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UniProtKB - Q8NER1 (TRPV1_HUMAN)

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Protein

Transient receptor potential cation channel subfamily V member 1

Gene

TRPV1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Ligand-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. 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. Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca2+-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.By similarity4 Publications

Miscellaneous

Responses evoked by low pH and heat, and capsaicin can be antagonized by capsazepine.

Enzyme regulationi

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). The channel is sensitized by ATP binding. Repeated stimulation with capsaicin gives rise to progressively smaller responses, due to desensitization. This desensitization is triggered by the influx of calcium ions and is inhibited by elevated ATP levels. Ca2+ and CALM displace ATP from its binding site and trigger a conformation change that leads to a closed, desensitized channel. Intracellular PIP2 inhibits desensitization. The double-knot toxin (DkTx) from the Chinese earth tiger tarantula activates the channel and traps it in an open conformation (By similarity). The Scolopendra mutilans RhTx toxin potentiates the heat activation pathway mediated by this channel by binding to the charge-rich outer pore region (in an activated state) (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei116ATPBy similarity1
Binding sitei156ATPBy similarity1
Binding sitei161ATPBy similarity1
Binding sitei165ATPBy similarity1
Binding sitei512AgonistBy similarity1
Binding sitei550AgonistBy similarity1
Sitei557Important for agonist bindingBy similarity1
Metal bindingi647Calcium; shared with neighboring subunitsBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi200 – 203ATPBy similarity4
Nucleotide bindingi211 – 212ATPBy similarity2

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionCalcium channel, Calmodulin-binding, Ion channel
Biological processCalcium transport, Ion transport, Transport
LigandATP-binding, Calcium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-3295583 TRP channels
SIGNORiQ8NER1

Protein family/group databases

TCDBi1.A.4.2.13 the transient receptor potential ca(2+) channel (trp-cc) family

Names & Taxonomyi

Protein namesi
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 namesi
Name:TRPV1
Synonyms:VR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000196689.11
HGNCiHGNC:12716 TRPV1
MIMi602076 gene
neXtProtiNX_Q8NER1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 433CytoplasmicBy similarityAdd BLAST433
Transmembranei434 – 454HelicalBy similarityAdd BLAST21
Topological domaini455 – 471ExtracellularBy similarityAdd BLAST17
Transmembranei472 – 497HelicalBy similarityAdd BLAST26
Topological domaini498 – 510CytoplasmicBy similarityAdd BLAST13
Transmembranei511 – 531HelicalBy similarityAdd BLAST21
Topological domaini532 – 535ExtracellularBy similarity4
Transmembranei536 – 556HelicalBy similarityAdd BLAST21
Topological domaini557 – 571CytoplasmicBy similarityAdd BLAST15
Transmembranei572 – 599HelicalBy similarityAdd BLAST28
Topological domaini600 – 658ExtracellularBy similarityAdd BLAST59
Transmembranei659 – 687HelicalBy similarityAdd BLAST29
Topological domaini688 – 839CytoplasmicBy similarityAdd BLAST152

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi511Y → A: Loss of sensitivity to capsaicin. 1 Publication1
Mutagenesisi550T → I: Reduces sensitivity to capsaicin 40-fold. 1 Publication1

Organism-specific databases

DisGeNETi7442
OpenTargetsiENSG00000196689
PharmGKBiPA37329

Chemistry databases

ChEMBLiCHEMBL4794
DrugBankiDB00316 Acetaminophen
DB00132 Alpha-Linolenic Acid
DB00168 Aspartame
DB06774 Capsaicin
DB00159 Icosapent
GuidetoPHARMACOLOGYi507

Polymorphism and mutation databases

BioMutaiTRPV1
DMDMi296452849

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153381 – 839Transient receptor potential cation channel subfamily V member 1Add BLAST839

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei117Phosphoserine; by PKA and PKDBy similarity1
Modified residuei145Phosphothreonine; by PKA; in vitroBy similarity1
Modified residuei371Phosphothreonine; by PKA; in vitroBy similarity1
Modified residuei502Phosphoserine; by PKC/PRKCEBy similarity1
Glycosylationi604N-linked (GlcNAc...) asparagineBy similarity1
Modified residuei705PhosphothreonineBy similarity1
Modified residuei775PhosphoserineBy similarity1
Modified residuei801Phosphoserine; by PKC/PRKCE and PKC/PRKCZBy similarity1
Modified residuei821PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation by PKA reverses capsaicin-induced dephosphorylation at multiple sites, probably including Ser-117 as a major phosphorylation site. Phosphorylation 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

