentiation (GO:0042093) ISS
  • T-helper 17 cell differentiation (GO:0072539) ISS
RORγ inhibitors are under development for the treatment of autoimmune diseases such as psoriasis and rheumatoid arthritis [105] ...
Enzymes
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
3-phosphoinositide dependent protein kinase 1
(PDK1 family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) IEA
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • regulation of mast cell degranulation (GO:0043304) IEA
  • T cell receptor signaling pathway (GO:0050852) TAS
In addition to its role in oncology, in mouse studies, PDK1 is reported to play a part in regulating insulin sensitivity (and inhibiting adipose tissue inflammation), via the Pdk1/Foxo1 pathway and expression of Ccr2 [121] ...
5-LOX
(Lipoxygenases)
  • neutrophil degranulation (GO:0043312) TAS
5LOX is included in GtoImmuPdb because of its involvement in eicosanoid turnover.
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
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • alpha-beta T cell differentiation (GO:0046632) IEA
  • activated T cell proliferation (GO:0050798) IEA
  • B cell receptor signaling pathway (GO:0050853) IEA
  • negative regulation of ubiquitin-protein transferase activity (GO:0051444) IDA
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
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 [47] ...
ADAM8
(M12: Astacin/Adamalysin)
  • positive regulation of T cell differentiation in thymus (GO:0033089) ISS
  • activation of MAPK activity involved in innate immune response (GO:0035419) ISS
  • neutrophil degranulation (GO:0043312) TAS
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) [197] ...
Adenosine deaminase
(Adenosine turnover)
  • germinal center B cell differentiation (GO:0002314) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • positive regulation of T cell differentiation in thymus (GO:0033089) IEA
  • T cell activation (GO:0042110) IDA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
  • positive regulation of T cell receptor signaling pathway (GO:0050862) IEA
Adenosine deaminase deficiency causes immunodeficiency (ADA deficiency or ADA-SCID). Around 30 known genotypes are associated with this autosomal recessive metabolic disorder. Mitotically active cells such as developing T cells and B cells are susceptible to this deficiency, expaining the resulting ...
Arginase I
(Arginase)
  • neutrophil degranulation (GO:0043312) TAS
The role of ARG1 in immuno-oncology is reviewed in [2] ...
BLK proto-oncogene, Src family tyrosine kinase
(Src family)
  • B cell receptor signaling pathway (GO:0050853) IDA
BLK is a B cell-specific kinase. In Blk knockout mice B cells develop normally and show unaltered in vitro activation and humoral immune responses to T cell-dependent and -independent antigens, a result which is indicative of functional redundancy of Blk in B cell development and immune responses [241] ...
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 [29] ...
B-Raf proto-oncogene, serine/threonine kinase
(RAF family)
  • 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
  • T cell receptor signaling pathway (GO:0050852) IEA
BRAFV600E- immuno-oncology [2] ...
Bruton tyrosine kinase
(Tec family)
  • B cell affinity maturation (GO:0002344) IEA
  • histamine secretion by mast cell (GO:0002553) IEA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • negative regulation of B cell proliferation (GO:0030889) IEA
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • B cell activation (GO:0042113) TAS
  • positive regulation of B cell differentiation (GO:0045579) TAS
  • B cell receptor signaling pathway (GO:0050853) 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 [29] ...
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
CAMKIV has been implicated in the differentiation of Th17 cells, suggesting CAMKIV as a target for therapeutic intervention in Th17-driven autoimmune diseases [131] ...
Caspase 3
(C14: Caspase)
  • negative regulation of B cell proliferation (GO:0030889) IEA
  • negative regulation of activated T cell proliferation (GO:0046007) 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 [190] ...
Caspase 8
(C14: Caspase)
  • natural killer cell activation (GO:0030101) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • T cell activation (GO:0042110) TAS
  • B cell activation (GO:0042113) TAS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
Roles of apoptotic caspases extending beyond cell death, for example, mediating cellular immune processes such as inflammasome modulation, necroptosis and pro-inflammatory cytokine processing have been reported [159] ...
cathepsin B
(C1: Papain)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • neutrophil degranulation (GO:0043312) TAS
Cathepsins B, H and L have become important therapeutic targets as their proteolytic activity has been implicated in several pathological inflammatory conditions, such as arthritis and periodontitis. Therefore, pharmacological inhibitors of these enzymes are in development as novel therapeutics.
cathepsin C
(C1: Papain)
  • neutrophil degranulation (GO:0043312) TAS
Cathepsin C is a lysosomal cysteine protease constitutively expressed at high levels in lung, kidney, liver and spleen. As well as activity in lysosomal protein degradation, catheposin C also plays a key role in the activation of granule serine proteases in cytotoxic T cells, natural killer cells (g ...
cathepsin G
(S1: Chymotrypsin)
  • neutrophil degranulation (GO:0043312) TAS
Cathepsin G is a leukocyte serine protease of the chymotrypsin family, related to neutrophil elastase and the granzymes. It is stored in azurophil granules and acts intracellularly to degrade ingested host pathogens and axtracellularly to breakdown ECM components at sites of inflammation. Cathepsin ...
cathepsin H
(C1: Papain)
  • immune response-regulating signaling pathway (GO:0002764) IDA
  • neutrophil degranulation (GO:0043312) TAS
Cathepsin H may act as a pro-granzyme B convertase [65] ...
cathepsin L
(C1: Papain)
  • toll-like receptor signaling pathway (GO:0002224) TAS
Cathepsins B, H and L have become important therapeutic targets as their proteolytic activity has been implicated in several pathological inflammatory conditions, such as arthritis and periodontitis. Therefore, pharmacological inhibitors of these enzymes are in development as novel therapeutics.
cathepsin S
(C1: Papain)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • neutrophil degranulation (GO:0043312) TAS
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 factor D
(3.4.21.46 Complement factor D)
  • neutrophil degranulation (GO:0043312) TAS
A protease component of the alternative complement pathway; responsible for cleaving complement factor B ...
conserved helix-loop-helix ubiquitous kinase
(IKK family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
Ikkα is one of the catalytic subunits of the IκB kinase (IKK) complex, an upstream component of the NF-κB signal transduction cascade; NF-κB signaling being involved in propagating the cellular response to inflammation. IKK frees NF-κB from its inhibitory interaction with IκBα (inhibitor of kappa B), allowing NF-κB translocation to the nucleus where it modulates transcriptional activity. Additional functions of Ikkα beyond NF-κB activation are reviewed in [104] ...
C-terminal Src kinase
(Csk family)
  • T cell costimulation (GO:0031295) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • regulation of Fc receptor mediated stimulatory signaling pathway (GO:0060368) IBA
CSK is an inhibitory regulator of Src family kinases, a family of protein tyrosine kinases indispensable to the initiation of signal transduction via ITAM-bearing immunoreceptors, and cytokine, growth factor, and pattern recognition receptor signalling. CSK phosphorylates an inhibitory tyrosine residue at the C terminus of Src kinases, leading to autoinhibition. CSK-induced Src kinase inhibition can also be mediated by binding to PEST family receptor tyrosine phosphatases [252] ...
