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Targets Associated to Immuno Processes - Barrier integrity

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

Barrier integrity Download as CSV
GPCRs
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
5-HT2A receptor
(5-Hydroxytryptamine receptors)
  • virus receptor activity (GO:0001618) IEA
The chemoattractant properties of 5-HT on human eosinophils is mediated by 5-HT2A receptor [7] ...
AT1 receptor
(Angiotensin receptors)
  • viral entry into host cell (GO:0046718) IDA
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 [70] ...
CCR5
(Chemokine receptors)
  • virus receptor activity (GO:0001618) IEA
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 [1] ...
CXCR4
(Chemokine receptors)
  • virus receptor activity (GO:0001618) 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 [63,68,78-79] ...
GPR15
(Class A Orphans)
  • virus receptor activity (GO:0001618) IDA
  • viral entry into host cell (GO:0046718) IDA
Several lines of evidence suggest that GPR15 is a chemoattractant receptor supporting the trafficking of T effector cells to the colon [25,51,53,71] ...
Enzymes
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
Aminopeptidase N
(M1: Aminopeptidase N)
  • virus receptor activity (GO:0001618) IEA
Pharmacological inhibitors of APN are being investigated to counter the dysregulated APN expression that has been associated with inflammatory diseases [6,46] ...
beta adrenergic receptor kinase 1
(Beta-adrenergic receptor kinases (βARKs))
  • viral entry into host cell (GO:0046718) IMP
GRK2 (βARK1) expression and activity are downregulated in lymphocytes from RA patients [44] ...
cathepsin B
(C1: Papain)
  • viral entry into host cell (GO:0046718) IEA
Cathepsins B, H and L have become important therapeutic targets as their proteolytic activity has been implicated in several pathological inflammatory conditions, such as arthritis and periodontitis. Therefore, pharmacological inhibitors of these enzymes are in development as novel therapeutics.
cathepsin L
(C1: Papain)
  • receptor-mediated endocytosis of virus by host cell (GO:0019065) IDA
  • viral entry into host cell (GO:0046718) IDA
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.
phosphoinositide kinase, FYVE-type zinc finger containing
(1-phosphatidylinositol-3-phosphate 5-kinase family)
  • receptor-mediated endocytosis of virus by host cell (GO:0019065) IDA
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 [8] ...
SRC proto-oncogene, non-receptor tyrosine kinase
(Src family)
  • entry of bacterium into host cell (GO:0035635) TAS
Src family tyrosine kinases act as general modulators of immune cell signaling, playing diverse signaling functions, both inhibitory and stimulatory, in immunoreceptor and integrin signaling pathways [45] ...
tripartite motif containing 21
(2.3.2.27 RING-type E3 ubiquitin transferase)
  • regulation of viral entry into host cell (GO:0046596) IBA
  • positive regulation of viral entry into host cell (GO:0046598) IEA
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 [56,62,75] ...
tripartite motif containing 38
(2.3.2.27 RING-type E3 ubiquitin transferase)
  • regulation of viral entry into host cell (GO:0046596) IBA
  • positive regulation of viral entry into host cell (GO:0046598) IDA
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 [82] ...
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)
  • virus receptor activity (GO:0001618) IDA
  • viral entry into host cell (GO:0046718) IMP
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 [26] ...
CIITA
(NOD-like receptor family)
  • negative regulation of viral entry into host cell (GO:0046597) IDA
CIITA is a transcriptional coactivator for the transcription factor RFX5 [69] ...
herpes virus entry mediator
(Immune checkpoint catalytic receptors, Tumour necrosis factor (TNF) receptor family)
  • virus receptor activity (GO:0001618) IEA
HSV viral envelope glycoprotein D (gD) binds to this protein and thereby gains entry to the cell. HVEM binds to several TRAFadaptor proteins to mediate intracellular signalling and activation of the immune response.
KIT proto-oncogene, receptor tyrosine kinase
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • melanocyte adhesion (GO:0097326) ISS
Stem cell factor (SCF) and its receptor KIT (c-KIT) play an essential part in mast cell biology. In addition to CSF/KIT-mediated regulation of mast cell development, proliferation and survival, KIT is also reported to be involved in the adhesion of mast cells to human airway epithelial cells (a homing and adhesion role), suggesting a mechanism that could be targeted for anti-asthmatic potential [24] ...
