Targets Associated to Immuno Processes - Inflammation
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Targets Associated to Immuno Processes
Full documentation can be found in the GtoImmuPdb immuno cell type data documentation (PDF). ✖ |
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| GPCRs | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| ACKR1 (Chemokine receptors) |
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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 [112] ... | ||
| ACKR2 (Chemokine receptors) |
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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. | ||
| ADGRE2 (Adhesion Class GPCRs) |
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ADGRE2 is included in GtoImmuPdb because its tissue expression profile and its ability to activate secretion of inflammatory cytokines (IL-8, TNF) by monocytes and macrophages [273] ... | ||
| ADGRE5 (Adhesion Class GPCRs) |
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ADGRE5 is included in GtoImmuPdb because its tissue expression profile and the phenotypes expressed by mouse ADGRE5 knockouts suggest an involvement in inflammation. | ||
| A1 receptor (Adenosine receptors) |
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Adenosine exerts anti-inflammatory effects on a number of immune cells types. These effects are mediated by the adenosine G portein-coupled receptors. All four adenosine receptors are expressed on the surface of mouse invariant NKT (iNKT) cells. The specific role of the A1 receptor in ade ... | ||
| A2A receptor (Adenosine receptors) |
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Agonist stimulation of the A2A and A3 receptors down-regulates production of the pro-inflammatory mediators TNF-α and IL-8 in human synoviocytes [664] ... | ||
| A2B receptor (Adenosine receptors) |
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A2B receptor is discussed in this immuno-oncology review [4] ... | ||
| A3 receptor (Adenosine receptors) |
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Agonist stimulation of the A2A and A3 receptors down-regulates production of the pro-inflammatory mediators TNF-α and IL-8 in human synoviocytes [664] ... | ||
| AT1 receptor (Angiotensin receptors) |
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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 [591] ... | ||
| AT2 receptor (Angiotensin receptors) |
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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 [430] ... | ||
| BLT1 receptor (Leukotriene receptors) |
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The human BLT1 receptor is the high affinity leukotriene B4 receptor, involved in mediating chemotaxis and activation of several leukocyte populations, including granulocytes, monocytes/macrophages, and lymphocytes [549] ... | ||
| BLT2 receptor (Leukotriene receptors) |
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The human BLT2 receptor is the low affinity leukotriene B4 receptor, and may be involved in maintaining intestinal barrier function (leading to colitis) and eosinophilic airway inflammation. BLT2 receptor is considered to be the principal mediator of leukotriene B4 effects in synovial tissues from patients with rheumatoid arthritis [251] ... | ||
| B1 receptor (Bradykinin receptors) |
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Bradykinin ... | ||
| B2 receptor (Bradykinin receptors) |
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Bradykinin is a vasoactive, pain inducing and pro-inflammatory (phlogistic) kinin released during acute inflammation, and its receptors, B1 and B2, are expressed on eosinophils, and neutrophils. The B2 receptor antagonist icatibant was evaluated in a Phase 2 trial for osteoarthritis [153] ... | ||
| C3a receptor (Complement peptide receptors) |
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Complement C3a receptor 1 is the receptor for complement factor C3a, a component of the alternative complement cascade. It can have pro-inflammatory actions, but can also counteract the proinflammatory effects of C5a. The complement system plays a critical role intestinal immune homeostasis. In particular, C3 and the C3aR have been identified as being involved in regulating the intestinal immune response during chronic colitis [626,694] ... |
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| C5a1 receptor (Complement peptide receptors) |
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C5aR is typically associated with the compement cascade and innate immunity. MorphoSys have an anti-C5aR monoclonal antibody (MOR210; TJ210) 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 [270,402,460-461] ... |
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| C5a2 receptor (Complement peptide receptors) |
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C5aR is typically associated with the compement cascade and innate immunity. However, the complement C5a receptor 2 may act as a decoy receptor for C5a, as it has no reported G protein signalling capacity. | ||
| CB1 receptor (Cannabinoid receptors) |
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CB1 receptor is involved in controlling mast cell degranulation and maturation [615] ... | ||
| CB2 receptor (Cannabinoid receptors) |
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CB2 receptor on eosinophils mainly mediates anti-inflammatory and immunomodulatory actions e.g. downregulation of pro-inflammatory mediator release. Pharmacological targeting with the CB2 receptor selective antagonist SR144528 attenuates the recruitment of eosinophils and ear swelling in a murine chronic contact dermatitis model [479] ... | ||
| CCR1 (Chemokine receptors) |
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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. | ||
| CCR2 (Chemokine receptors) |
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CCR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CCR2 is discussed in relation to immuno-oncology in [4] ... | ||
| CCR3 (Chemokine receptors) |
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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) |
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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 [593] ... |
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| CCR5 (Chemokine receptors) |
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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 [4] ... | ||
| CCR6 (Chemokine receptors) |
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CCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. CCR6 is expressed on a variety of immune cells including memory and regulatory T-cells [330,378] ... | ||
| CCR7 (Chemokine receptors) |
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CCR7 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| CCRL2 (Chemokine receptors) |
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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) |
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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. |
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| CXCR1 (Chemokine receptors) |
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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 [4] ... | ||
| CXCR2 (Chemokine receptors) |
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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 [4] ... | ||
| CXCR3 (Chemokine receptors) |
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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. In the cancer setting cytokines are known to establish an immunosuppressive milieu that is condusive to tumour progression. CXCR3 and its ligands have specifically been identified as being associated with this mechanism in pancreatic ductal adenocarcinoma [94] ... |
