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Protein

Transient receptor potential cation channel subfamily A member 1

Gene

TRPA1

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

Functioni

Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta9-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).By similarity3 Publications

Activity regulationi

Inhibited by ruthenium red, a potent blocker of TRPV channels.1 Publication

GO - Molecular functioni

  • calcium channel activity Source: Reactome
  • calcium-release channel activity Source: UniProtKB
  • channel activity Source: ProtInc
  • identical protein binding Source: IntAct
  • temperature-gated cation channel activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionIon channel
Biological processIon transport, Sensory transduction, Transport

Enzyme and pathway databases

ReactomeiR-HSA-3295583 TRP channels

Protein family/group databases

TCDBi1.A.4.6.3 the transient receptor potential ca(2+) channel (trp-cc) family

Names & Taxonomyi

Protein namesi
Recommended name:
Transient receptor potential cation channel subfamily A member 1
Alternative name(s):
Ankyrin-like with transmembrane domains protein 1
Transformation-sensitive protein p120
Gene namesi
Name:TRPA1
Synonyms:ANKTM1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000104321.10
HGNCiHGNC:497 TRPA1
MIMi604775 gene
neXtProtiNX_O75762

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 – 719Cytoplasmic1 PublicationAdd BLAST719
Transmembranei720 – 740Helical; Name=11 PublicationAdd BLAST21
Topological domaini741 – 764Extracellular1 PublicationAdd BLAST24
Transmembranei765 – 785Helical; Name=21 PublicationAdd BLAST21
Topological domaini786 – 803Cytoplasmic1 PublicationAdd BLAST18
Transmembranei804 – 824Helical; Name=31 PublicationAdd BLAST21
Topological domaini825 – 829Extracellular1 Publication5
Transmembranei830 – 850Helical; Name=41 PublicationAdd BLAST21
Topological domaini851 – 873Cytoplasmic1 PublicationAdd BLAST23
Transmembranei874 – 894Helical; Name=51 PublicationAdd BLAST21
Topological domaini895 – 901Extracellular1 Publication7
Intramembranei902 – 922Pore-forming1 PublicationAdd BLAST21
Topological domaini923 – 934Extracellular1 PublicationAdd BLAST12
Transmembranei935 – 956Helical; Name=61 PublicationAdd BLAST22
Topological domaini957 – 1119Cytoplasmic1 PublicationAdd BLAST163

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Episodic pain syndrome, familial, 1 (FEPS1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant neurologic disorder characterized by onset in infancy of episodic debilitating upper body pain triggered by fasting, cold, and physical stress. The period of intense pain is accompanied by breathing difficulties, tachycardia, sweating, generalized pallor, peribuccal cyanosis, and stiffness of the abdominal wall. Affected individuals do not manifest altered pain sensitivity outside the episodes.
See also OMIM:615040
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069737855N → S in FEPS1; 5-fold increase in inward current when stimulated by the agonist cinnamaldehyde compared to wild-type at normal neuronal resting potential; consistent with a gain of function mutation. 1 PublicationCorresponds to variant dbSNP:rs398123010EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi8989
MalaCardsiTRPA1
MIMi615040 phenotype
OpenTargetsiENSG00000104321
Orphaneti391389 Familial episodic pain syndrome with predominantly upper body involvement

Chemistry databases

ChEMBLiCHEMBL6007
DrugBankiDB00825 Menthol
GuidetoPHARMACOLOGYi485

Polymorphism and mutation databases

BioMutaiTRPA1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153691 – 1119Transient receptor potential cation channel subfamily A member 1Add BLAST1119

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi192 ↔ 665AlternateBy similarity
Disulfide bondi462 ↔ 665AlternateBy similarity
Disulfide bondi608 ↔ 621AlternateBy similarity
Disulfide bondi621 ↔ 665AlternateBy similarity
Glycosylationi747N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi753N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

TRPA1 activation by electrophiles occurs though covalent modification of specific cysteine residues in the N-terminal cytoplasmic domain.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO75762
PeptideAtlasiO75762
PRIDEiO75762
ProteomicsDBi50181

PTM databases

iPTMnetiO75762
PhosphoSitePlusiO75762

Expressioni

Tissue specificityi

Expressed at very low level. Expressed at very low level in human fibroblasts and at a moderate level in liposarcoma cells.1 Publication

Gene expression databases

BgeeiENSG00000104321 Expressed in 104 organ(s), highest expression level in oocyte
CleanExiHS_TRPA1
ExpressionAtlasiO75762 baseline and differential
GenevisibleiO75762 HS

Interactioni

Subunit structurei

Homotetramer (PubMed:25389312, PubMed:25855297). Interacts with TMEM100 (By similarity).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-11722999,EBI-11722999

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114471, 2 interactors
DIPiDIP-61520N
IntActiO75762, 2 interactors
MINTiO75762
STRINGi9606.ENSP00000262209

