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Targets Associated to Immuno Processes - Cytokine production & signalling

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Cytokine production & signalling
GPCRs
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
5-HT2B receptor
(5-Hydroxytryptamine receptors)
  • positive regulation of cytokine production (GO:0001819) IDA
  • positive regulation of cytokine secretion (GO:0050715) ISS
The expression of 5-HT2B receptors on immune cells indicates that it plays some part in immune/inflammatory responses [591] ...
ACKR1
(Chemokine receptors)
  • regulation of chemokine production (GO:0032642) IBA
  • chemokine-mediated signaling pathway (GO:0070098) IEA
ACKR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. Studies in ACKR1 null mice, and analysis of ACKR1 SNPs in asthmatic patients with poorly controlled symptoms, suggest a role for this cytokine receptor in the temporal regulation of asthma pathophysiology and symptoms [101] ...
ACKR2
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
ACKR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
ACKR3
(Chemokine receptors)
  • C-C chemokine receptor activity (GO:0016493) IBA
  • C-X-C chemokine receptor activity (GO:0016494) IMP
  • chemokine-mediated signaling pathway (GO:0070098) IMP
ACKR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. ACKR3 binds the chemokine CXCL12 (stromal cell-derived factor 1, SDF-1 which is also a ligand for CXCR4). ACKR3 is an atypical receptor in that it does not activate G-protein-mediated signaling but induces β-arrestin recruitment [268] ...
ACKR4
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) IDA
  • C-C chemokine receptor activity (GO:0016493) IBA
ACKR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
A2B receptor
(Adenosine receptors)
  • positive regulation of vascular endothelial growth factor production (GO:0010575) IEA
  • positive regulation of chemokine production (GO:0032722) IEA
  • positive regulation of interleukin-6 production (GO:0032755) IEA
A2B receptor is discussed in this immuno-oncology review [2] ...
AT1 receptor
(Angiotensin receptors)
  • positive regulation of cytokine secretion (GO:0050715) IEA
Accumulating evidence suggests that regulation of the mutually antagonistic angiotensin receptors AT1 and AT2 is essential for maintaining control of inflammation and that an imbalance between these two receptors has pathophysiological potential [523] ...
AT2 receptor
(Angiotensin receptors)
  • positive regulation of cytokine secretion (GO:0050715) IEA
AT2 receptors have been have been identified on human immunocompetent cells, and selective AT2 receptor activation stimulates an anti-inflammatory effect (reduces production of pro-inflammatory cytokines TNFα, IL-6, and IL-10 after LPS challenge) in human monocytes [375] ...
C3a receptor
(Complement peptide receptors)
  • positive regulation of vascular endothelial growth factor production (GO:0010575) IEA
Complement C3a receptor 1 is the receptor for complement factor C3a, a component of the alternative complement cascade. It can have pro-inflammatory actions, but can also counteract the proinflammatory effects of C5a.
The complement system plays a critical role intestinal immune homeostasis. In particular, C3 and the C3aR have been identified as being involved in regulating the intestinal immune response during chronic colitis [547,604] ...
C5a1 receptor
(Complement peptide receptors)
  • positive regulation of vascular endothelial growth factor production (GO:0010575) IEA
C5aR is typically associated with the compement cascade and innate immunity.
MorphoSys have an anti-C5aR monoclonal antibody (MOR210) in preclinical development as an immuno-oncology agent. The goal of anti-C5aR therapy is to reduce the effects that activation of the C5a/C5aR axis has on promoting cancer cell migration and invasiveness [237,354,406-407] ...
C5a2 receptor
(Complement peptide receptors)
  • negative regulation of tumor necrosis factor production (GO:0032720) IMP
  • negative regulation of interleukin-6 secretion (GO:1900165) IMP
  • regulation of interleukin-8 secretion (GO:2000482) IMP
C5aR is typically associated with the compement cascade and innate immunity. However, the complement C5a receptor 2 may act as a decoy receptor for C5a, as it has no reported G protein signalling capacity.
CCR1
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) IDA
  • C-C chemokine receptor activity (GO:0016493) IDA
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • chemokine-mediated signaling pathway (GO:0070098) IDA
CCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR10
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) IDA
  • C-C chemokine receptor activity (GO:0016493) IBA
CCR10 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR2
(Chemokine receptors)
  • regulation of T cell cytokine production (GO:0002724) ISS
  • chemokine receptor activity (GO:0004950) TAS
  • regulation of vascular endothelial growth factor production (GO:0010574) ISS
  • C-C chemokine receptor activity (GO:0016493) IBA
  • cytokine-mediated signaling pathway (GO:0019221) IDA
  • positive regulation of interferon-gamma production (GO:0032729) ISS
  • positive regulation of interleukin-2 production (GO:0032743) ISS
  • positive regulation of tumor necrosis factor production (GO:0032760) IMP
  • positive regulation of tumor necrosis factor biosynthetic process (GO:0042535) ISS
  • chemokine-mediated signaling pathway (GO:0070098) 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] ...
CCR3
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
CCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR4
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
CCR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
In disease states CCR4 is involved in recruiting T helper type 2 cell (Th2) subsets in autoimmune disorders such as asthma, allergic rhinitis, and atopic dermatitis [525] ...
CCR5
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IDA
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • positive regulation of interleukin-6 production (GO:0032755) IMP
  • positive regulation of tumor necrosis factor production (GO:0032760) IMP
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IMP
CCR5 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CCR5 is discussed in relation to immuno-oncology in [2] ...
CCR6
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IDA
CCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. CCR6 is expressed on a variety of immune cells including memory and regulatory T-cells [289,333] ...
CCR7
(Chemokine receptors)
  • C-C chemokine receptor activity (GO:0016493) ISS
  • regulation of interferon-gamma production (GO:0032649) ISS
  • positive regulation of interleukin-12 production (GO:0032735) ISS
  • positive regulation of tumor necrosis factor production (GO:0032760) IC
  • C-C motif chemokine 19 receptor activity (GO:0038117) IDA
  • C-C motif chemokine 21 receptor activity (GO:0038121) IDA
  • regulation of interleukin-1 beta secretion (GO:0050706) ISS
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IC
  • cellular response to cytokine stimulus (GO:0071345) IDA
  • interleukin-12 secretion (GO:0072610) 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.
CCR8
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
CCR8 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)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
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 [605] ...
CCRL2
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
CCRL2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. However, the nomenclature of CCLR2 for this receptor and its classification as a member of the chemokine receptor family is prov ...
chemerin receptor 1
(Chemerin receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • negative regulation of interleukin-12 production (GO:0032695) ISS
Studies in CMKLR1 (chemerin receptor 1) knockout mice highlight the role of this receptor in inflammation and obesity. Chemerin receptor 1 is activated by the lipid-derived, anti-inflammatory autacoid ligand resolvin E1. As its name suggests, reslovin E1 is involved in resolving physiological inflammatory responses. The metabolically stable resolvin E1 analogue, RX-10045 (navamepent) has completed Phase 2 clinical trials in several occular inflammation indications. In relation to multiple sclerosis (MS), clinical EAE is significantly reduced in CMKLR1 KO mice. Taking this in to consideration with data that confirm CMKLR1 expression by the main effector cells in MS, this protein is judged to be a novel and tractable target for therapeutic intervention in MS. CMKLR1 antagonists are being pursued as anti-inflammatory agents. The selective CMKLR1 antagonist CCX832 was developed by ChemoCentryx and GlaxoSmithKline as a potential anti-psoriatic medication, but development appears to have halted at Phase 1. is a CMKLR1 antagonist that has shown efficacious effects applicable to MS in vitro and in vivo [201] ...
CXCR1
(Chemokine receptors)
  • interleukin-8 receptor activity (GO:0004918) IDA
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
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)
  • interleukin-8 receptor activity (GO:0004918) IDA
  • chemokine receptor activity (GO:0004950) IDA
  • C-C chemokine receptor activity (GO:0016493) IBA
  • C-X-C chemokine receptor activity (GO:0016494) IDA
  • interleukin-8-mediated signaling pathway (GO:0038112) IDA
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] ...
CXCR3
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
  • chemokine (C-C motif) ligand 11 production (GO:0071954) IDA
  • C-X-C chemokine receptor activity (GO:0016494) IEA
CXCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR3 is the receptor for CXCL9, -10 and -11, three CXC chemokines that are preferentially expressed on Th1 lymphocytes.
CXCR4
(Chemokine receptors)
  • C-C chemokine receptor activity (GO:0016493) IBA
  • C-X-C chemokine receptor activity (GO:0016494) NAS
  • C-X-C motif chemokine 12 receptor activity (GO:0038147) IDA
  • CXCL12-activated CXCR4 signaling pathway (GO:0038160) IDA
  • cellular response to cytokine stimulus (GO:0071345) IDA
  • positive regulation of macrophage migration inhibitory factor signaling pathway (GO:2000448) IEA
CXCR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. Due to its role in cancer cell homing and metastasis the CXCR4-CXCL12 axis is a potential target for cancer therapy [469,498,585,596] ...
CXCR5
(Chemokine receptors)
  • C-C chemokine receptor activity (GO:0016493) IBA
  • C-X-C chemokine receptor activity (GO:0016494) IEA
CXCR5 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CXCR6
(Chemokine receptors)
  • C-C chemokine receptor activity (GO:0016493) IBA
  • C-X-C chemokine receptor activity (GO:0016494) IEA
CXCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR6 is upregulated by IL-2 and IL-15 [570] ...
CX3CR1
(Chemokine receptors)
  • cytokine receptor activity (GO:0004896) IMP
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
  • cytokine-mediated signaling pathway (GO:0019221) IMP
  • negative regulation of interleukin-1 beta production (GO:0032691) ISS
  • regulation of tumor necrosis factor biosynthetic process (GO:0042534) ISS
  • chemokine-mediated signaling pathway (GO:0070098) IMP
  • C-X3-C chemokine receptor activity (GO:0016495) 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.
D2 receptor
(Dopamine receptors)
  • positive regulation of glial cell-derived neurotrophic factor secretion (GO:1900168) IDA
D2 receptor-mediated anti-inflammatory effects in the kidney have a protective effect. In contrast, impaired D2 receptor function results in renal inflammation and organ damage [651] ...
EP3 receptor
(Prostanoid receptors)
  • cellular response to interleukin-1 (GO:0071347) IEP
Foudi et al. (2012) [177] ...
EP4 receptor
(Prostanoid receptors)
  • negative regulation of tumor necrosis factor production (GO:0032720) IMP
  • positive regulation of interleukin-8 production (GO:0032757) IMP
  • negative regulation of cytokine secretion (GO:0050710) ISS
  • negative regulation of interleukin-1 alpha secretion (GO:0050712) IMP
  • positive regulation of cytokine secretion (GO:0050715) ISS
  • response to interleukin-1 (GO:0070555) IEP
  • cellular response to interleukin-1 (GO:0071347) IEP
  • negative regulation of tumor necrosis factor secretion (GO:1904468) IMP
  • negative regulation of endothelin secretion (GO:1904471) IMP
  • positive regulation of interleukin-10 secretion (GO:2001181) IMP
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 [635] ...
FFA2 receptor
(Free fatty acid receptors)
  • positive regulation of cytokine production involved in immune response (GO:0002720) ISS
  • positive regulation of chemokine production (GO:0032722) ISS
  • positive regulation of interleukin-8 secretion (GO:2000484) IMP
FFAR2 is a GPCR activated by short-chain fatty acids, and evidence suggests that FFAR2 (and FFAR3) mediate beneficial effects associated with a fiber-rich diet. These GPCRs are of interest as targets for the treatment of inflammatory and metabolic diseases. FFAR2 is included in GtoImmuPdb as it is highly expressed on immune cells, in particular neutrophils, and evidence points to a role in diseases with dysfunctional neutrophil responses, such as inflammatory bowel disease (IBD). A Phase 2 trial of the clinical candidate GLPG0974 in ulcerative colitis has been completed (see NCT0182932).
In vitro and in vivo studies suggest that the short-chain fatty acid/FFAR2 axis is modulated by metabolites of cholera toxin, that are produced by gut microbiota, which leads to enhanced mucosal antibody responses against enteric pathogen infection [629] ...
FFA3 receptor
(Free fatty acid receptors)
  • positive regulation of cytokine production involved in immune response (GO:0002720) ISS
  • positive regulation of chemokine production (GO:0032722) ISS
FFA3 has been included in GtoImmuPdb as its expression has been detected in immune cells [68] ...
FPR1
(Formylpeptide receptors)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
The primary function of FPR1 is recognition of formylpeptides. Detection of bacterial N-formylpeptides via FPR1 activates immune-cell chemotaxis and cytokine release, making this GPCR an important component of the host defense mechanism.

Osei-Owusu et al. (2019) demonstrated that FPR1 on immune cells is the target of the needle cap protein (LcrV; Uniprot accession P0C7U7) of Yersinia pestis (the plague bacterium), via which the bacteria destroy host immune cells [426] ...
GPR35
(Class A Orphans)
  • chemokine receptor activity (GO:0004950) ISO
  • C-X-C chemokine receptor activity (GO:0016494) IMP
  • chemokine-mediated signaling pathway (GO:0070098) IDA
GPR35 is expressed by dendritic cells, macrophages, and granulocytes, all of which show chemotactic response to CXCL17 [446] ...
PAF receptor
(Platelet-activating factor receptor)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • cytokine production (GO:0001816) IEA
  • positive regulation of tumor necrosis factor production (GO:0032760) IEA
  • positive regulation of interleukin-6 biosynthetic process (GO:0045410) IEA
PAF deficiency results in defective inflammatory response to infection in mice.
PAR1
(Proteinase-activated receptors)
  • regulation of interleukin-1 beta production (GO:0032651) ISS
  • positive regulation of interleukin-8 secretion (GO:2000484) IDA
  • positive regulation of interleukin-6 secretion (GO:2000778) IDA
PAR1 has been found to mediate the effects of neutrophil elastase (NE) on γδ T cell activation, as the PAR1 inhibitor abrogates NE (from neutrophils)-induced activation of these T cells [565] ...