OX40
(Tumour necrosis factor (TNF) receptor family)
  • virus receptor activity (GO:0001618) IEA
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 [80] ...
TYRO3 protein tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • virus receptor activity (GO:0001618) IDA
TYRO3 is a negative regulator of type 2 immunity [9] ...
Other Protein Targets
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
amyloid P component, serum
(Serum pentraxins)
  • negative regulation of viral entry into host cell (GO:0046597) IDA
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 [17] ...
CD209 molecule
(C-type lectin-like receptors (CLRs))
  • virus receptor activity (GO:0001618) IDA
  • viral entry into host cell (GO:0046718) IDA
DC-SIGN is a pathogen-recognition receptor involved in initiating the primary immune response to various viral and bacterial pathogens, as well as antigen presentation and initiation of the adaptive immune response.
CD4
(CD molecules)
  • positive regulation of viral entry into host cell (GO:0046598) IDA
  • virus receptor activity (GO:0001618) IEA
CD4 is being targeted for clinical utility in inflammatory diseases like rheumatoid arthritis (RA), neoplasms derived from T helper cells (T cell lymphomas and related malignancies), and for anti-HIV potential. Depending on the design of CD4 targeting antibodies, they can produce immunosuppressive effects via activation of Tregs and induction of tolerance, block HIV binding to CD4 to prevent HIV infection, or induce depletion of CD4+ T cells by apoptosis, ADCC, or CDC [36,76] ...
CD74
(CD molecules)
  • negative regulation of viral entry into host cell (GO:0046597) IDA
  • positive regulation of viral entry into host cell (GO:0046598) IDA
CD74 is a type II transmembrane glycoprotein which associates with the MHC class II α and β chains and directs the transport of class II molecules to lysosomal and endosomal compartments [10] ...
CD80
(Other immune checkpoint proteins, CD molecules)
  • virus receptor activity (GO:0001618) IEA
CD80 (B7-1) is expressed on dendritic cells and activated B cells and monocytes. It is required to provide a costimulatory signal necessary for T cell activation and survival. CD80 works in concert with CD86 to prime T cells. CD80 binds CD28 and CTLA-4 on T cells. It is the interaction with CTLA-4 t ...
CD86
(Other immune checkpoint proteins, CD molecules)
  • virus receptor activity (GO:0001618) IEA
CD86 (B7-2) is a type I membrane immunoglobulin. It is expressed on antigen-presenting cells and in association with CD80 provides the costimulatory signal necessary for T cell activation and survival. CD86 interacts with CD28 or CTLA-4 on T cells. It is the interaction with CTLA-4 that is targeted ...
nectin cell adhesion molecule 4
(Immunoglobulin C2-set domain-containing proteins)
  • virus receptor activity (GO:0001618) IEA
Nectin 4 is the target of the immuno-oncology monoclonal antibody enfortumab vedotin, which was FDA approved in 2019 as a therapy for locally advanced/metastatic urothelial cancer that has been previously treated using a PD-1 or PD-L1 immune checkpoint inhibitor and platinum-containing chemotherap ...
neural cell adhesion molecule 1 (CD56)
(CD molecules)
  • virus receptor activity (GO:0001618) IEA
CD56 is expressed by neurons, glia, skeletal muscle and natural killer (NK) cells. The CD56bright NK cell subset, predominantly present in secondary lymphoid tissues, are capable of high levels of cytokine production, are enriched at inflammatory sites [12] ...
neuropilin 1
(Neuropilins and Plexins)
  • viral entry into host cell (GO:0046718) IDA
NRP1 is expressed on several types of immune cells (e.g. T cells, dendritic cells) [64,73] ...
PVR cell adhesion molecule
(Immunoglobulin like domain containing proteins)
  • virus receptor activity (GO:0001618) IEA
The PVR protein (a.k.a. CD155) is a single-pass immunoglobulin-like adhesion molecule. It plays a role in modulating natural killer and T cell-mediated immunity. PVR expression is upregulated in response to exposure to different stimuli, such as Toll-like receptor activation or T cell receptor stimulation [34,83] ...