DNA-dependent protein kinase catalytic subunit
(Other PIKK family kinases)
  • B cell lineage commitment (GO:0002326) IEA
  • T cell lineage commitment (GO:0002360) IEA
  • protein ubiquitination (GO:0016567) TAS
  • T cell differentiation in thymus (GO:0033077) IEA
  • T cell receptor V(D)J recombination (GO:0033153) 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 ...
elastase, neutrophil expressed
(S1: Chymotrypsin)
  • neutrophil degranulation (GO:0043312) TAS
Neutrophil elastase (NE) is a serine proteinase with broad substrate specificity. It is stored in azurophil granules within neutrophils and is involved primarily in host defence. However, in addition to attacking proteins on invading microorganisms, secreted NE also hydrolyzes proteins of the host e ...
eukaryotic translation initiation factor 2 alpha kinase 4
(GCN2 subfamily)
  • T cell activation involved in immune response (GO:0002286) ISS
GCN2 is a so-called 'stress kinase'. It phosphorylates serine 51 on the global transcription factor eIF2α upon activation by uncharged tRNA; tRNAs accumulate when amino acid levels are depleted. Phospho-eIF2α blocks translation to cause proliferative arrest.

GCN2 plays several roles in the immune system. It is required for dendritic cell activation and antigen presentation. The GCN2 stress response is required for both optimal proliferation of CD8+ T cells after antigen stimulation, and trafficking to lymphoid organs, i.e. for normal cytotoxic T cell function [250] ...
FER tyrosine kinase
(Fer family)
  • negative regulation of mast cell activation involved in immune response (GO:0033007) ISS
  • Fc-epsilon receptor signaling pathway (GO:0038095) ISS
  • regulation of mast cell degranulation (GO:0043304) IBA
FER acts downstream of the activated high affinity immunoglobulin epsilon receptor (FCεR1) and plays a role in FCεR1-mediated signaling in mast cells, regulation of mast cell degranulation, leukocyte recruitment, and leukocyte extravasation following bacterial lipopolysaccharide (LPS ...
FGR proto-oncogene, Src family tyrosine kinase
(Src family)
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • positive regulation of mast cell degranulation (GO:0043306) ISS
  • neutrophil degranulation (GO:0043312) TAS
Fgr may be involved in neutrophil migration, potentially via binding to intergrins [24] ...
FYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • negative regulation of protein ubiquitination (GO:0031397) IEA
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell activation (GO:0042110) IBA
  • activated T cell proliferation (GO:0050798) IEA
  • T cell receptor signaling pathway (GO:0050852) IDA
Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [193] ...
Haem oxygenase 1
(Haem oxygenase)
  • negative regulation of mast cell degranulation (GO:0043305) IEA
Heme oxygenase (HO) is a rate-limiting enzyme in the catabolism of heme, catalyzing the oxidative cleavage of heme (Fe-protoporphyrin-IX) to render equimolar amounts of biliverdin, ferrous iron (Fe2+), and carbon monoxide (CO).

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

HO1 has antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, playing an important role in the prevention of vascular inflammation and atherogenesis (reviewed in [10] ...
HCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • innate immune response-activating signal transduction (GO:0002758) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
Hck is thought to be involved in neutrophil migration, potentially via binding to intergrins [24] ...
IL2 inducible T-cell kinase
(Tec family)
  • NK T cell differentiation (GO:0001865) IBA
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell activation (GO:0042110) TAS
  • T cell receptor signaling pathway (GO:0050852) 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 [29] ...
indoleamine 2,3-dioxygenase 1
(1.13.11.- Dioxygenases)
  • negative regulation of T cell proliferation (GO:0042130) 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 [100,249] ...
inhibitor of nuclear factor kappa B kinase subunit beta
(IKK family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
Iκβ kinase β (IKK-2) is the pivotal enzyme component of the Iκβ kinase (IKK) complex, a complex crucial in regulating expression and activation of inflammatory mediators in airway epithelium. IKK-2 is an attractive target for development of pharmaceutical inhibitors with antiinflammatory action as treatments for asthma and chronic obstructive pulmonary disease (COPD) [3,27,33,224] ...
inhibitor of nuclear factor kappa B kinase subunit epsilon
(IKK family)
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
IKKε is the only inducible IKK family member. Expression is induced in response to LPS, viral infection and several cytokines. IKKε expression is restricted to pancreas, thymus, spleen and peripheral blood leukocytes. This is in contrast to all other IKK family kinases which are cons ...
INPP5D
(Inositol polyphosphate phosphatases)
  • negative regulation of B cell proliferation (GO:0030889) IEA
  • positive regulation of B cell differentiation (GO:0045579) IEA
  • T cell receptor signaling pathway (GO:0050852) TAS
SHIP1 activators are proposed as novel anti-inflammatory agents e.g. rosiptor (AQX-1125) which is in Phase 2 and 3 clinical trials [182,230] ...
interleukin 1 receptor associated kinase 1
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 2 signaling pathway (GO:0034134) IMP
  • toll-like receptor 4 signaling pathway (GO:0034142) IBA
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
One of the two proximal mediators of IL-1 signaling via the IL-1 receptor, plays a part in IL-1-induced upregulation of the transcription factor NF-κB, the other being IRAK2. Interacts with other proteins including TRAF6, Myd88, CHUK, IKK2 and TLR4.
interleukin 1 receptor associated kinase 2
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
interleukin 1 receptor associated kinase 3
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) ISS
IRAK3 expression is restricted to monocytes and macrophages.
interleukin 1 receptor associated kinase 4
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
IRAK4 is essential for most innate immune responses to bacteria and viruses, and IRAK4 deficiency (caused by mutations) has been shown to result in recurrent invasive pneumococcal disease [167] ...
IP3 kinase B
(Inositol 1,4,5-trisphosphate 3-kinases)
  • positive thymic T cell selection (GO:0045059) 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 [170] ...
Janus kinase 3
(Janus kinase (JakA) family)
  • B cell differentiation (GO:0030183) ISS
  • positive regulation of T cell proliferation (GO:0042102) IBA
  • negative regulation of T-helper 1 cell differentiation (GO:0045626) ISS
  • negative regulation of T cell activation (GO:0050868) ISS
Psoriatic skin samples show elevated JAK3 (and JAK1) expression, with signalling predominantly through STAT3 [7] ...
LCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • T cell differentiation (GO:0030217) IMP
  • T cell costimulation (GO:0031295) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • B cell receptor signaling pathway (GO:0050853) IBA
  • positive regulation of T cell receptor signaling pathway (GO:0050862) NAS
  • positive regulation of T cell activation (GO:0050870) IDA
  • regulation of lymphocyte activation (GO:0051249) NAS
Phosphorylation and activation of Lck is an early and critical step in pre-TCR (T cell receptor) and TCR signalling. Activated Lck phosphorylates immunoreceptor tyrosine-based activation motifs of the ζ chain of the TCR leading to recruitment and activation of ZAP-70 tyrosine kinase, and activation of downstream MAPKs and NF-κB. TCR-based signals are required at several stages of T-cell development and it is thought that Lck is the major contributor to TCR signal transduction (with the related Src tyrosine kinase Fyn also playing a role) [193] ...
