TRPA1_MOUSE
ID TRPA1_MOUSE Reviewed; 1125 AA.
AC Q8BLA8; Q0VBN5;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Transient receptor potential cation channel subfamily A member 1 {ECO:0000312|MGI:MGI:3522699};
DE AltName: Full=Ankyrin-like with transmembrane domains protein 1 {ECO:0000250|UniProtKB:O75762};
DE AltName: Full=Wasabi receptor {ECO:0000303|PubMed:31447178};
GN Name=Trpa1 {ECO:0000312|MGI:MGI:3522699};
GN Synonyms=Anktm1 {ECO:0000303|PubMed:12654248};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=C57BL/6J;
RX PubMed=12654248; DOI=10.1016/s0092-8674(03)00158-2;
RA Story G.M., Peier A.M., Reeve A.J., Eid S.R., Mosbacher J., Hricik T.R.,
RA Earley T.J., Hergarden A.C., Anderson D.A., Hwang S.W., McIntyre P.,
RA Jegla T., Bevan S., Patapoutian A.;
RT "ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated
RT by cold temperatures.";
RL Cell 112:819-829(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=15483558; DOI=10.1038/nature03066;
RA Corey D.P., Garcia-Anoveros J., Holt J.R., Kwan K.Y., Lin S.-Y.,
RA Vollrath M.A., Amalfitano A., Cheung E.-L.M., Derfler B.H., Duggan A.,
RA Geleoc G.S.G., Gray P.A., Hoffman M.P., Rehm H.L., Tamasauskas D.,
RA Zhang D.-S.;
RT "TRPA1 is a candidate for the mechanosensitive transduction channel of
RT vertebrate hair cells.";
RL Nature 432:723-730(2004).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=15194861; DOI=10.1097/01.wnr.0000126559.35631.54;
RA Smith M.P., Beacham D., Ensor E., Koltzenburg M.;
RT "Cold-sensitive, menthol-insensitive neurons in the murine sympathetic
RT nervous system.";
RL NeuroReport 15:1399-1403(2004).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15046718; DOI=10.1016/s0896-6273(04)00150-3;
RA Bandell M., Story G.M., Hwang S.W., Viswanath V., Eid S.R., Petrus M.J.,
RA Earley T.J., Patapoutian A.;
RT "Noxious cold ion channel TRPA1 is activated by pungent compounds and
RT bradykinin.";
RL Neuron 41:849-857(2004).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=15843607; DOI=10.1523/jneurosci.0013-05.2005;
RA Nagata K., Duggan A., Kumar G., Garcia-Anoveros J.;
RT "Nociceptor and hair cell transducer properties of TRPA1, a channel for
RT pain and hearing.";
RL J. Neurosci. 25:4052-4061(2005).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16564016; DOI=10.1016/j.cell.2006.02.023;
RA Bautista D.M., Jordt S.E., Nikai T., Tsuruda P.R., Read A.J., Poblete J.,
RA Yamoah E.N., Basbaum A.I., Julius D.;
RT "TRPA1 mediates the inflammatory actions of environmental irritants and
RT proalgesic agents.";
RL Cell 124:1269-1282(2006).
RN [9]
RP ACTIVITY REGULATION.
RX PubMed=17567811; DOI=10.1523/jneurosci.0623-07.2007;
RA Kim D., Cavanaugh E.J.;
RT "Requirement of a soluble intracellular factor for activation of transient
RT receptor potential A1 by pungent chemicals: role of inorganic
RT polyphosphates.";
RL J. Neurosci. 27:6500-6509(2007).
RN [10]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF CYS-415; CYS-422 AND CYS-622.
RX PubMed=17237762; DOI=10.1038/nature05544;
RA Macpherson L.J., Dubin A.E., Evans M.J., Marr F., Schultz P.G.,
RA Cravatt B.F., Patapoutian A.;
RT "Noxious compounds activate TRPA1 ion channels through covalent
RT modification of cysteines.";
RL Nature 445:541-545(2007).
RN [11]
RP SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=21873995; DOI=10.1038/nchembio.640;
RA Takahashi N., Kuwaki T., Kiyonaka S., Numata T., Kozai D., Mizuno Y.,
RA Yamamoto S., Naito S., Knevels E., Carmeliet P., Oga T., Kaneko S.,
RA Suga S., Nokami T., Yoshida J., Mori Y.;
RT "TRPA1 underlies a sensing mechanism for O2.";
RL Nat. Chem. Biol. 7:701-711(2011).