PAR2
(Proteinase-activated receptors)
  • positive regulation of cytokine secretion involved in immune response (GO:0002741) IDA
  • negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804) IDA
  • chemokine (C-C motif) ligand 2 secretion (GO:0035926) IDA
  • interleukin-1 beta secretion (GO:0050702) IDA
  • interleukin-10 secretion (GO:0072608) IDA
  • interferon-gamma secretion (GO:0072643) ISS
  • chemokine secretion (GO:0090195) IDA
  • negative regulation of chemokine secretion (GO:0090198) IDA
  • positive regulation of interleukin-8 secretion (GO:2000484) IDA
  • positive regulation of interleukin-6 secretion (GO:2000778) 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) [185] ...
S1P1 receptor
(Lysophospholipid (S1P) receptors)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
S1P1R activation by agonists downregulates allergic inflammation (i.e. it has an inhibitory effect) [245,248,497] ...
S1P3 receptor
(Lysophospholipid (S1P) receptors)
  • cytokine production (GO:0001816) IEA
  • regulation of interleukin-1 beta production (GO:0032651) IEA
In the immune system S1P receptors regulate immune cell trafficking and mitogenesis, are involved in immune-modulation, and suppression of innate immune T cell responses.
succinate receptor
(Succinate receptor)
  • interleukin-1 beta production (GO:0032611) IMP
Succinate acts an an alarmin that triggers the initiation and propagation of danger signals resulting from tissue injury or inflammatory stimuli. It acts through the succinate receptor, SUCNR1. SUCNR1-expressing macrophages release succinate that acts in an autocrine and paracrine feed-forward loop that elevates SUCNR1 expression and leads to enhanced IL-1β production [337] ...
XCR1
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
  • response to cytokine (GO:0034097) IDA
XCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. XCR1 is expressed by a subset of dendritic cells [319] ...
Ion Channels
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
nicotinic acetylcholine receptor α7 subunit
(Nicotinic acetylcholine receptors)
  • negative regulation of interleukin-1 beta production (GO:0032691) IMP
  • negative regulation of interleukin-6 production (GO:0032715) IMP
  • negative regulation of tumor necrosis factor production (GO:0032720) IDA
Included in Guide to Immunopharmacology as CHRNA7 knockout aggravates rheumatoid arthritis in mice [576] ...
P2X7
(P2X receptors)
  • positive regulation of interleukin-1 beta production (GO:0032731) IMP
  • positive regulation of cytokine secretion (GO:0050715) IMP
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IDA
  • positive regulation of interleukin-6 production (GO:0032755) IEA
  • positive regulation of interleukin-1 alpha secretion (GO:0050717) IEA
The P2X7 receptor is involved in NLRP3-type inflammasome formation, and subsequent maturation of IL-1β [336,472] ...
TRPM4
(Transient Receptor Potential channels)
  • regulation of T cell cytokine production (GO:0002724) IDA
TRPM4 is expressed on human T cells, mouse dendritic cells, human and mouse monocytes/macrophages, and mouse mast cells [434] ...
TRPV1
(Transient Receptor Potential channels)
  • cellular response to cytokine stimulus (GO:0071345) IDA
  • cellular response to tumor necrosis factor (GO:0071356) IEA
Several lines of evidence suggest that TRPV1 is implicated in some inflammatory processes [22,45,348,356,496] ...
TRPV4
(Transient Receptor Potential channels)
  • positive regulation of monocyte chemotactic protein-1 production (GO:0071639) IEA
  • positive regulation of macrophage inflammatory protein 1 alpha production (GO:0071642) IEA
  • positive regulation of chemokine (C-C motif) ligand 5 production (GO:0071651) IEA
  • positive regulation of chemokine (C-X-C motif) ligand 1 production (GO:2000340) IEA
  • positive regulation of interleukin-6 secretion (GO:2000778) IEA
Expressed on mouse neutrophils [434] ...
Nuclear Hormone Receptors
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
Farnesoid X receptor
(1H. Liver X receptor-like receptors)
  • interleukin-17 secretion (GO:0072615) IDA
  • negative regulation of interferon-gamma secretion (GO:1902714) IDA
  • negative regulation of tumor necrosis factor secretion (GO:1904468) IDA
  • negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804) IEA
  • negative regulation of interleukin-1 production (GO:0032692) IEA
  • negative regulation of interleukin-2 production (GO:0032703) IEA
  • negative regulation of interleukin-6 production (GO:0032715) IEA
  • negative regulation of monocyte chemotactic protein-1 production (GO:0071638) 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) [503] ...
Liver X receptor-α
(1H. Liver X receptor-like receptors)
  • negative regulation of interferon-gamma-mediated signaling pathway (GO:0060336) NAS
Liver X receptors (LXR) are involved in the regulation of lipid metabolism and inflammatory responses. As such they are novel drug targets for cholesterol homeostasis (hypercholesterolaemia), inflammation, and with potential therapeutic effects in neurodegenerative diseases [619] ...
Liver X receptor-β
(1H. Liver X receptor-like receptors)
  • negative regulation of interferon-gamma-mediated signaling pathway (GO:0060336) NAS
Liver X receptors are involved in the regulation of lipid metabolism and inflammatory responses. LXRs are drug targets for cholesterol homeostasis (hypercholesterolaemia), inflammation, and with therapeutic potential in neurodegenerative diseases [619] ...
Peroxisome proliferator-activated receptor-γ
(1C. Peroxisome proliferator-activated receptors)
  • negative regulation of cytokine production (GO:0001818) IMP
  • negative regulation of interferon-gamma-mediated signaling pathway (GO:0060336) IMP
PPARγ agonists have anti-inflammatory effects. Full PPARγ agonists can cause undesireable weight gain, but partial agonists are devoid of this adverse effect and retain the anti-inflammatory effects of PPARγ modulation.
The PPARγ agonist boosts the inflammatory phenotype of microglia and enhances their phagocytic capacity [310] ...
RAR-related orphan receptor-γ
(1F. Retinoic acid-related orphans)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • interleukin-17 production (GO:0032620) IDA
  • interleukin-17 secretion (GO:0072615) IMP
RORγ is a nuclear receptor transcription factor that acts as an immune cell master control switch (most likely associated with expression of the RORγt isoform). This receptor is an essential regulator of type 17 effector T cell differentiation and function. RORγt inhibitors (antagonists and inverse agonists) [135,189,409,529] ...
Retinoic acid receptor-γ
(1B. Retinoic acid receptors)
  • cellular response to leukemia inhibitory factor (GO:1990830) IEA
Retinoid drugs reduce the proinflammatory factors and disrupt the immunoinflammatory cascade associated with acne vulgaris. RARγ is one of the molecular targets of anti-acne retinoid family drugs. RARγ-selective retinoid derivatives are being investigated as topical agents, which are exp ...
Enzymes
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
5-LOX
(Lipoxygenases)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • interleukin-18-mediated signaling pathway (GO:0035655) TAS
5-LOX is included in GtoImmuPdb because of its involvement in eicosanoid turnover and because it is being actively pursued as a molecular target for the development of novel anti-inflammatory therapeutics [520] ...
ABL proto-oncogene 1, non-receptor tyrosine kinase
(Abl family)
  • positive regulation of interleukin-2 secretion (GO:1900042) IEA
  • positive regulation of interferon-gamma secretion (GO:1902715) IEA
Included in GtoImmuPdb based on its association with leukemia.
aconitate decarboxylase 1
(Itaconate biosynthesis)
  • negative regulation of type I interferon production (GO:0032480) ISS
  • cellular response to interferon-beta (GO:0035458) ISS
  • cellular response to interferon-gamma (GO:0071346) ISS
  • cellular response to interleukin-1 (GO:0071347) ISS
  • cellular response to tumor necrosis factor (GO:0071356) ISS
Itaconate (itaconic acid) is generated from the citric acid (TCA) cycle intermediate cis-aconitic acid which is produced by mitochondria. Itaconate is synthesised by the enzyme aconitate decarboxylase 1 (referred to as immunoresponsive gene 1 or IRG1). Its synthesis links metabolism to immunity and it plays an important role in the macrophage-based immune response [120,150] ...
ADAM10
(M12: Astacin/Adamalysin)
  • response to tumor necrosis factor (GO:0034612) IDA
ADAM10 has been identified as the primary physiologically relevant sheddase responsible for cleavage of , and regulation of ICOS/ICOSL-dependent immune responses [349] ...
ADAM17
(M12: Astacin/Adamalysin)
  • positive regulation of chemokine production (GO:0032722) IMP
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • positive regulation of tumor necrosis factor-mediated signaling pathway (GO:1903265) IMP
The proteolytic activity of ADAM17 (a type I transmembrane metalloproteinase; a.k.a.TNF-alpha converting enzyme or TACE) is involved in the shedding of the extracellular domains of several transmembrane proteins e.g. cytokines (TNFα), growth factors, receptors (IL-6R and TNF-R for example) and adhesion molecules. Cleavage of substrates, including TNFα, IL-6R and L-selectin, produce pro-inflammatory effects stimulating both innate and acquired immune responses. ADAM17 activity is crucial during development (ADAM17 knockout is embryonic lethal), and it has been shown that the soluble IL-6R/IL-6 complex generates agonist-like signals in a process termed IL-6 trans-signaling. The generation and maintenance of several inflammatory and autoimmune diseases is driven by IL-6 trans-signaling [95] ...
ADAM33
(M12: Astacin/Adamalysin)
  • regulation of cytokine biosynthetic process (GO:0042035) NAS
ADAM33 is implicated in the pathology of asthma [574] ...
ADAM8
(M12: Astacin/Adamalysin)
  • positive regulation of tumor necrosis factor (ligand) superfamily member 11 production (GO:2000309) ISS
ADAM8 is reported to drive acute allergen-induced airway inflammation in a mouse model, and effect negated by ADAM8-deficiency (antibody-induced or gene knockout) [440] ...
Arginase I
(Arginase)
  • negative regulation of interferon-gamma-mediated signaling pathway (GO:0060336) IMP
  • cellular response to interleukin-4 (GO:0071353) IEA
  • negative regulation of T-helper 2 cell cytokine production (GO:2000552) IEA
The role of ARG1 in immuno-oncology is reviewed in [2] ...
Arginase II
(Arginase)
  • negative regulation of tumor necrosis factor production (GO:0032720) IMP
  • cellular response to interferon-gamma (GO:0071346) IEP
  • cellular response to interleukin-4 (GO:0071353) IEP
  • regulation of interleukin-1 beta secretion (GO:0050706) IEA
  • negative regulation of macrophage inflammatory protein 1 alpha production (GO:0071641) IEA
  • negative regulation of chemokine (C-C motif) ligand 4 production (GO:0071644) IEA
  • negative regulation of chemokine (C-C motif) ligand 5 production (GO:0071650) IEA
  • negative regulation of tumor necrosis factor secretion (GO:1904468) IEA
  • negative regulation of interleukin-17 secretion (GO:1905077) IEA
  • negative regulation of interleukin-13 secretion (GO:2000666) IEA
The role of ARG2 in immuno-oncology is reviewed in [2] ...
beta adrenergic receptor kinase 1
(Beta-adrenergic receptor kinases (βARKs))
  • positive regulation of interleukin-6 biosynthetic process (GO:0045410) IMP
  • cellular response to chemokine (GO:1990869) IDA
GRK2 (βARK1) expression and activity are downregulated in lymphocytes from RA patients [345] ...
Bruton tyrosine kinase
(Tec family)
  • regulation of B cell cytokine production (GO:0002721) TAS
  • negative regulation of cytokine production (GO:0001818) IEA
  • cellular response to interleukin-7 (GO:0098761) IEA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [43] ...
casein kinase 2, beta polypeptide subunit
(Casein kinase 2 (CK2) family)
  • adiponectin-activated signaling pathway (GO:0033211) IDA
CSNK2B is included in Guide to IMMUNOPHARMACOLOGY as it is a subunit of the casein kinase 2 complex.
Caspase 1
(C14: Caspase)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • interleukin-1 beta production (GO:0032611) IGI
  • positive regulation of interleukin-1 beta production (GO:0032731) IMP
  • positive regulation of cytokine secretion (GO:0050715) IMP
  • positive regulation of interleukin-1 alpha secretion (GO:0050717) IMP
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IDA
  • cellular response to cytokine stimulus (GO:0071345) TAS
  • cellular response to interferon-gamma (GO:0071346) IMP
  • positive regulation of tumor necrosis factor-mediated signaling pathway (GO:1903265) IMP
Caspase 1 is also known as interleukin-1beta (IL-1α) converting enzyme (ICE). Amongst its substrates are the precursors of the inflammatory cytokines IL-1β and IL-18, which it proteolytically cleaves into active mature peptides.
Caspase 3
(C14: Caspase)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • response to tumor necrosis factor (GO:0034612) TAS
Defective caspase 3 expression in immune effector cells may influence susceptibility to Kawasaki disease, an acute vasculitis syndrome affecting small- and medium-sized arteries of infants and children [424] ...
Caspase 4
(C14: Caspase)
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IGI
  • positive regulation of tumor necrosis factor-mediated signaling pathway (GO:1903265) IDA
Recognition of cytoplasmic lipopolysaccharide (LPS) by Inflammatory caspases including caspases-4 and -5 leads to pyroptosis and secretion of inflammatory mediators [515-516] ...
Caspase 8
(C14: Caspase)
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) TAS
  • positive regulation of interleukin-1 beta production (GO:0032731) IMP
  • response to tumor necrosis factor (GO:0034612) IMP
Roles of apoptotic caspases extending beyond cell death, for example, mediating cellular immune processes such as inflammasome modulation, necroptosis and pro-inflammatory cytokine processing have been reported [358] ...
cathepsin B
(C1: Papain)
  • response to cytokine (GO:0034097) IEP
  • response to interleukin-4 (GO:0070670) IEP
Cathepsins B, H and L have become important therapeutic targets as their proteolytic activity has been implicated in several pathological inflammatory conditions, such as arthritis and periodontitis. Therefore, pharmacological inhibitors of these enzymes are in development as novel therapeutics.
chitinase acidic
(Chitinases)
  • positive regulation of chemokine secretion (GO:0090197) IDA
AMCase has been shown to be produced during type 2 inflammatory responses [657] ...
chymase 1
(S1: Chymotrypsin)
  • interleukin-1 beta biosynthetic process (GO:0050720) IDA
Chymase is a chymotrypsin-like serine protease that is expressed by mast cells. Amongst its activities, chymase is involved in the conversion of angiotensin (AT) I to ATII, its protease activity cleaves latent TGFβ1 and IL-1β in the cellular environment to generate the active cytokines, and it can further stimulate mast cell degranulation in a self-amplification loop. The potential of chymase as a drug target for inflammatory and gastrointestinal disorders is reviewed by Heuston and Hyland (2012) [227] ...
component of inhibitor of nuclear factor kappa B kinase complex
(IKK family)
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) TAS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) IBA
  • interleukin-1-mediated signaling pathway (GO:0070498) TAS
  • cellular response to tumor necrosis factor (GO:0071356) IDA
  • positive regulation of interferon-alpha secretion (GO:1902741) IMP
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 [239] ...
