Q8NER1 (TRPV1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transient receptor potential cation channel subfamily V member 1
Short name=TrpV1

Alternative name(s):
Capsaicin receptor
Osm-9-like TRP channel 1
Short name=OTRPC1
Vanilloid receptor 1

Gene names

Name:	TRPV1
Synonyms:	VR1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	839 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor-activated 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. May be 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. 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 By similarity. Ref.1 Ref.2 Ref.3
Enzyme regulation	Channel activity is activated via the interaction with PIRT and phosphatidylinositol 4,5-bisphosphate (PIP2). Both PIRT and PIP2 are required to activate channel activity By similarity.
Subunit structure	Self-associates. Probably homotetramer. May also form a heteromeric channel with TRPV3. Interacts with calmodulin, PIRT, PRKCM and CSK. Interacts with PRKCG and NTRK1, probably by forming a trimeric complex By similarity. Ref.9
Subcellular location	Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein By similarity. Cell projection › dendritic spine membrane; Multi-pass membrane protein By similarity.
Tissue specificity	Widely expressed at low levels. 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 and the infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts, and the secretory portion of eccrine sweat glands (at protein level). Ref.1 Ref.2 Ref.10
Domain	The association domain (AD) is necessary for self-association By similarity.
Post-translational modification	Phosphorylation by PKA reverses capsaicin-induced dephosphorylation at multiple sites, probably including Ser-117 as a major phosphorylation site. Phoshphorylation by CAMKII seems to regulate binding to vanilloids. Phosphorylated and modulated by PRKCE, PRKCM and probably PRKCZ. Dephosphorylation by calcineurin seems to lead to receptor desensitization and phosphorylation by CAMKII recovers activity By similarity.
Miscellaneous	Responses evoked by low pH and heat, and capsaicin can be antagonized by capsazepine.
Sequence similarities	Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV1 sub-subfamily. [View classification] Contains 6 ANK repeats.
Sequence caution	The sequence AAG43467.1 differs from that shown. Reason: Frameshift at position 498.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Cell junction Cell membrane Cell projection Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Polymorphism
Domain	ANK repeat Repeat Transmembrane Transmembrane helix
Ligand	ATP-binding Calcium Calmodulin-binding Nucleotide-binding
Molecular function	Calcium channel Ion channel
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell surface receptor signaling pathway Traceable author statement PubMed 9349813. Source: ProtInc chemosensory behavior Traceable author statement PubMed 9349813. Source: ProtInc thermoception Inferred from direct assay PubMed 123456. Source: MGI
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW dendritic spine membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement PubMed 9349813. Source: ProtInc postsynaptic membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium channel activity Traceable author statement PubMed 9349813. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 839	839	Transient receptor potential cation channel subfamily V member 1		PRO_0000215338
Regions
	Topological domain	1 – 433	433	Cytoplasmic Potential
	Transmembrane	434 – 454	21	Helical; Potential
	Topological domain	455 – 476	22	Extracellular Potential
	Transmembrane	477 – 497	21	Helical; Potential
	Topological domain	498 – 513	16	Cytoplasmic Potential
	Transmembrane	514 – 534	21	Helical; Potential
	Topological domain	535	1	Extracellular Potential
	Transmembrane	536 – 556	21	Helical; Potential
	Topological domain	557 – 579	23	Cytoplasmic Potential
	Transmembrane	580 – 600	21	Helical; Potential
	Intramembrane	611 – 647	37	Pore-forming; Probable
	Transmembrane	660 – 680	21	Helical; Potential
	Topological domain	681 – 839	159	Cytoplasmic Potential
	Repeat	111 – 153	43	ANK 1
	Repeat	154 – 200	47	ANK 2
	Repeat	201 – 247	47	ANK 3
