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transient receptor potential cation channel subfamily V member 1; osm-9-like TRP channel 1; vanilloid receptor 1; VR1 capsaicin receptor (TRPV1, OTRPC1)
Function:
1) receptor-activated non-selective Ca+ channel
2) detection of noxious chemical & thermal stimuli
3) mediates proton influx
4) intracellular acidosis in nociceptive neurons
5) mediation of inflammatory pain & hyperalgesia
- itch receptor [2]
6) sensitized by phosphatidylinositol second messenger system activated by receptor tyrosine kinases involving PKC & PLC
7) may form heteromeric channel with TRPV3
8) interacts with calmodulin, PRKCM, CSK, PRKCG, NTRK1
9) phosphorylation by PKA reverses capsaicin-induced
10) dephosphorylation at multiple sites, probably including Ser-117 (major phosphorylation site)
11) phosphorylation by CAMK2 regulates binding to vanilloids
12) phosphorylated & modulated by PKCM & PKCZ
13) dephosphorylation by calcineurin desensitizatizes receptor; phosphorylation by CAMKII recovers activity
14) responses evoked by low pH & heat, & capsaicin, antagonized by capsazepine
Structure: self-associates, homotetramer
Compartment: cell membrane
Alternative splicing: named isoforms=2
Expression:
- widely expressed at low levels
- expressed in nerves & joints
- expression is elevated in dorsal root ganglia
- in skin, expressed in cutaneous sensory nerve fibers, mast cells, epidermal keratinocytes, dermal blood vessels, the inner root sheet & infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts, secretory portion of eccrine sweat glands
Comparative biology:
- inhibition of TRPV1 extends lifespan of mice & improves insulin sensitivity [3]
General
Ca+2 channel
glycoprotein
phosphoprotein
transient receptor potential cation channel subfamily V (TRPV)
transmembrane 6 protein
Properties
SIZE: MW = 95 kD
entity length = 839 aa
COMPARTMENT: cellular membrane
MOTIF: cytoplasmic domain {1-433}
MOTIF: Ser phosphorylation site {S117}
Thr phosphorylation site {T145}
ankyrin repeat
NAME: ankyrin repeat
SITE: 201-230
ankyrin repeat
NAME: ankyrin repeat
SITE: 248-277
ankyrin repeat
NAME: ankyrin repeat
SITE: 333-362
Thr phosphorylation site {T371}
transmembrane domain {434-454}
exoplasmic loop {455-476}
transmembrane domain {477-497}
cytoplasmic loop {498-513}
MOTIF: Ser phosphorylation site {S502}
transmembrane domain {514-534}
exoplasmic loop {535-535}
transmembrane domain {536-556}
cytoplasmic loop {557-579}
transmembrane domain {580-600}
exoplasmic loop {601-659}
MOTIF: N-glycosylation site {N604}
transmembrane domain {660-680}
cytoplasmic domain {681-839}
MOTIF: AD {685-713}
Thr phosphorylation site {T705}
calmodulin binding site
SITE: 768-802
FOR-BINDING-OF: calmodulin
Ser phosphorylation site {S775}
PIP2i {778-793}
Ser phosphorylation site {S801}
Ser phosphorylation site {S821}
ION-PERMEABILITY: Ca+2
Database Correlations
OMIM 602076
UniProt Q8NER1
PFAM correlations
References
- UniProt :accession Q8NER1
- Mishra SK, Hoon MA.
The cells and circuitry for itch responses in mice.
Science 2013 May 24; 340:968
PMID: 23704570
- Steven Coles cites Dillin et al at UC Berkeley &
The Salk Institute for Biological Studies to appear
in the journal Cell.
GRG bulletin board May 22, 2014 & May 27, 2014