TRPV1_CAVPO
ID TRPV1_CAVPO Reviewed; 839 AA.
AC Q6R5A3; Q8K1W1;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 129.
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 Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=Dunkin-Hartley; TISSUE=Spinal ganglion;
RX PubMed=12243775; DOI=10.1016/s0028-3908(02)00122-3;
RA Savidge J., Davis C., Shah K., Colley S., Phillips E., Ranasinghe S.,
RA Winter J., Kotsonis P., Rang H.P., McIntyre P.;
RT "Cloning and functional characterisation of the guinea-pig vanilloid
RT receptor 1.";
RL Neuropharmacology 43:450-456(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spinal ganglion;
RA Coombs S., Peck A., Cortright D.;
RT "Cavia porcellus TRPV1.";
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Ligand-activated non-selective calcium permeant cation
CC channel involved in detection of noxious chemical and thermal stimuli
CC (PubMed:12243775). Seems to mediate proton influx and may be involved
CC in intracellular acidosis in nociceptive neurons. Involved in mediation
CC of inflammatory pain and hyperalgesia. Sensitized by a
CC phosphatidylinositol second messenger system activated by receptor
CC tyrosine kinases, which involves PKC isozymes and PCL. Activation by
CC vanilloids, like capsaicin, and temperatures higher than 42 degrees
CC Celsius, exhibits a time- and Ca(2+)-dependent outward rectification,
CC followed by a long-lasting refractory state. Mild extracellular acidic
CC pH (6.5) potentiates channel activation by noxious heat and vanilloids,
CC whereas acidic conditions (pH <6) directly activate the channel. Can be
CC activated by endogenous compounds, including 12-hydroperoxytetraenoic
CC acid and bradykinin. Acts as ionotropic endocannabinoid receptor with
CC central neuromodulatory effects. Triggers a form of long-term
CC depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in
CC the hippocampus and nucleus accumbens by affecting AMPA receptors
CC endocytosis (By similarity). {ECO:0000250|UniProtKB:O35433,
CC ECO:0000269|PubMed:12243775}.
CC -!- ACTIVITY REGULATION: Channel activity is activated via the interaction
CC with PIRT and phosphatidylinositol 4,5-bisphosphate (PIP2). Both PIRT
CC and PIP2 are required to activate channel activity. The channel is
CC sensitized by ATP binding. Repeated stimulation with capsaicin gives
CC rise to progressively smaller responses, due to desensitization. This
CC desensitization is triggered by the influx of calcium ions and is
CC inhibited by elevated ATP levels. Ca(2+) and CALM displace ATP from its
CC binding site and trigger a conformation change that leads to a closed,
CC desensitized channel. Intracellular PIP2 inhibits desensitization. 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).
CC {ECO:0000250, 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:12243775}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O35433}. Note=Mostly, but not exclusively
CC 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, probably including Ser-118 as a
CC major phosphorylation site. Phosphorylation by CAMKII seems to regulate
CC binding to vanilloids. Phosphorylated and modulated by PRKCE, PRKCM and
CC probably PRKCZ. Dephosphorylation by calcineurin seems to lead to
CC receptor desensitization and phosphorylation by CAMKII recovers
CC activity. {ECO:0000250|UniProtKB:O35433}.
CC -!- MISCELLANEOUS: Responses evoked by low pH and heat, and capsaicin can
CC be antagonized by capsazepine.
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; AJ492922; CAD37814.2; -; mRNA.
DR EMBL; AY513245; AAS13460.1; -; mRNA.
DR RefSeq; NP_001166123.1; NM_001172652.1.
DR AlphaFoldDB; Q6R5A3; -.
DR SMR; Q6R5A3; -.
DR STRING; 10141.ENSCPOP00000009106; -.
DR BindingDB; Q6R5A3; -.
DR ChEMBL; CHEMBL5132; -.
DR Ensembl; ENSCPOT00000010234; ENSCPOP00000009106; ENSCPOG00000010142.
DR GeneID; 100135466; -.
DR KEGG; cpoc:100135466; -.
DR CTD; 7442; -.
DR eggNOG; KOG3676; Eukaryota.
DR GeneTree; ENSGT00940000160870; -.
DR InParanoid; Q6R5A3; -.
DR OMA; YQYLHQN; -.
DR OrthoDB; 693004at2759; -.
DR TreeFam; TF314711; -.
DR PRO; PR:Q6R5A3; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
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:0051219; F:phosphoprotein binding; IEA:Ensembl.
DR GO; GO:0097603; F:temperature-gated ion channel activity; IEA:Ensembl.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISS:UniProtKB.
DR GO; GO:0048266; P:behavioral response to pain; IEA:Ensembl.
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:0050968; P:detection of chemical stimulus involved in sensory perception of pain; IEA:Ensembl.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IEA:Ensembl.
DR GO; GO:0050960; P:detection of temperature stimulus involved in thermoception; IEA:Ensembl.