COX-2
(Cyclooxygenase)
  • positive regulation of vascular endothelial growth factor production (GO:0010575) ISS
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • response to cytokine (GO:0034097) ISO
  • positive regulation of transforming growth factor beta production (GO:0071636) ISS
  • positive regulation of fibroblast growth factor production (GO:0090271) ISS
  • positive regulation of platelet-derived growth factor production (GO:0090362) ISS
  • response to tumor necrosis factor (GO:0034612) IEA
The cyclooxygenase enzymes are included in GtoImmuPdb as they are involved in the production of inflammatory mediators, and are long-standing anti-inflammatory drug targets. The role of COX-2 in immuno-oncology is reviewed in [2] ...
C-terminal Src kinase
(Csk family)
  • negative regulation of interleukin-6 production (GO:0032715) IEA
CSK is an inhibitory regulator of Src family kinases, a family of protein tyrosine kinases indispensable to the initiation of signal transduction via ITAM-bearing immunoreceptors, and cytokine, growth factor, and pattern recognition receptor signalling. CSK phosphorylates an inhibitory tyrosine residue at the C terminus of Src kinases, leading to autoinhibition. CSK-induced Src kinase inhibition can also be mediated by binding to PEST family receptor tyrosine phosphatases [579] ...
dual oxidase 1
(NADPH oxidases)
  • cytokine-mediated signaling pathway (GO:0019221) IDA
DUOX1 participates in innate immune responses to epithelial injury and allergens, and in the development of allergic diseases [573] ...
ectonucleoside triphosphate diphosphohydrolase 1
(Hydrolases)
  • response to interferon-beta (GO:0035456) IEP
  • cellular response to interferon-alpha (GO:0035457) IEP
  • cellular response to tumor necrosis factor (GO:0071356) IEP
Via the conversion of ADP/ATP to AMP (CD39; ENTPD1) and AMP to adenosine (CD73; NT5E) these ectonucleotidase enzymes are crucial to the regulation of purinergic signals delivered to immune cells [19] ...
elastase, neutrophil expressed
(S1: Chymotrypsin)
  • negative regulation of chemokine biosynthetic process (GO:0045079) IDA
  • negative regulation of interleukin-8 biosynthetic process (GO:0045415) IDA
  • positive regulation of interleukin-8 biosynthetic process (GO:0045416) IDA
Neutrophil elastase (NE) is a serine proteinase with broad substrate specificity. It is stored in azurophil granules within neutrophils and is involved primarily in host defence. However, in addition to attacking proteins on invading microorganisms, secreted NE also hydrolyzes proteins of the host extracellular matrix, such as collagen-IV and elastin, hence its role in degenerative and inflammatory diseases. NE functions as a promoter of γδ T cell activation via a protease-activated receptor (PAR1)-dependent mechanism [565] ...
eukaryotic translation initiation factor 2 alpha kinase 2
(Other PEK family kinases)
  • positive regulation of cytokine production (GO:0001819) ISS
  • positive regulation of chemokine production (GO:0032722) ISS
  • response to interferon-alpha (GO:0035455) IDA
Protein kinase-R (EIF2AK2) is activated by virally-introduced double-stranded RNA (dsRNA), and is therefore involved in protection against viral infection. Protein activator of the interferon-induced protein kinase EIF2AK2 (PACT; PRKRA) also activates protein kinase-R. Activated protein kinase-R phosphorylates the eukaryotic translation initiation factor eIF2α inhibiting viral protein synthesis [184] ...
FER tyrosine kinase
(Fer family)
  • cytokine-mediated signaling pathway (GO:0019221) IMP
  • cellular response to macrophage colony-stimulating factor stimulus (GO:0036006) IMP
  • Kit signaling pathway (GO:0038109) ISS
  • interleukin-6-mediated signaling pathway (GO:0070102) IMP
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)
  • positive regulation of cytokine secretion (GO:0050715) ISS
Fgr may be involved in neutrophil migration, potentially via binding to intergrins [36] ...
FYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [432] ...
glycogen synthase kinase 3 beta
(GSK subfamily)
  • cellular response to interleukin-3 (GO:0036016) ISS
  • cellular response to erythropoietin (GO:0036018) IEP
GSK3β plays an essential function in T cell differentiation and proliferation, and its activity is inhibited following antigen-driven T cell activation [50-51,346,418] ...
Haem oxygenase 1
(Haem oxygenase)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • positive regulation of chemokine biosynthetic process (GO:0045080) TAS
  • negative regulation of mast cell cytokine production (GO:0032764) 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 [21] ...
HCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
Hck is thought to be involved in neutrophil migration, potentially via binding to intergrins [36] ...
heparanase
(3.2.1.- Glycosidases)
  • positive regulation of vascular endothelial growth factor production (GO:0010575) IDA
Heparanase has been studied as a novel drug target associated with the immune response and inflammation [99-100] ...
histone deacetylase 3
(3.5.1.- Histone deacetylases (HDACs))
  • negative regulation of interleukin-1 production (GO:0032692) ISO
  • negative regulation of tumor necrosis factor production (GO:0032720) ISO
A 2017 study reports that HDAC3 (more so than HDACs -6, -1/2, or -8) regulates inflammatory gene expression in rheumatoid arthritis fibroblast-like synoviocytes, and is required for type I IFN production [17] ...
IL2 inducible T cell kinase
(Tec family)
  • cytokine production (GO:0001816) ISS
  • interferon-gamma production (GO:0032609) IEA
  • interleukin-4 production (GO:0032633) IEA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [43] ...
indoleamine 2,3-dioxygenase 1
(1.13.11.- Dioxygenases)
  • cytokine production involved in inflammatory response (GO:0002534) IEA
  • negative regulation of interleukin-10 production (GO:0032693) IEA
  • positive regulation of interleukin-12 production (GO:0032735) IEA
The indoleamine 2,3 dioxygenase (IDO) branch of the kynurenine (KYN) pathway of tryptophan metabolism has been intensely studied in relation to immune tolerance and allergy. IDO is generally considered to be a tolerogenic, immunosuppressive enzyme, that is induced by IFN-γ. It provides a negative feedback pathway that limits uncontrolled immune responses. Its immunosuppressive actions arise from its promotion of tryptophan depletion, and elevation of KYN metabolite levels. The aryl hydrocarbon receptor serves as a receptor for KYN and should be considered when evaluating the IDO-KYN pathway in immune homeostasis and its potential to modulate innate and adaptive immune responses [290] ...
Inducible NOS
(Nitric oxide synthases)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • response to tumor necrosis factor (GO:0034612) IMP
  • cellular response to cytokine stimulus (GO:0071345) ISO
  • cellular response to interleukin-1 (GO:0071347) IEP
  • cellular response to tumor necrosis factor (GO:0071356) IEP
  • interleukin-6 secretion (GO:0072604) IDA
  • interleukin-8 secretion (GO:0072606) IDA
  • regulation of cytokine production involved in inflammatory response (GO:1900015) IDA
  • cellular response to interferon-gamma (GO:0071346) IEA
The role of iNOS in immuno-oncology is reviewed in [2] ...
inhibitor of nuclear factor kappa B kinase subunit beta
(IKK family)
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) TAS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) IMP
  • interleukin-1-mediated signaling pathway (GO:0070498) IMP
  • cellular response to tumor necrosis factor (GO:0071356) IDA
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) [39,58,527] ...
inhibitor of nuclear factor kappa B kinase subunit epsilon
(IKK family)
  • negative regulation of type I interferon production (GO:0032480) TAS
  • response to interferon-beta (GO:0035456) IMP
  • response to type I interferon (GO:0034340) IEA
  • positive regulation of type I interferon-mediated signaling pathway (GO:0060340) IEA
IKKε is the only inducible IKK family member. Expression is induced in response to LPS, viral infection and several cytokines. IKKε expression is restricted to pancreas, thymus, spleen and peripheral blood leukocytes. This is in contrast to all other IKK family kinases which are cons ...
INPP5D
(Inositol polyphosphate phosphatases)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • negative regulation of interleukin-6 biosynthetic process (GO:0045409) IEA
SHIP1 activators are proposed as novel anti-inflammatory agents e.g. rosiptor (AQX-1125) which is in Phase 2 and 3 clinical trials [405,539] ...
interleukin 1 receptor associated kinase 1
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • regulation of cytokine-mediated signaling pathway (GO:0001959) IMP
  • cytokine-mediated signaling pathway (GO:0019221) IBA
  • positive regulation of type I interferon production (GO:0032481) IMP
  • type I interferon signaling pathway (GO:0060337) IMP
  • interleukin-1-mediated signaling pathway (GO:0070498) IMP
  • response to interleukin-1 (GO:0070555) IMP
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)
  • regulation of cytokine-mediated signaling pathway (GO:0001959) IMP
  • cytokine-mediated signaling pathway (GO:0019221) IBA
  • interleukin-1-mediated signaling pathway (GO:0070498) IMP
  • response to interleukin-1 (GO:0070555) IMP
IRAK2 is one of the proximal mediators of IL-1 signalling via the IL-1 receptor, the other being IRAK1. It plays a part in IL-1-induced upregulation of the transcription factor NF-κB. IRAK2 interacts with TRAF6 and Myd88.
interleukin 1 receptor associated kinase 3
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • negative regulation of cytokine-mediated signaling pathway (GO:0001960) IC
  • negative regulation of macrophage cytokine production (GO:0010936) ISS
  • cytokine-mediated signaling pathway (GO:0019221) ISS
  • negative regulation of interleukin-12 production (GO:0032695) IMP
  • negative regulation of interleukin-6 production (GO:0032715) IMP
  • negative regulation of tumor necrosis factor production (GO:0032720) IMP
  • interleukin-1-mediated signaling pathway (GO:0070498) IMP
  • response to interleukin-1 (GO:0070555) IMP
IRAK3 expression is restricted to monocytes and macrophages.
interleukin 1 receptor associated kinase 4
(Interleukin-1 receptor-associated kinase (IRAK) family)
IRAK4 is involved in Myddosome formation which regulates transcription factor activation and drives cytokine production to effect anti-pathogen responses and inflammation [156,396].
  • cytokine-mediated signaling pathway (GO:0019221) IBA
  • interleukin-1-mediated signaling pathway (GO:0070498) IBA
  • cytokine production (GO:0001816) IEA
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 [374] ...
Janus kinase 1
(Janus kinase (JakA) family)
JAK1 is crucial for mediating the intracellular signals for a range of type I and type II cytokines, and for type I and type II interferons (IFN-α/β and IFN-γ respectively) following ligand-receptor interaction.
  • cytokine-mediated signaling pathway (GO:0019221) IBA
  • interleukin-12-mediated signaling pathway (GO:0035722) TAS
  • interleukin-15-mediated signaling pathway (GO:0035723) TAS
  • cellular response to interleukin-3 (GO:0036016) IDA
  • interleukin-2-mediated signaling pathway (GO:0038110) IDA
  • interleukin-7-mediated signaling pathway (GO:0038111) TAS
  • interleukin-9-mediated signaling pathway (GO:0038113) TAS
  • interleukin-21-mediated signaling pathway (GO:0038114) TAS
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
  • type I interferon signaling pathway (GO:0060337) TAS
  • interleukin-6-mediated signaling pathway (GO:0070102) TAS
  • interleukin-27-mediated signaling pathway (GO:0070106) TAS
  • interleukin-35-mediated signaling pathway (GO:0070757) TAS
  • cellular response to interleukin-7 (GO:0098761) IDA
The JAK1 tyrosine kinase is crucial for signaling of certain type I and type II cytokines, via receptors belonging to the IL-2, IL-4 and IL-6 receptor families as well as neurotrophin-1 and leptin receptors (all type I cytokine receptors). JAK1 is also involved in signalling via type I ...
Janus kinase 2
(Janus kinase (JakA) family)
  • cytokine-mediated signaling pathway (GO:0019221) IDA
  • positive regulation of tumor necrosis factor production (GO:0032760) ISS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) IDA
  • response to tumor necrosis factor (GO:0034612) IDA
  • interleukin-12-mediated signaling pathway (GO:0035722) IDA
  • cellular response to interleukin-3 (GO:0036016) IDA
  • interleukin-23-mediated signaling pathway (GO:0038155) TAS
  • positive regulation of tumor necrosis factor biosynthetic process (GO:0042535) ISS
  • positive regulation of interleukin-1 beta biosynthetic process (GO:0050725) ISS
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
  • interleukin-6-mediated signaling pathway (GO:0070102) TAS
  • interleukin-27-mediated signaling pathway (GO:0070106) TAS
  • response to interleukin-12 (GO:0070671) IDA
  • interleukin-35-mediated signaling pathway (GO:0070757) TAS
  • response to granulocyte macrophage colony-stimulating factor (GO:0097012) NAS
  • positive regulation of interleukin-1 beta production (GO:0032731) IEA
JAK2 signal transduction is a critical mediator of the immune response and is implicated in autoimmune conditions and in graft-versus-host disease (GvHD). The pro-inflammatory effects of IL-6, IL-12, and IL-23 on T cells are mediated via JAK2 [47,49,533] ...