Leukotriene A4 hydrolase
(Leukotriene and lipoxin metabolism)
  • neutrophil degranulation (GO:0043312) TAS
LTA4H is an established anti-inflammatory target. Expression has been identified in some cancer cells, where it may play a role in the development and progression of cancers associated with chronic inflammation, suggesting that LTA4H inhibitors may have efficacy as anti-cancer therapeutics [52] ...
Leukotriene A4 hydrolase
(Leukotriene and lipoxin metabolism)
  • neutrophil degranulation (GO:0043312) TAS
LTA4H is an established anti-inflammatory target. Expression has been identified in some cancer cells, where it may play a role in the development and progression of cancers associated with chronic inflammation, suggesting that LTA4H inhibitors may have efficacy as anti-cancer therapeutics [52] ...
Leukotriene A4 hydrolase
(Leukotriene and lipoxin metabolism)
  • neutrophil degranulation (GO:0043312) TAS
LTA4H is an established anti-inflammatory target. Expression has been identified in some cancer cells, where it may play a role in the development and progression of cancers associated with chronic inflammation, suggesting that LTA4H inhibitors may have efficacy as anti-cancer therapeutics [52] ...
LYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc receptor mediated stimulatory signaling pathway (GO:0002431) ISS
  • histamine secretion by mast cell (GO:0002553) IEA
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) ISS
  • Fc receptor mediated inhibitory signaling pathway (GO:0002774) ISS
  • negative regulation of B cell proliferation (GO:0030889) IBA
  • T cell costimulation (GO:0031295) TAS
  • regulation of mast cell activation (GO:0033003) ISS
  • negative regulation of toll-like receptor 2 signaling pathway (GO:0034136) ISS
  • negative regulation of toll-like receptor 4 signaling pathway (GO:0034144) ISS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • regulation of mast cell degranulation (GO:0043304) ISS
  • B cell receptor signaling pathway (GO:0050853) IEA
  • regulation of B cell receptor signaling pathway (GO:0050855) ISS
  • positive regulation of B cell receptor signaling pathway (GO:0050861) IEA
  • positive regulation of Fc receptor mediated stimulatory signaling pathway (GO:0060369) IEA
LYN is a Src family tyrosine kinase, expressed predominantly in hematopoietic cells, but also in neural, liver, and adipose tissues. LYN appears to function as a rheostat to modulate B cell signaling, and can be activating or inhibitory in action, depending on the B cell receptor and interacting protein complement present in particular cells [81,84,245] ...
mitogen-activated protein kinase 1
(ERK subfamily)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • neutrophil degranulation (GO:0043312) TAS
  • T cell receptor signaling pathway (GO:0050852) IEA
  • B cell receptor signaling pathway (GO:0050853) IEA
In endothelial cells of the vasculature, and in activated human mast cells, ERK serves as an anti-inflammatory signal that suppresses production of pro-inflammatory mediators [126,155] ...
mitogen-activated protein kinase kinase kinase 7
(TAK1 subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • positive regulation of T cell activation (GO:0050870) IC
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
TAK1 (MAP3K7) mediates signaling downstream of multiple cytokine receptors and is functionally important in mitogen, immune, and inflammatory signaling pathways [66,214] ...
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.
MMP8
(M10: Matrix metallopeptidase)
  • neutrophil degranulation (GO:0043312) TAS
MMP8 is included in GtoImmuPdb based on its potential protective role in asthma.
MMP9
(M10: Matrix metallopeptidase)
  • neutrophil degranulation (GO:0043312) 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 [136] ...
otulin
(C101: OTULIN peptidase)
  • protein ubiquitination (GO:0016567) TAS
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IMP
Otulin is reported as a negative regulator of inflammation and autoimmunity [68] ...
p21 (RAC1) activated kinase 1
(PAKA subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
PAK1 is reported to modulate a pro-inflammatory PPARγ/NF-κB cascade in intestinal inflammation, that may be relevant in inflammatory bowel disease and colitis-associated cancer [69] ...
p21 (RAC1) activated kinase 2
(PAKA subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
Pharmacological inhibition of PAK2 has immunosuppressive effects [186] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • T cell costimulation (GO:0031295) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
PI3Kα is 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)
  • T cell costimulation (GO:0031295) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
PI3Kα is 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)
  • natural killer cell differentiation (GO:0001779) TAS
  • natural killer cell activation (GO:0030101) TAS
  • T cell differentiation (GO:0030217) TAS
  • T cell activation (GO:0042110) TAS
  • B cell activation (GO:0042113) TAS
  • mast cell degranulation (GO:0043303) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • B cell receptor signaling pathway (GO:0050853) 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)
  • natural killer cell differentiation (GO:0001779) TAS
  • natural killer cell activation (GO:0030101) TAS
  • T cell differentiation (GO:0030217) TAS
  • T cell activation (GO:0042110) TAS
  • B cell activation (GO:0042113) TAS
  • mast cell degranulation (GO:0043303) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • B cell receptor signaling pathway (GO:0050853) 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)
  • T cell proliferation (GO:0042098) TAS
  • T cell activation (GO:0042110) TAS
  • mast cell degranulation (GO:0043303) 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)
  • T cell proliferation (GO:0042098) TAS
  • T cell activation (GO:0042110) TAS
  • mast cell degranulation (GO:0043303) TAS
The role of PIK3CG in immuno-oncology is reviewed in [2] ...
phosphodiesterase 5A
(Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs))
  • negative regulation of T cell proliferation (GO:0042130) IEA
The role of PDE5A in immuno-oncology is reviewed in [2] ...
phosphoinositide-3-kinase regulatory subunit 1
(Phosphatidylinositol kinases)
  • B cell differentiation (GO:0030183) IEA
  • T cell costimulation (GO:0031295) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
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 [153] ...
PLCγ1
(Phosphoinositide-specific phospholipase C)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [88,213] ...
PLCγ2
(Phosphoinositide-specific phospholipase C)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • follicular B cell differentiation (GO:0002316) IEA
  • B cell differentiation (GO:0030183) ISS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) ISS
  • B cell receptor signaling pathway (GO:0050853) ISS
Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [88,213] ...
proteasome subunit beta 8
(T1: Proteasome)
  • protein polyubiquitination (GO:0000209) TAS
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • anaphase-promoting complex-dependent catabolic process (GO:0031145) TAS
  • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle (GO:0051436) TAS
  • positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition (GO:0051437) TAS
PSMB8 is a component of the immunoproteasome [80] ...
proteinase 3
(S1: Chymotrypsin)
  • neutrophil degranulation (GO:0043312) TAS
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 [133] ...
protein kinase C beta
(Alpha subfamily)
  • B cell activation (GO:0042113) ISS
  • B cell receptor signaling pathway (GO:0050853) ISS
  • positive regulation of B cell receptor signaling pathway (GO:0050861) ISS
PKCβ is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C delta
(Delta subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • B cell proliferation (GO:0042100) IEA
  • neutrophil activation (GO:0042119) IDA
  • neutrophil degranulation (GO:0043312) TAS
PKCδ is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C epsilon
(Eta subfamily)
  • macrophage activation involved in immune response (GO:0002281) IEA
  • negative regulation of protein ubiquitination (GO:0031397) IEA
  • TRAM-dependent toll-like receptor 4 signaling pathway (GO:0035669) ISS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
PKCε is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C eta
(Eta subfamily)
  • positive regulation of B cell receptor signaling pathway (GO:0050861) IMP
PKCη is included in GtoImmuPdb based on the involvement of other PKC isozymes in immune processes.
protein kinase C gamma
(Alpha subfamily)
  • negative regulation of protein ubiquitination (GO:0031397) IDA
PKCγ is included in GtoImmuPdb based on the involvement of other PKC isozymes in immune processes.
protein kinase C theta
(Delta subfamily)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • positive regulation of T cell proliferation (GO:0042102) IEA
  • T cell receptor signaling pathway (GO:0050852) TAS
  • positive regulation of T cell activation (GO:0050870) ISS
  • positive regulation of T-helper 2 cell activation (GO:2000570) ISS
PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [17] ...