RN [12]
RP DISULFIDE BONDS.
RX PubMed=22207754; DOI=10.1074/jbc.m111.329748;
RA Wang L., Cvetkov T.L., Chance M.R., Moiseenkova-Bell V.Y.;
RT "Identification of in vivo disulfide conformation of TRPA1 ion channel.";
RL J. Biol. Chem. 287:6169-6176(2012).
RN [13]
RP FUNCTION.
RX PubMed=24140646; DOI=10.4049/jimmunol.1300300;
RA Oh M.H., Oh S.Y., Lu J., Lou H., Myers A.C., Zhu Z., Zheng T.;
RT "TRPA1-dependent pruritus in IL-13-induced chronic atopic dermatitis.";
RL J. Immunol. 191:5371-5382(2013).
RN [14]
RP STRUCTURE BY ELECTRON MICROSCOPY (16 ANGSTROMS), AND SUBUNIT.
RX PubMed=21908607; DOI=10.1074/jbc.m111.288993;
RA Cvetkov T.L., Huynh K.W., Cohen M.R., Moiseenkova-Bell V.Y.;
RT "Molecular architecture and subunit organization of TRPA1 ion channel
RT revealed by electron microscopy.";
RL J. Biol. Chem. 286:38168-38176(2011).
RN [15]
RP INTERACTION WITH TMEM100.
RX PubMed=25640077; DOI=10.1016/j.neuron.2014.12.065;
RA Weng H.J., Patel K.N., Jeske N.A., Bierbower S.M., Zou W., Tiwari V.,
RA Zheng Q., Tang Z., Mo G.C., Wang Y., Geng Y., Zhang J., Guan Y.,
RA Akopian A.N., Dong X.;
RT "Tmem100 Is a regulator of TRPA1-TRPV1 complex and contributes to
RT persistent pain.";
RL Neuron 85:833-846(2015).
RN [16]
RP ACTIVITY REGULATION.
RX PubMed=29703838; DOI=10.1085/jgp.201711876;
RA Samanta A., Kiselar J., Pumroy R.A., Han S., Moiseenkova-Bell V.Y.;
RT "Structural insights into the molecular mechanism of mouse TRPA1 activation
RT and inhibition.";
RL J. Gen. Physiol. 150:751-762(2018).
RN [17]
RP ACTIVITY REGULATION.
RX PubMed=31447178; DOI=10.1016/j.cell.2019.07.014;
RA Lin King J.V., Emrick J.J., Kelly M.J.S., Herzig V., King G.F.,
RA Medzihradszky K.F., Julius D.;
RT "A cell-penetrating scorpion toxin enables mode-specific modulation of
RT TRPA1 and pain.";
RL Cell 178:1362-1374(2019).
CC -!- FUNCTION: Receptor-activated non-selective cation channel involved in
CC pain detection and possibly also in cold perception, oxygen
CC concentration perception, cough, itch, and inner ear function
CC (PubMed:24140646). Shows 8-fold preference for divalent over monovalent
CC cations. Has a central role in the pain response to endogenous
CC inflammatory mediators and to a diverse array of irritants, such as
CC allylthiocyanate (AITC) found in mustard oil or wasabi, cinnamaldehyde,
CC diallyl disulfide (DADS) from garlic, and acrolein, an irritant from
CC tears gas and vehicle exhaust fumes (PubMed:16564016). Acts also as an
CC ionotropic cannabinoid receptor by being activated by delta(9)-
CC tetrahydrocannabinol (THC), the psychoactive component of marijuana. Is
CC activated by a large variety of structurally unrelated electrophilic
CC and non-electrophilic chemical compounds. Electrophilic ligands
CC activate TRPA1 by interacting with critical N-terminal Cys residues in
CC a covalent manner, whereas mechanisms of non-electrophilic ligands are
CC not well determined. May be a component for the mechanosensitive
CC transduction channel of hair cells in inner ear, thereby participating
CC in the perception of sounds. Probably operated by a
CC phosphatidylinositol second messenger system.
CC {ECO:0000250|UniProtKB:O75762, ECO:0000269|PubMed:12654248,
CC ECO:0000269|PubMed:15046718, ECO:0000269|PubMed:15483558,
CC ECO:0000269|PubMed:15843607, ECO:0000269|PubMed:16564016,
CC ECO:0000305|PubMed:24140646}.
