Q8NET8 (TRPV3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transient receptor potential cation channel subfamily V member 3
Short name=TrpV3

Alternative name(s):
Vanilloid receptor-like 3
Short name=VRL-3

Gene names

Name:

TRPV3

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	790 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Putative receptor-activated non-selective calcium permeant cation channel. It is activated by innocuous (warm) temperatures and shows an increased response at noxious temperatures greater than 39 degrees Celsius. Activation exhibits an outward rectification. May associate with TRPV1 and may modulate its activity. Is a negative regulator of hair growth and cycling: TRPV3-coupled signaling suppresses keratinocyte proliferation in hair follicles and induces apoptosis and premature hair follicle regression (catagen). Ref.1 Ref.2 Ref.4
Subunit structure	May form a heteromeric channel with TRPV1. Interacts with TRPV1. Ref.1
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Abundantly expressed in CNS. Widely expressed at low levels. Detected in dorsal root ganglion (at protein level). Expressed in the keratinocyte layers of the outer root sheath and, to lesser extent, to the matrix of the hair follicles (at protein level). Ref.1 Ref.2 Ref.4
Involvement in disease	Olmsted syndrome (OLMS) [MIM:614594]: A rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma and periorificial keratotic plaques with severe itching at all lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas. The digital constriction may progress to autoamputation of fingers and toes. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6
Sequence similarities	Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV3 sub-subfamily. [View classification] Contains 3 ANK repeats.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Palmoplantar keratoderma
Domain	ANK repeat Repeat Transmembrane Transmembrane helix
Ligand	Calcium
Molecular function	Calcium channel Ion channel
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of hair cycle Inferred from mutant phenotype Ref.4. Source: UniProtKB response to temperature stimulus Inferred from electronic annotation. Source: Compara
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	calcium channel activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8NET8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8NET8-2)

Also known as: A;

The sequence of this isoform differs from the canonical sequence as follows:
     759-759: T → TA

Isoform 3 (identifier: Q8NET8-3)

Also known as: B;

