TRPV1_RABIT
ID TRPV1_RABIT Reviewed; 842 AA.
AC Q6RX08;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Transient receptor potential cation channel subfamily V member 1;
DE Short=TrpV1;
DE AltName: Full=Osm-9-like TRP channel 1;
DE Short=OTRPC1;
DE AltName: Full=Vanilloid receptor 1;
GN Name=Trpv1;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF TYR-514; LEU-550 AND ILE-553.
RX PubMed=14996838; DOI=10.1074/jbc.m312577200;
RA Gavva N.R., Klionsky L., Qu Y., Shi L., Tamir R., Edenson S., Zhang T.J.,
RA Viswanadhan V.N., Toth A., Pearce L.V., Vanderah T.W., Porreca F.,
RA Blumberg P.M., Lile J., Sun Y., Wild K., Louis J.C., Treanor J.J.;
RT "Molecular determinants of vanilloid sensitivity in TRPV1.";
RL J. Biol. Chem. 279:20283-20295(2004).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-650.
RX PubMed=11035011; DOI=10.1074/jbc.m006184200;
RA Nilius B., Vennekens R., Prenen J., Hoenderop J.G., Droogmans G.,
RA Bindels R.J.M.;
RT "The single pore residue Asp542 determines Ca2+ permeation and Mg2+ block
RT of the epithelial Ca2+ channel.";
RL J. Biol. Chem. 276:1020-1025(2001).
CC -!- FUNCTION: Ligand-activated non-selective calcium permeant cation
CC channel involved in detection of noxious chemical and thermal stimuli
CC (PubMed:14996838, PubMed:11035011). Seems to mediate proton influx and
CC may be involved in intracellular acidosis in nociceptive neurons.
CC Involved in mediation of inflammatory pain and hyperalgesia. Sensitized
CC by a phosphatidylinositol second messenger system activated by receptor
CC tyrosine kinases, which involves PKC isozymes and PCL. Can be activated
CC by endogenous compounds, including 12-hydroperoxytetraenoic acid and
CC bradykinin. Acts as ionotropic endocannabinoid receptor with central
CC neuromodulatory effects. Triggers a form of long-term depression
CC (TRPV1-LTD) mediated by the endocannabinoid anandamine in the
CC hippocampus and nucleus accumbens by affecting AMPA receptors
CC endocytosis (By similarity). Activation by vanilloids, like capsaicin,
CC and temperatures higher than 42 degrees Celsius, exhibits a time- and
CC Ca(2+)-dependent outward rectification, followed by a long-lasting
CC refractory state. Mild extracellular acidic pH (6.5) potentiates
CC channel activation by noxious heat and vanilloids, whereas acidic
CC conditions (pH <6) directly activate the channel (By similarity).
CC {ECO:0000250|UniProtKB:O35433, ECO:0000269|PubMed:11035011,
CC ECO:0000269|PubMed:14996838}.
CC -!- ACTIVITY REGULATION: The channel is sensitized by ATP binding. Repeated
CC stimulation with capsaicin gives rise to progressively smaller
CC responses, due to desensitization. This desensitization is triggered by
CC the influx of calcium ions and is inhibited by elevated ATP levels.
CC Ca(2+) and CALM displace ATP from its binding site and trigger a
CC conformation change that leads to a closed, desensitized channel. The
CC double-knot toxin (DkTx) from the Chinese earth tiger tarantula
CC activates the channel and traps it in an open conformation (By
CC similarity). The Scolopendra mutilans RhTx toxin potentiates the heat
CC activation pathway mediated by this channel by binding to the charge-
CC rich outer pore region (in an activated state) (By similarity). Channel
CC activity is activated via the interaction with PIRT and
CC phosphatidylinositol 4,5-bisphosphate (PIP2). Both PIRT and PIP2 are
CC required to activate channel activity. Intracellular PIP2 inhibits
CC desensitization (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q704Y3}.
CC -!- SUBUNIT: Interacts with PIRT (By similarity). Homotetramer. May also
CC form a heteromeric channel with TRPV3. Interacts with CALM, PRKCM and
CC CSK. Interacts with PRKCG and NTRK1, probably by forming a trimeric
CC complex (By similarity). Interacts with the Scolopendra mutilans RhTx
CC toxin (By similarity). Interacts with TMEM100 (By similarity).
