Transient receptor potential cation channel subfamily V member 1
Also known as: TRPV1, VR1
Function
Non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Activated by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius. Upon activation, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis.
Classification
- Family (Pfam)
- PF00023 Ank, PF12796 Ank_2, PF00520 Ion_trans
- InterPro
- Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ion_trans_dom, TRPV, TrpV1-4
- Functional cluster
- Serine/Threonine Protein Kinases
Experimental structures · PDB · 8
- 6L93 X-ray 4.47A
- 8GF8 EM 2.90A
- 8GF9 EM 2.58A
- 8GFA EM 2.29A
- 8JQR EM 2.75A
- 8X94 EM 2.55A
- 8YCP EM 2.87A
- 9P6B EM 2.74A
A predicted model is available from AlphaFold.
Gene Ontology · 30
- GO:0032591 dendritic spine membrane
- GO:0098982 GABA-ergic synapse
- GO:0016020 membrane
- GO:0005886 plasma membrane
- GO:0045211 postsynaptic membrane
- GO:0005524 ATP binding
- GO:0005262 calcium channel activity
- GO:0005516 calmodulin binding
- GO:0005231 excitatory extracellular ligand-gated monoatomic ion channel activity
- GO:0005230 extracellular ligand-gated monoatomic ion channel activity
- GO:0015278 intracellularly gated calcium channel activity
- GO:0046872 metal ion binding
- GO:0035091 phosphatidylinositol binding
- GO:0051219 phosphoprotein binding
- GO:0097603 temperature-gated ion channel activity
- GO:0004888 transmembrane signaling receptor activity
- GO:0005245 voltage-gated calcium channel activity
- GO:0098703 calcium ion import across plasma membrane
- GO:0070588 calcium ion transmembrane transport
- GO:0007166 cell surface receptor signaling pathway
- GO:0071468 cellular response to acidic pH
- GO:0071312 cellular response to alkaloid
- GO:0071318 cellular response to ATP
- GO:0034605 cellular response to heat
- GO:0007635 chemosensory behavior
- GO:0050965 detection of temperature stimulus involved in sensory perception of pain
- GO:0000122 negative regulation of transcription by RNA polymerase II
- GO:0051289 protein homotetramerization
- GO:1901594 response to capsazepine
- GO:0050955 thermoception
Drugs targeting this protein · 13
- ACETAMINOPHEN opener
- RESINIFERATOXIN agonist
- SB-705498 antagonist
- NGD-8243 antagonist
- AMG-517 antagonist
- MAVATREP antagonist
- CAPSAICIN opener
- ZUCAPSAICIN agonist
- AZD1386 antagonist
- ABT-102 antagonist
- GRC-6211 antagonist
- JTS-653 antagonist
- DWP05195 antagonist
Related proteins · sequence + function similarity
- Transient receptor potential cation channel subfamily V member 1 0.98
- Transient receptor potential cation channel subfamily V member 1 0.98
- Transient receptor potential cation channel subfamily V member 1 0.98
- Transient receptor potential cation channel subfamily V member 1 0.97
- Transient receptor potential cation channel subfamily V member 1 0.96
- Transient receptor potential cation channel subfamily V member 4 0.90
- Transient receptor potential cation channel subfamily V member 4 0.89
- Transient receptor potential cation channel subfamily V member 4 0.89
- Transient receptor potential cation channel subfamily V member 4 0.89
- Transient receptor potential cation channel subfamily V member 3 0.88
- Transient receptor potential cation channel subfamily V member 3 0.87
- Transient receptor potential cation channel subfamily V member 2 0.86
Co-cited proteins · studied together in the literature
- Transient receptor potential cation channel subfamily V member 3 1 shared papers
- Transient receptor potential cation channel subfamily V member 1 1 shared papers
- Transient receptor potential cation channel subfamily V member 1 1 shared papers
- Phosphofurin acidic cluster sorting protein 2 1 shared papers
- NAD-dependent protein deacetylase sirtuin-1 1 shared papers
- Histone deacetylase 1 1 shared papers
Literature · 11 cited papers
- Human TRPV1 structure and inhibition by the analgesic SB-366791. Nat. Commun. · 2023
- A recurrent de novo PACS2 heterozygous missense variant causes neonatal-onset developmental epileptic encephalopathy, facial dysmorphism, and cerebellar dysgenesis. Am. J. Hum. Genet. · 2018
- DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature · 2006
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Molecular determinants of vanilloid sensitivity in TRPV1. J. Biol. Chem. · 2004
- Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures. Exp. Dermatol. · 2004
- TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature · 2002
- The tissue distribution and functional characterization of human VR1. Biochem. Biophys. Res. Commun. · 2001
- Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome Res. · 2001
- Pharmacological differences between human and rat vanilloid receptor 1 (VR1). Br. J. Pharmacol. · 2001
- Cloning and functional expression of a human orthologue of rat vanilloid receptor-1. Pain · 2000