The sequence of this isoform differs from the canonical sequence as follows:
     760-765: DFNKIQ → GTVAVR
     766-790: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 790	790	Transient receptor potential cation channel subfamily V member 3		PRO_0000215345
Regions
	Topological domain	1 – 439	439	Cytoplasmic Potential
	Transmembrane	440 – 460	21	Helical; Potential
	Topological domain	461 – 487	27	Extracellular Potential
	Transmembrane	488 – 508	21	Helical; Potential
	Topological domain	509 – 523	15	Cytoplasmic Potential
	Transmembrane	524 – 544	21	Helical; Potential
	Topological domain	545	1	Extracellular Potential
	Transmembrane	546 – 566	21	Helical; Potential
	Topological domain	567 – 589	23	Cytoplasmic Potential
	Transmembrane	590 – 610	21	Helical; Potential
	Intramembrane	621 – 637	17	Pore-forming; Potential
	Transmembrane	650 – 670	21	Helical; Potential
	Topological domain	671 – 790	120	Cytoplasmic Potential
	Repeat	214 – 243	30	ANK 1
	Repeat	261 – 291	31	ANK 2
	Repeat	340 – 369	30	ANK 3
Natural variations
	Alternative sequence	759	1	T → TA in isoform 2.		VSP_013433
	Alternative sequence	760 – 765	6	DFNKIQ → GTVAVR in isoform 3.		VSP_013434
	Alternative sequence	766 – 790	25	Missing in isoform 3.		VSP_013435
	Natural variant	25	1	I → V. Ref.1 Corresponds to variant rs322965 [ dbSNP | Ensembl ].		VAR_052388
	Natural variant	117	1	R → G. Ref.1 Corresponds to variant rs322937 [ dbSNP | Ensembl ].		VAR_052389
	Natural variant	573	1	G → C in OLMS; gain of function mutation; results in constitutive channel activation. Ref.5		VAR_067920
	Natural variant	573	1	G → S in OLMS; gain of function mutation; results in constitutive channel activation. Ref.5 Ref.6		VAR_067921
	Natural variant	692	1	W → G in OLMS; gain of function mutation; results in constitutive channel activation. Ref.5		VAR_067922
	Natural variant	774	1	T → I. Corresponds to variant rs7212634 [ dbSNP | Ensembl ].		VAR_052390
Experimental info
	Sequence conflict	283	1	E → G in AAM80558. Ref.3
	Sequence conflict	283	1	E → G in AAM80559. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 26, 2005. Version 2. Checksum: 31EB9973C015B611	FASTA	790	90,636
	10 20 30 40 50 60 MKAHPKEMVP LMGKRVAAPS GNPAILPEKR PAEITPTKKS AHFFLEIEGF EPNPTVAKTS 70 80 90 100 110 120 PPVFSKPMDS NIRQCISGNC DDMDSPQSPQ DDVTETPSNP NSPSAQLAKE EQRRKKRRLK 130 140 150 160 170 180 KRIFAAVSEG CVEELVELLV ELQELCRRRH DEDVPDFLMH KLTASDTGKT CLMKALLNIN 190 200 210 220 230 240 PNTKEIVRIL LAFAEENDIL GRFINAEYTE EAYEGQTALN IAIERRQGDI AALLIAAGAD 250 260 270 280 290 300 VNAHAKGAFF NPKYQHEGFY FGETPLALAA CTNQPEIVQL LMEHEQTDIT SRDSRGNNIL 310 320 330 340 350 360 HALVTVAEDF KTQNDFVKRM YDMILLRSGN WELETTRNND GLTPLQLAAK MGKAEILKYI 370 380 390 400 410 420 LSREIKEKRL RSLSRKFTDW AYGPVSSSLY DLTNVDTTTD NSVLEITVYN TNIDNRHEML 430 440 450 460 470 480 TLEPLHTLLH MKWKKFAKHM FFLSFCFYFF YNITLTLVSY YRPREEEAIP HPLALTHKMG 490 500 510 520 530 540 