CC Interacts with PACS2 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:O35433, ECO:0000250|UniProtKB:Q704Y3,
CC ECO:0000250|UniProtKB:Q8NER1}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000250|UniProtKB:O35433}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O35433}. Cell projection, dendritic spine
CC membrane {ECO:0000250|UniProtKB:O35433}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O35433}. Cell membrane
CC {ECO:0000269|PubMed:11035011, ECO:0000269|PubMed:14996838}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:O35433}. Note=Mostly, but not
CC exclusively expressed in postsynaptic dendritic spines.
CC {ECO:0000250|UniProtKB:O35433}.
CC -!- DOMAIN: The association domain (AD) is necessary for self-association.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation by PKA reverses capsaicin-induced
CC dephosphorylation at multiple sites. Phosphorylation by CAMKII seems to
CC regulate binding to vanilloids. Phosphorylated and modulated by PRKCE,
CC PRKCM and probably PRKCZ. Dephosphorylation by calcineurin seems to
CC lead to receptor desensitization and phosphorylation by CAMKII recovers
CC activity. {ECO:0000250|UniProtKB:O35433}.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. TrpV
CC subfamily. TRPV1 sub-subfamily. {ECO:0000305}.
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DR EMBL; AY487342; AAR34458.1; -; mRNA.
DR RefSeq; NP_001075635.1; NM_001082166.1.
DR STRING; 9986.ENSOCUP00000010529; -.
DR GeneID; 100008926; -.
DR KEGG; ocu:100008926; -.
DR CTD; 7442; -.
DR eggNOG; KOG3676; Eukaryota.
DR InParanoid; Q6RX08; -.
DR OrthoDB; 693004at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0032591; C:dendritic spine membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0015278; F:calcium-release channel activity; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; ISS:UniProtKB.
DR GO; GO:0005230; F:extracellular ligand-gated ion channel activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISS:UniProtKB.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0071468; P:cellular response to acidic pH; ISS:UniProtKB.
DR GO; GO:0071312; P:cellular response to alkaloid; ISS:UniProtKB.
DR GO; GO:0071318; P:cellular response to ATP; ISS:UniProtKB.
DR GO; GO:0034605; P:cellular response to heat; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:1901594; P:response to capsazepine; ISS:UniProtKB.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR024862; TRPV.
DR InterPro; IPR024863; TRPV1.
DR InterPro; IPR008347; TrpV1-4.
DR PANTHER; PTHR10582; PTHR10582; 1.
DR PANTHER; PTHR10582:SF17; PTHR10582:SF17; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR PRINTS; PR01768; TRPVRECEPTOR.
DR SMART; SM00248; ANK; 4.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
PE 1: Evidence at protein level;
KW ANK repeat; ATP-binding; Calcium; Calcium channel; Calcium transport;
KW Calmodulin-binding; Cell membrane; Cell projection; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Postsynaptic cell membrane; Reference proteome; Repeat;
KW Synapse; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..842
FT /note="Transient receptor potential cation channel
FT subfamily V member 1"
FT /id="PRO_0000215340"
FT TOPO_DOM 1..435
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 436..456
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 457..474
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 475..500
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 501..513
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 514..534
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 535..538
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 539..559
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 560..574
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 575..602
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 603..661
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 662..690
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 691..842
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT REPEAT 113..155
FT /note="ANK 1"
FT REPEAT 156..202
FT /note="ANK 2"
FT REPEAT 203..249
FT /note="ANK 3"
FT REPEAT 250..285
FT /note="ANK 4"
FT REPEAT 286..334
FT /note="ANK 5"
FT REPEAT 335..361
FT /note="ANK 6"
FT REGION 1..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 688..716
FT /note="AD"
FT /evidence="ECO:0000250"
FT REGION 771..805
FT /note="Interaction with calmodulin"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT REGION 781..796
FT /note="Required for PIP2-mediated channel inhibition"
FT MOTIF 647..650
FT /note="Selectivity filter"
FT /evidence="ECO:0000305|PubMed:11035011"
FT BINDING 118
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 158
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 163
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 167
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 202..205
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 213..214
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 514..515
FT /ligand="resiniferatoxin"
FT /ligand_id="ChEBI:CHEBI:8809"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 560
FT /ligand="resiniferatoxin"
FT /ligand_id="ChEBI:CHEBI:8809"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 650
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:Q9R186"
FT MOD_RES 147
FT /note="Phosphothreonine; by PKA; in vitro"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT MOD_RES 373
FT /note="Phosphothreonine; by PKA; in vitro"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT MOD_RES 505
FT /note="Phosphoserine; by PKC/PRKCE"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT MOD_RES 708
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT MOD_RES 778
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT MOD_RES 804
FT /note="Phosphoserine; by PKC/PRKCE and PKC/PRKCZ"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT MOD_RES 824
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT CARBOHYD 607
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT MUTAGEN 514
FT /note="Y->A: Reduces sensitivity to capsaicin more than
FT 100-fold; when associated with T-553."