Janus kinase 3
(Janus kinase (JakA) family)
  • negative regulation of dendritic cell cytokine production (GO:0002731) ISS
  • cytokine-mediated signaling pathway (GO:0019221) IBA
  • negative regulation of interleukin-10 production (GO:0032693) ISS
  • negative regulation of interleukin-12 production (GO:0032695) ISS
  • interleukin-15-mediated signaling pathway (GO:0035723) TAS
  • interleukin-4-mediated signaling pathway (GO:0035771) IDA
  • interleukin-2-mediated signaling pathway (GO:0038110) TAS
  • interleukin-7-mediated signaling pathway (GO:0038111) TAS
  • interleukin-9-mediated signaling pathway (GO:0038113) TAS
  • interleukin-21-mediated signaling pathway (GO:0038114) TAS
  • response to interleukin-2 (GO:0070669) TAS
  • response to interleukin-4 (GO:0070670) IDA
  • response to interleukin-15 (GO:0070672) TAS
  • response to interleukin-9 (GO:0071104) TAS
  • cellular response to cytokine stimulus (GO:0071345) IMP
Psoriatic skin samples show elevated JAK3 (and JAK1) expression, with signalling predominantly through STAT3 [13] ...
kynurenine 3-monooxygenase
(1.14.13.9 Kynurenine 3-monooxygenase)
  • cellular response to interleukin-1 (GO:0071347) IEA
GSK180-induced inhibition of KMO prevents multiple organ failure in rodent models of acute pancreatitis which is caused by excessive alcohol consumption [381] ...
LYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • regulation of cytokine production (GO:0001817) ISS
  • cytokine secretion (GO:0050663) IEA
  • regulation of cytokine secretion (GO:0050707) 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 [178,183,564] ...
mitogen-activated protein kinase 1
(ERK subfamily)
  • cellular response to tumor necrosis factor (GO:0071356) IEA
  • cellular response to granulocyte macrophage colony-stimulating factor stimulus (GO:0097011) 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 [283,355] ...
mitogen-activated protein kinase 11
(p38 subfamily)
  • cellular response to interleukin-1 (GO:0071347) IDA
  • positive regulation of interleukin-12 secretion (GO:2001184) IMP
p38 MAP kinases are ubiquitous, highly conserved enzymes which regulate the production of proinflammatory mediators (such as TNFα and IL-1) in response to inflammatory cytokines or environmental stress [211-212,313,441,466,593] ...
mitogen-activated protein kinase 13
(p38 subfamily)
  • positive regulation of interleukin-6 production (GO:0032755) IMP
  • cellular response to interleukin-1 (GO:0071347) IDA
p38 MAP kinases are ubiquitous, highly conserved enzymes which regulate the production of proinflammatory mediators (such as TNFα and IL-1) in response to inflammatory cytokines or environmental stress [211-212,313,441,466,593] ...
mitogen-activated protein kinase 14
(p38 subfamily)
  • regulation of cytokine production involved in inflammatory response (GO:1900015) IDA
  • positive regulation of interleukin-12 secretion (GO:2001184) IMP
  • positive regulation of cytokine secretion involved in immune response (GO:0002741) IEA
  • cellular response to tumor necrosis factor (GO:0071356) IEA
p38 MAP kinases are ubiquitous, highly conserved enzymes which regulate the production of proinflammatory mediators (such as TNFα and IL-1) in response to inflammatory cytokines or environmental stress [211-212,313,441,466,593] ...
mitogen-activated protein kinase 8
(JNK subfamily)
  • cellular response to cytokine stimulus (GO:0071345) TAS
  • cellular response to interleukin-1 (GO:0071347) IEP
By regulating AP-1 transcriptional activity in response to cytokine activation, JNK1 contributes to the production of immunomodulators such as RANTES, IL-8 and GM-CSF .
mitogen-activated protein kinase 9
(JNK subfamily)
  • positive regulation of chemokine production (GO:0032722) IMP
  • cellular response to interleukin-1 (GO:0071347) IEP
  • cellular response to tumor necrosis factor (GO:0071356) IEP
Experimental evidence suggests that JNK2 is important in T-cell differentiation [257,491,542,627] ...
mitogen-activated protein kinase kinase kinase 14
(STE-unique family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
NIK is a kinase that operates downstream of several TNF family receptors, including BAFF (TNFRSF13C), TWEAK (TNFRSF12A), CD40 (TNFRSF5), and OX40 (TNFRSF4), and which mediates non-canonical NF-κB signaling. BAFF, TWEAK, CD40, and OX40 are implicated in the pathogenesis of inflammatory diseases including systemic lupus erythematosus (SLE) [63] ...
mitogen-activated protein kinase kinase kinase 5
(STE11 family)
  • cellular response to tumor necrosis factor (GO:0071356) IEA
ASK1 is included in the GToImmuP as it is a molecular target for anti-fibrotic drug development. This kinase acts upstream of p38 MAPK and JNK kinases [247] ...
mitogen-activated protein kinase kinase kinase 7
(TAK1 subfamily)
  • positive regulation of T cell cytokine production (GO:0002726) IMP
  • positive regulation of interleukin-2 production (GO:0032743) IMP
  • interleukin-1-mediated signaling pathway (GO:0070498) TAS
TAK1 (MAP3K7) mediates signaling downstream of multiple cytokine receptors and is functionally important in mitogen, immune, and inflammatory signaling pathways [136,494] ...
mitogen-activated protein kinase kinase kinase kinase 3
(KHS subfamily)
  • response to tumor necrosis factor (GO:0034612) IDA
GLK (KHS2; MAP4K3) is ubiquitously expressed. It is involved in cellular responses to stress and inflammation [148] ...
MMP1
(M10: Matrix metallopeptidase)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
Overexpression of MMP-1 degrades extracellular matrix causing damage to the colon mucosa in patients with ulcerative colitis. The MMP-1 promotes secretion of TNFα causing futher damage. Levels of MMP-1 and TNFα correlate with disease severity [595] ...
MMP12
(M10: Matrix metallopeptidase)
  • negative regulation of type I interferon-mediated signaling pathway (GO:0060339) IEA
  • positive regulation of type I interferon-mediated signaling pathway (GO:0060340) IEA
  • positive regulation of interferon-alpha secretion (GO:1902741) IEA
MMP12 is included in GtoImmuPdb based on its reported involvement in asthma and potential as a asthma therapeutic target.
MMP2
(M10: Matrix metallopeptidase)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • response to cytokine (GO:0034097) IEP
  • cellular response to cytokine stimulus (GO:0071345) IEP
  • cellular response to interleukin-1 (GO:0071347) IEP
MMP2 is included in GtoImmuPdb based on its potential involvement in asthma.
MMP3
(M10: Matrix metallopeptidase)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • response to cytokine (GO:0034097) IEP
  • response to tumor necrosis factor (GO:0034612) IEP
  • response to interleukin-1 (GO:0070555) IEP
  • cellular response to interleukin-1 (GO:0071347) IEP
MMP3 is included in GtoImmuPdb based on its reported involvement in inflammatory diseases.
MMP8
(M10: Matrix metallopeptidase)
  • negative regulation of interleukin-10 production (GO:0032693) ISS
  • positive regulation of interleukin-6 production (GO:0032755) ISS
  • positive regulation of tumor necrosis factor secretion (GO:1904469) ISS
MMP8 is included in GtoImmuPdb based on its potential protective role in asthma.
MMP9
(M10: Matrix metallopeptidase)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • response to tumor necrosis factor (GO:0034612) IEP
  • cellular response to cytokine stimulus (GO:0071345) IEP
  • cellular response to interleukin-1 (GO:0071347) IEP
  • cellular response to tumor necrosis factor (GO:0071356) IEP
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 [305] ...
mPGES1
(Prostaglandin synthases)
  • response to cytokine (GO:0034097) IEA
Inhibition of mPGES-1 is proposed as a potentially safer alternative to COX-2 inhibition for the treatment of pain and inflammation, with a reduced risk of cardiovascular side effects [428] ...
otulin
(C101: OTULIN peptidase)
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) IDA
Otulin is reported as a negative regulator of inflammation and autoimmunity [139] ...
p21 (RAC1) activated kinase 2
(PAKA subfamily)
  • interleukin-12-mediated signaling pathway (GO:0035722) TAS
Pharmacological inhibition of PAK2 has immunosuppressive effects [416] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
PI3Kα is primarily recognised for its oncogenic function. We have included it in GtoImmuPdb based on its numerous GO immune process associations.
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases)
  • cytokine production (GO:0001816) TAS
  • cytokine-mediated signaling pathway (GO:0019221) TAS
PI3Kδ is preferentially expressed in cells of hemopoietic lineage and is involved in neutrophil chemotaxis. It is the only PI3K isoform with expression restricted to leukocytes. Genetic and pharmacological inactivation of PI3Kδ indicates its importantance for the function of T cells, B cell, mast cells and neutrophils. PI3kδ is a promising target for drugs for preventing or treating inflammation, autoimmunity and transplant rejection [219] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases)
  • cytokine production (GO:0001816) TAS
The role of PI3Kγ in immuno-oncology is reviewed in [2] ...
phosphodiesterase 4B
(Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs))
  • positive regulation of interferon-gamma production (GO:0032729) IMP
  • positive regulation of interleukin-2 production (GO:0032743) IMP
PDE4 is a drug target, whose inhibition has anti-inflammatory action. PDE4 inhibitors have already entered clinical use, being employed in the treatment of inflammatory skin conditions such as psoriatic arthritis () and atopic dermatitis (). PDE4B is the predominant phosphodiesterase subtype in monocytes and neutrophils and this is thought to be the sub-type central to inflammatory action of phosphodiesterases [590] ...
phosphodiesterase 4D
(Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs))
  • positive regulation of interferon-gamma production (GO:0032729) IMP
  • positive regulation of interleukin-2 production (GO:0032743) IMP
  • positive regulation of interleukin-5 production (GO:0032754) IMP
The selective PDE4 inhibitor (OPA-15406) has been shown to inhibit PDE4D3 [419] ...
phosphoinositide-3-kinase regulatory subunit 1
(Phosphatidylinositol kinases)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • positive regulation of tumor necrosis factor production (GO:0032760) IEA
p85α is included in GtoImmuPdb as it is the regulatory subunit of several PI3Ks (e.g. PI3Kδ and PI3Kγ) with roles in leukocyte biology and therefore important for immunity [350] ...
PLCγ2
(Phosphoinositide-specific phospholipase C)
  • positive regulation of type I interferon production (GO:0032481) IEA
Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [193,493] ...
proteasome 20S subunit beta 8
(T1: Proteasome)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • type I interferon signaling pathway (GO:0060337) TAS
  • interleukin-1-mediated signaling pathway (GO:0070498) TAS
PSMB8 is a component of the immunoproteasome [170] ...
proteinase 3
(S1: Chymotrypsin)
  • cytokine-mediated signaling pathway (GO:0019221) 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 [294] ...
protein kinase C alpha
(Delta subfamily)
  • response to interleukin-1 (GO:0070555) IMP
PKCα is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C delta
(Delta subfamily)
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • interleukin-10 production (GO:0032613) IEA
  • interleukin-12 production (GO:0032615) IEA
PKCδ is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C iota
(Iota subfamily)
  • response to interleukin-1 (GO:0070555) IEA
PKCι is included in GtoImmuPdb based on the involvement of other PKC isozymes in immune processes.
protein kinase C theta
(Delta subfamily)
  • positive regulation of interleukin-17 production (GO:0032740) ISS
  • positive regulation of interleukin-4 production (GO:0032753) ISS
  • positive regulation of interleukin-2 biosynthetic process (GO:0045086) IEA
PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [25] ...
protein kinase C zeta
(Iota subfamily)
  • positive regulation of interleukin-4 production (GO:0032753) ISS
  • positive regulation of T-helper 2 cell cytokine production (GO:2000553) ISS
  • positive regulation of interleukin-5 secretion (GO:2000664) ISS
  • positive regulation of interleukin-13 secretion (GO:2000667) ISS
  • positive regulation of interleukin-10 secretion (GO:2001181) ISS
PKCζ is included in GtoImmuPdb based on its GO process associations.
protein kinase, DNA-activated, catalytic subunit
(Other PIKK family kinases)
  • positive regulation of type I interferon production (GO:0032481) TAS
Protein kinase, DNA-activated, catalytic polypeptide (DNA-PKcs) principally acts to repair DNA in a process called non-homologous end joining (NHEJ). NHEJ is required for V(D)J recombination (somatic recombination) in developing lymphocytes during the early stages of T and B cell maturation. DNA-PKc ...
protein tyrosine kinase 2 beta
(Fak family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) IMP
  • interleukin-2-mediated signaling pathway (GO:0038110) TAS
  • chemokine-mediated signaling pathway (GO:0070098) ISS
FAK and Pyk2 are phosphorylated downstream of the T cell antigen receptor (TCR) to bring about receptor-specific (e.g. chemokine and integrin receptors) T cell development and activation [102] ...
protein tyrosine phosphatase non-receptor type 22
(Protein tyrosine phosphatases non-receptor type (PTPN))
  • positive regulation of type I interferon production (GO:0032481) IMP
  • negative regulation of tumor necrosis factor production (GO:0032720) IMP
  • positive regulation of interferon-beta secretion (GO:0035549) IMP
  • positive regulation of granzyme B production (GO:0071663) IMP
  • negative regulation of interleukin-6 secretion (GO:1900165) IMP
  • positive regulation of interferon-gamma secretion (GO:1902715) IMP
  • positive regulation of interferon-alpha secretion (GO:1902741) IMP
  • negative regulation of interleukin-8 secretion (GO:2000483) IMP
PTPN22 is a lymphoid-specific, inducible protein tyrosine phosphatase [118] ...
receptor interacting serine/threonine kinase 1
(Receptor interacting protein kinase (RIPK) family)
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) TAS
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • positive regulation of tumor necrosis factor production (GO:0032760) IDA
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • response to tumor necrosis factor (GO:0034612) IMP
  • cellular response to tumor necrosis factor (GO:0071356) IDA
  • positive regulation of tumor necrosis factor-mediated signaling pathway (GO:1903265) IEA
RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [402,476,518,584] ...
receptor interacting serine/threonine kinase 2
(Receptor interacting protein kinase (RIPK) family)
  • positive regulation of interferon-alpha production (GO:0032727) NAS
  • positive regulation of interferon-beta production (GO:0032728) NAS
  • positive regulation of interleukin-12 production (GO:0032735) NAS
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IDA
  • interleukin-1-mediated signaling pathway (GO:0070498) TAS
  • response to interleukin-1 (GO:0070555) IMP
  • positive regulation of cytokine-mediated signaling pathway (GO:0001961) IEA
  • positive regulation of chemokine production (GO:0032722) IEA
  • positive regulation of interferon-gamma production (GO:0032729) IEA
  • positive regulation of interleukin-2 production (GO:0032743) IEA
  • positive regulation of interleukin-6 production (GO:0032755) IEA
  • positive regulation of tumor necrosis factor production (GO:0032760) IEA
  • response to interleukin-12 (GO:0070671) IEA
  • response to interleukin-18 (GO:0070673) IEA
RIPK2 is involved in innate immune responses, mediating pro-inflammatory signaling from the bacterial peptidoglycan-sensing NOD1/NOD2 subfamily of innate immune pattern recognition receptors (PRRs) and signalling downstream from the Toll-like receptor (TLR) family of PRRs. Further evidence suggesting an inflammatory role is the targeting of RIPK2 (along with RIPK1/3) by the IAP family E3 ubiquitin ligases (enzymes playing a critical role in innate immunity) [414] ...
receptor interacting serine/threonine kinase 3
(Receptor interacting protein kinase (RIPK) family)
  • regulation of interferon-gamma production (GO:0032649) ISS
RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [402,476,518,584] ...