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ8NER1
PeptideAtlasiQ8NER1
PRIDEiQ8NER1
ProteomicsDBi73202

PTM databases

iPTMnetiQ8NER1
PhosphoSitePlusiQ8NER1

Expressioni

Tissue specificityi

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).3 Publications

Gene expression databases

BgeeiENSG00000196689
CleanExiHS_TRPV1
ExpressionAtlasiQ8NER1 baseline and differential
GenevisibleiQ8NER1 HS

Interactioni

Subunit structurei

Interacts with PIRT (By similarity). Homotetramer (By similarity). Interacts with TRPV3 and may also form a heteromeric channel with TRPV3 (PubMed:12077606). Interacts with CALM, PRKCM and CSK. Interacts with PRKCG and NTRK1, probably by forming a trimeric complex (By similarity). Interacts with the Scolopendra mutilans RhTx toxin (By similarity). Interacts with TMEM100 (By similarity).By similarity1 Publication

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB
  • identical protein binding Source: Ensembl
  • phosphoprotein binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi113281, 8 interactors
STRINGi9606.ENSP00000459962

Chemistry databases

BindingDBiQ8NER1

Structurei

3D structure databases

ProteinModelPortaliQ8NER1
SMRiQ8NER1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati111 – 153ANK 1Add BLAST43
Repeati154 – 200ANK 2Add BLAST47
Repeati201 – 247ANK 3Add BLAST47
Repeati248 – 283ANK 4Add BLAST36
Repeati284 – 332ANK 5Add BLAST49
Repeati333 – 359ANK 6Add BLAST27

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni115 – 116Important for channel activation by agonists and heatBy similarity2
Regioni685 – 713ADBy similarityAdd BLAST29
Regioni768 – 802Interaction with calmodulinBy similarityAdd BLAST35
Regioni778 – 793Required for PIP2-mediated channel inhibitionBy similarityAdd BLAST16

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi644 – 647Selectivity filterBy similarity4

Domaini

The association domain (AD) is necessary for self-association.By similarity

Sequence similaritiesi

Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV1 sub-subfamily. [View classification]Curated

Keywords - Domaini

ANK repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3676 Eukaryota
ENOG4110DG4 LUCA
GeneTreeiENSGT00550000074425
HOGENOMiHOG000234630
HOVERGENiHBG054085
InParanoidiQ8NER1
KOiK05222
PhylomeDBiQ8NER1
TreeFamiTF314711

Family and domain databases

CDDicd00204 ANK, 1 hit
Gene3Di1.25.40.20, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR005821 Ion_trans_dom
IPR004729 TRP_channel
IPR024862 TRPV
IPR024863 TRPV1
IPR008347 TRPV1-4_channel
PANTHERiPTHR10582 PTHR10582, 1 hit
PTHR10582:SF17 PTHR10582:SF17, 1 hit
PfamiView protein in Pfam
PF12796 Ank_2, 1 hit
PF00520 Ion_trans, 1 hit
PRINTSiPR01768 TRPVRECEPTOR
SMARTiView protein in SMART
SM00248 ANK, 4 hits
SUPFAMiSSF48403 SSF48403, 1 hit
TIGRFAMsiTIGR00870 trp, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8NER1-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MKKWSSTDLG AAADPLQKDT CPDPLDGDPN SRPPPAKPQL STAKSRTRLF 
        60         70         80         90        100
GKGDSEEAFP VDCPHEEGEL DSCPTITVSP VITIQRPGDG PTGARLLSQD 
       110        120        130        140        150
SVAASTEKTL RLYDRRSIFE AVAQNNCQDL ESLLLFLQKS KKHLTDNEFK 
       160        170        180        190        200
DPETGKTCLL KAMLNLHDGQ NTTIPLLLEI ARQTDSLKEL VNASYTDSYY 
       210        220        230        240        250
KGQTALHIAI ERRNMALVTL LVENGADVQA AAHGDFFKKT KGRPGFYFGE 
       260        270        280        290        300
LPLSLAACTN QLGIVKFLLQ NSWQTADISA RDSVGNTVLH ALVEVADNTA 
       310        320        330        340        350
DNTKFVTSMY NEILMLGAKL HPTLKLEELT NKKGMTPLAL AAGTGKIGVL 
       360        370        380        390        400
AYILQREIQE PECRHLSRKF TEWAYGPVHS SLYDLSCIDT CEKNSVLEVI 
       410        420        430        440        450
AYSSSETPNR HDMLLVEPLN RLLQDKWDRF VKRIFYFNFL VYCLYMIIFT 
       460        470        480        490        500
MAAYYRPVDG LPPFKMEKTG DYFRVTGEIL SVLGGVYFFF RGIQYFLQRR 
       510        520        530        540        550
PSMKTLFVDS YSEMLFFLQS LFMLATVVLY FSHLKEYVAS MVFSLALGWT 
       560        570        580        590        600
NMLYYTRGFQ QMGIYAVMIE KMILRDLCRF MFVYIVFLFG FSTAVVTLIE 
       610        620        630        640        650
DGKNDSLPSE STSHRWRGPA CRPPDSSYNS LYSTCLELFK FTIGMGDLEF 
       660        670        680        690        700
TENYDFKAVF IILLLAYVIL TYILLLNMLI ALMGETVNKI AQESKNIWKL 
       710        720        730        740        750
QRAITILDTE KSFLKCMRKA FRSGKLLQVG YTPDGKDDYR WCFRVDEVNW 
       760        770        780        790        800
TTWNTNVGII NEDPGNCEGV KRTLSFSLRS SRVSGRHWKN FALVPLLREA 
       810        820        830 
SARDRQSAQP EEVYLRQFSG SLKPEDAEVF KSPAASGEK
Length:839
Mass (Da):94,956
Last modified:May 18, 2010 - v2
Checksum:i7142F59D428827FB
GO
Isoform 2 (identifier: Q8NER1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-150: MKKWSSTDLG...KKHLTDNEFK → METLTPGHLQ...ACPDPPLCLS

