TRPA1_RAT
ID TRPA1_RAT Reviewed; 1125 AA.
AC Q6RI86;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Transient receptor potential cation channel subfamily A member 1 {ECO:0000312|RGD:1303284};
DE AltName: Full=Ankyrin-like with transmembrane domains protein 1 {ECO:0000312|RGD:1303284};
DE AltName: Full=Wasabi receptor {ECO:0000250|UniProtKB:O75762};
GN Name=Trpa1 {ECO:0000312|RGD:1303284};
GN Synonyms=Anktm1 {ECO:0000303|PubMed:14712238};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ACTIVITY REGULATION.
RC STRAIN=Sprague-Dawley; TISSUE=Trigeminal ganglion;
RX PubMed=14712238; DOI=10.1038/nature02282;
RA Jordt S.-E., Bautista D.M., Chuang H.-H., McKemy D.D., Zygmunt P.M.,
RA Hoegestaett E.D., Meng I.D., Julius D.;
RT "Mustard oils and cannabinoids excite sensory nerve fibres through the TRP
RT channel ANKTM1.";
RL Nature 427:260-265(2004).
RN [2]
RP TISSUE SPECIFICITY.
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 [3]
RP ACTIVITY REGULATION.
RX PubMed=21402443; DOI=10.1016/j.pain.2011.01.049;
RA Chen J., Joshi S.K., DiDomenico S., Perner R.J., Mikusa J.P., Gauvin D.M.,
RA Segreti J.A., Han P., Zhang X.F., Niforatos W., Bianchi B.R., Baker S.J.,
RA Zhong C., Simler G.H., McDonald H.A., Schmidt R.G., McGaraughty S.P.,
RA Chu K.L., Faltynek C.R., Kort M.E., Reilly R.M., Kym P.R.;
RT "Selective blockade of TRPA1 channel attenuates pathological pain without
RT altering noxious cold sensation or body temperature regulation.";
RL Pain 152:1165-1172(2011).
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. Shows 8-
CC fold preference for divalent over monovalent cations. Has a central
CC role in the pain response to endogenous inflammatory mediators and to a
CC diverse array of irritants, such as allylthiocyanate (AITC) found in
CC mustard oil or wasabi, cinnamaldehyde, diallyl disulfide (DADS) from
CC garlic, and acrolein, an irritant from tears gas and vehicle exhaust
CC fumes (By similarity). Acts also as an ionotropic cannabinoid receptor
CC by being activated by delta(9)-tetrahydrocannabinol (THC), the
CC psychoactive component of marijuana (By similarity). Is activated by a
CC large variety of structurally unrelated electrophilic and non-
CC electrophilic chemical compounds. Electrophilic ligands activate TRPA1
CC by interacting with critical N-terminal Cys residues in a covalent
CC manner, whereas mechanisms of non-electrophilic ligands are not well
CC determined. May be a component for the mechanosensitive transduction
CC channel of hair cells in inner ear, thereby participating in the
CC perception of sounds. Probably operated by a phosphatidylinositol
CC second messenger system (By similarity). {ECO:0000250|UniProtKB:O75762,
CC ECO:0000250|UniProtKB:Q8BLA8, ECO:0000269|PubMed:14712238}.
CC -!- ACTIVITY REGULATION: Inhibited by ruthenium red, a potent blocker of
CC TRPV channels (PubMed:14712238). Selectively inhibited by A-967079
CC (PubMed:21402443). {ECO:0000269|PubMed:14712238,
CC ECO:0000269|PubMed:21402443}.
CC -!- SUBUNIT: Homotetramer (By similarity). Interacts with TMEM100 (By
CC similarity). Interacts with EGLN1 (By similarity). Interacts with the
CC scorpion wasabi receptor toxin at the same site that electrophiles but
CC in a non-covalent manner (By similarity).
CC {ECO:0000250|UniProtKB:O75762, ECO:0000250|UniProtKB:Q8BLA8}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8BLA8};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in a subset of nociceptive
CC neurons. Expressed in dorsal root ganglia.
CC {ECO:0000269|PubMed:12654248}.
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 (By similarity). {ECO:0000250|UniProtKB:Q8BLA8}.
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 -!- 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; AY496961; AAS78661.1; -; mRNA.
DR RefSeq; NP_997491.1; NM_207608.1.
DR AlphaFoldDB; Q6RI86; -.
DR SMR; Q6RI86; -.
DR DIP; DIP-61522N; -.
DR STRING; 10116.ENSRNOP00000009874; -.
DR BindingDB; Q6RI86; -.
DR ChEMBL; CHEMBL5160; -.
DR DrugCentral; Q6RI86; -.
DR GuidetoPHARMACOLOGY; 485; -.
DR GlyGen; Q6RI86; 2 sites.
DR PaxDb; Q6RI86; -.
DR GeneID; 312896; -.
DR KEGG; rno:312896; -.
DR UCSC; RGD:1303284; rat.
DR CTD; 8989; -.
DR RGD; 1303284; Trpa1.
DR eggNOG; KOG0510; Eukaryota.
DR InParanoid; Q6RI86; -.
DR OrthoDB; 361612at2759; -.
DR PhylomeDB; Q6RI86; -.
DR Reactome; R-RNO-3295583; TRP channels.
DR PRO; PR:Q6RI86; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0032421; C:stereocilium bundle; ISO:RGD.
DR GO; GO:0005262; F:calcium channel activity; ISO:RGD.
DR GO; GO:0015278; F:calcium-release channel activity; ISS:UniProtKB.
DR GO; GO:0015267; F:channel activity; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0005216; F:ion channel activity; ISO:RGD.