CC -!- ACTIVITY REGULATION: A cytosolic factor (probably pyrophosphate,
CC polytriphosphate, polyP4, polyP25, polyP45, and/or polyP65) is
CC necessary for TRPA1 activation by irritants (PubMed:17567811). Such
CC factor acts by keeping TRPA1 in a agonist-sensitive state
CC (PubMed:17567811). Inhibited by the potent blocker of TRPV channels
CC ruthenium red, A-967079 (PubMed:15843607, PubMed:29703838,
CC PubMed:31447178). Activated by icilin, sulfhydryl reactive agent MTSEA,
CC N-methyl maleimide (NMM), and PF-4840154 (PubMed:17237762,
CC PubMed:29703838). {ECO:0000269|PubMed:15843607,
CC ECO:0000269|PubMed:17237762, ECO:0000269|PubMed:17567811,
CC ECO:0000269|PubMed:29703838, ECO:0000269|PubMed:31447178}.
CC -!- SUBUNIT: Homotetramer (PubMed:21908607). Interacts with TMEM100
CC (PubMed:25640077). Interacts with EGLN1 (PubMed:21873995). Interacts
CC with the scorpion wasabi receptor toxin at the same site that
CC electrophiles but in a non-covalent manner (By similarity).
CC {ECO:0000250|UniProtKB:O75762, ECO:0000269|PubMed:21908607,
CC ECO:0000269|PubMed:25640077}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12654248,
CC ECO:0000269|PubMed:15046718, ECO:0000269|PubMed:15483558,
CC ECO:0000269|PubMed:15843607}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in inner ear (at protein level).
CC Specifically expressed in a subset of nociceptive neurons. Expressed in
CC the same neurons that TRPV1. In contrast, it is not expressed in
CC neurons expressing TRPM8. Expressed in the superior cervical ganglion
CC of vagus nerve. Expressed in the inferior ganglion (nodose ganglion) of
CC vagus nerve (PubMed:21873995). Expressed in dorsal root ganglia neurons
CC (PubMed:21873995). {ECO:0000269|PubMed:12654248,
CC ECO:0000269|PubMed:15194861, ECO:0000269|PubMed:15483558,
CC ECO:0000269|PubMed:15843607, ECO:0000269|PubMed:21873995}.
CC -!- DEVELOPMENTAL STAGE: During utricle development, it is first expressed
CC at 15 dpc and 16 dpc and peaks at 17 dpc. It drops at 18 dpc but
CC increases again at 19 dpc, possibly corresponding to a second wave of
CC hair cells that are generated at 15 dpc. {ECO:0000269|PubMed:15483558}.
CC -!- DOMAIN: C-terminal helices from the four subunits associate to form
CC atypical coiled coil structure; this region is probably involved in
CC binding the inositol polyphosphates that are required for optimal
CC channel activity (in vitro). {ECO:0000250|UniProtKB:O75762}.
CC -!- DOMAIN: The ANK repeat domain consists of a convex stem structure
CC followed by a crescent-shaped structure that surrounds the protein
CC core. {ECO:0000250|UniProtKB:O75762}.
CC -!- PTM: TRPA1 activation by electrophiles occurs though covalent
CC modification of specific cysteine residues in the N-terminal
CC cytoplasmic domain (PubMed:17237762, PubMed:22207754).
CC {ECO:0000269|PubMed:17237762, ECO:0000269|PubMed:22207754}.
CC -!- PTM: Hydroxylation is required for TRPA1 activity inhibition in
CC normoxia. In hypoxia, the decrease in oxygen concentration diminishes
CC the activity of the hydroxylase EGLN1, thus relieving TRPA1 from
CC inhibition and ultimately leading to channel activation.
CC {ECO:0000250|UniProtKB:O75762}.
CC -!- PTM: Oxidation of Cys-634 and Cys-859 in hyperoxia may override the
CC hydroxylase EGLN1-mediated inhibition, causing TRPA1 activation.
CC {ECO:0000250|UniProtKB:O75762}.
CC -!- DISRUPTION PHENOTYPE: Mice display normal cold sensitivity and
CC unimpaired auditory function, suggesting that this channel is not
CC required for the initial detection of noxious cold or sound. However,
CC they exhibit pronounced deficits in bradykinin-evoked nociceptor
CC excitation and pain hypersensitivity. {ECO:0000269|PubMed:16564016}.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The power behind pain
CC - Issue 82 of May 2007;
CC URL="https://web.expasy.org/spotlight/back_issues/082";
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DR EMBL; AY231177; AAO43183.1; -; mRNA.