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| CXCR4 (Chemokine receptors) |
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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 [529,562,674,687] ... | ||
| CXCR5 (Chemokine receptors) |
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CXCR5 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| CXCR6 (Chemokine receptors) |
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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 [657] ... | ||
| CX3CR1 (Chemokine receptors) |
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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. | ||
| CysLT1 receptor (Leukotriene receptors) |
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CysLT1 is a receptor for cysteinyl-leukotrienes. Both CysLT1 and CysLT2 mediate cysteinyl-leukotriene-induced modulation of smooth muscle cell contraction, regulation of vascular permeability, and leukocyte activation. Selective inhibition of CysLT1 ... |
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| DP1 receptor (Prostanoid receptors) |
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DP1 receptor activation by prostaglandins mediates chemotaxis of pro-inflammatory cells such as basophils, eosinophils, and T cells. DP2 and DP1 may function to counteract each other's inflammatory action [260] ... | ||
| D2 receptor (Dopamine receptors) |
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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 [742] ... | ||
| EP1 receptor (Prostanoid receptors) |
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Foudi et al. (2012) [195] ... | ||
| EP2 receptor (Prostanoid receptors) |
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Foudi et al. (2012) [195] ... | ||
| EP3 receptor (Prostanoid receptors) |
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Foudi et al. (2012) [195] ... | ||
| EP4 receptor (Prostanoid receptors) |
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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 [722] ... | ||
| FFA2 receptor (Free fatty acid receptors) |
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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 [716] ... |
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| FFA3 receptor (Free fatty acid receptors) |
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FFA3 has been included in GtoImmuPdb as its expression has been detected in immune cells [79] ... | ||
| FFA4 receptor (Free fatty acid receptors) |
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FFA4 has been identified as a drug target in asthma and COPD [520] ... | ||
| FPR1 (Formylpeptide receptors) |
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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 [488] ... |
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| FPR2/ALX (Formylpeptide receptors, Leukotriene receptors) |
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Formyl peptide receptor type 2 (FPR2/ALX) activation by lipoxin A4 and annexin 1 has been linked to resolution of inflammation, via upregulation of anti-inflammatory cytokines including IL-10. Resolvin D1-mediated activation of FPR2/ALX appears to resolve salivary gland inflammation in a mouse model of Sjögren syndrome [677] ... | ||
| H1 receptor (Histamine receptors) |
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The H1 receptor was the first of the family to be targeted for clinical use, with antagonists (anti-histamines) developed that are still used widely to treat allergic inflammation such as rhinitis, allergic conjunctivitis, urticaria and even anaphylaxis. | ||
| H4 receptor (Histamine receptors) |
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H4 receptor is primarily expressed in mast cells and eosinophils, but is also found on human neutrophils and basophils, and plays an important role in modulating eosinophil chemotaxis [470,732] ... | ||
| GPR15 (Class A Orphans) |
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Several lines of evidence suggest that GPR15 is a chemoattractant receptor supporting the trafficking of T effector cells to the colon [236,459,472,622] ... | ||
| GPR183 (Class A Orphans) |
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Gpr183-deficient mice show a reduction in the early antibody response to a T-dependent antigen. GPR183-deficient B cells fail to migrate to the outer follicle and instead stay in the follicle centre [319,504] ... | ||
| GPR4 (Class A Orphans) |
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GPR4 is a proton sensing GPCR with emerging roles in a range of physiological processes [398] ... | ||
| MAS1 (Class A Orphans) |
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Experimental evidence from animal studies suggest a role for MAS1 in the anti-inflammatory pathway mediated by angiotensin-(1-7) [144,178] ... | ||
| MRGPRX2 (Class A Orphans) |
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Expression of MRGPRX2 was initially reported predominantly in sensory neurons of the dorsal root ganglion. More recently expression has been detected in human mast cells. In these cells the receptor is activated by the antimicrobial peptide LL-37, resulting in calcium mobilisation and degranulation [425,613] ... | ||
| IP receptor (Prostanoid receptors) |
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Although primarily recognised for vasodilatory and antihypertensive action in pulmonary arterial hypertension (PAH) the importance of PGI2 as an immunomodulatory agent has been investigated more recently. PGI2 regulates both the innate and adaptive immune systems and its effects are thought to be mainly anti-inflammatory or immunosuppressive, which may have implications for clinical use. Note also that the prostacyclin analog, cicaprost, exhibits potent anti-inflammatory activity in human primary immune cells [678] ... | ||
| NK1 receptor (Tachykinin receptors) |
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Expression in monocytes, macrophages and T helper cells suggests a role in inflammation/immunity. | ||
| P2Y6 receptor (P2Y receptors) |
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P2Y6R expression on airway epithelial cells is up-regulated during acute and chronic allergic airway inflammation, and selective antagonism of P2Y6R reduces typical features of experimental asthma [669] ... | ||
| PAF receptor (Platelet-activating factor receptor) |
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PAF deficiency results in defective inflammatory response to infection in mice. | ||
| PAR1 (Proteinase-activated receptors) |
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PAR1 has been found to mediate the effects of neutrophil elastase (NE) on γδ T cell activation, as the PAR1 inhibitor |
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| PAR2 (Proteinase-activated receptors) |
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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) [210] ... | ||
| S1P1 receptor (Lysophospholipid (S1P) receptors) |
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S1P1R activation by agonists downregulates allergic inflammation (i.e. it has an inhibitory effect) [279,282,561] ... | ||
| S1P3 receptor (Lysophospholipid (S1P) receptors) |
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| succinate receptor (Succinate receptor) |
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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 [381] ... | ||
| XCR1 (Chemokine receptors) |
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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 [364] ... | ||
| Ion Channels | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| P2X1 (P2X receptors) |