DR GO; GO:0002024; P:diet induced thermogenesis; IEA:Ensembl.
DR GO; GO:0001660; P:fever generation; IEA:Ensembl.
DR GO; GO:0006629; P:lipid metabolic process; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0002790; P:peptide secretion; IEA:Ensembl.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:1901594; P:response to capsazepine; ISS:UniProtKB.
DR GO; GO:0050954; P:sensory perception of mechanical stimulus; IEA:Ensembl.
DR GO; GO:0060083; P:smooth muscle contraction involved in micturition; IEA:Ensembl.
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 2: Evidence at transcript 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..839
FT /note="Transient receptor potential cation channel
FT subfamily V member 1"
FT /id="PRO_0000215337"
FT TOPO_DOM 1..434
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 435..455
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 456..473
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 474..499
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 500..512
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 513..533
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 534..537
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 538..558
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 559..573
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 574..601
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 602..658
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TRANSMEM 659..687
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT TOPO_DOM 688..839
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT REPEAT 112..154
FT /note="ANK 1"
FT REPEAT 155..201
FT /note="ANK 2"
FT REPEAT 202..248
FT /note="ANK 3"
FT REPEAT 249..284
FT /note="ANK 4"
FT REPEAT 285..333
FT /note="ANK 5"
FT REPEAT 334..360
FT /note="ANK 6"
FT REGION 1..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 82..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 685..713
FT /note="AD"
FT /evidence="ECO:0000250"
FT REGION 768..802
FT /note="Interaction with calmodulin"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT REGION 778..793
FT /note="Required for PIP2-mediated channel inhibition"
FT /evidence="ECO:0000250"
FT MOTIF 644..647
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT COMPBIAS 1..17
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 35..49
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 82..106
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 117
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 157
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 162
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 166
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 201..204
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 212..213
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 513..514
FT /ligand="resiniferatoxin"
FT /ligand_id="ChEBI:CHEBI:8809"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 552
FT /ligand="resiniferatoxin"
FT /ligand_id="ChEBI:CHEBI:8809"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 559
FT /ligand="resiniferatoxin"
FT /ligand_id="ChEBI:CHEBI:8809"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT BINDING 647
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 118
FT /note="Phosphoserine; by PKA and PKD"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT MOD_RES 146
FT /note="Phosphothreonine; by PKA; in vitro"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT MOD_RES 372
FT /note="Phosphothreonine; by PKA; in vitro"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT MOD_RES 504
FT /note="Phosphoserine; by PKC/PRKCE"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT MOD_RES 705
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT MOD_RES 775
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT MOD_RES 801
FT /note="Phosphoserine; by PKC/PRKCE and PKC/PRKCZ"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT MOD_RES 821
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35433"
FT CARBOHYD 606
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CONFLICT 24
FT /note="P -> T (in Ref. 1; CAD37814)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="L -> F (in Ref. 1; CAD37814)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 839 AA; 95244 MW; 33094EBF1B8159FC CRC64;
MKKRASVDSK ESEDPPQEDY SLDPLDVDAN SKTPPAKPHT FSVSKSRNRL FGKSDLEESS
PIDCSFREGE AASCPTITVS SVVTSPRPAD GPTSTRQLTQ DSIPTSAEKP LKLYDRRSIF
DAVAQNNCQD LDSLLPFLQK SKKRLTDTEF KDPETGKTCL LKAMLNLHNG QNDTISLLLD
IARQTNSLKE FVNASYTDSY YRGQTALHIA IERRNMVLVT LLVENGADVQ AAANGDFFKK
TKGRPGFYFG ELPLSLAACT NQLAIVKFLL QNSWQPADIS ARDSVGNTVL HALVEVADNT
ADNTKFVTSM YNEILILGAK LYPTLKLEEL TNKKGFTPLA LAASSGKIGV LAYILQREIP
EPECRHLSRK FTEWAYGPVH SSLYDLSCID TCEKNSVLEV IAYSSSETPN RHDMLLVEPL
NRLLQDKWDR FVKRIFYFNF FIYCLYMIIF TMAAYYRPVD GLPPYKMKNT VGDYFRVTGE
ILSVIGGFHF FFRGIQYFLQ RRPSVKTLFV DSYSEILFFV QSLFLLASVV LYFSHRKEYV
ACMVFSLALG WTNMLYYTRG FQQMGIYAVM IEKMILRDLC RFMFVYLVFL FGFSTAVVTL
IEDGKNESLS AEPHRWRGPG CRSAKNSYNS LYSTCLELFK FTIGMGDLEF TENYDFKAVF
IILLLAYVIL TYILLLNMLI ALMGETVNKI AQESKNIWKL QRAITILDTE KSFLKCMRKA
FRSGKLLQVG YTPDGKDDYR WCFRVDEVNW TTWNTNVGII NEDPGNCEGV KRTLSFSLRS
GRVSGRNWKN FALVPLLRDA STRDRHSAQP EEVHLKHFSG SLKPEDAEVF KDSAVPGEK