FT /evidence="ECO:0000269|PubMed:14996838"
FT MUTAGEN 550
FT /note="L->M: Confers sensitivity to capsaicin,
FT resiniferatoxin and other vanilloids and confers binding to
FT resiniferatoxin; when associated with T-553."
FT /evidence="ECO:0000269|PubMed:14996838"
FT MUTAGEN 553
FT /note="I->T: Confers sensitivity to capsaicin,
FT resiniferatoxin and other vanilloids and confers binding to
FT resiniferatoxin; when associated with M-550. Reduces
FT sensitivity to capsaicin more than 100-fold; when
FT associated with A-514."
FT /evidence="ECO:0000269|PubMed:14996838"
FT MUTAGEN 650
FT /note="D->A: Abolishes calcium permeability."
FT /evidence="ECO:0000269|PubMed:11035011"
FT MUTAGEN 650
FT /note="D->E,N,M: Attenuates calcium permeability."
FT /evidence="ECO:0000269|PubMed:11035011"
FT MUTAGEN 650
FT /note="D->K: Abolishes channel activity."
FT /evidence="ECO:0000269|PubMed:11035011"
SQ SEQUENCE 842 AA; 95003 MW; D9D6F755E8A8CDA7 CRC64;
MKRWVSLDSG ESEDPLPEDT CPDLLDGDSN AKPPPAKPHI FSTAKSRSRL FGKGDSEETS
PMDCSYEEGE LAPCPAITVS SVIIVQRSGD GPTCARQLSQ DSVAAAGAEK PLKLYDRRRI
FEAVAQNNCQ ELESLLCFLQ RSKKRLTDSE FKDPETGKTC LLKAMLNLHS GQNDTIPLLL
EIARQTDSLK EFVNASYTDS YYKGQTALHI AIERRNMALV TLLVENGADV QAAANGDFFK
KTKGRPGFYF GELPLSLAAC TNQLAIVKFL LQNSWQPADI SARDSVGNTV LHALVEVADN
TPDNTKFVTS MYNEILILGA KLHPTLKLEE LINKKGLTPL ALAAGSGKIG VLAYILQREI
LEPECRHLSR KFTEWAYGPV HSSLYDLSCI DTCERNSVLE VIAYSSSETP NRHDMLLVEP
LNRLLQDKWD RVVKRIFYFN FFVYCLYMII FTTAAYYRPV DGLPPYKLRN LPGDYFRVTG
EILSVAGGVY FFFRGIQYFL QRRPSMKALF VDSYSEMLFF VQALFMLATV VLYFSHCKEY
VATMVFSLAL GWINMLYYTR GFQQMGIYAV MIEKMILRDL CRFMFVYLVF LFGFSTAVVT
LIEDGKNSST SAESTSHRWR GFGCRSSDSS YNSLYSTCLE LFKFTIGMGD LEFTENYDFK
AVFIILLLAY VILTYILLLN MLIALMGETV NKIAQESKSI WKLQRAITIL DTEKGFLKCM
RKAFRSGKLL QVGYTPDGKD DCRWCFRVDE VNWTTWNTNV GIINEDPGNC EGVKRTLSFS
LRSGRVSGRN WKNFALVPLL RDASTRDRHP XPPEDVHLRP FVGSLKPGDA ELFKDSVAAA
EK