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)
  • 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) [96] ...
protein tyrosine kinase 2
(Fak family)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process (GO:2000060) ISS
FAK and Pyk2 are phosphorylated downstream of the T cell antigen receptor (TCR) to bring about receptor-specific T cell development and activation [51] ...
protein tyrosine kinase 2 beta
(Fak family)
  • marginal zone B cell differentiation (GO:0002315) ISS
  • regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process (GO:2000058) IDA
  • positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process (GO:2000060) IEA
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 [51] ...
RAB27A, member RAS oncogene family
(RAB subfamily)
  • neutrophil degranulation (GO:0043312) TAS
  • cytotoxic T cell degranulation (GO:0043316) IEA
  • natural killer cell degranulation (GO:0043320) IEA
Small molecule inhibitors of Rab27a-JFC1 binding, termed Nexinhibs (neutrophil exocytosis inhibitors) demonstrate the druggability of Rab GTPases and inhibition of exocytosis of azurophilic granules in human neutrophils without affecting other important innate immune responses, including phagocytosis and neutrophil extracellular trap production. These thus have potential use as an inhibitor of systemic inflammation [116] ...
receptor interacting serine/threonine kinase 1
(Receptor interacting protein kinase (RIPK) family)
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
RIPK1 and RIPK3 are involved in necroptosis [207,223,254] ...
receptor interacting serine/threonine kinase 2
(Receptor interacting protein kinase (RIPK) family)
  • positive regulation of protein ubiquitination (GO:0031398) IMP
  • positive regulation of immature T cell proliferation (GO:0033091) IEA
  • toll-like receptor 2 signaling pathway (GO:0034134) IDA
  • toll-like receptor 4 signaling pathway (GO:0034142) IEA
  • T cell proliferation (GO:0042098) IEA
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) IEA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
  • T cell receptor signaling pathway (GO:0050852) ISS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
  • nucleotide-binding oligomerization domain containing 1 signaling pathway (GO:0070427) IEA
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IDA
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) [185] ...
receptor interacting serine/threonine kinase 3
(Receptor interacting protein kinase (RIPK) family)
  • T cell differentiation in thymus (GO:0033077) ISS
  • regulation of activated T cell proliferation (GO:0046006) ISS
RIPK1 and RIPK3 are involved in necroptosis [207,223,254] ...
sirtuin 1
(3.5.1.- Histone deacetylases (HDACs))
  • protein ubiquitination (GO:0016567) IDA
  • proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161) IMP
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 [54] ...
spleen associated tyrosine kinase
(Syk family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • macrophage activation involved in immune response (GO:0002281) ISS
  • neutrophil activation involved in immune response (GO:0002283) ISS
  • leukocyte activation involved in immune response (GO:0002366) ISS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • positive regulation of mast cell degranulation (GO:0043306) IBA
  • regulation of neutrophil degranulation (GO:0043313) ISS
  • 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
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IBA
  • B cell receptor signaling pathway (GO:0050853) ISS
SYK plays a key role in coupling activated immunoreceptors to downstream cellular responses such as proliferation, differentiation, and phagocytosis. Mast cell, macrophage and B-cell activation (and release of inflammatory modulators) is disrupted by inhibition of SYK-mediated immunoreceptor signalling. Selective SYK inhibitors are being sought for a number of inflammatory conditions including rheumatoid arthritis, B-cell lymphoma and asthma/rhinitis [87,206] ...
SRC proto-oncogene, non-receptor tyrosine kinase
(Src family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
Src family tyrosine kinases act as general modulators of immune cell signaling, playing diverse signaling functions, both inhibitory and stimulatory, in immunoreceptor and integrin signaling pathways [151] ...
TANK binding kinase 1
(IKK family)
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • dendritic cell proliferation (GO:0044565) IEA
TBK1 belongs to the IKK-kinase family of enzymes. It is a ubiquitously expressed serine/threonine protein kinase, and constitutes a key regulatory node for several signaling pathways involved in the innate immune response that lead to induction of type I interferons. Several classes of innate sensors including the TLRs and retinoic acid-inducible gene 1 (RIG-I)-like helicases engage TBK1-IRF3 signaling pathways to regulate transcription of type I IFNs. In neuroinflammation TBK1 is involved in TLR-dependent [120] ...
tec protein tyrosine kinase
(Tec family)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • B cell receptor signaling pathway (GO:0050853) IDA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [29] ...
TXK tyrosine kinase
(Tec family)
  • T cell receptor signaling pathway (GO:0050852) 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 [29] ...
YES proto-oncogene 1, Src family tyrosine kinase
(Src family)
  • T cell costimulation (GO:0031295) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
Although primarily recognised for its oncogenic activity, we have iincluded YES1 in GtoImmuPdb based on its expression in cells of the immune system.
zeta chain of T-cell receptor associated protein kinase 70
(Syk family)
  • T cell differentiation (GO:0030217) NAS
  • T cell activation (GO:0042110) TAS
  • B cell activation (GO:0042113) TAS
  • 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
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
  • T cell receptor signaling pathway (GO:0050852) TAS
ZAP-70 has much lower intrinsic enzyme activity than SYK, and expression is restricted to T cells and NK cells [12] ...
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
  • negative regulation of lymphocyte activation (GO:0051250) IEA
All three TAM family receptor tyrosine kinases are involved in regulating inflammatory responses through a negative feedback loop. Specifically, AXL-Gas6 signalling is reported to induce autophagy in murine macrophages via inhibition of the NLRP3 inflammasome, an effect which reduces hepatic inflammation in a mouse model [93] ...
BAFF receptor
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • T cell costimulation (GO:0031295) IEA
  • B cell costimulation (GO:0031296) IEA
  • positive regulation of T cell proliferation (GO:0042102) IEA
A type III membrane bound receptor for B-cell activating factor (BAFF). BAFF enhances B-cell survival and hence regulates the peripheral B-cell population. It is suggested that overproduction of BAFF may enhance the survival of autoreactive B cells, an effect which may contribute in the pathogenesis ...
