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1.A.4.2.1
Vanilloid receptor subtype 1 (VR1 or TRPV1) (noxious, heat-sensitive [opens with increasing temperatures; e.g., >42°C]; also sensitive to acidic pH and voltage; serves as the receptor for the alkaloid irritant, capsaicin, for resiniferatoxin and for endo-cannabinoids (Murillo-Rodriguez et al. 2017). It is regulated by bradykinin and prostaglandin E2) (contains a C-terminal region, adjacent to the channel gate, that determines the coupling of stimulus sensing and channel opening (Garcia-Sanz et al., 2007; Matta and Ahern, 2007). Activated and sensitized by local anesthetics in sensory neurons (Leffler et al., 2008). A bivalent tarantula toxin activates the capsaicin receptor (TRPV1) by targeting the outer pore domain (Bohlen et al., 2010). Single-channel properties of TRPV1 are modulated by phosphorylation (Studer and McNaughton, 2010). TRPV1 mediates an itch associated response (Kim et al., 2011). The thermosensitive TRP channel pore turret is part of the temperature activation apparatus (Yang et al., 2010). Modular thermal sensors in temperature-gated transient receptor potential (TRP) channels have been identified (Yao et al., 2011). TRPV1 opening is associated with major structural rearrangements in the outer pore, including the pore helix and selectivity filter, as well as pronounced dilation of a hydrophobic constriction at the lower gate, suggesting a dual gating mechanism (Cao et al. 2013). Allosteric coupling between upper and lower gates may account for modulation exhibited by TRPV1 and other TRP channels (Liao et al. 2013).  Regulates longevity and metabolism by neuropeptides in mice (Riera et al. 2014).

Accession Number:O35433
Protein Name:VR1
Length:838
Molecular Weight:94948.00
Species:Rattus norvegicus (Rat) [10116]
Number of TMSs:7
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate protons, sodium ions, Ca2+

Cross database links:

Genevestigator: O35433
eggNOG: roNOG04377
DIP: DIP-46106N
RefSeq: NP_114188.1   
Entrez Gene ID: 83810   
Pfam: PF00023   
KEGG: rno:83810   

Gene Ontology

GO:0005829 C:cytosol
GO:0030425 C:dendrite
GO:0016021 C:integral to membrane
GO:0043025 C:neuronal cell body
GO:0005886 C:plasma membrane
GO:0045202 C:synapse
GO:0005524 F:ATP binding
GO:0005262 F:calcium channel activity
GO:0005516 F:calmodulin binding
GO:0017081 F:chloride channel regulator activity
GO:0006816 P:calcium ion transport
GO:0071363 P:cellular response to growth factor stimulus
GO:0071502 P:cellular response to temperature stimulus
GO:0007204 P:elevation of cytosolic calcium ion concentr...
GO:0014047 P:glutamate secretion
GO:0001774 P:microglial cell activation
GO:0090212 P:negative regulation of establishment of blo...
GO:0043065 P:positive regulation of apoptosis
GO:0060454 P:positive regulation of gastric acid secretion
GO:0045429 P:positive regulation of nitric oxide biosynt...
GO:0009408 P:response to heat
GO:0043434 P:response to peptide hormone stimulus
GO:0009268 P:response to pH

References (22)