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Functional P2X1 receptors are expressed by healthy human eosinophils [704] ... | ||
| P2X4 (P2X receptors) |
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P2X ligand-gated ion channels elicit pro-inflammatory immune responses upon activation by extracellular ATP that acts as a DAMP when released from damaged or infected cells [84,100] ... | ||
| P2X7 (P2X receptors) |
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The P2X7 receptor is involved in NLRP3-type inflammasome formation, and subsequent maturation of IL-1β [380,531] ... | ||
| TRPM2 (Transient Receptor Potential channels (TRP)) |
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Expressed on human T cells, mouse dendritic cells, human and mouse neutrophils and monocytes/macrophages, and mouse mast cells [496] ... | ||
| TRPM4 (Transient Receptor Potential channels (TRP)) |
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TRPM4 is expressed on human T cells, mouse dendritic cells, human and mouse monocytes/macrophages, and mouse mast cells [496] ... | ||
| TRPV1 (Transient Receptor Potential channels (TRP)) |
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Several lines of evidence suggest that TRPV1 is implicated in some inflammatory processes [29,60,394,404,555] ... | ||
| TRPV4 (Transient Receptor Potential channels (TRP)) |
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Expressed on mouse neutrophils [496] ... | ||
| Nuclear Hormone Receptors | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| Farnesoid X receptor (1H. Liver X receptor-like receptors) |
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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) [569] ... | ||
| Liver X receptor-α (1H. Liver X receptor-like receptors) |
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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 [709] ... | ||
| Liver X receptor-β (1H. Liver X receptor-like receptors) |
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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 [709] ... | ||
| Peroxisome proliferator-activated receptor-γ (1C. Peroxisome proliferator-activated receptors) |
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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 |
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| RAR-related orphan receptor-γ (1F. Retinoic acid-related orphans) |
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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) [146,214,463,599] ... | ||
| Enzymes | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| 3-phosphoinositide dependent protein kinase 1 (PDK1 family) |
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In addition to its role in oncology, in mouse studies, PDK1 is reported to play a part in regulating insulin sensitivity (and inhibiting adipose tissue inflammation), via the Pdk1/Foxo1 pathway and expression of Ccr2 [316] ... | ||
| 5-LOX (Lipoxygenases) |
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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 [588] ... | ||
| 8-oxoguanine DNA glycosylase (DNA glycosylases) |
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OGG1 has recognised roles in processes that are associated with innate and adaptive immunity [8,34] ... | ||
| ABL proto-oncogene 1, non-receptor tyrosine kinase (Abl family) |
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Included in GtoImmuPdb based on its association with leukemia. | ||
| aconitate decarboxylase 1 (Itaconate biosynthesis) |
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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 [129,168] ... | ||
| ADAM10 (M12: Astacin/Adamalysin) |
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ADAM10 has been identified as the primary physiologically relevant sheddase responsible for cleavage of |
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| ADAM17 (M12: Astacin/Adamalysin) |
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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 [105] ... | ||
| ADAM8 (M12: Astacin/Adamalysin) |
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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) [501] ... | ||
| Adenosine deaminase (Adenosine turnover) |
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Adenosine deaminase deficiency causes immunodeficiency (ADA deficiency or ADA-SCID). Around 30 known genotypes are associated with this autosomal recessive metabolic disorder. Mitotically active cells such as developing T cells and B cells are susceptible to this deficiency, expaining the resulting ... | ||
| alkaline ceramidase 3 (Alkaline ceramidases) |
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ACER3 may play a role in inflammation, since it is reported that loss of Acer3 in mice aggravates colitis and colitis-associated colorectal cancer [679] ... | ||
| αβ-Hydrolase 12 (2-Acylglycerol ester turnover) |
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The lysophosphatidylserine (lyso-PSs) and lysophosphatidylinositol (lyso-PI) class lipide are immunomodulators that regulate immunological and neurological processes. ABHD12 is one of a number of lyso-PS lipases that are implicated in lyso-PS-induced cytokine production. Pharmacological inhibition of ABHD12 augments inflammatory cytokine production in human macrophages, which suggests a role for this enzyme in (lyso)-PS/PI metabolism and signalling, and downstream immunological functions [474-475] ... | ||
| amine oxidase copper containing 3 (1.-.-.- Oxidoreductases) |
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As a membrane-bound glycoprotein AOC3 (a.k.a. SSAO, VAP-1) is expressed on the surface of endothelial cells when exposed to inflammatory conditions. It has been noted to mediate binding of lymphocytes to peripheral lymph node vascular endothelial cells, a process required for the recirculation of lymphocytes between blood and tissue. This activity profile has suggested AOC3 as a potential drug target for inflammatory and vascular diseases [554] ... | ||
| Arginase I (Arginase) |
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The role of ARG1 in immuno-oncology is reviewed in [4] ... | ||
| Arginase II (Arginase) |
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The role of ARG2 in immuno-oncology is reviewed in [4] ... | ||
| BLK proto-oncogene, Src family tyrosine kinase (Src family) |
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BLK is a B cell-specific kinase. In Blk knockout mice B cells develop normally and show unaltered in vitro activation and humoral immune responses to T cell-dependent and -independent antigens, a result which is indicative of functional redundancy of Blk in B cell development and immune responses [635] ... | ||
| Bruton tyrosine kinase (Tec family) |
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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 [56] ... | ||
| calcium/calmodulin dependent protein kinase IV (CAMK1 family) |
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CAMKIV has been implicated in the differentiation of Th17 cells, suggesting CAMKIV as a target for therapeutic intervention in Th17-driven autoimmune diseases [332] ... | ||
| Caspase 1 (C14: Caspase) |
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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 4 (C14: Caspase) |
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Recognition of cytoplasmic lipopolysaccharide (LPS) by Inflammatory caspases including caspases-4 and -5 leads to pyroptosis and secretion of inflammatory mediators [580-581] ... | ||
| Caspase 5 (C14: Caspase) |
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Recognition of cytoplasmic lipopolysaccharide (LPS) by Inflammatory caspases including caspases-4 and -5 leads to pyroptosis and secretion of inflammatory mediators [580-581] ... | ||