DR EMBL; AK045771; BAC32487.1; -; mRNA.
DR EMBL; BC120563; AAI20564.1; -; mRNA.
DR EMBL; BC131963; AAI31964.1; -; mRNA.
DR CCDS; CCDS35516.1; -.
DR RefSeq; NP_001335217.1; NM_001348288.1.
DR RefSeq; NP_808449.1; NM_177781.5.
DR AlphaFoldDB; Q8BLA8; -.
DR SMR; Q8BLA8; -.
DR DIP; DIP-61521N; -.
DR STRING; 10090.ENSMUSP00000043594; -.
DR BindingDB; Q8BLA8; -.
DR ChEMBL; CHEMBL1075310; -.
DR DrugCentral; Q8BLA8; -.
DR GuidetoPHARMACOLOGY; 485; -.
DR TCDB; 1.A.4.6.1; the transient receptor potential ca(2+) channel (trp-cc) family.
DR GlyGen; Q8BLA8; 2 sites.
DR iPTMnet; Q8BLA8; -.
DR PhosphoSitePlus; Q8BLA8; -.
DR PaxDb; Q8BLA8; -.
DR PRIDE; Q8BLA8; -.
DR ProteomicsDB; 258855; -.
DR Antibodypedia; 12262; 294 antibodies from 33 providers.
DR DNASU; 277328; -.
DR Ensembl; ENSMUST00000041447; ENSMUSP00000043594; ENSMUSG00000032769.
DR GeneID; 277328; -.
DR KEGG; mmu:277328; -.
DR UCSC; uc007ajc.1; mouse.
DR CTD; 8989; -.
DR MGI; MGI:3522699; Trpa1.
DR VEuPathDB; HostDB:ENSMUSG00000032769; -.
DR eggNOG; KOG0510; Eukaryota.
DR GeneTree; ENSGT00940000156118; -.
DR HOGENOM; CLU_006750_0_0_1; -.
DR InParanoid; Q8BLA8; -.
DR OMA; HWATEKN; -.
DR OrthoDB; 361612at2759; -.
DR PhylomeDB; Q8BLA8; -.
DR TreeFam; TF317264; -.
DR Reactome; R-MMU-3295583; TRP channels.
DR BioGRID-ORCS; 277328; 3 hits in 75 CRISPR screens.
DR PRO; PR:Q8BLA8; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8BLA8; protein.
DR Bgee; ENSMUSG00000032769; Expressed in lumbar dorsal root ganglion and 18 other tissues.
DR ExpressionAtlas; Q8BLA8; baseline and differential.
DR Genevisible; Q8BLA8; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISS:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0032421; C:stereocilium bundle; IDA:MGI.
DR GO; GO:0005262; F:calcium channel activity; IDA:MGI.
DR GO; GO:0015278; F:calcium-release channel activity; ISS:UniProtKB.
DR GO; GO:0015267; F:channel activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005216; F:ion channel activity; IDA:MGI.
DR GO; GO:1990760; F:osmolarity-sensing cation channel activity; ISO:MGI.
DR GO; GO:0097604; F:temperature-gated cation channel activity; ISS:UniProtKB.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISO:MGI.
DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; ISO:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:MGI.
DR GO; GO:0006816; P:calcium ion transport; IDA:MGI.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:MGI.
DR GO; GO:0071244; P:cellular response to carbon dioxide; ISO:MGI.
DR GO; GO:0070417; P:cellular response to cold; ISO:MGI.
DR GO; GO:0034605; P:cellular response to heat; ISO:MGI.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0071310; P:cellular response to organic substance; IDA:MGI.
DR GO; GO:0050968; P:detection of chemical stimulus involved in sensory perception of pain; IDA:MGI.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IMP:MGI.
DR GO; GO:1903793; P:positive regulation of anion transport; ISO:MGI.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:1904058; P:positive regulation of sensory perception of pain; ISO:MGI.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:1903522; P:regulation of blood circulation; ISO:MGI.
DR GO; GO:0098908; P:regulation of neuronal action potential; ISO:MGI.
DR GO; GO:0009409; P:response to cold; IDA:MGI.
DR GO; GO:0042542; P:response to hydrogen peroxide; IMP:MGI.
DR GO; GO:0014070; P:response to organic cyclic compound; IMP:BHF-UCL.
DR GO; GO:0010033; P:response to organic substance; ISS:UniProtKB.