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)
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) IEA
  • 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
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)
  • negative regulation of B cell proliferation (GO:0030889) ISS
  • negative regulation of T cell proliferation (GO:0042130) ISS
  • T cell receptor signaling pathway (GO:0050852) ISS
Expressed predominantly in the thymus, spleen and white blood cells. May play a role in T helper cell activation, inflammation and immune regulation. Signals via the TRADD adaptor protein to the NF-κB and MAPK8/JNK pathways.
DExD/H-box helicase 58
(RIG-I-like receptor family)
  • cytoplasmic pattern recognition receptor signaling pathway in response to virus (GO:0039528) TAS
  • RIG-I signaling pathway (GO:0039529) IMP
RIG-I is an intracellular sensor that responds to viral nucleic acids and activates downstream signaling, resulting in the induction of the type I interferon response [161] ...
DExH-box helicase 58
(RIG-I-like receptor family)
  • negative regulation of MDA-5 signaling pathway (GO:0039534) IMP
  • negative regulation of RIG-I signaling pathway (GO:0039536) IDA
  • positive regulation of MDA-5 signaling pathway (GO:1900245) ISS
  • positive regulation of RIG-I signaling pathway (GO:1900246) ISS
LGP2 binds RNA but does not participate in the signaling pathway that RIG-1 and MDA5 are part of, and is assumed to provide a negative feedback for IFNβ induction by sequestering pathogen-derived RNA.
Fas
(Tumour necrosis factor (TNF) receptor family)
  • negative thymic T cell selection (GO:0045060) IEA
  • regulation of lymphocyte differentiation (GO:0045619) 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 [238] ...
fms related tyrosine kinase 3
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • B cell differentiation (GO:0030183) ISS
  • lymphocyte proliferation (GO:0046651) 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 [196] ...
herpes virus entry mediator
(Tumour necrosis factor (TNF) receptor family)
  • T cell costimulation (GO:0031295) TAS
  • negative regulation of alpha-beta T cell proliferation (GO:0046642) IEA
HSV viral envelope glycoprotein D (gD) binds to this protein and thereby gains entry to the cell. HVEM binds to several TRAFadaptor proteins to mediate intracellular signalling and activation of the immune response.
integrin, alpha 4 subunit (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
(Integrins)
  • 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 [94] ...
integrin, alpha L subunit (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide)
(Integrins)
  • T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:0002291) IMP
  • neutrophil degranulation (GO:0043312) TAS
ITGAL associates with the beta 2 chain (ITGB2) integrin and CD18 to form the lymphocyte function-associated antigen-1 (LFA-1) complex. LFA-1 is crucial for leukocyte intercellular adhesion and costimulatory signaling in the immune system. Ligands for LFA-1 are the intercellular adhesion molecules (ICAMs) 1-3. ITGAL is the target of the withdrawn psoriasis monoclonal antibody drug efalizumab ...
integrin, beta 2 subunit (complement component 3 receptor 3 and 4 subunit)
(Integrins)
  • natural killer cell activation (GO:0030101) IEA
  • toll-like receptor 4 signaling pathway (GO:0034142) TAS
  • neutrophil degranulation (GO:0043312) TAS
ITGB2 is the beta component of the β2 integrins. It forms αβ heterodimers with the CD11 alpha subunits ITGAL (αL aka CD11a forming integrin LFA-1), ITGAM (αM aka CD11b, forming integrin Mac-1) and ITGAX (αX aka CD11c, forming integrin p150/95). These integrins are essential for leukocyte extravasion to sites of infection. Their absence causes a leukocyte adhesion deficiency, which manifests clinically as recurrent severe infections, defective wound healing and neutrophilia [129] ...
interferon α/β receptor 1
(Interferon receptor family)
  • T cell activation (GO:0042110) IEA
A subunit of the functional receptor for various interferons (NOT interferon γ).
interferon induced with helicase C domain 1
(RIG-I-like receptor family)
  • cytoplasmic pattern recognition receptor signaling pathway in response to virus (GO:0039528) TAS
  • MDA-5 signaling pathway (GO:0039530) IDA
MDA5 is an intracellualar RNA sensor. It recognizes longer double-stranded RNA sequences than RIG-1. In autoimmunity, MDA5 has been specifically linked with type I diabetes and anti-MDA5 autoantibodies can be detected in patients with certain connective tissue autoimmune conditions [4,102,169] ...
Interleukin-12 receptor, β1 subunit
(IL-12 receptor family)
  • positive regulation of activated T cell proliferation (GO:0042104) IDA
  • positive regulation of memory T cell differentiation (GO:0043382) ISS
  • positive regulation of T-helper 17 cell lineage commitment (GO:2000330) ISS
This protein is a subunit of both the IL-12 and IL-23 cytokine receptors.
Interleukin 13 receptor, α2
(IL-2 receptor family)
  • negative regulation of mast cell degranulation (GO:0043305) IEA
Interleukin 13 receptor, α2 acts as a high affinity decoy receptor for interleukin 13 that sequesters the ligand away from IL13Rα1 and is involved in down-regulating IL-13 responses in vivo. IL13ra2 null mice exhibit enhanced IL-13 responses [266] ...
Interleukin-18 1
(Immunoglobulin-like family of IL-1 receptors)
  • natural killer cell activation (GO:0030101) IEA
  • T-helper 1 cell differentiation (GO:0045063) IEA
Interleukin-18 1 protein (IL18R1) is the ligand binding subunit of the functional IL-18 receptor heterodimer.
Interleukin-1 receptor-like 1
(Immunoglobulin-like family of IL-1 receptors)
  • positive regulation of macrophage activation (GO:0043032) IEA
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 [83] ...
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 20 receptor, β subunit
(IL-10 receptor family)
  • immune response-inhibiting signal transduction (GO:0002765) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
Interleukin 20 receptor, β subunit is a component of the functional receptor heterodimers for interleukins 19, 20 and 24.
Interleukin 21 receptor
(IL-2 receptor family)
  • natural killer cell activation (GO:0030101) NAS
This is the ligand binding subunit of the functional heterodimeric receptor for interleukin 21.
Interleukin 23 receptor
(IL-12 receptor family)
  • positive regulation of natural killer cell proliferation (GO:0032819) IC
  • positive regulation of T cell proliferation (GO:0042102) IC
  • positive regulation of activated T cell proliferation (GO:0042104) IC
  • positive regulation of memory T cell differentiation (GO:0043382) ISS
  • positive regulation of NK T cell activation (GO:0051135) 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)
  • positive regulation of activated T cell proliferation (GO:0042104) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
  • positive regulation of T cell differentiation (GO:0045582) IEA
  • regulation of T cell homeostatic proliferation (GO:0046013) IEA
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)
  • negative regulation of macrophage activation (GO:0043031) NAS
Interleukin-4 receptor subunit α
(IL-2 receptor family)
  • positive regulation of macrophage activation (GO:0043032) IEA
  • positive regulation of mast cell degranulation (GO:0043306) IEA
  • negative regulation of T-helper 1 cell differentiation (GO:0045626) IEA
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) IEA
IL4R is the common ligand binding subunit shared by the IL-4 receptors type I (receptor for IL-4) and type II (receptor for IL-4 and IL-13). A gain-of-function mutation in IL4R has been associated with atopy, enhanced B cell isotype switching from mu to epsilon and therefore elevated IgE levels [99] ...