| Caspase 8 (C14: Caspase) |
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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 [406] ... | ||
| cathepsin C (C1: Papain) |
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Cathepsin C (CatC) is a lysosomal cysteine protease that is constitutively expressed at high levels in lung, kidney, liver and spleen. As well as activity in lysosomal protein degradation, cathepsin C also plays a key role in the activation of granule serine proteases in cytotoxic T cells, natural killer cells (granzymes A and B), mast cells (chymase and tryptase) and neutrophils (cathepsin G, neutrophil elastase, proteinase 3). Dysregulated activation of neutrophil elastase at inflammatory sites induces the release of pro-inflammatoy mediators and can lead to acute tissue injury. This mechanism is recognised as causing lung damage in neutrophil driven conditions such as asthma and COPD, and has driven the pharmaceutical industry to search for cathepsin C inhibitors with clinical utility (e.g. brensocatib; formerly AZD7986 and INS1007). SARS-CoV-2 and COVID-19: CatC has been proposed as a drug target to combat ARDS-associated inflammatory lung damage in patients with severe COVID-19. In this setting CatC inhibitors would be expected to protect the lungs from ARDS by reducing the observed virally-induced hyperinflammation that leads to diffuse alveolar collapse and pulmonary tissue damage [336] ... |
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| cathepsin G (S1: Chymotrypsin) |
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Cathepsin G is a leukocyte serine protease of the chymotrypsin family, related to neutrophil elastase and the granzymes. It is stored in azurophil granules and acts intracellularly to degrade ingested host pathogens and axtracellularly to breakdown ECM components at sites of inflammation. Cathepsin ... | ||
| cathepsin S (C1: Papain) |
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Cathepsin S is expressed in the lysosome of antigen presenting cells (dendritic cells, B-cells and macrophages) where it processes the invariant chain-MHC-II complex (a chaperone protein that prevents premature peptide loading) inside antigen presenting cells and in this way controls antigen presentation. Due to this role in antigen presentation, inhibition of cathepsin S is expected to cause immunosuppression [638] ... | ||
| chitinase acidic (Chitinases) |
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AMCase has been shown to be produced during type 2 inflammatory responses [751] ... | ||
| chymase 1 (S1: Chymotrypsin) |
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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) [257] ... | ||
| complement C1r (S1: Chymotrypsin) |
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A protease component of the C1-complex of the classical complement pathway. | ||
| complement C1s (S1: Chymotrypsin) |
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A protease component of the C1-complex of the classical complement pathway. | ||
| complement factor B (S1: Chymotrypsin) |
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A protease component of the alternative complement pathway. Cleaved by complement factor D ... | ||
| complement factor D (3.4.21.46 Complement factor D) |
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A protease component of the alternative complement pathway; responsible for cleaving complement factor B ... | ||
| component of inhibitor of nuclear factor kappa B kinase complex (IKK family) |
|
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 [272] ... | ||
| COX-1 (Cyclooxygenase) |
|
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. | ||
| COX-2 (Cyclooxygenase) |
|
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 [4] ... | ||
| C-terminal Src kinase (Csk family) |
|
CSK is an inhibitory regulator of Src family kinases, a family of protein tyrosine kinases indispensable to the initiation of signal transduction via ITAM-bearing immunoreceptors, and cytokine, growth factor, and pattern recognition receptor signalling. CSK phosphorylates an inhibitory tyrosine residue at the C terminus of Src kinases, leading to autoinhibition. CSK-induced Src kinase inhibition can also be mediated by binding to PEST family receptor tyrosine phosphatases [665] ... | ||
| Cyclic GMP-AMP synthase (Cyclic GMP-AMP synthase) |
|
Cyclic GMP-AMP synthase (cGAS) directly binds to cytosolic DNA, and in response catalyses the synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Thus cGAS acts as a sensor of DNA in the cytoplasm, which is an indicator of pathogen invasion [620] ... | ||
| death associated protein kinase 2 (Death-associated kinase (DAPK) family) |
|
DAPk2 is recognised as a regulator of apoptosis, autophagy and inflammation [213] ... | ||
| Ecto-5'-Nucleotidase (Adenosine turnover) |
|
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 [25] ... | ||
| elastase, neutrophil expressed (S1: Chymotrypsin) |
|
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 [646] ... | ||
| enhancer of zeste 2 polycomb repressive complex 2 subunit (2.1.1.43 Histone methyltransferases (HMTs)) |
|
EZH2 is involved in hematopoietic stem cell proliferation and differentiation, thymopoiesis and lymphopoiesis, with notable participation in regulating the differentiation and function of T cells. This role suggests potential applications in immune-mediated conditions, including autoimmune disorders [649] ... | ||
| eukaryotic translation initiation factor 2 alpha kinase 2 (Other PEK family kinases) |
|
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 [209] ... | ||
| eukaryotic translation initiation factor 2 alpha kinase 4 (GCN2 subfamily) |
|
GCN2 is a so-called 'stress kinase'. It phosphorylates serine 51 on the global transcription factor eIF2α upon activation by uncharged tRNA; tRNAs accumulate when amino acid levels are depleted. Phospho-eIF2α blocks translation to cause proliferative arrest. GCN2 plays several roles in the immune system. It is required for dendritic cell activation and antigen presentation. The GCN2 stress response is required for both optimal proliferation of CD8+ T cells after antigen stimulation, and trafficking to lymphoid organs, i.e. for normal cytotoxic T cell function [659] ... |
||
| FER tyrosine kinase (Fer family) |
|
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) |
|
Fgr may be involved in neutrophil migration, potentially via binding to intergrins [48] ... | ||
| FYN proto-oncogene, Src family tyrosine kinase (Src family) |
|
Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [493] ... | ||
| Haem oxygenase 1 (Haem oxygenase) |
|
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 [27] ... |
||
| HCK proto-oncogene, Src family tyrosine kinase (Src family) |
|
Hck is thought to be involved in neutrophil migration, potentially via binding to intergrins [48] ... | ||
| heparanase (3.2.1.- Glycosidases) |
|
Heparanase has been studied as a novel drug target associated with the immune response and inflammation [110-111] ... | ||
| indoleamine 2,3-dioxygenase 1 (1.13.11.- Dioxygenases) |
|
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 [331] ... | ||
| Inducible NOS (Nitric oxide synthases) |
|
The role of iNOS in immuno-oncology is reviewed in [4] ... | ||
| inhibitor of nuclear factor kappa B kinase subunit beta (IKK family) |
|
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) [52,69,595] ... | ||
| inhibitor of nuclear factor kappa B kinase subunit epsilon (IKK family) |
|
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 ... | ||
| interleukin 1 receptor associated kinase 1 (Interleukin-1 receptor-associated kinase (IRAK) family) |
|
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) |
|
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) |
|