	Repeat	248 – 283	36	ANK 4
	Repeat	284 – 332	49	ANK 5
	Repeat	333 – 359	27	ANK 6
	Region	685 – 713	29	AD By similarity
	Region	768 – 802	35	Interaction with calmodulin By similarity
	Region	778 – 793	16	Required for PIP2-mediated channel inhibition By similarity
Amino acid modifications
	Modified residue	117	1	Phosphoserine By similarity
	Modified residue	145	1	Phosphothreonine By similarity
	Modified residue	371	1	Phosphothreonine By similarity
	Modified residue	502	1	Phosphoserine; by PKC/PRKCE By similarity
	Modified residue	705	1	Phosphothreonine By similarity
	Modified residue	775	1	Phosphoserine By similarity
	Modified residue	801	1	Phosphoserine; by PKC/PRKCE By similarity
	Modified residue	821	1	Phosphoserine By similarity
	Glycosylation	604	1	N-linked (GlcNAc...) By similarity
Natural variations
	Natural variant	91	1	P → S. Ref.2 Corresponds to variant rs222749 [ dbSNP | Ensembl ].		VAR_057307
	Natural variant	469	1	T → I. Ref.2 Ref.5 Corresponds to variant rs224534 [ dbSNP | Ensembl ].		VAR_057308
	Natural variant	505	1	T → A. Corresponds to variant rs17633288 [ dbSNP | Ensembl ].		VAR_057309
	Natural variant	585	1	I → V. Ref.1 Corresponds to variant rs8065080 [ dbSNP | Ensembl ].		VAR_022246
Experimental info
	Mutagenesis	511	1	Y → A: Loss of sensitivity to capsaicin. Ref.11
	Mutagenesis	550	1	T → I: Reduces sensitivity to capsaicin 40-fold. Ref.11
	Sequence conflict	315	1	M → I in CAB95729. Ref.1
	Sequence conflict	315	1	M → I in AAG43467. Ref.2
	Sequence conflict	315	1	M → I in CAB89866. Ref.3
	Sequence conflict	315	1	M → I in AAM89472. Ref.4
	Sequence conflict	315	1	M → I in CAB66735. Ref.5
	Sequence conflict	315	1	M → I in EAW90497. Ref.7
	Sequence conflict	315	1	M → I in AAI32821. Ref.8
	Sequence conflict	315	1	M → I in AAI36634. Ref.8
	Sequence conflict	336	1	T → M in CAB89866. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q8NER1 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: 7142F59D428827FB	FASTA	839	94,956
	10 20 30 40 50 60 MKKWSSTDLG AAADPLQKDT CPDPLDGDPN SRPPPAKPQL STAKSRTRLF GKGDSEEAFP 70 80 90 100 110 120 VDCPHEEGEL DSCPTITVSP VITIQRPGDG PTGARLLSQD SVAASTEKTL RLYDRRSIFE 130 140 150 160 170 180 AVAQNNCQDL ESLLLFLQKS KKHLTDNEFK DPETGKTCLL KAMLNLHDGQ NTTIPLLLEI 190 200 210 220 230 240 ARQTDSLKEL VNASYTDSYY KGQTALHIAI ERRNMALVTL LVENGADVQA AAHGDFFKKT 250 260 270 280 290 300 KGRPGFYFGE LPLSLAACTN QLGIVKFLLQ NSWQTADISA RDSVGNTVLH ALVEVADNTA 310 320 330 340 350 360 DNTKFVTSMY NEILMLGAKL HPTLKLEELT NKKGMTPLAL AAGTGKIGVL AYILQREIQE 370 380 390 400 410 420 PECRHLSRKF TEWAYGPVHS SLYDLSCIDT CEKNSVLEVI AYSSSETPNR HDMLLVEPLN 430 440 450 460 470 480 RLLQDKWDRF VKRIFYFNFL VYCLYMIIFT MAAYYRPVDG LPPFKMEKTG DYFRVTGEIL 490 500 510 520 530 540 SVLGGVYFFF RGIQYFLQRR PSMKTLFVDS YSEMLFFLQS LFMLATVVLY FSHLKEYVAS 550 560 570 580 590 600 MVFSLALGWT NMLYYTRGFQ QMGIYAVMIE KMILRDLCRF MFVYIVFLFG FSTAVVTLIE 610 620 630 640 650 660 DGKNDSLPSE STSHRWRGPA CRPPDSSYNS LYSTCLELFK FTIGMGDLEF TENYDFKAVF 670 680 690 700 710 720 IILLLAYVIL TYILLLNMLI ALMGETVNKI AQESKNIWKL QRAITILDTE KSFLKCMRKA 730 740 750 760 770 780 FRSGKLLQVG YTPDGKDDYR WCFRVDEVNW TTWNTNVGII NEDPGNCEGV KRTLSFSLRS 790 800 810 820 830 SRVSGRHWKN FALVPLLREA SARDRQSAQP EEVYLRQFSG SLKPEDAEVF KSPAASGEK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and functional expression of a human orthologue of rat vanilloid receptor-1." Hayes P., Meadows H.J., Gunthorpe M., Harries M.H., Duckworth M.D., Cairns W., Harrison D.C., Clarke C., Ellington K., Prinjha R.K., Barton A.J., Medhurst A.D., Smith G.D., Topp S., Murdock P., Sanger G.J., Terrett J., Jenkins O. , Benham C.D., Randall A.D., Gloger I.S., Davis J.B. Pain 88:205-215(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, VARIANT VAL-585.
[2]	"The tissue distribution and functional characterization of human VR1." Cortright D.N., Crandall M., Sanchez J.F., Zou T., Krause J.E., White G. Biochem. Biophys. Res. Commun. 281:1183-1189(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, VARIANTS SER-91 AND ILE-469. Tissue: Spinal ganglion.
[3]	"Pharmacological differences between human and rat vanilloid receptor 1 (VR1)." McIntyre P., McLatchie L., Chambers A., Phillips E., Clarke M., Savidge J., Peacock M., Shah K., Winter J., Weerasekera N., Webb M., Rang H., Bevan S., James I. Br. J. Pharmacol. 132:1084-1094(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Spinal ganglion.