Interleukin-6 receptor, β subunit
(IL-6 receptor family)
  • positive regulation of T cell proliferation (GO:0042102) IMP
This is the common signal transducing subunit shared by members of the IL-6 family of cytokine receptors.
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
  • 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
  • T cell differentiation (GO:0030217) ISS
  • Fc receptor signaling pathway (GO:0038093) IDA
  • mast cell degranulation (GO:0043303) IMP
Stem cell factor (SCF) and its receptor KIT (c-KIT) play an essential part in mast cell biology. In addition to CSF/KIT-mediated regulation of mast cell development, proliferation and survival, KIT is also reported to be involved in the adhesion of mast cells to human airway epithelial cells (a homing and adhesion role), suggesting a mechanism that could be targeted for anti-asthmatic potential [90] ...
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 [50] ...
MER proto-oncogene, tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • natural killer cell differentiation (GO:0001779) IEA
  • negative regulation of lymphocyte activation (GO:0051250) IEA
Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [28,256] ...
NLRC3
(NOD-like receptor family)
  • T cell activation (GO:0042110) IEP
NLRC3 is an intracellular pattern recognition receptor of the innate immune system. It has been shown to directly interact with and inhibit the type I interferon response of the intracellular DNA sensor STING to cytosolic DNA, cyclic di-GMP (c-di-GMP), and DNA viruses [160,281] ...
NLRC4
(NOD-like receptor family)
  • ubiquitin-protein transferase activity (GO:0004842) IBA
As part of the innate inflammatory response to invading mobile bacteria, NLRC4 (Ipaf) in macrophages induces a pro-inflammatory response upon detection of cytosolic bacterial flagellin. In contrast, extracellular bacterial flagellin is detected by TLR5 [168] ...
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 [18] ...
NLRP6
(NOD-like receptor family)
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) IEA
NLRP6 is an intracellular pattern recognition receptor (PRR). It is a member of the NACHT, LRR and PYD domains-containing protein (NALP) subfamily of PRRs. The presence of NALPs in inflammasomes underlies their involvement in regulating proinflammatory caspases (esp. caspase 1) ...
NLRX1
(NOD-like receptor family)
  • negative regulation of RIG-I signaling pathway (GO:0039536) IEA
NLRX1 is an intracellular pattern recognition receptor that plays a role in host immunity to certain bacterial infections.
nucleotide binding oligomerization domain containing 1
(NOD-like receptor family)
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
NOD1 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing a D-glutamyl-meso-diaminopimelic acid (iE-DAP) moiety.
nucleotide binding oligomerization domain containing 2
(NOD-like receptor family)
  • activation of MAPK activity involved in innate immune response (GO:0035419) ISS
  • positive regulation of gamma-delta T cell activation (GO:0046645) ISS
  • positive regulation of B cell activation (GO:0050871) IDA
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IDA
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
  • T cell proliferation (GO:0042098) 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 [259] ...
RTP Type C
(Receptor tyrosine phosphatase (RTP) family)
  • T cell differentiation (GO:0030217) ISS
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • B cell proliferation (GO:0042100) ISS
  • positive regulation of T cell proliferation (GO:0042102) ISS
  • neutrophil degranulation (GO:0043312) TAS
  • T cell receptor signaling pathway (GO:0050852) IDA
  • B cell receptor signaling pathway (GO:0050853) ISS
  • positive regulation of antigen receptor-mediated signaling pathway (GO:0050857) ISS
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 [67] ...
TACI
(Tumour necrosis factor (TNF) receptor family)
  • 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).
TLR1
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 1 signaling pathway (GO:0034130) IEA
  • toll-like receptor TLR1:TLR2 signaling pathway (GO:0038123) TAS
  • macrophage activation (GO:0042116) NAS
TLR1/2 heterodimers detect and respond to bacterial triacyl lipopeptides [248] ...
TLR10
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 10 signaling pathway (GO:0034166) TAS
To date, ligands and biological functions of human TLR10 remain unclear. However, evidence suggests it plays a modulatory role with predominantly inhibitory (anti-inflammatory) effects [191] ...
TLR2
(Toll-like receptor family)
  • microglial cell activation (GO:0001774) IEA
  • lipopolysaccharide receptor activity (GO:0001875) TAS
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • signaling pattern recognition receptor activity (GO:0008329) IDA
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • toll-like receptor 2 signaling pathway (GO:0034134) IEA
  • toll-like receptor TLR1:TLR2 signaling pathway (GO:0038123) TAS
  • toll-like receptor TLR6:TLR2 signaling pathway (GO:0038124) TAS
  • neutrophil degranulation (GO:0043312) TAS
TLR1/2 and 2/6 heterodimers detect and initiate an immune response to triacylated and diacylated [177] ...
TLR3
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • microglial cell activation involved in immune response (GO:0002282) IEA
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • negative regulation of MyD88-independent toll-like receptor signaling pathway (GO:0034128) TAS
  • toll-like receptor 3 signaling pathway (GO:0034138) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
TLR3 is an endosomal anti-viral receptor [248] ...
TLR4
(Toll-like receptor family)
  • lipopolysaccharide receptor activity (GO:0001875) IDA
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • B cell proliferation involved in immune response (GO:0002322) IEA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • negative regulation of MyD88-independent toll-like receptor signaling pathway (GO:0034128) TAS
  • toll-like receptor 4 signaling pathway (GO:0034142) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • macrophage activation (GO:0042116) IMP
  • positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway (GO:0070430) IEA
  • positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070434) IEA
TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [31,202] ...
TLR5
(Toll-like receptor family)
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • toll-like receptor 5 signaling pathway (GO:0034146) TAS
TLR5 induces a pro-inflammatory response upon detection of extracellular bacterial flagellin from invading mobile bacteria [168] ...
TLR6
(Toll-like receptor family)
  • microglial cell activation (GO:0001774) IEA
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 6 signaling pathway (GO:0034150) IEA
  • toll-like receptor TLR6:TLR2 signaling pathway (GO:0038124) TAS
TLR6 forms heterodimers with TLR2 to detect a wide range of bacterial lipopeptides from bacterial cell membranes, and effect an immune response [79] ...
TLR7
(Toll-like receptor family)
  • microglial cell activation (GO:0001774) IEA
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
  • toll-like receptor 7 signaling pathway (GO:0034154) IBA
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
TLR7 is an endosomal receptor detecting ssRNA [248] ...
TLR8
(Toll-like receptor family)
  • microglial cell activation (GO:0001774) IEA
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
  • toll-like receptor 8 signaling pathway (GO:0034158) IDA
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
TLR8 is an endosomal receptor detecting ssRNA [248] ...
TLR9
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) IDA
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
TLR9 is an endosomal receptor detecting viral and bacterial CpG DNA and genomic DNA from some protozoan species [248] ...
transforming growth factor beta receptor 1
(Type I receptor serine/threonine kinases)
  • regulation of protein ubiquitination (GO:0031396) IDA
The role of TGFBR1 in immuno-oncology is reviewed in [2] ...
tumor necrosis factor receptor 2
(Tumour necrosis factor (TNF) receptor family)
  • neutrophil degranulation (GO:0043312) TAS
We have included TNFR2 in GtoImmuPdb based on it being a receptor for lymphotoxin-α, a cytotoxic protein performing a variety of important roles in immune system development and regulation [91,181] ...