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 [176,450]. |
|
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 [427] ... | |
| 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. |
|
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) |
|
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 [61,63,604] ... | ||
| Janus kinase 3 (Janus kinase (JakA) family) |
|
Psoriatic skin samples show elevated JAK3 (and JAK1) expression, with signalling predominantly through STAT3 [19] ... | ||
| LCK proto-oncogene, Src family tyrosine kinase (Src family) |
|
Phosphorylation and activation of Lck is an early and critical step in pre-TCR (T cell receptor) and TCR signalling. Activated Lck phosphorylates immunoreceptor tyrosine-based activation motifs of the ζ chain of the TCR leading to recruitment and activation of ZAP-70 tyrosine kinase, and activation of downstream MAPKs and NF-κB. TCR-based signals are required at several stages of T-cell development and it is thought that Lck is the major contributor to TCR signal transduction (with the related Src tyrosine kinase Fyn also playing a role) [493] ... | ||
| LYN proto-oncogene, Src family tyrosine kinase (Src family) |
|
LYN is a Src family tyrosine kinase, expressed predominantly in hematopoietic cells, but also in neural, liver, and adipose tissues. LYN appears to function as a rheostat to modulate B cell signaling, and can be activating or inhibitory in action, depending on the B cell receptor and interacting protein complement present in particular cells [196,207,645] ... | ||
| lysine demethylase 6B (1.14.11.- Histone demethylases) |
|
In relation to the immune system, overexpression of KDM6B (JMJD3) is associated with inflammation [156-157] ... | ||
| mitogen-activated protein kinase 1 (ERK subfamily) |
|
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 [324,403] ... | ||
| mitogen-activated protein kinase 13 (p38 subfamily) |
|
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 [238-239,359,502,527,684] ... | ||
| mitogen-activated protein kinase 14 (p38 subfamily) |
|
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 [238-239,359,502,527,684] ... | ||
| mitogen-activated protein kinase kinase kinase 5 (STE11 family) |
|
ASK1 is included in the GToImmuPdb as it is a molecular target for anti-fibrotic drug development. This kinase acts upstream of p38 MAPK and JNK kinases [281] ... | ||
| mitogen-activated protein kinase kinase kinase 7 (TAK1 subfamily) |
|
TAK1 (MAP3K7) mediates signaling downstream of multiple cytokine receptors and is functionally important in mitogen, immune, and inflammatory signaling pathways [147,552] ... | ||
| mitogen-activated protein kinase kinase kinase kinase 2 (KHS subfamily) |
|
In vitro analyses suggest that GCK plays important roles in the innate immune response and cell signalling [123] ... | ||
| MMP12 (M10: Matrix metallopeptidase) |
|
MMP12 is included in GtoImmuPdb based on its reported involvement in asthma and potential as a asthma therapeutic target. | ||
| MMP14 (M10: Matrix metallopeptidase) |
|
MMP14 is included in GtoImmuPdb based on its contribution to degradation of collagenous cartilage matrix in rheumatoid arthritis. An anti-MMP14 antibody, DX-2400 [164] ... | ||
| MMP3 (M10: Matrix metallopeptidase) |
|
MMP3 is included in GtoImmuPdb based on its reported involvement in inflammatory diseases. | ||
| MMP8 (M10: Matrix metallopeptidase) |
|
MMP8 is included in GtoImmuPdb based on its potential protective role in asthma. | ||
| MMP9 (M10: Matrix metallopeptidase) |
|
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 [347] ... | ||
| mPGES1 (Prostaglandin synthases) |
|
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 [490] ... | ||
| NADPH oxidase 4 (NADPH oxidases) |
|
Nox4 is a known driver of the fibrotic process. We have included Nox4 in GToImmunoPdb based on the association between fibrosis and inflammation. | ||
| otulin (C101: OTULIN peptidase) |
|
Otulin is reported as a negative regulator of inflammation and autoimmunity [149] ... | ||
| p21 (RAC1) activated kinase 1 (PAKA subfamily) |
|
PAK1 is reported to modulate a pro-inflammatory PPARγ/NF-κB cascade in intestinal inflammation, that may be relevant in inflammatory bowel disease and colitis-associated cancer [150] ... | ||
| p21 (RAC1) activated kinase 2 (PAKA subfamily) |
|
Pharmacological inhibition of PAK2 has immunosuppressive effects [476] ... | ||
| peptidyl arginine deiminase 4 (3.5.3.15 Peptidyl arginine deiminases (PADI)) |
|
PADI4 is essential for neutrophil extracellular trap (NET) formation (NETosis) in pathogen elimination. PADI4-formed NETs containing hypercitrullinated histone H3 are detected in several systemic autoimmune diseases, including lupus and rheumatoid arthritis [198] ... | ||
| peptidylprolyl isomerase A (Peptidyl-prolyl cis/trans isomerases) |
|
Cyclophilin A (CypA) is well known as a specific binding protein for cyclosporin A (CsA) [242] ... | ||
| phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases) |
|
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) |
Also involved in neutrophil superoxide generation. |
|
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 [247] ... | |
| phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases) |
Neutrophil degranulation (GO:0043312) [441,653]. |
|
The role of PI3Kγ in immuno-oncology is reviewed in [4] ... | |
| phosphodiesterase 4B (Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs)) |
|
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 ( |
||
| phosphoinositide-3-kinase regulatory subunit 1 (Phosphatidylinositol kinases) |
|
p85α is included in GtoImmuPdb as it is the regulatory subunit of several PI3Ks (e.g. PI3Kδ and PI3Kγ) with roles in leukocyte biology and therefore important for immunity [396] ... | ||
| phosphoinositide kinase, FYVE-type zinc finger containing (1-phosphatidylinositol-3-phosphate 5-kinase family) |
|
PIKfyve is a class III PI kinase. Evidence is revealing a crucial role for PIKfyve in Toll-like receptor (TLR) signaling via production of the cytokines IL-12 and IL-23 [91] ... | ||
| PLA2-G7 (Phospholipase A2, Hydrolases) |
|
PLA2-G7 (also referred to as Lp-PLA2) is a pro-inflammatory enzyme. It cleaves oxidatively damaged phospholipid substrates to generate pro-inflammatory mediators including lysophosphatidylcholine and oxidized nonesterified fatty acids [401] ... | ||
| PLCγ1 (Phosphoinositide-specific phospholipase C) |
|
Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [219,551] ... | ||
| PLCγ2 (Phosphoinositide-specific phospholipase C) |
|
Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [219,551] ... | ||
| proteinase 3 (S1: Chymotrypsin) |
|
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 [335] ... | ||
| protein kinase C delta (Delta subfamily) |
Neutrophil chemotaxis (GO:0030593) |
|
PKCδ is included in GtoImmuPdb based on its GO immune process associations. | |
| protein kinase C epsilon (Eta subfamily) |
|
PKCε is included in GtoImmuPdb based on its GO immune process associations. | ||
| protein kinase C gamma (Alpha subfamily) |
|
PKCγ is included in GtoImmuPdb based on the involvement of other PKC isozymes in immune processes. | ||
| protein kinase C theta (Delta subfamily) |
|
PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [38] ... | ||
| protein kinase C zeta (Iota subfamily) |
|
PKCζ is included in GtoImmuPdb based on its GO process associations. | ||
| protein kinase, DNA-activated, catalytic subunit (Other PIKK family kinases) |
|
Protein kinase, DNA-activated, catalytic polypeptide (DNA-PKcs) principally acts to repair DNA in a process called non-homologous end joining (NHEJ). NHEJ is required for V(D)J recombination (somatic recombination) in developing lymphocytes during the early stages of T and B cell maturation. DNA-PKc ... | ||
| protein tyrosine kinase 2 (Fak family) |
|