WLQLLGRMFV LIWAMCISVK EGIAIFLLRP SDLQSILSDA WFHFVFFIQA VLVILSVFLY 550 560 570 580 590 600 LFAYKEYLAC LVLAMALGWA NMLYYTRGFQ SMGMYSVMIQ KVILHDVLKF LFVYIVFLLG 610 620 630 640 650 660 FGVALASLIE KCPKDNKDCS SYGSFSDAVL ELFKLTIGLG DLNIQQNSKY PILFLFLLIT 670 680 690 700 710 720 YVILTFVLLL NMLIALMGET VENVSKESER IWRLQRARTI LEFEKMLPEW LRSRFRMGEL 730 740 750 760 770 780 CKVAEDDFRL CLRINEVKWT EWKTHVSFLN EDPGPVRRTD FNKIQDSSRN NSKTTLNAFE 790 EVEEFPETSV
	Isoform 2 (A) [UniParc]. Checksum: 264D20FFF12791C4	FASTA	791	90,707
	10 20 30 40 50 60 MKAHPKEMVP LMGKRVAAPS GNPAILPEKR PAEITPTKKS AHFFLEIEGF EPNPTVAKTS 70 80 90 100 110 120 PPVFSKPMDS NIRQCISGNC DDMDSPQSPQ DDVTETPSNP NSPSAQLAKE EQRRKKRRLK 130 140 150 160 170 180 KRIFAAVSEG CVEELVELLV ELQELCRRRH DEDVPDFLMH KLTASDTGKT CLMKALLNIN 190 200 210 220 230 240 PNTKEIVRIL LAFAEENDIL GRFINAEYTE EAYEGQTALN IAIERRQGDI AALLIAAGAD 250 260 270 280 290 300 VNAHAKGAFF NPKYQHEGFY FGETPLALAA CTNQPEIVQL LMEHEQTDIT SRDSRGNNIL 310 320 330 340 350 360 HALVTVAEDF KTQNDFVKRM YDMILLRSGN WELETTRNND GLTPLQLAAK MGKAEILKYI 370 380 390 400 410 420 LSREIKEKRL RSLSRKFTDW AYGPVSSSLY DLTNVDTTTD NSVLEITVYN TNIDNRHEML 430 440 450 460 470 480 TLEPLHTLLH MKWKKFAKHM FFLSFCFYFF YNITLTLVSY YRPREEEAIP HPLALTHKMG 490 500 510 520 530 540 WLQLLGRMFV LIWAMCISVK EGIAIFLLRP SDLQSILSDA WFHFVFFIQA VLVILSVFLY 550 560 570 580 590 600 LFAYKEYLAC LVLAMALGWA NMLYYTRGFQ SMGMYSVMIQ KVILHDVLKF LFVYIVFLLG 610 620 630 640 650 660 FGVALASLIE KCPKDNKDCS SYGSFSDAVL ELFKLTIGLG DLNIQQNSKY PILFLFLLIT 670 680 690 700 710 720 YVILTFVLLL NMLIALMGET VENVSKESER IWRLQRARTI LEFEKMLPEW LRSRFRMGEL 730 740 750 760 770 780 CKVAEDDFRL CLRINEVKWT EWKTHVSFLN EDPGPVRRTA DFNKIQDSSR NNSKTTLNAF 790 EEVEEFPETS V
	Isoform 3 (B) [UniParc]. Checksum: 710D3545A7107B73	FASTA	765	87,661
	10 20 30 40 50 60 MKAHPKEMVP LMGKRVAAPS GNPAILPEKR PAEITPTKKS AHFFLEIEGF EPNPTVAKTS 70 80 90 100 110 120 PPVFSKPMDS NIRQCISGNC DDMDSPQSPQ DDVTETPSNP NSPSAQLAKE EQRRKKRRLK 130 140 150 160 170 180 KRIFAAVSEG CVEELVELLV ELQELCRRRH DEDVPDFLMH KLTASDTGKT CLMKALLNIN 190 200 210 220 230 240 PNTKEIVRIL LAFAEENDIL GRFINAEYTE EAYEGQTALN IAIERRQGDI AALLIAAGAD 250 260 270 280 290 300 VNAHAKGAFF NPKYQHEGFY FGETPLALAA CTNQPEIVQL LMEHEQTDIT SRDSRGNNIL 310 320 330 340 350 360 HALVTVAEDF KTQNDFVKRM YDMILLRSGN WELETTRNND GLTPLQLAAK MGKAEILKYI 370 380 390 400 410 420 LSREIKEKRL RSLSRKFTDW AYGPVSSSLY DLTNVDTTTD NSVLEITVYN TNIDNRHEML 430 440 450 460 470 480 TLEPLHTLLH MKWKKFAKHM FFLSFCFYFF YNITLTLVSY YRPREEEAIP HPLALTHKMG 490 500 510 520 530 540 WLQLLGRMFV LIWAMCISVK EGIAIFLLRP SDLQSILSDA WFHFVFFIQA VLVILSVFLY 550 560 570 580 590 600 LFAYKEYLAC LVLAMALGWA NMLYYTRGFQ SMGMYSVMIQ KVILHDVLKF LFVYIVFLLG 610 620 630 640 650 660 FGVALASLIE KCPKDNKDCS SYGSFSDAVL ELFKLTIGLG DLNIQQNSKY PILFLFLLIT 670 680 690 700 710 720 YVILTFVLLL NMLIALMGET VENVSKESER IWRLQRARTI LEFEKMLPEW LRSRFRMGEL 730 740 750 760 CKVAEDDFRL CLRINEVKWT EWKTHVSFLN EDPGPVRRTG TVAVR