[4]	Lee D., Ha I. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[5]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-469. Tissue: Testis.
[6]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[9]	"TRPV3 is a temperature-sensitive vanilloid receptor-like protein." Smith G.D., Gunthorpe M.J., Kelsell R.E., Hayes P.D., Reilly P., Facer P., Wright J.E., Jerman J.C., Walhin J.-P., Ooi L., Egerton J., Charles K.J., Smart D., Randall A.D., Anand P., Davis J.B. Nature 418:186-190(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TRPV3.
[10]	"Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures." Staender S., Moormann C., Schumacher M., Buddenkotte J., Artuc M., Shpacovitch V., Brzoska T., Lippert U., Henz B.M., Luger T.A., Metze D., Steinhoff M. Exp. Dermatol. 13:129-139(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[11]	"Molecular determinants of vanilloid sensitivity in TRPV1." Gavva N.R., Klionsky L., Qu Y., Shi L., Tamir R., Edenson S., Zhang T.J., Viswanadhan V.N., Toth A., Pearce L.V., Vanderah T.W., Porreca F., Blumberg P.M., Lile J., Sun Y., Wild K., Louis J.C., Treanor J.J. J. Biol. Chem. 279:20283-20295(2004) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TYR-511 AND THR-550.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ277028 mRNA. Translation: CAB95729.1. AF196175 mRNA. Translation: AAG43466.1. AF196176 mRNA. Translation: AAG43467.1. Frameshift. AJ272063 mRNA. Translation: CAB89866.2. AY131289 mRNA. Translation: AAM89472.1. AL136801 mRNA. Translation: CAB66735.1. AC027796 Genomic DNA. No translation available. CH471108 Genomic DNA. Translation: EAW90497.1. BC132820 mRNA. Translation: AAI32821.1. BC136633 mRNA. Translation: AAI36634.1.
IPI	IPI00874241.
PIR	JC7621.
RefSeq	NP_061197.4. NM_018727.5. NP_542435.2. NM_080704.3. NP_542436.2. NM_080705.3. NP_542437.2. NM_080706.3.
UniGene	Hs.579217. Hs.655380.
3D structure databases
ProteinModelPortal	Q8NER1.
SMR	Q8NER1. Positions 112-359.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000174621.
PTM databases
PhosphoSite	Q8NER1.
Polymorphism databases
DMDM	296452849.
Proteomic databases
PaxDb	Q8NER1.
PRIDE	Q8NER1.
Protocols and materials databases
DNASU	7442.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000399756; ENSP00000382659; ENSG00000196689. ENST00000399759; ENSP00000382661; ENSG00000196689. ENST00000571088; ENSP00000461007; ENSG00000196689.
GeneID	7442.
KEGG	hsa:7442.
UCSC	uc010vrr.2. human.
Organism-specific databases
CTD	7442.
GeneCards	GC17M003469.
H-InvDB	HIX0013428. HIX0079948.
HGNC	HGNC:12716. TRPV1.
MIM	602076. gene.
neXtProt	NX_Q8NER1.
PharmGKB	PA37329.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG278734.
HOVERGEN	HBG054085.
KO	K05222.
OrthoDB	EOG48WC1B.
Enzyme and pathway databases
Pathway_Interaction_DB	pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma. mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.
Gene expression databases
ArrayExpress	Q8NER1.
Bgee	Q8NER1.
CleanEx	HS_TRPV1.
Genevestigator	Q8NER1.
GermOnline	ENSG00000196689. Homo sapiens.
Family and domain databases
Gene3D	1.25.40.20. 2 hits.
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR004729. TRP_channel. IPR008347. TRPV1-4_channel. IPR024863. TRPV1_channel. IPR024862. TRPV_channel. [Graphical view]
PANTHER	PTHR10582. PTHR10582. 1 hit. PTHR10582:SF5. PTHR10582:SF5. 1 hit.
Pfam	PF00023. Ank. 2 hits. [Graphical view]
PRINTS	PR01768. TRPVRECEPTOR.
SMART	SM00248. ANK. 4 hits. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit.
TIGRFAMs	TIGR00870. trp. 1 hit.
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q8NER1.
ChEMBL	CHEMBL4794.
DrugBank	DB00132. Alpha-Linolenic Acid. DB00168. Aspartame. DB00159. Icosapent.
GenomeRNAi	7442.
NextBio	29140.
SOURCE	Search...

Entry information

Entry name

TRPV1_HUMAN

Accession

Primary (citable) accession number: Q8NER1
Secondary accession number(s): A2RUA9 , Q9H0G9, Q9H303, Q9H304, Q9NQ74, Q9NY22

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2005
Last sequence update:	May 18, 2010
Last modified:	April 3, 2013
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.