[1] “The capsaicin receptor: a heat-activated ion channel in the pain pathway.”  Caterina M.J.et.al.   9349813
[2] “Molecular cloning of an N-terminal splice variant of the capsaicin receptor. Loss of N-terminal domain suggests functional divergence among capsaicin receptor subtypes.”  Schumacher M.A.et.al.   10644739
[3] “Propofol activates vanilloid receptor channels expressed in human embryonic kidney 293 cells.”  Tsutsumi S.et.al.   11578842
[4] “The genomic organization of the gene encoding the vanilloid receptor: evidence for multiple splice variants.”  Xue Q.et.al.   11549313
[5] “Identification of an aspartic residue in the P-loop of the vanilloid receptor that modulates pore properties.”  Garcia-Martinez C.et.al.   10931826
[6] “Induction of vanilloid receptor channel activity by protein kinase C.”  Premkumar L.S.et.al.   11140687
[7] “Biochemical characterization of the vanilloid receptor 1 expressed in a dorsal root ganglia derived cell line.”  Jahnel R.et.al.   11683872
[8] “Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.”  Chuang H.H.et.al.   11418861
[9] “Direct phosphorylation of capsaicin receptor VR1 by protein kinase Cepsilon and identification of two target serine residues.”  Numazaki M.et.al.   11884385
[10] “Protein kinase C(alpha) is required for vanilloid receptor 1 activation. Evidence for multiple signaling pathways.”  Olah Z.et.al.   12095983
[11] “cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation.”  Bhave G.et.al.   12194871
[12] “Structural determinant of TRPV1 desensitization interacts with calmodulin.”  Numazaki M.et.al.   12808128
[13] “Protein kinase C phosphorylation sensitizes but does not activate the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1).”  Bhave G.et.al.   14523239
[14] “A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity.”  Prescott E.D.et.al.   12764195
[15] “Modulation of TRPV1 by nonreceptor tyrosine kinase, c-Src kinase.”  Jin X.et.al.   15084474
[16] “Agonist recognition sites in the cytosolic tails of vanilloid receptor 1.”  Jung J.et.al.   12228246
[17] “Phosphorylation of vanilloid receptor 1 by Ca2+/calmodulin-dependent kinase II regulates its vanilloid binding.”  Jung J.et.al.   14630912
[18] “Molecular determinants of vanilloid sensitivity in TRPV1.”  Gavva N.R.et.al.   14996838
[19] “TRPV1 acts as proton channel to induce acidification in nociceptive neurons.”  Hellwig N.et.al.   15173182
[20] “Interaction between protein kinase Cmu and the vanilloid receptor type 1.”  Wang Y.et.al.   15471852
[21] “Identification of a tetramerization domain in the C-terminus of the vanilloid receptor.”  Garcia-Sanz N.et.al.   15190102
[22] “The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity.”  Lishko P.V.et.al.   17582331
Structure:
2NYJ   2PNN   3J5P   3J5Q   3J5R   3SUI   3J9J   5irx     

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FASTA formatted sequence
1:	MEQRASLDSE ESESPPQENS CLDPPDRDPN CKPPPVKPHI FTTRSRTRLF GKGDSEEASP 
61:	LDCPYEEGGL ASCPIITVSS VLTIQRPGDG PASVRPSSQD SVSAGEKPPR LYDRRSIFDA 
121:	VAQSNCQELE SLLPFLQRSK KRLTDSEFKD PETGKTCLLK AMLNLHNGQN DTIALLLDVA 
181:	RKTDSLKQFV NASYTDSYYK GQTALHIAIE RRNMTLVTLL VENGADVQAA ANGDFFKKTK 
241:	GRPGFYFGEL PLSLAACTNQ LAIVKFLLQN SWQPADISAR DSVGNTVLHA LVEVADNTVD 
301:	NTKFVTSMYN EILILGAKLH PTLKLEEITN RKGLTPLALA ASSGKIGVLA YILQREIHEP 
361:	ECRHLSRKFT EWAYGPVHSS LYDLSCIDTC EKNSVLEVIA YSSSETPNRH DMLLVEPLNR 
421:	LLQDKWDRFV KRIFYFNFFV YCLYMIIFTA AAYYRPVEGL PPYKLKNTVG DYFRVTGEIL 
481:	SVSGGVYFFF RGIQYFLQRR PSLKSLFVDS YSEILFFVQS LFMLVSVVLY FSQRKEYVAS 
541:	MVFSLAMGWT NMLYYTRGFQ QMGIYAVMIE KMILRDLCRF MFVYLVFLFG FSTAVVTLIE 
601:	DGKNNSLPME STPHKCRGSA CKPGNSYNSL YSTCLELFKF TIGMGDLEFT ENYDFKAVFI 
661:	ILLLAYVILT YILLLNMLIA LMGETVNKIA QESKNIWKLQ RAITILDTEK SFLKCMRKAF 
721:	RSGKLLQVGF TPDGKDDYRW CFRVDEVNWT TWNTNVGIIN EDPGNCEGVK RTLSFSLRSG 
781:	RVSGRNWKNF ALVPLLRDAS TRDRHATQQE EVQLKHYTGS LKPEDAEVFK DSMVPGEK