References

[1]	"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH TRPV1, VARIANTS VAL-25 AND GLY-117.
[2]	"TRPV3 is a calcium-permeable temperature-sensitive cation channel." Xu H., Ramsey I.S., Kotecha S.A., Moran M.M., Chong J.A., Lawson D., Ge P., Lilly J., Silos-Santiago I., Xie Y., DiStefano P.S., Curtis R., Clapham D.E. Nature 418:181-186(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
[3]	"Human TRPV3, a new member of the vanilloid receptor family." Poea-Guyon S., Renard S., Chalon P., Kaghad M., Caput D., Besnard F. Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
[4]	"Activation of transient receptor potential vanilloid-3 inhibits human hair growth." Borbiro I., Lisztes E., Toth B.I., Czifra G., Olah A., Szollosi A.G., Szentandrassy N., Nanasi P.P., Peter Z., Paus R., Kovacs L., Biro T. J. Invest. Dermatol. 131:1605-1614(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS NEGATIVE REGULATOR OF HAIR GROWTH, TISSUE SPECIFICITY.
[5]	"Exome sequencing reveals mutations in TRPV3 as a cause of Olmsted syndrome." Lin Z., Chen Q., Lee M., Cao X., Zhang J., Ma D., Chen L., Hu X., Wang H., Wang X., Zhang P., Liu X., Guan L., Tang Y., Yang H., Tu P., Bu D., Zhu X. , Wang K., Li R., Yang Y. Am. J. Hum. Genet. 90:558-564(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OLMS SER-573; CYS-573 AND GLY-692, CHARACTERIZATION OF VARIANTS OLMS SER-573; CYS-573 AND GLY-692.
[6]	"Recurrent heterozygous missense mutation, p.Gly573Ser, in the TRPV3 gene in an Indian boy with sporadic Olmsted syndrome." Lai-Cheong J.E., Sethuraman G., Ramam M., Stone K., Simpson M.A., McGrath J.A. Br. J. Dermatol. 167:440-442(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT OLMS SER-573.
+	Additional computationally mapped references.

Web resources

Transient receptor potential cation channel, subfamily V, member 3 (TRPV3)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ487035 mRNA. Translation: CAD31711.2. AF514998 mRNA. Translation: AAM54027.1. AY118267 mRNA. Translation: AAM80558.1. AY118268 mRNA. Translation: AAM80559.1.
IPI	IPI00329641. IPI00555580. IPI00555796.
RefSeq	NP_659505.1. NM_145068.3.
UniGene	Hs.446255.
3D structure databases
ProteinModelPortal	Q8NET8.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000301365.
Protein family/group databases
TCDB	1.A.4.2.9. transient receptor potential Ca2+ channel (TRP-CC) family.
PTM databases
PhosphoSite	Q8NET8.
Polymorphism databases
DMDM	62901456.
Proteomic databases
PaxDb	Q8NET8.
PRIDE	Q8NET8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000301365; ENSP00000301365; ENSG00000167723. ENST00000572519; ENSP00000460215; ENSG00000167723. ENST00000576742; ENSP00000461518; ENSG00000167723.
GeneID	162514.
KEGG	hsa:162514.
UCSC	uc002fvr.2. human. uc002fvt.1. human. uc002fvu.3. human.
Organism-specific databases
CTD	162514.
GeneCards	GC17M003363.
H-InvDB	HIX0013427.
HGNC	HGNC:18084. TRPV3.
MIM	607066. gene. 614594. phenotype.
neXtProt	NX_Q8NET8.
Orphanet	659. Olmsted syndrome.
PharmGKB	PA38481.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG278734.
HOGENOM	HOG000234630.
HOVERGEN	HBG054085.
KO	K04972.
OMA	SAHFFLE.
PhylomeDB	Q8NET8.
Gene expression databases
ArrayExpress	Q8NET8.
Bgee	Q8NET8.
CleanEx	HS_TRPV3.
Genevestigator	Q8NET8.
GermOnline	ENSG00000167723. Homo sapiens.
Family and domain databases
Gene3D	1.25.40.20. 1 hit.
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR005821. Ion_trans_dom. IPR008347. TRPV1-4_channel. IPR024866. TRPV3_channel. IPR024862. TRPV_channel. [Graphical view]
PANTHER	PTHR10582. PTHR10582. 1 hit. PTHR10582:SF6. PTHR10582:SF6. 1 hit.
Pfam	PF00023. Ank. 2 hits. PF12796. Ank_2. 1 hit. PF00520. Ion_trans. 1 hit. [Graphical view]
PRINTS	PR01768. TRPVRECEPTOR.
SMART	SM00248. ANK. 4 hits. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit.
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 2 hits. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q8NET8.
ChEMBL	CHEMBL5522.
DrugBank	DB00825. Menthol.
GenomeRNAi	162514.
NextBio	88185.
SOURCE	Search...

Entry information

Entry name

TRPV3_HUMAN

Accession

Primary (citable) accession number: Q8NET8
Secondary accession number(s): Q8NDW7, Q8NET9, Q8NFH2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2005
Last sequence update:	April 26, 2005
Last modified:	May 1, 2013
This is version 84 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.