Rho associated coiled-coil containing protein kinase 2
(Rho kinase)
  • positive regulation of connective tissue growth factor production (GO:0032723) ISS
  • positive regulation of fibroblast growth factor production (GO:0090271) ISS
ROCK2 plays a role in controlling T-cell plasticity and macrophage polarization, skewing polarization towards M1-type macrophages [645] ...
sirtuin 1
(3.5.1.- Histone deacetylases (HDACs))
  • macrophage cytokine production (GO:0010934) ISS
  • negative regulation of tumor necrosis factor production (GO:0032720) ISO
  • leptin-mediated signaling pathway (GO:0033210) ISS
  • cellular response to tumor necrosis factor (GO:0071356) IDA
  • cellular response to leukemia inhibitory factor (GO:1990830) IEA
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 [110] ...
sphingosine kinase 2
(Sphingosine kinase)
  • cytokine secretion involved in immune response (GO:0002374) ISS
  • interleukin-6 secretion (GO:0072604) ISS
  • interleukin-13 secretion (GO:0072611) ISS
  • tumor necrosis factor secretion (GO:1990774) ISS
SK2 is involved in regulating interleukin (IL)-12/interferon gamma (IFN-γ) and histone deacetylase-1/2 (HDAC-1/2) signalling, and is considered to be an anti-inflammatory enzyme with potential druggability for the treatment of autoimmune and inflammatory diseases [464] ...
sPLA2-1B
(Phospholipase A2)
  • interleukin-8 production (GO:0032637) ISS
sPLA2 enzymes catalyze the first step of the arachidonic acid pathway, so are inextricably involved in the production of arachadonic acid for inflammatory mediator synthesis. Excess sPLA2 activity is suggested to contribute to several inflammatory diseases. The sPLA2-1B isozyme has been reported to induce leukotriene B4 (LTB4) production in human neutrophils, using a mechanism independent of arachadonic acid generation [312] ...
spleen associated tyrosine kinase
(Syk family)
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) IMP
  • positive regulation of interleukin-4 production (GO:0032753) ISS
  • interleukin-2-mediated signaling pathway (GO:0038110) TAS
  • interleukin-3-mediated signaling pathway (GO:0038156) ISS
  • positive regulation of tumor necrosis factor biosynthetic process (GO:0042535) IMP
  • positive regulation of interleukin-10 biosynthetic process (GO:0045082) IMP
  • positive regulation of interleukin-12 biosynthetic process (GO:0045084) IMP
  • positive regulation of interleukin-6 biosynthetic process (GO:0045410) IMP
  • positive regulation of interleukin-8 biosynthetic process (GO:0045416) IMP
  • positive regulation of monocyte chemotactic protein-1 production (GO:0071639) IMP
  • positive regulation of type I interferon production (GO:0032481) IEA
  • positive regulation of interleukin-3 biosynthetic process (GO:0045401) IEA
  • positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process (GO:0045425) IEA
  • positive regulation of cytokine secretion (GO:0050715) IEA
SYK plays a key role in coupling activated immunoreceptors to downstream cellular responses such as proliferation, differentiation, and phagocytosis. Mast cell, macrophage and B-cell activation (and release of inflammatory modulators) is disrupted by inhibition of SYK-mediated immunoreceptor signalling. Selective SYK inhibitors are being sought for a number of inflammatory conditions including rheumatoid arthritis, B-cell lymphoma and asthma/rhinitis [191,474] ...
SRC proto-oncogene, non-receptor tyrosine kinase
(Src family)
  • response to interleukin-1 (GO:0070555) IMP
  • positive regulation of cytokine secretion (GO:0050715) IEA
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 [347] ...
TANK binding kinase 1
(IKK family)
  • regulation of type I interferon production (GO:0032479) TAS
  • negative regulation of type I interferon production (GO:0032480) TAS
  • positive regulation of type I interferon production (GO:0032481) TAS
  • type I interferon production (GO:0032606) TAS
  • positive regulation of interferon-alpha production (GO:0032727) IDA
  • positive regulation of interferon-beta production (GO:0032728) IDA
  • cellular response to cytokine stimulus (GO:0071345) TAS
  • positive regulation of interferon-beta biosynthetic process (GO:0045359) IEA
  • positive regulation of type I interferon-mediated signaling pathway (GO:0060340) IEA
TBK1 belongs to the IKK-kinase family of enzymes. It is a ubiquitously expressed serine/threonine protein kinase, and constitutes a key regulatory node for several signaling pathways involved in the innate immune response that lead to induction of type I interferons. Several classes of innate sensors including the TLRs and retinoic acid-inducible gene 1 (RIG-I)-like helicases engage TBK1-IRF3 signaling pathways to regulate transcription of type I IFNs. In neuroinflammation TBK1 is involved in TLR-dependent [273] ...
tec protein tyrosine kinase
(Tec family)
  • cytokine-mediated signaling pathway (GO:0019221) 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 [43] ...
tripartite motif containing 21
(2.3.2.27 RING-type E3 ubiquitin transferase)
  • regulation of type I interferon production (GO:0032479) TAS
  • response to interferon-gamma (GO:0034341) IDA
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
Tripartite motif-containing (TRIM) superfamily proteins are critical in a variety of biological processes in innate immunity and are important for eradication of invading pathogens [427,467,580] ...
tripartite motif containing 38
(2.3.2.27 RING-type E3 ubiquitin transferase)
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • regulation of interferon-beta production (GO:0032648) IEA
TRIM38 catalyses the ubiquitination of Lys48 of the Toll-like receptor (TLR) adaptor protein TICAM1 (commonly referred to as TRIF) which mediates its proteosomal degradation. This action has been shown to inhibit TLR3-driven type I interferon signaling of the innate immune response [621] ...
TXK tyrosine kinase
(Tec family)
  • cytokine production (GO:0001816) ISS
  • interferon-gamma production (GO:0032609) IGI
  • interleukin-4 production (GO:0032633) IGI
  • positive regulation of interferon-gamma production (GO:0032729) IDA
  • positive regulation of interferon-gamma-mediated signaling pathway (GO:0060335) IDA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [43] ...
tyrosine kinase 2
(Janus kinase (JakA) family)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • interleukin-12-mediated signaling pathway (GO:0035722) TAS
  • interleukin-23-mediated signaling pathway (GO:0038155) TAS
  • type I interferon signaling pathway (GO:0060337) TAS
  • interleukin-27-mediated signaling pathway (GO:0070106) TAS
TYK2 was the first member of the Janus kinase family to be identified. It associates with the cytoplasmic domain of type I and type II cytokine receptors, where it phosphorylates receptor subunits and facilitates signalling downstream of the receptors for the p40-containing cytokines IL-12 and IL-23 via activation of STAT-dependent transcription factors. It also mediates Type I IFN-driven responses [537] ...
Catalytic Receptors
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
4-1BB
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
4-1BB is a costimulatory receptor that is highly expressed on both T cells and NK cells in the tumour environment. Since activation of 4-1BB produces an immunostimulatory effect that supports the immune cells involved in tumour control it is a target for immuno-oncology drug development [357] ...
AXL receptor tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • negative regulation of cytokine production (GO:0001818) IGI
  • positive regulation of cytokine-mediated signaling pathway (GO:0001961) IDA
  • negative regulation of interferon-gamma production (GO:0032689) IDA
  • cellular response to interferon-alpha (GO:0035457) IDA
  • negative regulation of tumor necrosis factor production (GO:0032720) 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 [210] ...
BAFF receptor
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • positive regulation of interferon-gamma biosynthetic process (GO:0045078) IEA
A type III membrane bound receptor for B-cell activating factor (BAFF). BAFF enhances B-cell survival and hence regulates the peripheral B-cell population. It is suggested that overproduction of BAFF may enhance the survival of autoreactive B cells, an effect which may contribute in the pathogenesis ...
B cell maturation antigen
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
B-cell maturation antigen (BCMA) is a cell surface receptor for B-cell activating factor (BAFF). It interacts with various TRAF family adaptor proteins to modulate cell survival and proliferation, via NF-κB and MAPK8/JNK signal transduction pathways. BCMA is highly plasma cell-selective for malignant plasma cells from multiple myeloma (MM) patients, and is being investigated as a target for T-cell redirecting therapies to tackle relapsed/refractory MM [225,315] ...
CD27
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • positive regulation of interferon-gamma biosynthetic process (GO:0045078) NAS
CD27 (TNFRSF7) is a co-stimulatory immune checkpoint molecule that is expressed on various immune cells, including T cells and NK (natural killer) cells. The endogenous ligand for CD27 is CD70. CD27 interacts with various TRAF adaptor proteins and apoptosis regulatory protein SIVA (SIVA1). It has been recognized as playing an important role in priming, enhancing and sustaining a productive anti-cancer (CD8 T cell) adaptive immune response. CD27 is an immuno-oncology target [71,572] ...
CD30
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • positive regulation of tumor necrosis factor biosynthetic process (GO:0042535) IDA
  • positive regulation of TRAIL biosynthetic process (GO:0045556) IDA
Expressed by activated T and B cells. Interacts with TRAF2 and TRAF5 to elicit downstream signalling events (NF-κB activation). CD30 may protect against autoimmunity by limiting the proliferative potential of autoreactive CD8 effector T cells. CD30 is the target of the approved anti-lymphoma monoclonal antibody drug brentuximab vedotin ...
CD40
(Immune checkpoint catalytic receptors, Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • positive regulation of interleukin-12 production (GO:0032735) IEA
  • response to interferon-gamma (GO:0034341) IEA
  • cellular response to erythropoietin (GO:0036018) IEA
  • cellular response to interleukin-1 (GO:0071347) IEA
  • cellular response to tumor necrosis factor (GO:0071356) IEA
CD40 is a stimulatory receptor and a member of the tumor necrosis factor receptor superfamily (TNFRSF). It is expressed on a variety of immune cells, including macrophages, B cells, and dendritic cells (DCs). CD40 plays a key role in the activation of the immune system. Endogenous ligand is CD154 (C ...
CIITA
(NOD-like receptor family)
  • response to interferon-gamma (GO:0034341) IDA
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • cellular response to interferon-gamma (GO:0071346) IEA
CIITA is a transcriptional coactivator for the transcription factor RFX5 [502] ...
colony stimulating factor 1 receptor
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • macrophage colony-stimulating factor receptor activity (GO:0005011) IMP
  • cytokine-mediated signaling pathway (GO:0019221) IMP
  • cellular response to macrophage colony-stimulating factor stimulus (GO:0036006) IMP
  • macrophage colony-stimulating factor signaling pathway (GO:0038145) ISS
  • cellular response to cytokine stimulus (GO:0071345) ISS
  • positive regulation of chemokine secretion (GO:0090197) IMP
Activation of the CSF1R induces myeloid proliferation, and in the tumour microenvironment this promotes M1 to M2 polarization and accumulation of tumour-associated macrophages (TAMs). The CSF1R is therefore being investigated as an immuno-oncology drug target [2] ...
Cytokine receptor common β subunit
(IL-3 receptor family)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • cytokine receptor activity (GO:0004896) IEA
  • cellular response to interleukin-3 (GO:0036016) IEA
  • interleukin-5-mediated signaling pathway (GO:0038043) IEA
  • interleukin-3-mediated signaling pathway (GO:0038156) IEA
This a signal transducing protein subunit shared by the functional receptor heterodimers for the cytokines IL-3, IL-5 and GM-CSF, with each receptor having a unique ligand binding alpha subunit.
Cytokine receptor-like factor 2
(IL-2 receptor family)
  • cytokine receptor activity (GO:0004896) IDA
  • cytokine-mediated signaling pathway (GO:0019221) IDA
  • T-helper 2 cell cytokine production (GO:0035745) IDA
  • interleukin-7-mediated signaling pathway (GO:0038111) TAS
  • positive regulation of interleukin-5 secretion (GO:2000664) IMP
Cytokine receptor-like factor 2 is the signal transducing subunit of the functional heterodimeric receptor for thymic stromal lymphopoietin (TSLP). Ligand binding is attributed to the interleukin-7 receptor subunit α.
death receptor 3
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) TAS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
In the absence of any other exogenous signals, activation of DR3 causes proliferation of FoxP3+ regulatory T cells [504] ...
death receptor 6
(Tumour necrosis factor (TNF) receptor family)
  • cellular response to tumor necrosis factor (GO:0071356) IDA
  • negative regulation of interleukin-5 secretion (GO:2000663) ISS
  • negative regulation of interleukin-13 secretion (GO:2000666) ISS
  • negative regulation of interleukin-10 secretion (GO:2001180) 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.
decoy receptor 3
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
The protein product of the TNFRSF6B gene, known as decoy receptor 3 (DcR3), is a soluble endogenous receptor for three TNF family peptide ligands, LIGHT, TL1A and Fas ligand. DcR3 competes for ligand binding with death receptors. DcR3 suppresses LIGHT and FAS ligand induced apoptosis and T cell activation, and increases monocyte adhesion to endothelial cells via NF-κB activation [625] ...