FAK and Pyk2 are phosphorylated downstream of the T cell antigen receptor (TCR) to bring about receptor-specific T cell development and activation [113] ... | ||
| protein tyrosine kinase 2 beta (Fak family) |
|
FAK and Pyk2 are phosphorylated downstream of the T cell antigen receptor (TCR) to bring about receptor-specific (e.g. chemokine and integrin receptors) T cell development and activation [113] ... | ||
| protein tyrosine phosphatase non-receptor type 11 (Protein tyrosine phosphatases non-receptor type (PTPN)) |
|
SHP2 regulates programmed cell death 1 (PD-1)-mediated signal transduction and it is therefore involved in immune checkpoint modulation. | ||
| protein tyrosine phosphatase non-receptor type 22 (Protein tyrosine phosphatases non-receptor type (PTPN)) |
|
PTPN22 is a lymphoid-specific, inducible protein tyrosine phosphatase [127] ... | ||
| RAB27A, member RAS oncogene family (RAB subfamily) |
|
Small molecule inhibitors of Rab27a-JFC1 binding, termed Nexinhibs (neutrophil exocytosis inhibitors) demonstrate the druggability of Rab GTPases and inhibition of exocytosis of azurophilic granules in human neutrophils without affecting other important innate immune responses, including phagocytosis and neutrophil extracellular trap production. These thus have potential use as an inhibitor of systemic inflammation [304] ... | ||
| receptor interacting serine/threonine kinase 1 (Receptor interacting protein kinase (RIPK) family) |
|
RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [456,536,585,672] ... | ||
| receptor interacting serine/threonine kinase 2 (Receptor interacting protein kinase (RIPK) family) |
|
RIPK2 is involved in innate immune responses, mediating pro-inflammatory signaling from the bacterial peptidoglycan-sensing NOD1/NOD2 subfamily of innate immune pattern recognition receptors (PRRs) and signalling downstream from the Toll-like receptor (TLR) family of PRRs. Further evidence suggesting an inflammatory role is the targeting of RIPK2 (along with RIPK1/3) by the IAP family E3 ubiquitin ligases (enzymes playing a critical role in innate immunity) [471] ... | ||
| receptor interacting serine/threonine kinase 3 (Receptor interacting protein kinase (RIPK) family) |
|
RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [456,536,585,672] ... | ||
| sphingosine kinase 1 (Sphingosine kinase) |
|
The sphingosine kinases (SPHK1 and SPHK2; SK1, SK2) are key enzymes within the sphingolipid metabolism pathway that promote tumour growth and pathologic inflammation. SK1-selective inhibitors include PF-543 [566-567] ... | ||
| sphingosine kinase 2 (Sphingosine kinase) |
|
The sphingosine kinases (SPHK1 and SPHK2; SK1, SK2) are key enzymes within the sphingolipid metabolism pathway that promote tumour growth and pathologic inflammation. 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 [524] ... | ||
| sPLA2-1B (Phospholipase A2) |
|
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 [356] ... | ||
| spleen associated tyrosine kinase (Syk family) |
|
SYK plays a key role in coupling activated immunoreceptors to downstream cellular responses such as proliferation, differentiation, and phagocytosis. Mast cell, macrophage and B-cell activation (and release of inflammatory modulators) is disrupted by inhibition of SYK-mediated immunoreceptor signalling. Selective SYK inhibitors are being sought for a number of inflammatory conditions including rheumatoid arthritis, B-cell lymphoma and asthma/rhinitis [217,535] ... | ||
| SRC proto-oncogene, non-receptor tyrosine kinase (Src family) |
|
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 [393] ... | ||
| TANK binding kinase 1 (IKK family) |
|
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 [315] ... | ||
| transglutaminase 2 (2.3.2.13 Transglutaminases) |
|
TGM2 upregulation by amyloid β (Aβ)1-42 in THP-1 monocytes increases pro-inflammatory mediators, including IL-1β and IL-6. A transglutaminase inhibitor can blunt this activation, suggesting that TGM2 up-regulation is involved in the pro-inflammatory effect of Aβ1-42 on monocytes [139] ... | ||
| tripartite motif containing 21 (2.3.2.27 RING-type E3 ubiquitin transferase) |
|
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 [489,528,668] ... | ||
| tripartite motif containing 38 (2.3.2.27 RING-type E3 ubiquitin transferase) |
|
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 [710] ... | ||
| TXK tyrosine kinase (Tec family) |
|
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [56] ... | ||
| tyrosine kinase 2 (Janus kinase (JakA) family) |
|
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 [608] ... | ||
| vanin 1 (Hydrolases) |
|
Mounting evidence indicates that vanin 1 is involved in inflammation associated with diseases including systemic lupus erythematosus [624] ... | ||
| YES proto-oncogene 1, Src family tyrosine kinase (Src family) |
|
Although primarily recognised for its oncogenic activity, we have iincluded YES1 in GtoImmuPdb based on its expression in cells of the immune system. | ||
| zeta chain of T cell receptor associated protein kinase 70 (Syk family) |
|
ZAP-70 has much lower intrinsic enzyme activity than SYK, and expression is restricted to T cells and NK cells [30] ... | ||
| Catalytic Receptors | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| AXL receptor tyrosine kinase (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family) |
|
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 [237] ... | ||
| CD40 (Immune checkpoint catalytic receptors, Tumour necrosis factor (TNF) receptor family) |
|
CD40 is a stimulatory receptor and a member of the tumor necrosis factor receptor superfamily (TNFRSF). It is expressed on a variety of immune cells, including macrophages, B cells, and dendritic cells (DCs). CD40 plays a key role in the activation of the immune system. Endogenous ligand is CD154 (C ... | ||
| CIITA (NOD-like receptor family) |
|
CIITA is a transcriptional coactivator for the transcription factor RFX5 [568] ... | ||
| colony stimulating factor 1 receptor (Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family) |
|
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 [4] ... | ||
| Cytokine receptor-like factor 2 (IL-2 receptor family) |
|
Cytokine receptor-like factor 2 is the signal transducing subunit of the functional heterodimeric receptor for thymic stromal lymphopoietin (TSLP). Ligand binding is attributed to the interleukin-7 receptor subunit α. | ||
| DExD/H-box helicase 58 (RIG-I-like receptor family) |
|
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 [416] ... | ||
| DExH-box helicase 58 (RIG-I-like receptor family) |
|
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. | ||
| Fc fragment of IgE receptor Ig (Fc epsilon receptors) |
|
The FCER1G protein is a gamma subunit that is utilised as part of the high affinity IgE receptor (a key complex involved in mediating allergic reactions) and other Fc receptors. | ||
| glucocorticoid-induced TNF receptor (Tumour necrosis factor (TNF) receptor family) |
|
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. | ||
| Granulocyte colony-stimulating factor receptor (Prolactin receptor family) |
|
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) |
|
HSV viral envelope glycoprotein D (gD) binds to this protein and thereby gains entry to the cell. HVEM binds to several TRAFadaptor proteins to mediate intracellular signalling and activation of the immune response. | ||
| integrin, alpha 4 subunit (antigen CD49D, alpha 4 subunit of VLA-4 receptor) (Integrins) |
|
Integrin subunit alpha 4 is the alpha subunit of the α4β1 lymphocyte homing receptor. The cytoplasmic domain of α4 binds tightly to paxillin, a signaling adaptor protein, and this interaction promotes increased cell migration and inhibits cell spreading [240] ... | ||
| integrin, alpha L subunit (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide) (Integrins) |
|