Show »
Length:837
Mass (Da):94,211
Checksum:iD662DD6094BDCA56
GO

Sequence cautioni

The sequence AAG43467 differs from that shown. Reason: Frameshift at position 498.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti336T → M in CAB89866 (PubMed:11226139).Curated1
Sequence conflicti552M → V in ABA06605 (Ref. 5) 1 Publication1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05730791P → S1 PublicationCorresponds to variant dbSNP:rs222749Ensembl.1
Natural variantiVAR_071244315M → I8 PublicationsCorresponds to variant dbSNP:rs222747Ensembl.1
Natural variantiVAR_057308469T → I2 PublicationsCorresponds to variant dbSNP:rs224534Ensembl.1
Natural variantiVAR_057309505T → A. Corresponds to variant dbSNP:rs17633288Ensembl.1
Natural variantiVAR_022246585I → V2 PublicationsCorresponds to variant dbSNP:rs8065080Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0568621 – 150MKKWS…DNEFK → METLTPGHLQPSPSSPRPRA APGSLGRVTRRRLSRWIALT RKVSWTPARPSQSALLSPSR GQETAPPVPGCCPRTLSPPA PRRPSGSMIAGVSLKPLLRI TARIWRACCSSCRRARSTSQ TTSSKVAPALGSGRAPALAC PDPPLCLS in isoform 2. 1 PublicationAdd BLAST150

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
DQ177332 mRNA Translation: ABA06605.1
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
CCDSiCCDS45576.1 [Q8NER1-1]
PIRiJC7621
RefSeqiNP_061197.4, NM_018727.5 [Q8NER1-1]
NP_542435.2, NM_080704.3 [Q8NER1-1]
NP_542436.2, NM_080705.3 [Q8NER1-1]
NP_542437.2, NM_080706.3 [Q8NER1-1]
UniGeneiHs.579217
Hs.655380

Genome annotation databases

EnsembliENST00000399756; ENSP00000382659; ENSG00000196689 [Q8NER1-1]
ENST00000399759; ENSP00000382661; ENSG00000196689 [Q8NER1-1]
ENST00000571088; ENSP00000461007; ENSG00000196689 [Q8NER1-1]
ENST00000572705; ENSP00000459962; ENSG00000196689 [Q8NER1-1]
GeneIDi7442
KEGGihsa:7442
UCSCiuc010vrr.3 human [Q8NER1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTRPV1_HUMAN
AccessioniPrimary (citable) accession number: Q8NER1
Secondary accession number(s): A2RUA9
, Q3LU47, Q9H0G9, Q9H303, Q9H304, Q9NQ74, Q9NY22
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: May 18, 2010
Last modified: June 20, 2018
This is version 146 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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