DR GO; GO:0048265; P:response to pain; IDA:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:MGI.
DR GO; GO:0019233; P:sensory perception of pain; ISO:MGI.
DR GO; GO:0050955; P:thermoception; IDA:MGI.
DR GO; GO:0014832; P:urinary bladder smooth muscle contraction; ISO:MGI.
DR Gene3D; 1.25.40.20; -; 4.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR005821; Ion_trans_dom.
DR Pfam; PF00023; Ank; 1.
DR Pfam; PF12796; Ank_2; 5.
DR Pfam; PF00520; Ion_trans; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 14.
DR SUPFAM; SSF48403; SSF48403; 2.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 9.
PE 1: Evidence at protein level;
KW ANK repeat; Cell membrane; Coiled coil; Disulfide bond; Glycoprotein;
KW Hydroxylation; Ion channel; Ion transport; Membrane; Oxidation;
KW Reference proteome; Repeat; Sensory transduction; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1125
FT /note="Transient receptor potential cation channel
FT subfamily A member 1"
FT /id="PRO_0000215370"
FT TOPO_DOM 1..721
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT TRANSMEM 722..742
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT TOPO_DOM 743..767
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT TRANSMEM 768..788
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT TOPO_DOM 789..806
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT TRANSMEM 807..827
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT TOPO_DOM 828..832
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT TRANSMEM 833..853
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT TOPO_DOM 854..876
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT TRANSMEM 877..897
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:O75762, ECO:0000255"
FT TOPO_DOM 898..904
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT INTRAMEM 905..925
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT TOPO_DOM 926..937
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT TRANSMEM 938..959
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT TOPO_DOM 960..1125
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT REPEAT 63..94
FT /note="ANK 1"
FT REPEAT 98..127
FT /note="ANK 2"
FT REPEAT 131..161
FT /note="ANK 3"
FT REPEAT 165..194
FT /note="ANK 4"
FT REPEAT 198..227
FT /note="ANK 5"
FT REPEAT 239..268
FT /note="ANK 6"
FT REPEAT 272..301
FT /note="ANK 7"
FT REPEAT 309..338
FT /note="ANK 8"
FT REPEAT 342..371
FT /note="ANK 9"
FT REPEAT 413..442
FT /note="ANK 10"
FT REPEAT 446..475
FT /note="ANK 11"
FT REPEAT 482..511
FT /note="ANK 12"
FT REPEAT 514..543
FT /note="ANK 13"
FT REPEAT 548..577
FT /note="ANK 14"
FT COILED 1044..1073
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT BINDING 415
FT /ligand="(E)-cinnamaldehyde"
FT /ligand_id="ChEBI:CHEBI:16731"
FT /ligand_note="agonist"
FT /note="covalent"
FT /evidence="ECO:0000305|PubMed:17237762"
FT BINDING 422
FT /ligand="(E)-cinnamaldehyde"
FT /ligand_id="ChEBI:CHEBI:16731"
FT /ligand_note="agonist"
FT /note="covalent"
FT /evidence="ECO:0000305|PubMed:17237762"
FT BINDING 622
FT /ligand="(E)-cinnamaldehyde"
FT /ligand_id="ChEBI:CHEBI:16731"
FT /ligand_note="agonist"
FT /note="covalent; Cys highly reactive"
FT /evidence="ECO:0000250|UniProtKB:O75762,
FT ECO:0000305|PubMed:17237762"
FT BINDING 642
FT /ligand="(E)-cinnamaldehyde"
FT /ligand_id="ChEBI:CHEBI:16731"
FT /ligand_note="agonist"
FT /note="covalent"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT BINDING 666
FT /ligand="(E)-cinnamaldehyde"
FT /ligand_id="ChEBI:CHEBI:16731"
FT /ligand_note="agonist"
FT /note="covalent"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT BINDING 712
FT /ligand="(E)-cinnamaldehyde"
FT /ligand_id="ChEBI:CHEBI:16731"
FT /ligand_note="agonist"
FT /note="covalent"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT BINDING 1048..1054
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol)"
FT /ligand_id="ChEBI:CHEBI:57880"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT SITE 623
FT /note="Key residue for activation by the scorpion wasabi
FT receptor toxin"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT SITE 635
FT /note="Important residue for activation by the scorpion
FT wasabi receptor toxin"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT SITE 647
FT /note="Important residue for activation by the scorpion
FT wasabi receptor toxin"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT MOD_RES 395
FT /note="4-hydroxyproline; transient"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT MOD_RES 634
FT /note="Cysteine sulfenic acid (-SOH); transient; in
FT hyperoxia"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT MOD_RES 859
FT /note="Cysteine sulfenic acid (-SOH); transient; in
FT hyperoxia"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT CARBOHYD 749
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 755
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 193..666
FT /note="Alternate"
FT /evidence="ECO:0000269|PubMed:22207754"
FT DISULFID 463..666
FT /note="Alternate"
FT /evidence="ECO:0000269|PubMed:22207754"
FT DISULFID 609..622
FT /note="Alternate"
FT /evidence="ECO:0000269|PubMed:22207754"
FT DISULFID 622..666
FT /note="Alternate"
FT /evidence="ECO:0000269|PubMed:22207754"
FT DISULFID 634..859
FT /note="Alternate; transient; in hyperoxia; unknown whether
FT inter- or intrachain"
FT /evidence="ECO:0000250|UniProtKB:O75762"
FT MUTAGEN 415
FT /note="C->S: Very important decrease in cinnamaldehyde or
FT cold-evoked response."