TYRO3 protein tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • natural killer cell differentiation (GO:0001779) IEA
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) ISS
  • negative regulation of lymphocyte activation (GO:0051250) IEA
TYRO3 is a negative regulator of type 2 immunity [48] ...
Transporters
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
NRAMP1
(SLC11 family of proton-coupled metal ion transporters)
  • T cell proliferation involved in immune response (GO:0002309) ISS
  • macrophage activation (GO:0042116) ISS
  • neutrophil degranulation (GO:0043312) TAS
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 [37,225-226] ...
Peptide transporter 4
(SLC15 family of peptide transporters)
  • neutrophil degranulation (GO:0043312) TAS
SLC15A3 and SLC15A4, are preferentially expressed by dendritic cells, especially after TLR stimulation [176] ...
Other Protein Targets
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
advanced glycosylation end-product specific receptor
(Immunoglobulins)
  • positive regulation of activated T cell proliferation (GO:0042104) IMP
  • regulation of CD4-positive, alpha-beta T cell activation (GO:2000514) IDA
RAGE is a single chain, membrane bound immunoglobulin type protein [180,217,272] ...
baculoviral IAP repeat containing 2
(Inhibitors of apoptosis (IAP) protein family)
  • protein polyubiquitination (GO:0000209) IDA
  • ubiquitin-protein transferase activity (GO:0004842) IDA
  • regulation of toll-like receptor signaling pathway (GO:0034121) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • regulation of RIG-I signaling pathway (GO:0039535) TAS
  • proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161) IDA
  • regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
  • positive regulation of protein K63-linked ubiquitination (GO:1902523) IDA
  • positive regulation of protein K48-linked ubiquitination (GO:1902524) IDA
  • positive regulation of protein monoubiquitination (GO:1902527) IDA
Cellular inhibitors of apoptosis proteins BIRC2 and BIRC3 are required for efficient caspase-1 activation by the inflammasome [135] ...
baculoviral IAP repeat containing 3
(Inhibitors of apoptosis (IAP) protein family)
  • ubiquitin-protein transferase activity (GO:0004842) IDA
  • positive regulation of protein ubiquitination (GO:0031398) IDA
  • regulation of toll-like receptor signaling pathway (GO:0034121) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • regulation of RIG-I signaling pathway (GO:0039535) TAS
  • regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
Cellular inhibitor of apoptosis proteins (cIAPs) suppress apoptosis thereby promoting cell survival, and participate in the immune response (e.g. negative regulation of the necrosome, inflammasome and ripoptosome. In asthma, cIAPs extend the survival of neutrophils, macrophages and eosinophils, prolonging the inflammation. The minor alleles of single nucleotide polymorphisms in BIRC3 are shown to correlate with reduced numbers of circulating eosinophils and neutrophils, suggesting a protective effect against the development of asthma[211] ...
BCL2, apoptosis regulator
(B-cell lymphoma 2 (Bcl-2) protein family)
  • protein polyubiquitination (GO:0000209) IDA
  • B cell lineage commitment (GO:0002326) IEA
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • T cell differentiation in thymus (GO:0033077) IEA
  • B cell proliferation (GO:0042100) IDA
  • CD8-positive, alpha-beta T cell lineage commitment (GO:0043375) IEA
  • B cell receptor signaling pathway (GO:0050853) IMP
The role of Bcl-2 family members in immunity and disease is reviewed in [74] ...
CD19
(CD molecules)
  • B cell receptor signaling pathway (GO:0050853) IBA
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 ...
CD2
(CD molecules)
  • natural killer cell activation (GO:0030101) NAS
  • positive regulation of myeloid dendritic cell activation (GO:0030887) NAS
  • T cell activation (GO:0042110) TAS
  • 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 [273] ...
CD209 molecule
(C-type lectin-like receptors (CLRs))
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • regulation of T cell proliferation (GO:0042129) IDA
DC-SIGN is a pathogen-recognition receptor involved in initiating the primary immune response to various viral and bacterial pathogens, as well as antigen presentation and initiation of the adaptive immune response.
CD20 (membrane-spanning 4-domains, subfamily A, member 1)
(CD molecules)
  • B cell proliferation (GO:0042100) NAS
CD20 is a B cell antigen, involved in B cell development and maturation to antibody-producing plasma cells [58] ...
CD28
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • 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 alpha-beta T cell proliferation (GO:0046641) IEA
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
  • T cell receptor signaling pathway (GO:0050852) 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 [237] ...
CD300a
(CD molecules)
  • negative regulation of B cell proliferation (GO:0030889) IMP
  • negative regulation of mast cell activation involved in immune response (GO:0033007) IDA
  • negative regulation of MyD88-dependent toll-like receptor signaling pathway (GO:0034125) IMP
  • negative regulation of mast cell degranulation (GO:0043305) IDA
  • neutrophil degranulation (GO:0043312) TAS
  • regulation of T cell receptor signaling pathway (GO:0050856) IDA
  • negative regulation of B cell receptor signaling pathway (GO:0050859) IDA
  • negative regulation of NK T cell activation (GO:0051134) IDA
  • negative regulation of neutrophil activation (GO:1902564) IDA
  • negative regulation of eosinophil activation (GO:1902567) IDA
CD300a is a member of the CD300 family of leucocyte surface receptors [34] ...
CD33
(CD molecules)
  • neutrophil degranulation (GO:0043312) TAS
CD33 (SIGLEC-3) is a myeloid cell I-type (Ig-type) lectin that binds glycans containing sialic acids [86] ...
CD38
(CD molecules)
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • B cell receptor signaling pathway (GO:0050853) 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 [92] ...
CD3e
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
  • positive regulation of T cell proliferation (GO:0042102) IMP
  • T cell activation (GO:0042110) NAS
  • negative thymic T cell selection (GO:0045060) IEA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
  • T cell receptor signaling pathway (GO:0050852) TAS
CD3e is part of the CD3/TCR complex that mediates T-cell receptor signal transduction. Defects in this gene cause severe immunodeficiency [70,227] ...
CD6
(CD molecules)
  • immunological synapse formation (GO:0001771) IMP
  • positive regulation of T cell proliferation (GO:0042102) IMP
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 [175] ...
CD74
(CD molecules)
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • regulation of macrophage activation (GO:0043030) NAS
  • 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
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 [59] ...
CD79B
(CD molecules)
  • B cell differentiation (GO:0030183) IBA
  • B cell receptor signaling pathway (GO:0050853) 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 [173,219] ...
CD80
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
  • T cell activation (GO:0042110) IC
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) NAS
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
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)
  • T cell proliferation involved in immune response (GO:0002309) IEA
  • T cell costimulation (GO:0031295) TAS
  • toll-like receptor 3 signaling pathway (GO:0034138) IEA
  • positive regulation of activated T cell proliferation (GO:0042104) IEA
  • T cell activation (GO:0042110) IC
  • B cell activation (GO:0042113) 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 ...