DExD/H-box helicase 58
(RIG-I-like receptor family)
  • positive regulation of myeloid dendritic cell cytokine production (GO:0002735) ISS
  • negative regulation of type I interferon production (GO:0032480) TAS
  • positive regulation of granulocyte macrophage colony-stimulating factor production (GO:0032725) IDA
  • positive regulation of interferon-alpha production (GO:0032727) IDA
  • positive regulation of interferon-beta production (GO:0032728) IDA
  • positive regulation of interleukin-6 production (GO:0032755) IDA
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • regulation of type III interferon production (GO:0034344) TAS
  • positive regulation of interferon-beta secretion (GO:0035549) IMP
  • cytoplasmic pattern recognition receptor signaling pathway in response to virus (GO:0039528) TAS
  • RIG-I signaling pathway (GO:0039529) IMP
  • positive regulation of response to cytokine stimulus (GO:0060760) IMP
  • positive regulation of interferon-alpha secretion (GO:1902741) IMP
  • positive regulation of tumor necrosis factor secretion (GO:1904469) IMP
  • positive regulation of interleukin-6 secretion (GO:2000778) 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 [367] ...
DExH-box helicase 58
(RIG-I-like receptor family)
  • negative regulation of type I interferon production (GO:0032480) IDA
  • positive regulation of type I interferon production (GO:0032481) ISS
  • 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.
Eythropoietin receptor
(Prolactin receptor family)
  • erythropoietin receptor activity (GO:0004900) IDA
A non-hematopoietic EPOR-containing receptor, called the innate repair receptor (IRR) or tissue-protective receptor, down-modulates the damaging effects of the immune response to tissue injury [64] ...
Fas
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) ISO
  • response to cytokine (GO:0034097) IEP
  • cellular response to cytokine stimulus (GO:0071345) IEP
  • cellular response to interleukin-1 (GO:0071347) IEP
  • cellular response to tumor necrosis factor (GO:0071356) IEP
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 [549] ...
fibroblast growth factor receptor 1
(Type V RTKs: FGF (fibroblast growth factor) receptor family)
  • negative regulation of fibroblast growth factor production (GO:0090272) IEA
A FGFR1 isoform (FGFR1(IIIc)) in complex with the Klotho protein (KL; Q9UEF7) forms a high affinity receptor for .
In the choroid plexus (the interface between the brain and immune system) Klotho enhances FGF23 signalling and activation of the NLRP3 inflammasome in resident macrophages, in a system that regulates the level of immune system activation at the blood-brain barrier. Experimental evidence from mice suggests that age-related decline of Klotho in the choroid plexus may be part of the mechanism responisble for "inflammaging", the progressive systemic increase in brain inflammation that is believed to contribute to neurodegeneration in old age [656] ...
fms related tyrosine kinase 3
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • cytokine receptor activity (GO:0004896) ISS
  • cytokine-mediated signaling pathway (GO:0019221) ISS
  • negative regulation of interleukin-6 production (GO:0032715) IMP
  • negative regulation of tumor necrosis factor production (GO:0032720) IMP
  • positive regulation of interferon-alpha production (GO:0032727) IMP
  • positive regulation of interferon-gamma production (GO:0032729) IMP
  • positive regulation of interleukin-12 production (GO:0032735) IMP
  • cellular response to cytokine stimulus (GO:0071345) ISS
  • positive regulation of interferon-gamma secretion (GO:1902715) IMP
  • positive regulation of interferon-alpha secretion (GO:1902741) IMP
  • positive regulation of interleukin-12 secretion (GO:2001184) IMP
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 [438] ...
glucocorticoid-induced TNF receptor
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) TAS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
GITR appears to act as a co-stimulatory immune checkpoint molecule. T cell activation induces GITR expression. GITR inhibits the suppressive activity of Treg cells and promotes survival of Teff cells.
GM-CSF receptor, α subunit
(IL-3 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • granulocyte colony-stimulating factor receptor activity (GO:0004902) IDA
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • cellular response to granulocyte macrophage colony-stimulating factor stimulus (GO:0097011) IDA
This is the ligand binding subunit of the functional GM-CSF receptor complex.
Granulocyte colony-stimulating factor receptor
(Prolactin receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • interleukin-3 receptor activity (GO:0004912) IBA
  • cytokine-mediated signaling pathway (GO:0019221) TAS
This nuclear receptor mediates the effects of the cytokine, colony stimulating factor 3 (CSF3). CSF3 regulates the production, differentiation, and function of granulocytes.
herpes virus entry mediator
(Immune checkpoint catalytic receptors, Tumour necrosis factor (TNF) receptor family)
  • positive regulation of cytokine secretion involved in immune response (GO:0002741) IBA
  • tumor necrosis factor-activated receptor activity (GO:0005031) TAS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
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)
  • cellular response to cytokine stimulus (GO:0071345) IEA
Integrin subunit alpha 4 is the alpha subunit of the α4β1 lymphocyte homing receptor. The cytoplasmic domain of α4 binds tightly to paxillin, a signaling adaptor protein, and this interaction promotes increased cell migration and inhibits cell spreading [213] ...
integrin, beta 2 subunit (complement component 3 receptor 3 and 4 subunit)
(Integrins)
  • cytokine-mediated signaling pathway (GO:0019221) 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). Beta2-integrins are essential for leukocyte extravasation to sites of infection (i.e. leukocyte trafficking), and other immunological processes including neutrophil phagocytosis and ROS production, and T cell activation. Their absence causes a leukocyte adhesion deficiency, which manifests clinically as recurrent severe infections, defective wound healing and neutrophilia [287] ...
interferon α/β receptor 1
(Interferon receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • interferon receptor activity (GO:0004904) IMP
  • type I interferon receptor activity (GO:0004905) IDA
  • cytokine-mediated signaling pathway (GO:0019221) IBA
  • positive regulation of interferon-beta production (GO:0032728) IMP
  • positive regulation of interferon-gamma production (GO:0032729) IGI
  • cellular response to interferon-alpha (GO:0035457) ISS
  • type I interferon biosynthetic process (GO:0045351) IMP
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IMP
  • type I interferon signaling pathway (GO:0060337) IDA
IFNAR1 is a subunit of the functional receptor for type I interferons (NOT interferon γ). Type I interferons (IFN) exhibit an established anti-viral action. However, type I IFN signalling also appears to play a role in impaired resistance to a range of other pathogens (e.g. bacterial infection) [88,403] ...
Interferon α/β receptor 2
(Interferon receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • type I interferon receptor activity (GO:0004905) IDA
  • cytokine-mediated signaling pathway (GO:0019221) IBA
  • response to interferon-alpha (GO:0035455) IDA
  • response to interferon-beta (GO:0035456) IMP
  • type I interferon signaling pathway (GO:0060337) IDA
  • regulation of type I interferon-mediated signaling pathway (GO:0060338) TAS
A subunit of the functional receptor for various interferons (NOT interferon γ).
Interferon γ receptor 1
(Interferon receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • interferon-gamma receptor activity (GO:0004906) TAS
  • cytokine-mediated signaling pathway (GO:0019221) IBA
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
  • positive regulation of tumor necrosis factor secretion (GO:1904469) ISS
A subunit of the functional receptor for interferon γ.
Interferon γ receptor 2
(Interferon receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • interferon-gamma receptor activity (GO:0004906) TAS
  • cytokine-mediated signaling pathway (GO:0019221) IBA
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
A subunit of the functional receptor for interferon γ.
interferon induced with helicase C domain 1
(RIG-I-like receptor family)
  • negative regulation of type I interferon production (GO:0032480) TAS
  • positive regulation of interferon-alpha production (GO:0032727) IMP
  • positive regulation of interferon-beta production (GO:0032728) IDA
  • regulation of type III interferon production (GO:0034344) TAS
  • positive regulation of interferon-beta secretion (GO:0035549) IMP
  • cytoplasmic pattern recognition receptor signaling pathway in response to virus (GO:0039528) TAS
  • MDA-5 signaling pathway (GO:0039530) IDA
  • positive regulation of response to cytokine stimulus (GO:0060760) IMP
  • positive regulation of interferon-alpha secretion (GO:1902741) IMP
  • positive regulation of tumor necrosis factor secretion (GO:1904469) IMP
  • positive regulation of interleukin-6 secretion (GO:2000778) IMP
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 [5,234,378] ...
Interferon-λ receptor subunit 1
(IL-10 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • cytokine-mediated signaling pathway (GO:0019221) IBA
  • response to type III interferon (GO:0034342) ISS
Interferon-λ receptor subunit 1 is the ligand binding component of the functional heterodimeric receptor for interferons λ1, λ2 and λ3
Interleukin 10 receptor, α subunit
(IL-10 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • interleukin-10 receptor activity (GO:0004920) IBA
  • cytokine-mediated signaling pathway (GO:0019221) IBA
Interleukin 10 receptor, α subunit is a component of the functional IL-10 receptor heterodimer.
Interleukin 10 receptor, β subunit
(IL-10 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • interleukin-10 receptor activity (GO:0004920) IBA
  • cytokine-mediated signaling pathway (GO:0019221) IBA
Interleukin 10 receptor, β subunit is a component of the functional receptor heterodimers for interleukins 10 and 22 and for interferons λ1, λ2 and λ3.
Interleukin-11 receptor, α subunit
(IL-6 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • interleukin-11 receptor activity (GO:0004921) IBA
  • cytokine-mediated signaling pathway (GO:0019221) TAS
This is the ligand-binding component of the functional receptor for interleukin 11.
Interleukin-12 receptor, β1 subunit
(IL-12 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • positive regulation of interferon-gamma production (GO:0032729) IDA
  • interleukin-12-mediated signaling pathway (GO:0035722) TAS
  • interleukin-23-mediated signaling pathway (GO:0038155) TAS
  • cellular response to interferon-gamma (GO:0071346) IDA
This protein is a subunit of both the IL-12 and IL-23 cytokine receptors.
Interleukin-12 receptor, β2 subunit
(IL-12 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • positive regulation of interferon-gamma production (GO:0032729) IDA
  • response to cytokine (GO:0034097) IMP
  • interleukin-12-mediated signaling pathway (GO:0035722) TAS
  • interleukin-35-mediated signaling pathway (GO:0070757) TAS
  • interferon-gamma production (GO:0032609) IEA
This protein is a subunit of the functional receptor heterodimer for the IL-12 cytokine.
Interleukin 13 receptor, α2
(IL-2 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • cytokine-mediated signaling pathway (GO:0019221) TAS
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 [614] ...
Interleukin-13 receptor subunit α1
(IL-2 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • interleukin-13 receptor activity (GO:0016515) IBA
  • cytokine-mediated signaling pathway (GO:0019221) TAS
Interleukin-13 receptor subunit α1 is a component of the functional heterodimeric receptor for interleukin 13 and the (type II) IL-4 receptor.
Interleukin-15 receptor subunit α
(IL-2 receptor family)
  • cytokine receptor activity (GO:0004896) TAS
  • interleukin-15-mediated signaling pathway (GO:0035723) IMP
  • interleukin-15 receptor activity (GO:0042010) IDA
This is the ligand binding subunit of the functional IL-15 receptor complex.
Interleukin 17 receptor A
(IL-17 receptor family)
  • interleukin-17 receptor activity (GO:0030368) IBA
  • positive regulation of interleukin-23 production (GO:0032747) IDA
  • cellular response to cytokine stimulus (GO:0071345) ISO
  • interleukin-17-mediated signaling pathway (GO:0097400) TAS
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) IEA
  • positive regulation of interleukin-5 secretion (GO:2000664) IEA
  • positive regulation of interleukin-13 secretion (GO:2000667) IEA
This protein is a common subunit shared by the heterodimeric receptors for interleukins 17 (A, B , C and F) and 25.
Interleukin 17 receptor B
(IL-17 receptor family)
  • cytokine receptor activity (GO:0004896) NAS
  • interleukin-17 receptor activity (GO:0030368) IBA
  • interleukin-17-mediated signaling pathway (GO:0097400) TAS
  • positive regulation of interleukin-5 secretion (GO:2000664) IEA
  • positive regulation of interleukin-13 secretion (GO:2000667) IEA
IL17RB is a subunit of the heterodimeric interleukin-25 receptor.
interleukin 17 receptor C
(IL-17 receptor family)
  • interleukin-17 receptor activity (GO:0030368) IDA
  • interleukin-17-mediated signaling pathway (GO:0097400) TAS
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) IEA
  • positive regulation of interleukin-6 secretion (GO:2000778) IEA
This is a subunit of the heterodimeric interleukin-17 receptor.
Interleukin-17 receptor D
(IL-17 receptor family)
  • interleukin-17 receptor activity (GO:0030368) IBA
IL17RD acts as an inhibitor of proinflammatory cytokine signaling (by limiting NF-κB translocation to the nucleus) [179] ...
Interleukin 17 receptor E
(IL-17 receptor family)
  • interleukin-17 receptor activity (GO:0030368) IBA
  • interleukin-17-mediated signaling pathway (GO:0097400) TAS
This is a component of the heterodimeric interleukin-17C receptor.
Interleukin-18 receptor 1
(Immunoglobulin-like family of IL-1 receptors)
  • positive regulation of interferon-gamma production (GO:0032729) IDA
  • interleukin-18-mediated signaling pathway (GO:0035655) IDA
  • cellular response to cytokine stimulus (GO:0071345) TAS
  • positive regulation of T-helper 1 cell cytokine production (GO:2000556) IDA
  • interleukin-1 receptor activity (GO:0004908) IEA
  • interleukin-18 receptor activity (GO:0042008) 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)
  • interleukin-33 receptor activity (GO:0002114) IBA
  • cytokine receptor activity (GO:0004896) TAS
  • interleukin-33-mediated signaling pathway (GO:0038172) TAS
  • interleukin-1 receptor activity (GO:0004908) IEA
  • negative regulation of interferon-gamma production (GO:0032689) IEA
  • positive regulation of interleukin-5 production (GO:0032754) IEA
  • positive regulation of chemokine secretion (GO:0090197) 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 [182] ...
Interleukin-1 receptor-like 2
(Immunoglobulin-like family of IL-1 receptors)
  • cytokine receptor activity (GO:0004896) ISS
  • interleukin-1 receptor activity (GO:0004908) TAS
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • cellular response to cytokine stimulus (GO:0071345) TAS
  • interleukin-1, type I, activating receptor activity (GO:0004909) IEA
  • positive regulation of interleukin-6 production (GO:0032755) IEA
Interleukin-1 receptor-like 2 is one of the subunits of the functional receptor for IL-36.