FT /evidence="ECO:0000269|PubMed:17237762"
FT MUTAGEN 422
FT /note="C->S: Important decrease in cinnamaldehyde or cold-
FT evoked response."
FT /evidence="ECO:0000269|PubMed:17237762"
FT MUTAGEN 622
FT /note="C->S: Almost complete loss in cinnamaldehyde or
FT cold-evoked response."
FT /evidence="ECO:0000269|PubMed:17237762"
SQ SEQUENCE 1125 AA; 128467 MW; CD718BF3ED4AC291 CRC64;
MKRGLRRILL PEERKEVQGV VYRGVGEDMD CSKESFKVDI EGDMCRLEDF IKNRRKLSKY
EDENLCPLHH AAAEGQVELM ELIINGSSCE VLNIMDGYGN TPLHCAAEKN QVESVKFLLS
QGANPNLRNR NMMSPLHIAV HGMYNEVIKV LTEHKATNIN LEGENGNTAL MSTCAKDNSE
ALQILLEKGA KLCKSNKWGD YPVHQAAFSG AKKCMELILA YGEKNGYSRE THINFVNHKK
ASPLHLAVQS GDLDMIKMCL DNGAHIDMME NAKCMALHFA ATQGATDIVK LMISSYTGSS
DIVNAVDGNQ ETLLHRASLF DHHDLAEYLI SVGADINSTD SEGRSPLILA TASASWNIVN
LLLCKGAKVD IKDHLGRNFL HLTVQQPYGL RNLRPEFMQM QHIKELVMDE DNDGCTPLHY
ACRQGVPVSV NNLLGFNVSI HSKSKDKKSP LHFAASYGRI NTCQRLLQDI SDTRLLNEGD
LHGMTPLHLA AKNGHDKVVQ LLLKKGALFL SDHNGWTALH HASMGGYTQT MKVILDTNLK
CTDRLDEEGN TALHFAAREG HAKAVAMLLS YNADILLNKK QASFLHIALH NKRKEVVLTT
IRNKRWDECL QVFTHNSPSN RCPIMEMVEY LPECMKVLLD FCMIPSTEDK SCQDYHIEYN
FKYLQCPLSM TKKVAPTQDV VYEPLTILNV MVQHNRIELL NHPVCREYLL MKWCAYGFRA
HMMNLGSYCL GLIPMTLLVV KIQPGMAFNS TGIINGTSST HEERIDTLNS FPIKICMILV
FLSSIFGYCK EVIQIFQQKR NYFLDYNNAL EWVIYTTSII FVLPLFLNIP AYMQWQCGAI
AIFFYWMNFL LYLQRFENCG IFIVMLEVIF KTLLRSTGVF IFLLLAFGLS FYVLLNFQDA
FSTPLLSLIQ TFSMMLGDIN YRDAFLEPLF RNELAYPVLT FGQLIAFTMF VPIVLMNLLI
GLAVGDIAEV QKHASLKRIA MQVELHTNLE KKLPLWYLRK VDQRSTIVYP NRPRHGRMLR
FFHYFLNMQE TRQEVPNIDT CLEMEILKQK YRLKDLTSLL EKQHELIKLI IQKMEIISET
EDEDNHCSFQ DRFKKERLEQ MHSKWNFVLN AVKTKTHCSI SHPDF