CREB binding protein
(Non-enzymatic BRD containing proteins)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. PMID: 26261308 ...
CS1 (CD319)
(CD molecules)
  • natural killer cell activation (GO:0030101) NAS
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) [127] ...
C-type lectin domain family 4 member A
(C-type lectin-like receptors (CLRs))
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
C-type lectin domain family 4 member E
(C-type lectin-like receptors (CLRs))
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell differentiation involved in immune response (GO:0002292) IEA
  • Fc-gamma receptor signaling pathway (GO:0038094) 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)) [40] ...
C-type lectin domain family 6 member A
(C-type lectin-like receptors (CLRs))
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
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 ...
C-type lectin domain family 7 member A
(C-type lectin-like receptors (CLRs))
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • leukocyte activation involved in immune response (GO:0002366) IEA
  • signaling pattern recognition receptor activity (GO:0008329) IDA
  • T cell activation (GO:0042110) TAS
Dectin-1 is a pattern recognition receptor involved in initiating the innate immune response upon recognition of various β(1,3)-linked and β(1,6)-linked glucans from fungi and plants. It mediates phagocytosis and the production of inflammatory mediators [39] ...
cytotoxic T-lymphocyte-associated protein 4 (CD152)
(CD molecules)
  • negative regulation of B cell proliferation (GO:0030889) IMP
  • T cell costimulation (GO:0031295) TAS
  • negative regulation of T cell proliferation (GO:0042130) IEA
  • negative regulation of regulatory T cell differentiation (GO:0045590) IDA
  • B cell receptor signaling pathway (GO:0050853) 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 [165] ...
E1A binding protein p300
(Non-enzymatic BRD containing proteins)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • 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)
  • IgE receptor activity (GO:0019767) IEA
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • positive regulation of mast cell degranulation (GO:0043306) 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)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • neutrophil activation involved in immune response (GO:0002283) IBA
  • T cell differentiation involved in immune response (GO:0002292) IBA
  • Fc receptor mediated stimulatory signaling pathway (GO:0002431) IBA
  • IgE receptor activity (GO:0019767) IBA
  • Fc-gamma receptor signaling pathway (GO:0038094) IBA
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • positive regulation of mast cell degranulation (GO:0043306) IEA
  • neutrophil degranulation (GO:0043312) TAS
  • mast cell activation (GO:0045576) IEA
heat shock protein 90 alpha family class B member 1
(Heat shock proteins)
  • regulation of protein ubiquitination (GO:0031396) IDA
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • neutrophil degranulation (GO:0043312) TAS
heat shock protein 90 beta family member 1
(Heat shock proteins)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • ubiquitin-dependent ERAD pathway (GO:0030433) IMP
HSP90B1 is an endoplasmic reticulum chaperone required for proper folding and cell surface export of newly synthesized Toll-like receptor and integrin (CD11a, CD18 and CD49d) proteins. In its absence TLR responses are ablated, and there is no innate response to microbial stimuli [204] ...
immunoglobulin heavy constant epsilon
(Immunoglobulins)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • B cell receptor signaling pathway (GO:0050853) 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 ...
LAG3 (CD223)
(CD molecules)
  • negative regulation of T cell activation (GO:0050868) IEA
LAG3 (CD223) is a T cell inhibitory receptor and immune checkpoint being investigated as a cancer immunotherapeutic target [8] ...
leucine rich repeat containing 32
(Leucine-rich repeat proteins)
  • negative regulation of activated T cell proliferation (GO:0046007) IEA
GARP is expressed on the surface of T regulatory (Treg) cells and binds latent (inactive) TGF-β1. GARP is also involved in the activation of TGF-β1 [62] ...
lymphocyte antigen 96
(Lymphocyte antigens)
  • lipopolysaccharide receptor activity (GO:0001875) IDA
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • negative regulation of MyD88-independent toll-like receptor signaling pathway (GO:0034128) TAS
  • toll-like receptor 4 signaling pathway (GO:0034142) ISS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
LY96 (MD2) is a binding partner of Toll-like receptor 4 (TLR4), required to initiate an innate immune response to bacterial lipopolysaccharide (LPS). The signaling complex also contains CD14 co-receptor [130] ...
membrane spanning 4-domains A2
(Fc epsilon receptors)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
The protein product of the MS4A2 gene is the β subunit of the FCεRI. It has commonly known as FCER1B. The IgE-receptor (FCεRI), is a tetramer composed of an α, β, and 2 disulfide-linked γ chains expressed on the surface of mast cells and basophils that is crucial for mediating the allergic response. It has been suggested that cytoplasmic FCER1B that is not associated with FCεRI complexes may act as a negative regulator of the signalling pathway to degranulation by sequestering important signalling partners such as the Lyn tyrosine kinase [188] ...
myeloid cell nuclear differentiation antigen
(Absent in melanoma (AIM)-like receptors (ALRs))
  • negative regulation of B cell proliferation (GO:0030889) IMP
  • neutrophil degranulation (GO:0043312) TAS
  • B cell receptor signaling pathway (GO:0050853) IMP
MNDA can be detected exclusively in nuclei of hematopoietic cells of the monocyte lineage. Expression is induced by interferon α [36] ...
programmed cell death 1 (CD279)
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
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 [192] ...
programmed cell death 1 ligand 1 (CD274)
(CD molecules)
  • T cell costimulation (GO:0031295) IDA
  • positive regulation of T cell proliferation (GO:0042102) TAS
  • negative regulation of activated T cell proliferation (GO:0046007) IMP
PD-L1 is an endogenous ligand of the checkpoint receptor programmed cell death 1 (PD-1). Engagement of PD-1 by PD-L1 has immunosuppressive action. Both the ligand and receptor are being pursued as targets for novel oncology therapeutics, as over-expression of either of these proteins is a mechanism used by tumour cells to evade immune detection and destruction. Antibody-based therapies targeting the PD-1/PD-L1 pathway augment immune responses and eliminate tumour-induced tolerance. Clinically this action has been observed as regression in various tumour types, including melanoma, renal cell carcinoma [192] ...
transmembrane protein 173
(Other pattern recognition receptors)
  • neutrophil degranulation (GO:0043312) TAS
STING functions as a major regulator of the innate immune response to viral and bacterial infections. Located in the endoplasmic reticulum, it acts as a pattern recognition receptor, activating type I interferon (IFN) responses upon direct binding to a variety of different cyclic-di-nucleotides (for example of pathogenic origin) [20,41,108-109] ...
X-linked inhibitor of apoptosis
(Inhibitors of apoptosis (IAP) protein family)
  • ubiquitin-protein transferase activity (GO:0004842) IDA
  • positive regulation of protein ubiquitination (GO:0031398) IDA
  • ubiquitin protein ligase activity (GO:0061630) EXP
  • regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
  • positive regulation of protein linear polyubiquitination (GO:1902530) IDA
Mouse experiments suggest that XIAP regulates innate immune responses (to Listeria monocytogenes infection) by potentiating synergy between Toll-like receptors (TLRs) and NOD-like receptors (NLRs) through activation of JNK- and NF-κB-dependent signaling [26] ...