An antibody that mimics IL-36RA's antagonist activity at the IL-36 receptor (MAB92) has been described [181] ...
Interleukin 1 receptor, type I
(Immunoglobulin-like family of IL-1 receptors)
  • interleukin-1 receptor activity (GO:0004908) IDA
  • interleukin-1, type I, activating receptor activity (GO:0004909) TAS
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • positive regulation of interferon-gamma production (GO:0032729) IDA
  • interleukin-1-mediated signaling pathway (GO:0070498) IDA
  • response to interleukin-1 (GO:0070555) IDA
  • positive regulation of T-helper 1 cell cytokine production (GO:2000556) IDA
  • positive regulation of interleukin-1-mediated signaling pathway (GO:2000661) IEA
This is one of the subunits of the functional IL-1 receptor type I heterodimer.
Interleukin 1 receptor, type II
(Immunoglobulin-like family of IL-1 receptors)
  • interleukin-1 receptor activity (GO:0004908) TAS
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • interleukin-1-mediated signaling pathway (GO:0070498) TAS
  • interleukin-1, type II, blocking receptor activity (GO:0004910) IEA
  • negative regulation of interleukin-1 alpha secretion (GO:0050712) IEA
  • negative regulation of cytokine production involved in inflammatory response (GO:1900016) IEA
  • negative regulation of interleukin-1-mediated signaling pathway (GO:2000660) IEA
IL-1R2 acts as a decoy receptor for IL-1β, thus reducing IL-1β binding/activation of IL-1R1. IL-1R2 thereby acts to down-regulate IL-1 responses [194,400] ...
Interleukin 20 receptor, α subunit
(IL-10 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • cytokine-mediated signaling pathway (GO:0019221) IBA
Interleukin 20 receptor, α subunit is a component of the functional receptor heterodimer for interleukin 20.
Interleukin 20 receptor, β subunit
(IL-10 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • cytokine-mediated signaling pathway (GO:0019221) IBA
  • negative regulation of interferon-gamma production (GO:0032689) IEA
  • negative regulation of interleukin-2 production (GO:0032703) IEA
  • positive regulation of interleukin-10 production (GO:0032733) IEA
  • positive regulation of interleukin-4 production (GO:0032753) 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)
  • interleukin-21 receptor activity (GO:0001532) NAS
  • cytokine receptor activity (GO:0004896) IDA
  • interleukin-21-mediated signaling pathway (GO:0038114) TAS
This is the ligand binding subunit of the functional heterodimeric receptor for interleukin 21.
Interleukin 22 receptor, α1 subunit
(IL-10 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • interferon receptor activity (GO:0004904) TAS
  • cytokine-mediated signaling pathway (GO:0019221) IBA
IL22RA1 is a subunit in the heterodimeric receptors for interleukins 20 and 24 (which bind to the interleukin-22α1/20β heteromer) and IL-22 (which binds to the interleukin-22α1/10β heteromer).
Interleukin-22 receptor α2
(IL-10 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • cytokine-mediated signaling pathway (GO:0019221) IBA
  • interleukin-22 receptor activity (GO:0042018) IDA
IL22RA2 (a.k.a. IL-22 binding protein) appears to act as a high affinity, soluble monomeric decoy receptor for IL-22 capable of neutralizeing the potent antimicrobial activity of IL-22 [140,168] ...
Interleukin 23 receptor
(IL-12 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • negative regulation of interleukin-10 production (GO:0032693) IMP
  • positive regulation of granulocyte macrophage colony-stimulating factor production (GO:0032725) IC
  • positive regulation of interferon-gamma production (GO:0032729) IDA
  • positive regulation of interleukin-12 production (GO:0032735) IDA
  • positive regulation of interleukin-17 production (GO:0032740) IC
  • response to interferon-gamma (GO:0034341) IDA
  • interleukin-23-mediated signaling pathway (GO:0038155) TAS
  • interleukin-23 receptor activity (GO:0042020) ISO
This is one of the subunits of the functional IL-23 receptor heterodimer.
Interleukin 27 receptor, alpha
(IL-6 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • interleukin-27 receptor activity (GO:0045509) IBA
  • interleukin-27-mediated signaling pathway (GO:0070106) TAS
  • interleukin-35-mediated signaling pathway (GO:0070757) TAS
  • positive regulation of interferon-gamma production (GO:0032729) IEA
  • negative regulation of interleukin-6 secretion (GO:1900165) IEA
  • negative regulation of tumor necrosis factor secretion (GO:1904468) IEA
  • negative regulation of interleukin-17 secretion (GO:1905077) 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)
  • interleukin-2 receptor activity (GO:0004911) IBA
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • interleukin-2-mediated signaling pathway (GO:0038110) TAS
IL2RA is a ligand binding component of the IL-2R complex. This subunit is the molecular target of the approved biologics daclizumab (including daclizumab beta) and basiliximab. Another anti-CD25 mAb, inolimomab, has received orphan drug designation from the EMA, for the treatment of graft-versus-host disease. Phase 3 findings for this drug and indication are reported in [524] ...
Interleukin-2 receptor subunit β
(IL-2 receptor family)
  • interleukin-2 receptor activity (GO:0004911) IDA
  • cytokine-mediated signaling pathway (GO:0019221) IDA
  • interleukin-15-mediated signaling pathway (GO:0035723) IMP
  • interleukin-2-mediated signaling pathway (GO:0038110) TAS
  • interleukin-15 receptor activity (GO:0042010) IDA
IL2RB is a ligand binding component of the IL-2R and is required to elevate ligand affinity. It also a component of the IL-15R.
Interleukin-2 receptor subunit γ
(IL-2 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • interleukin-15-mediated signaling pathway (GO:0035723) IMP
  • interleukin-2-mediated signaling pathway (GO:0038110) TAS
  • interleukin-7-mediated signaling pathway (GO:0038111) TAS
  • interleukin-9-mediated signaling pathway (GO:0038113) TAS
  • interleukin-21-mediated signaling pathway (GO:0038114) TAS
  • interleukin-15 receptor activity (GO:0042010) IDA
  • interleukin-4-mediated signaling pathway (GO:0035771) IEA
IL2RG is a common signal transducing subunit shared by the receptors for several different cytokines, namely the IL-2 receptor heterotrimer, the IL-4 receptor type I, the IL-7 receptor, the IL-9 receptor, the IL-15 receptor and the IL-21 receptor.
Interleukin-31 receptor, α subunit
(IL-6 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • T-helper 2 cell cytokine production (GO:0035745) IEA
Interleukin 3 receptor, α subunit
(IL-3 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • interleukin-3 receptor activity (GO:0004912) TAS
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • interleukin-3-mediated signaling pathway (GO:0038156) IDA
This is the ligand binding subunit of the functional IL-3 receptor complex.
Anti-IL-3RA monoclonal antibodies (mAbs) are being investigated for the treatment of IL-3RA (CD123) positive hematological malignancies [16,296] ...
Interleukin-4 receptor subunit α
(IL-2 receptor family)
  • interleukin-4 receptor activity (GO:0004913) TAS
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • cytokine receptor activity (GO:0004896) IEA
  • positive regulation of chemokine secretion (GO:0090197) 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 [226] ...
Interleukin 5 receptor, α subunit
(IL-3 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • interleukin-5 receptor activity (GO:0004914) TAS
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • regulation of interleukin-5 production (GO:0032674) IEA
This is the ligand binding subunit of the functional IL-5 receptor complex.
Interleukin-6 receptor, α subunit
(IL-6 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • cytokine-mediated signaling pathway (GO:0019221) IDA
  • negative regulation of interleukin-8 production (GO:0032717) NAS
  • positive regulation of chemokine production (GO:0032722) IDA
  • positive regulation of interferon-gamma production (GO:0032729) IBA
  • positive regulation of interleukin-6 production (GO:0032755) IDA
  • response to cytokine (GO:0034097) IDA
  • interleukin-6-mediated signaling pathway (GO:0070102) IMP
  • ciliary neurotrophic factor-mediated signaling pathway (GO:0070120) IMP
  • ciliary neurotrophic factor receptor activity (GO:0004897) IEA
  • interleukin-6 receptor activity (GO:0004915) IEA
IL6R polymorphisms are associated with asthma risk [169] ...
Interleukin-6 receptor, β subunit
(IL-6 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • ciliary neurotrophic factor receptor activity (GO:0004897) IDA
  • positive regulation of vascular endothelial growth factor production (GO:0010575) TAS
  • cytokine-mediated signaling pathway (GO:0019221) IDA
  • response to cytokine (GO:0034097) IDA
  • oncostatin-M-mediated signaling pathway (GO:0038165) IMP
  • interleukin-27 receptor activity (GO:0045509) IC
  • interleukin-6-mediated signaling pathway (GO:0070102) IMP
  • negative regulation of interleukin-6-mediated signaling pathway (GO:0070104) IDA
  • interleukin-27-mediated signaling pathway (GO:0070106) IMP
  • ciliary neurotrophic factor-mediated signaling pathway (GO:0070120) IDA
  • interleukin-35-mediated signaling pathway (GO:0070757) TAS
  • interleukin-6 receptor activity (GO:0004915) IEA
  • interleukin-11 receptor activity (GO:0004921) IEA
  • leukemia inhibitory factor receptor activity (GO:0004923) IEA
  • oncostatin-M receptor activity (GO:0004924) IEA
  • interleukin-11-mediated signaling pathway (GO:0038154) IEA
This is the common signal transducing subunit shared by members of the IL-6 family of cytokine receptors [485] ...
Interleukin-7 receptor subunit α
(IL-2 receptor family)
  • cytokine receptor activity (GO:0004896) IDA
  • interleukin-7 receptor activity (GO:0004917) TAS
  • interleukin-7-mediated signaling pathway (GO:0038111) TAS
This is the ligand binding subunit of the functional IL-7 receptor complex.
Effimmune are developing anti-IL7Rα monoclonal antibodies (e.g. OSE-127 [453] ...
Interleukin 9 receptor
(IL-2 receptor family)
  • interleukin-9 receptor activity (GO:0004919) TAS
  • interleukin-9-mediated signaling pathway (GO:0038113) TAS
The functional IL-9 receptor is a heterodimer of the ligand binding IL-9 receptor subunit and the interleukin 2 receptor γ (IL2RG) subunit. IL2RG is a common signal transducing subunit shared by the receptors for several different cytokines, including those for interleukin-2, -4, -7, and -15. ...
KIT proto-oncogene, receptor tyrosine kinase
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • dendritic cell cytokine production (GO:0002371) ISS
  • cytokine-mediated signaling pathway (GO:0019221) IDA
  • mast cell cytokine production (GO:0032762) IDA
  • Kit signaling pathway (GO:0038109) IDA
  • erythropoietin-mediated signaling pathway (GO:0038162) ISS
  • stem cell factor receptor activity (GO:0005020) IEA
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 [200] ...
lymphotoxin β receptor
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
Interaction of the lymphotoxin β receptor (LTBR) with its ligand is required for the development and organization of the secondary lymphoid organs and is involved in chemokine release (reported to induce interleukin 8 gene expression [98] ...
macrophage stimulating 1 receptor
(Type X RTKs: HGF (hepatocyte growth factor) receptor family)
  • macrophage colony-stimulating factor receptor activity (GO:0005011) TAS
The role of RON in immuno-oncology is reviewed in [2] ...
MER proto-oncogene, tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • negative regulation of cytokine production (GO:0001818) IEA
Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [40,587] ...
MET proto-oncogene, receptor tyrosine kinase
(Type X RTKs: HGF (hepatocyte growth factor) receptor family)
  • regulation of interleukin-6 production (GO:0032675) IMP
  • cellular response to interleukin-6 (GO:0071354) IEP
  • negative regulation of transforming growth factor beta production (GO:0071635) IMP
The leucine-rich repeat (LRR)-containing protein InlB of Listeria monocytogenes is reported to mediate bacterial entry in to non-phagocytic host cells by binding to the MET proto-oncogene, receptor tyrosine kinase (MET, or hepatocyte growth factor receptor, HGFR) [57] ...
NLRC3
(NOD-like receptor family)
  • negative regulation of interferon-alpha production (GO:0032687) ISS
  • negative regulation of interferon-beta production (GO:0032688) ISS
  • negative regulation of interleukin-1 beta production (GO:0032691) IMP
  • negative regulation of interleukin-12 production (GO:0032695) IMP
  • negative regulation of interleukin-6 production (GO:0032715) IDA
  • negative regulation of tumor necrosis factor production (GO:0032720) IDA
  • negative regulation of cytokine production involved in inflammatory response (GO:1900016) ISS
NLRC3 is an intracellular pattern recognition receptor of the innate immune system. It has been shown to directly interact with and inhibit the type I interferon response of the intracellular DNA sensor STING to cytosolic DNA, cyclic di-GMP (c-di-GMP), and DNA viruses [360,649] ...
NLRC4
(NOD-like receptor family)
  • interleukin-1 beta secretion (GO:0050702) IDA
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 [377] ...
NLRC5
(NOD-like receptor family)
  • negative regulation of type I interferon production (GO:0032480) TAS
  • positive regulation of interferon-gamma-mediated signaling pathway (GO:0060335) IDA
  • negative regulation of type I interferon-mediated signaling pathway (GO:0060339) IDA
  • positive regulation of type I interferon-mediated signaling pathway (GO:0060340) IDA
NLRC5 is an intracellular pattern recognition receptor mediating an innate immune response to viral infection [399] ...
NLRP1
(NOD-like receptor family)
  • positive regulation of interleukin-1 beta secretion (GO:0050718) ISS
NLRP1 is a cytosolic sensor of bacterial infection and regulator of the resulting innate immune response [96] ...
NLRP10
(NOD-like receptor family)
  • positive regulation of interleukin-1 alpha secretion (GO:0050717) IMP
  • positive regulation of interleukin-8 secretion (GO:2000484) IMP
  • positive regulation of interleukin-6 secretion (GO:2000778) IMP
NLRP10 is an intracellular pattern recognition receptor (PRR) that has apoptotic and anti-inflammatory functions [249] ...