ITGAL associates with the beta 2 chain (ITGB2) integrin and CD18 to form the lymphocyte function-associated antigen-1 (LFA-1) complex. LFA-1 is crucial for leukocyte intercellular adhesion and costimulatory signaling in the immune system. Ligands for LFA-1 are the intercellular adhesion molecules (ICAMs) 1-3. ITGAL is the target of the withdrawn psoriasis monoclonal antibody drug efalizumab ... | ||
| integrin, beta 2 subunit (complement component 3 receptor 3 and 4 subunit) (Integrins) |
|
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 [328] ... | ||
| interferon α/β receptor 1 (Interferon receptor family) |
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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) [97,457] ... | ||
| Interferon α/β receptor 2 (Interferon receptor family) |
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A subunit of the functional receptor for various interferons (NOT interferon γ). | ||
| Interferon γ receptor 1 (Interferon receptor family) |
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A subunit of the functional receptor for interferon γ. | ||
| Interferon γ receptor 2 (Interferon receptor family) |
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A subunit of the functional receptor for interferon γ. | ||
| interferon induced with helicase C domain 1 (RIG-I-like receptor family) |
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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 [9,267,432] ... | ||
| Interferon-λ receptor subunit 1 (IL-10 receptor family) |
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Interferon-λ receptor subunit 1 is the ligand binding component of the functional heterodimeric receptor for interferons λ1, λ2 and λ3 | ||
| Interleukin 10 receptor, β subunit (IL-10 receptor family) |
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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-12 receptor, β1 subunit (IL-12 receptor family) |
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This protein is a subunit of both the IL-12 and IL-23 cytokine receptors. | ||
| Interleukin 13 receptor, α2 (IL-2 receptor family) |
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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 [702] ... | ||
| Interleukin-15 receptor subunit α (IL-2 receptor family) |
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This is the ligand binding subunit of the functional IL-15 receptor complex. | ||
| Interleukin 17 receptor A (IL-17 receptor family) |
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This protein is a common subunit shared by the heterodimeric receptors for interleukins 17 (A, B , C and F) and 25. | ||
| interleukin 17 receptor C (IL-17 receptor family) |
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This is a subunit of the heterodimeric interleukin-17 receptor. | ||
| Interleukin 17 receptor E (IL-17 receptor family) |
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This is a component of the heterodimeric interleukin-17C receptor. | ||
| Interleukin-18 receptor 1 (Immunoglobulin-like family of IL-1 receptors) |
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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) |
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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 [205] ... | ||
| Interleukin-1 receptor-like 2 (Immunoglobulin-like family of IL-1 receptors) |
|
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 [204] ... |
||
| Interleukin 1 receptor, type I (Immunoglobulin-like family of IL-1 receptors) |
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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) |
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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 [220,454] ... | ||
| Interleukin 20 receptor, β subunit (IL-10 receptor family) |
|
Interleukin 20 receptor, β subunit is a component of the functional receptor heterodimers for interleukins 19, 20 and 24. | ||
| Interleukin-22 receptor α2 (IL-10 receptor family) |
|
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 [155,188] ... | ||
| Interleukin 23 receptor (IL-12 receptor family) |
|
This is one of the subunits of the functional IL-23 receptor heterodimer. | ||
| Interleukin 27 receptor, alpha (IL-6 receptor family) |
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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) |
|
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 [592] ... | ||
| Interleukin-2 receptor subunit β (IL-2 receptor family) |
|
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) |
|
IL2RG is a common signal transducing subunit shared by the receptors for several different cytokines, namely the IL-2 receptor heterotrimer, the IL-4 receptor type I, the IL-7 receptor, the IL-9 receptor, the IL-15 receptor and the IL-21 receptor. | ||
| Interleukin-31 receptor, α subunit (IL-6 receptor family) |
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| Interleukin-4 receptor subunit α (IL-2 receptor family) |
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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 [255] ... | ||
| Interleukin 5 receptor, α subunit (IL-3 receptor family) |
|
This is the ligand binding subunit of the functional IL-5 receptor complex. | ||
| Interleukin-6 receptor, α subunit (IL-6 receptor family) |
|
IL6R polymorphisms are associated with asthma risk [189] ... | ||
| Interleukin-6 receptor, β subunit (IL-6 receptor family) |
|
This is the common signal transducing subunit shared by members of the IL-6 family of cytokine receptors [543] ... | ||
| KIT proto-oncogene, receptor tyrosine kinase (Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family) |
|
Stem cell factor (SCF) and its receptor KIT (c-KIT) play an essential part in mast cell biology. In addition to CSF/KIT-mediated regulation of mast cell development, proliferation and survival, KIT is also reported to be involved in the adhesion of mast cells to human airway epithelial cells (a homing and adhesion role), suggesting a mechanism that could be targeted for anti-asthmatic potential [229] ... | ||
| lymphotoxin β receptor (Tumour necrosis factor (TNF) receptor family) |
|
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 [109] ... | ||
| macrophage stimulating 1 receptor (Type X RTKs: HGF (hepatocyte growth factor) receptor family) |
|
The role of RON in immuno-oncology is reviewed in [4] ... | ||
| membrane spanning 4-domains A2 (Fc epsilon receptors) |
|
The protein product of the MS4A2 gene is the β subunit of the FCεRI. It has commonly known as FCER1B. The IgE-receptor (FCεRI), is a tetramer composed of an α, β, and 2 disulfide-linked γ chains expressed on the surface of mast cells and basophils that is crucial for mediating the allergic response. It has been suggested that cytoplasmic FCER1B that is not associated with FCεRI complexes may act as a negative regulator of the signalling pathway to degranulation by sequestering important signalling partners such as the Lyn tyrosine kinase [482] ... | ||
| MER proto-oncogene, tyrosine kinase (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family) |
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Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [54,676] ... | ||
| MET proto-oncogene, receptor tyrosine kinase (Type X RTKs: HGF (hepatocyte growth factor) receptor family) |
|
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) [68] ... | ||
| NLRC3 (NOD-like receptor family) |
|
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 [408,740] ... | ||
| NLRC4 (NOD-like receptor family) |
|
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 [431] ... | ||
| NLRC5 (NOD-like receptor family) |
|
NLRC5 is an intracellular pattern recognition receptor mediating an innate immune response to viral infection [453] ... | ||
| NLRP1 (NOD-like receptor family) |
|