DR GO; GO:1990760; F:osmolarity-sensing cation channel activity; IDA:RGD.
DR GO; GO:0097604; F:temperature-gated cation channel activity; ISS:UniProtKB.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:RGD.
DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; IDA:RGD.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; ISO:RGD.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISO:RGD.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:RGD.
DR GO; GO:0071313; P:cellular response to caffeine; IEP:RGD.
DR GO; GO:0071244; P:cellular response to carbon dioxide; IDA:RGD.
DR GO; GO:0070417; P:cellular response to cold; IMP:RGD.
DR GO; GO:0034605; P:cellular response to heat; IMP:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:RGD.
DR GO; GO:0071310; P:cellular response to organic substance; ISO:RGD.
DR GO; GO:0050968; P:detection of chemical stimulus involved in sensory perception of pain; ISO:RGD.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; ISO:RGD.
DR GO; GO:1903793; P:positive regulation of anion transport; IMP:RGD.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:RGD.
DR GO; GO:1904058; P:positive regulation of sensory perception of pain; IMP:RGD.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:1903522; P:regulation of blood circulation; IMP:RGD.
DR GO; GO:0098908; P:regulation of neuronal action potential; IMP:RGD.
DR GO; GO:0009409; P:response to cold; ISO:RGD.
DR GO; GO:0042542; P:response to hydrogen peroxide; ISO:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; ISO:RGD.
DR GO; GO:0010033; P:response to organic substance; ISS:UniProtKB.
DR GO; GO:0048265; P:response to pain; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:RGD.
DR GO; GO:0019233; P:sensory perception of pain; IMP:RGD.
DR GO; GO:0050955; P:thermoception; ISO:RGD.
DR GO; GO:0014832; P:urinary bladder smooth muscle contraction; IMP:RGD.
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; 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 2: Evidence at transcript 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_0000215371"
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"
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:0000250|UniProtKB:Q8BLA8"
FT BINDING 422
FT /ligand="(E)-cinnamaldehyde"
FT /ligand_id="ChEBI:CHEBI:16731"
FT /ligand_note="agonist"
FT /note="covalent"
FT /evidence="ECO:0000250|UniProtKB:Q8BLA8"
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:0000250|UniProtKB:Q8BLA8"
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:0000250|UniProtKB:Q8BLA8"
FT DISULFID 463..666
FT /note="Alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BLA8"
FT DISULFID 609..622
FT /note="Alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BLA8"
FT DISULFID 622..666
FT /note="Alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8BLA8"
FT DISULFID 634..859
FT /note="Alternate; transient; in hyperoxia; unknown whether
FT inter- or intrachain"
FT /evidence="ECO:0000250|UniProtKB:O75762"
SQ SEQUENCE 1125 AA; 128602 MW; 32A6FB51EDCBB4B5 CRC64;
MKRSLRRVLR PEERKEVQGV VYRGVGKDMD CSKESFKVDI EGDMCRLEAF IKNRRKLSKY
EDENLCLLHH AAAEGQVELM QLIINGSSCE ALNVMDDYGN TPLHWAAEKN QVESVKFLLS
QGANPNLRNR NMMAPLHIAV QGMYNEVIKV LTEHKATNIN LEGENGNTAL MSTCAKDNSE
ALQILLEKGA KLCKSNKWGD YPVHQAAFSG AKRCMELILA YGEKTGYSRE AHINFVNHKK
ASPLHLAVQS GDLDMIKMCL DSGAHIDMME NAKCMALHFA ATQGATDIVK LMISSYTGSS
DIVNAVDGNQ ETLLHRASLF DHHDLADYLI SVGADINSTD SEGRSPLILA TASASWNIVN
LLLSKGAKVD IKDHLGRNFL HLTVQQPYGL RNLRPEFLQM QHIKELVMDE DNDGCTPLHY
ACRQGAPVSV NNLLRFNVSV HSKSKDKKSP LHFAASYGRI NTCQRLLQDI SDTRLLNEGD
LHGMTPLHLA AKNGHDKVVQ LLLKKGALFL SDHNGWTALH HASMGGYTQT MKVILDTNLK
CTDRLDEEGN TALHFAAREG HAKAVAMLLS YNADILLNKK QASFLHIALH NKRKEVVLTT
IRSKRWDECL QVFTHDSPSN RCPIMEMVEY LPECMKVLLD FCMIPSTEDK SCQDYHIEYN
FKYLQCPLSM TKKVTPTQDV IYEPLTILNV MVQHNRIELL NHPVCREYLL MKWCAYGFRA
HMMNLGSYCL GLIPMTLLVV KIQPGMAFNS TGIINETIST HEERINTLNS FPLKICMILV
FLSSIFGYCK EVVQIFQQKR NYFLDYNNAL EWVIYTTSMI FVLPLFLDIP AYMQWQCGAI
AIFFYWMNFL LYLQRFENCG IFIVMLEVIF KTLLRSTGVF IFLLLAFGLS FYVLLNFQDA
FSTPLLSLIQ TFSMMLGDIN YRDAFLEPLF RNELAYPVLT FGQLIAFTMF VPIVLMNLLI
GLAVGDIAEV QKHASLKRIA MQVELHTNLE KKLPFWYLRK VDQRSTIVYP NRPRHGRMLR
FFHYFLSMQE TRQEAPNIDT CLEMEILKQK YRLKDLTSLL EKQHELIKLI IQKMEIISET
EDEDNHCSFQ DRFKKERLEQ MHSKWNFVLN AVKTKTHCSI SHPDI