NLRP3
(NOD-like receptor family)
  • positive regulation of interleukin-4 production (GO:0032753) ISS
  • negative regulation of interleukin-1 beta secretion (GO:0050713) IMP
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IDA
  • positive regulation of T-helper 2 cell cytokine production (GO:2000553) ISS
  • cytokine secretion involved in immune response (GO:0002374) IEA
  • interleukin-1 beta production (GO:0032611) IEA
  • interleukin-18 production (GO:0032621) IEA
  • positive regulation of interleukin-13 production (GO:0032736) IEA
  • positive regulation of interleukin-5 production (GO:0032754) IEA
  • interleukin-1 secretion (GO:0050701) IEA
NLRP3 is a component of the NLRP3 inflammasome, a protein complex which activates caspase-1, and plays an important role in the regulation of inflammation and apoptosis (pyroptosis). Drug-like NLRP3 inhibitors are under investigation as novel therapeutics for the treatment of autoinflammatory diseases and neuroinflammation, as an alternative to anti-IL-1 therapies such as , and [26,361] ...
NLRP7
(NOD-like receptor family)
  • negative regulation of interleukin-1 beta secretion (GO:0050713) IMP
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IBA
  • cellular response to interleukin-1 (GO:0071347) IEP
  • negative regulation of cytokine production involved in inflammatory response (GO:1900016) IMP
NLRP7 is an intracellular pattern recognition receptor (PRR). It is a member of the NACHT, LRR and PYD domains-containing protein (NALP) subfamily of PRRs. The presence of NALPs in inflammasomes underlies their involvement in regulating proinflammatory caspases (esp. caspase 1) ...
NLRX1
(NOD-like receptor family)
  • negative regulation of type I interferon production (GO:0032480) TAS
  • negative regulation of interferon-beta production (GO:0032688) IEA
  • negative regulation of interleukin-6 production (GO:0032715) IEA
  • 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)
  • interleukin-8 biosynthetic process (GO:0042228) IDA
  • interleukin-1-mediated signaling pathway (GO:0070498) TAS
  • positive regulation of interleukin-1 beta production (GO:0032731) IEA
  • positive regulation of interleukin-6 production (GO:0032755) IEA
  • positive regulation of tumor necrosis factor production (GO:0032760) IEA
NOD1 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing a D-glutamyl-meso-diaminopimelic acid (iE-DAP) moiety.

Mutations in NOD proteins are implicated in various inflammatory diseases associated with aberrant NF-κB activ ...
nucleotide binding oligomerization domain containing 2
(NOD-like receptor family)
  • cytokine production involved in immune response (GO:0002367) IMP
  • cytokine secretion involved in immune response (GO:0002374) IMP
  • negative regulation of interferon-gamma production (GO:0032689) IMP
  • negative regulation of interleukin-12 production (GO:0032695) IDA
  • negative regulation of interleukin-18 production (GO:0032701) IMP
  • negative regulation of interleukin-2 production (GO:0032703) IMP
  • negative regulation of tumor necrosis factor production (GO:0032720) IMP
  • positive regulation of interleukin-1 beta production (GO:0032731) IMP
  • positive regulation of interleukin-10 production (GO:0032733) ISS
  • positive regulation of interleukin-12 production (GO:0032735) IDA
  • positive regulation of interleukin-17 production (GO:0032740) IMP
  • positive regulation of interleukin-6 production (GO:0032755) IDA
  • positive regulation of interleukin-8 production (GO:0032757) IMP
  • positive regulation of tumor necrosis factor production (GO:0032760) IDA
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IDA
  • interleukin-1-mediated signaling pathway (GO:0070498) TAS
  • macrophage inflammatory protein-1 alpha production (GO:0071608) IMP
  • positive regulation of monocyte chemotactic protein-1 production (GO:0071639) IMP
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) IDA
  • positive regulation of dendritic cell cytokine production (GO:0002732) IEA
NOD2 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing muramyl dipeptide (MDP).

Mutations in NOD proteins are implicated in various inflammatory diseases associated with aberrant NF-κB activity; NF-κB being a major ...
Oncostatin M-specific receptor, β subunit
(IL-6 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • oncostatin-M receptor activity (GO:0004924) IDA
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • response to cytokine (GO:0034097) IDA
  • oncostatin-M-mediated signaling pathway (GO:0038165) IMP
Oncostatin M-specific receptor, β subunit (OSMR) is a component of two functional heterodimeric receptor complexes:
1. OSMR+ interleukin-6 receptor, β subunit (IL6ST) forms the receptor for oncostatin M
2. OSMR+ interleukin-31 receptor, α subunit forms the recept ...
osteoprotegerin
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
The protein product of the TNFRSF11B gene, osteoprotegerin, acts as a soluble decoy receptor for RANK ligand (RANKL) and for TRAIL. Experimental evidence links the RANK/RANKL signalling pathway with the inflammatory activation of microglial cells relevant in the development of infection-induced perinatal brain injury [280] ...
OX40
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) IBA
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • negative regulation of cytokine secretion (GO:0050710) IBA
The OX40/OX40L pair is involved in late T-cell costimulatory signaling and both are transiently expressed following antigen recognition, and blocking OX40/OX40L is reported to prevent the development of disease in in vivo autoimmune and inflammatory disease models [602] ...
receptor activator of NF-kappa B
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) ISS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) ISS
  • response to cytokine (GO:0034097) IMP
  • response to tumor necrosis factor (GO:0034612) ISS
  • response to interleukin-1 (GO:0070555) ISS
  • TNFSF11-mediated signaling pathway (GO:0071847) IMP
  • positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling (GO:0071848) IMP
RANK is the receptor for RANK-ligand (RANKL). It is associated with immune cell function and lymph node development, in addition to bone remodeling and repair, thermal regulation, and mammary gland development. Signals to NF-κB and JNK via TRAF adaptor proteins.
RTP Type C
(Receptor tyrosine phosphatase (RTP) family)
  • negative regulation of cytokine-mediated signaling pathway (GO:0001960) ISS
  • regulation of interleukin-8 production (GO:0032677) IDA
  • positive regulation of tumor necrosis factor production (GO:0032760) ISS
  • negative regulation of interleukin-2 biosynthetic process (GO:0045085) ISS
  • positive regulation of interleukin-2 biosynthetic process (GO:0045086) 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 [138] ...
single Ig and TIR domain containing
(Immunoglobulin-like family of IL-1 receptors)
  • negative regulation of cytokine-mediated signaling pathway (GO:0001960) ISS
  • negative regulation of chemokine biosynthetic process (GO:0045079) ISS
  • cellular response to cytokine stimulus (GO:0071345) TAS
IL-1R8 has been identified as a natural killer (NK) cell checkpoint that is involved in regulating NK cells' anti-viral and anti-tumour effector functions [382] ...
TACI
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
TACI is a lymphocyte-specific TNF superfamily receptor expressed on B cells. Endogenous ligands include APRIL, BAFF and CAML. Defects in the function of TACI can underlie immunodeficiencies and autoimmune diseases. A TACI-IgG Fc fusion protein named RC18 will be evaluated in Phase 3 clinical trials ...
TEK receptor tyrosine kinase
(Type XII RTKs: TIE family of angiopoietin receptors)
  • positive regulation of cytokine secretion involved in immune response (GO:0002741) IDA
In inflammation, angiopoietin-2 (ANG2) antagonism of TIE2 initiates a positive feedback loop via forkhead box O1 (FOXO1) activation, which drives further ANG2 expression and enhances vascular remodeling and leakage [284] ...
TLR1
(Toll-like receptor family)
  • positive regulation of tumor necrosis factor biosynthetic process (GO:0042535) ISS
  • positive regulation of interleukin-6 biosynthetic process (GO:0045410) ISS
  • positive regulation of interleukin-8 secretion (GO:2000484) IGI
TLR1/2 heterodimers detect and respond to bacterial triacyl lipopeptides [569] ...
TLR10
(Toll-like receptor family)
  • regulation of cytokine secretion (GO:0050707) IEA
To date, ligands and biological functions of human TLR10 remain unclear. However, evidence suggests it plays a modulatory role with predominantly inhibitory (anti-inflammatory) effects [425] ...
TLR2
(Toll-like receptor family)
  • cytokine secretion involved in immune response (GO:0002374) IMP
  • regulation of dendritic cell cytokine production (GO:0002730) IDA
  • interleukin-10 production (GO:0032613) IDA
  • tumor necrosis factor production (GO:0032640) ISS
  • negative regulation of interleukin-12 production (GO:0032695) IMP
  • negative regulation of interleukin-17 production (GO:0032700) IMP
  • positive regulation of chemokine production (GO:0032722) IDA
  • positive regulation of interferon-beta production (GO:0032728) ISS
  • positive regulation of interleukin-12 production (GO:0032735) ISS
  • positive regulation of interleukin-18 production (GO:0032741) ISS
  • positive regulation of interleukin-6 production (GO:0032755) IDA
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • positive regulation of tumor necrosis factor production (GO:0032760) ISS
  • positive regulation of tumor necrosis factor biosynthetic process (GO:0042535) IMP
  • positive regulation of cytokine secretion (GO:0050715) IGI
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IGI
  • positive regulation of macrophage cytokine production (GO:0060907) IMP
  • cellular response to interferon-gamma (GO:0071346) IDA
  • positive regulation of cellular response to macrophage colony-stimulating factor stimulus (GO:1903974) IDA
  • positive regulation of tumor necrosis factor secretion (GO:1904469) IGI
  • positive regulation of interleukin-8 secretion (GO:2000484) IGI
  • positive regulation of interleukin-6 secretion (GO:2000778) IGI
  • positive regulation of interleukin-10 production (GO:0032733) IEA
TLR1/2 and 2/6 heterodimers detect and initiate an immune response to triacylated and diacylated [394] ...
TLR3
(Toll-like receptor family)
  • positive regulation of type I interferon production (GO:0032481) IDA
  • positive regulation of chemokine production (GO:0032722) IDA
  • positive regulation of interferon-beta production (GO:0032728) ISS
  • positive regulation of interleukin-12 production (GO:0032735) ISS
  • positive regulation of interleukin-6 production (GO:0032755) IDA
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • positive regulation of tumor necrosis factor production (GO:0032760) ISS
  • positive regulation of interferon-gamma biosynthetic process (GO:0045078) IDA
  • positive regulation of interferon-alpha biosynthetic process (GO:0045356) IDA
  • positive regulation of interferon-beta biosynthetic process (GO:0045359) IDA
  • regulation of dendritic cell cytokine production (GO:0002730) IEA
  • positive regulation of type III interferon production (GO:0034346) IEA
  • cellular response to interferon-beta (GO:0035458) IEA
  • positive regulation of chemokine biosynthetic process (GO:0045080) IEA
  • cellular response to interferon-gamma (GO:0071346) IEA
TLR3 is an endosomal anti-viral receptor [569] ...
TLR4
(Toll-like receptor family)
  • negative regulation of interferon-gamma production (GO:0032689) ISS
  • negative regulation of interleukin-17 production (GO:0032700) ISS
  • negative regulation of interleukin-23 production (GO:0032707) ISS
  • negative regulation of interleukin-6 production (GO:0032715) ISS
  • negative regulation of tumor necrosis factor production (GO:0032720) ISS
  • positive regulation of chemokine production (GO:0032722) IDA
  • positive regulation of interferon-alpha production (GO:0032727) ISS
  • positive regulation of interferon-beta production (GO:0032728) ISS
  • positive regulation of interferon-gamma production (GO:0032729) ISS
  • positive regulation of interleukin-1 production (GO:0032732) ISS
  • positive regulation of interleukin-10 production (GO:0032733) ISS
  • positive regulation of interleukin-12 production (GO:0032735) ISS
  • positive regulation of interleukin-6 production (GO:0032755) IDA
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • positive regulation of tumor necrosis factor production (GO:0032760) ISS
  • positive regulation of tumor necrosis factor biosynthetic process (GO:0042535) IDA
  • positive regulation of interleukin-12 biosynthetic process (GO:0045084) IDA
  • positive regulation of interleukin-1 biosynthetic process (GO:0045362) NAS
  • positive regulation of interleukin-13 biosynthetic process (GO:0045368) NAS
  • positive regulation of interleukin-6 biosynthetic process (GO:0045410) NAS
  • positive regulation of interleukin-8 biosynthetic process (GO:0045416) IDA
  • interleukin-1 beta secretion (GO:0050702) ISS
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IDA
  • cellular response to interferon-gamma (GO:0071346) IDA
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) ISS
  • positive regulation of cellular response to macrophage colony-stimulating factor stimulus (GO:1903974) IDA
  • positive regulation of chemokine (C-C motif) ligand 2 secretion (GO:1904209) IMP
  • regulation of tumor necrosis factor secretion (GO:1904467) ISO
  • positive regulation of interleukin-8 secretion (GO:2000484) IDA
  • positive regulation of interleukin-6 secretion (GO:2000778) IMP
  • regulation of dendritic cell cytokine production (GO:0002730) IEA
  • interferon-gamma production (GO:0032609) IEA
  • positive regulation of interferon-beta biosynthetic process (GO:0045359) IEA
  • positive regulation of macrophage cytokine production (GO:0060907) IEA
TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [52,455] ...
TLR5
(Toll-like receptor family)
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • regulation of cytokine secretion (GO:0050707) IEA
TLR5 induces a pro-inflammatory response upon detection of extracellular bacterial flagellin from invading mobile bacteria [377] ...
TLR6
(Toll-like receptor family)
  • positive regulation of interleukin-12 biosynthetic process (GO:0045084) NAS
  • positive regulation of interleukin-6 biosynthetic process (GO:0045410) ISS
  • interleukin-1 beta secretion (GO:0050702) ISS
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) ISS
  • negative regulation of tumor necrosis factor secretion (GO:1904468) IGI
  • negative regulation of interleukin-8 secretion (GO:2000483) IGI
TLR6 forms heterodimers with TLR2 to detect a wide range of bacterial lipopeptides (LP) from bacterial cell membranes, and effect an immune response [164] ...
TLR7
(Toll-like receptor family)
  • positive regulation of chemokine production (GO:0032722) IDA
  • positive regulation of interleukin-6 production (GO:0032755) IBA
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • positive regulation of interferon-gamma biosynthetic process (GO:0045078) IDA