NLRP1 is a cytosolic sensor of bacterial infection and regulator of the resulting innate immune response [106] ... | ||
| NLRP10 (NOD-like receptor family) |
|
NLRP10 is an intracellular pattern recognition receptor (PRR) that has apoptotic and anti-inflammatory functions [284] ... | ||
| NLRP13 (NOD-like receptor family) |
|
NLRP proteins are critical components of inflammasome complexes and are thereby involved in inflammasome-mediated activation of proinflammatory caspases. NLRP13 has the typical PYD-NACHT-LRR domain structure common to the NLRP protein family [648] ... | ||
| NLRP14 (NOD-like receptor family) |
|
NLRP proteins are critical components of inflammasome complexes and are thereby involved in inflammasome-mediated activation of proinflammatory caspases. NLRP14 has the typical PYD-NACHT-LRR domain structure common to the NLRP protein family [648] ... | ||
| NLRP3 (NOD-like receptor family) |
|
NLRP3 is a component of the NLRP3 inflammasome, a protein complex which activates caspase-1, and plays an important role in the regulation of inflammation and apoptosis (pyroptosis). Drug-like NLRP3 inhibitors are under investigation as novel therapeutics for the treatment of autoinflammatory diseases and neuroinflammation, as an alternative to anti-IL-1 therapies such as |
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| NLRP6 (NOD-like receptor family) |
|
NLRP6 is an intracellular pattern recognition receptor (PRR). It is a member of the NACHT, LRR and PYD domains-containing protein (NALP) subfamily of PRRs. The presence of NALPs in inflammasomes underlies their involvement in regulating proinflammatory caspases (esp. caspase 1) ... | ||
| NLRP7 (NOD-like receptor family) |
|
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) |
|
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) |
|
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) |
|
NOD2 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing muramyl dipeptide (MDP). Mutations in NOD proteins are implicated in various inflammatory diseases associated with aberrant NF-κB activity; NF-κB being a major ... |
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| Oncostatin M-specific receptor, β subunit (IL-6 receptor family) |
|
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 ... |
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| OX40 (Tumour necrosis factor (TNF) receptor family) |
|
The OX40/OX40L pair is involved in late T-cell costimulatory signalling and both are transiently expressed following antigen recognition. Blocking OX40/OX40L is reported to prevent the development of disease in in vivo autoimmune and inflammatory disease models [692] ... | ||
| receptor activator of NF-kappa B (Tumour necrosis factor (TNF) receptor family) |
|
RANK is the receptor for RANK-ligand (RANKL). It is associated with immune cell function and lymph node development, in addition to bone remodeling and repair, thermal regulation, and mammary gland development. Signals to NF-κB and JNK via TRAF adaptor proteins. | ||
| RTP Type C (Receptor tyrosine phosphatase (RTP) family) |
|
CD45 is a high molecular weight cell surface glycoprotein expressed by cells of hematopoietic origin. Alternate transcripts lead to expression of isoforms that differ in their extracellular (ligand binding) domain (potentially facilitating differential and/or cell type specific biological functions [148] ... | ||
| single Ig and TIR domain containing (Immunoglobulin-like family of IL-1 receptors) |
|
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 [435] ... | ||
| TEK receptor tyrosine kinase (Type XII RTKs: TIE family of angiopoietin receptors) |
|
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 [326] ... | ||
| TLR1 (Toll-like receptor family) |
|
TLR1/2 heterodimers detect and respond to bacterial triacyl lipopeptides [656] ... | ||
| TLR10 (Toll-like receptor family) |
|
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 [486] ... | ||
| TLR2 (Toll-like receptor family) |
|
TLR1/2 and 2/6 heterodimers detect and initiate an immune response to triacylated and diacylated [447] ... | ||
| TLR3 (Toll-like receptor family) |
|
TLR3 is an endosomal anti-viral receptor [656] ... | ||
| TLR4 (Toll-like receptor family) |
|
TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [64,514] ... | ||
| TLR5 (Toll-like receptor family) |
|
TLR5 induces a pro-inflammatory response upon detection of extracellular bacterial flagellin from invading mobile bacteria [431] ... | ||
| TLR6 (Toll-like receptor family) |
|
TLR6 forms heterodimers with TLR2 to detect a wide range of bacterial lipopeptides (LP) from bacterial cell membranes, and effect an immune response [185] ... | ||
| TLR7 (Toll-like receptor family) |
|
TLR7 is an endosomal receptor detecting ssRNA [656] ... | ||
| TLR8 (Toll-like receptor family) |
|
TLR8 is an endosomal receptor detecting ssRNA [656] ... | ||
| TLR9 (Toll-like receptor family) |
|
TLR9 is an endosomal receptor detecting viral and bacterial CpG DNA and genomic DNA from some protozoan species [656] ... | ||
| tumor necrosis factor receptor 1 (Tumour necrosis factor (TNF) receptor family) |
|
We have included TNFR1 in GtoImmuPdb based on it being a receptor for lymphotoxin-α, a cytotoxic protein performing a variety of important roles in immune system development and regulation [234,458] ... | ||
| tumor necrosis factor receptor 2 (Tumour necrosis factor (TNF) receptor family) |
|
TNFR2 is a receptor for lymphotoxin-α, and the membrane form of tumour necrosis factor (TNF). It plays a variety of important roles in immune system development and regulation [234,458] ... | ||
| TYRO3 protein tyrosine kinase (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family) |
|
TYRO3 is a negative regulator of type 2 immunity [107] ... | ||
| Transporters | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| NRAMP1 (SLC11 family of proton-coupled metal ion transporters) |
|
NRAMP1 / SLC11A1 appears to be involved in macrophage antimicrobial action against intracellular pathogens, and although its precise mechanism is not fully resolved, evidence indicates its involvement in the activation of phagocytes and synthesis of proinflammatory cytokines. Polymorphisms in the human SLC11A1 gene have been associated with susceptibility to several infections [77,596,601] ... | ||
| Peptide transporter 3 (SLC15 family of peptide transporters) |
|
SLC15A3 and SLC15A4 are preferentially expressed by cells within the lymphatic system, including dendritic cells. Expression of these two genes is upregulated in response to TLR stimulation [446,597] ... | ||
| Peptide transporter 4 (SLC15 family of peptide transporters) |
|
SLC15A4 is an oligopeptide transporter that is expressed in early endosomes, and which is involved in NOD1-dependent NF-κB signaling [358] ... | ||
| Other Protein Targets | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| absent in melanoma 2 (Absent in melanoma (AIM)-like receptors (ALRs)) |
|
AIM2 primarily senses cytosolic DNA and initiates formation of an inflammasome to drive IL-1β cleavage and secretion. | ||
| advanced glycosylation end-product specific receptor (Immunoglobulin like domain containing proteins) |
|
RAGE is a single chain, membrane bound immunoglobulin type protein [452,564,714] ... | ||
| amyloid P component, serum (Serum pentraxins) |
|
Serum amyloid P or pentraxin 2 is a multi-function circulating plasma protein. It exhibits activity as a soluble pattern recognition receptor of the innate immune system, that can bind DNA and histones when these are released from damaged cells. A recombinant form of human pentraxin 2 (PRM-151; Promedior) has been reported as an anti-fibrotic immunomodulator [172] ... |
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| baculoviral IAP repeat containing 2 (Inhibitors of apoptosis (IAP) protein family) |
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