Chemistry databases

BindingDBiO75762

Structurei

3D structure databases

ProteinModelPortaliO75762
SMRiO75762
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati62 – 92ANK 1Sequence analysis1 PublicationAdd BLAST31
Repeati97 – 126ANK 2Sequence analysis1 PublicationAdd BLAST30
Repeati130 – 160ANK 3Sequence analysis1 PublicationAdd BLAST31
Repeati164 – 193ANK 4Sequence analysis1 PublicationAdd BLAST30
Repeati197 – 226ANK 5Sequence analysis1 PublicationAdd BLAST30
Repeati238 – 267ANK 6Sequence analysis1 PublicationAdd BLAST30
Repeati271 – 301ANK 7Sequence analysis1 PublicationAdd BLAST31
Repeati308 – 337ANK 8Sequence analysis1 PublicationAdd BLAST30
Repeati341 – 370ANK 9Sequence analysis1 PublicationAdd BLAST30
Repeati374 – 403ANK 101 PublicationAdd BLAST30
Repeati412 – 441ANK 11Sequence analysis1 PublicationAdd BLAST30
Repeati445 – 474ANK 12Sequence analysis1 PublicationAdd BLAST30
Repeati481 – 510ANK 13Sequence analysis1 PublicationAdd BLAST30
Repeati513 – 542ANK 14Sequence analysis1 PublicationAdd BLAST30
Repeati547 – 576ANK 15Sequence analysis1 PublicationAdd BLAST30
Repeati579 – 609ANK 16Sequence analysis1 PublicationAdd BLAST31

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1046 – 1052Inositolphosphate binding1 Publication7

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili1042 – 10711 PublicationAdd BLAST30

Domaini

C-terminal helices from the four subunits associate to form atypical coiled coil structure; this region is probably involved in binding the inositol polyphosphates that are required for optimal channel activity (in vitro).1 Publication
The ANK repeat domain consists of a convex stem structure formed by five ANK repeats and 11 additional ANK repeats that form a crescent-shaped structure that surrounds the protein core.1 Publication

Sequence similaritiesi

Keywords - Domaini

ANK repeat, Coiled coil, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0510 Eukaryota
COG0666 LUCA
GeneTreeiENSGT00920000149074
HOGENOMiHOG000044486
HOVERGENiHBG059027
InParanoidiO75762
KOiK04984
OMAiYYIEYNF
OrthoDBiEOG091G01BG
PhylomeDBiO75762
TreeFamiTF317264

Family and domain databases

CDDicd00204 ANK, 4 hits
Gene3Di1.25.40.20, 4 hits
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR005821 Ion_trans_dom
IPR030288 TRPA1/painless
PANTHERiPTHR24190 PTHR24190, 1 hit
PfamiView protein in Pfam
PF12796 Ank_2, 6 hits
PF00520 Ion_trans, 1 hit
PRINTSiPR01415 ANKYRIN
SMARTiView protein in SMART
SM00248 ANK, 14 hits
SUPFAMiSSF48403 SSF48403, 2 hits
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 9 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

O75762-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKRSLRKMWR PGEKKEPQGV VYEDVPDDTE DFKESLKVVF EGSAYGLQNF
60 70 80 90 100
NKQKKLKRCD DMDTFFLHYA AAEGQIELME KITRDSSLEV LHEMDDYGNT
110 120 130 140 150
PLHCAVEKNQ IESVKFLLSR GANPNLRNFN MMAPLHIAVQ GMNNEVMKVL
160 170 180 190 200
LEHRTIDVNL EGENGNTAVI IACTTNNSEA LQILLKKGAK PCKSNKWGCF
210 220 230 240 250
PIHQAAFSGS KECMEIILRF GEEHGYSRQL HINFMNNGKA TPLHLAVQNG
260 270 280 290 300
DLEMIKMCLD NGAQIDPVEK GRCTAIHFAA TQGATEIVKL MISSYSGSVD
310 320 330 340 350
IVNTTDGCHE TMLHRASLFD HHELADYLIS VGADINKIDS EGRSPLILAT
360 370 380 390 400
ASASWNIVNL LLSKGAQVDI KDNFGRNFLH LTVQQPYGLK NLRPEFMQMQ
410 420 430 440 450
QIKELVMDED NDGCTPLHYA CRQGGPGSVN NLLGFNVSIH SKSKDKKSPL
460 470 480 490 500
HFAASYGRIN TCQRLLQDIS DTRLLNEGDL HGMTPLHLAA KNGHDKVVQL
510 520 530 540 550
LLKKGALFLS DHNGWTALHH ASMGGYTQTM KVILDTNLKC TDRLDEDGNT
560 570 580 590 600
ALHFAAREGH AKAVALLLSH NADIVLNKQQ ASFLHLALHN KRKEVVLTII
610 620 630 640 650
RSKRWDECLK IFSHNSPGNK CPITEMIEYL PECMKVLLDF CMLHSTEDKS
660 670 680 690 700
CRDYYIEYNF KYLQCPLEFT KKTPTQDVIY EPLTALNAMV QNNRIELLNH
710 720 730 740 750
PVCKEYLLMK WLAYGFRAHM MNLGSYCLGL IPMTILVVNI KPGMAFNSTG
760 770 780 790 800
IINETSDHSE ILDTTNSYLI KTCMILVFLS SIFGYCKEAG QIFQQKRNYF
810 820 830 840 850
MDISNVLEWI IYTTGIIFVL PLFVEIPAHL QWQCGAIAVY FYWMNFLLYL
860 870 880 890 900
QRFENCGIFI VMLEVILKTL LRSTVVFIFL LLAFGLSFYI LLNLQDPFSS
910 920 930 940 950
PLLSIIQTFS MMLGDINYRE SFLEPYLRNE LAHPVLSFAQ LVSFTIFVPI
960 970 980 990 1000
VLMNLLIGLA VGDIAEVQKH ASLKRIAMQV ELHTSLEKKL PLWFLRKVDQ
1010 1020 1030 1040 1050
KSTIVYPNKP RSGGMLFHIF CFLFCTGEIR QEIPNADKSL EMEILKQKYR
1060 1070 1080 1090 1100
LKDLTFLLEK QHELIKLIIQ KMEIISETED DDSHCSFQDR FKKEQMEQRN
1110
SRWNTVLRAV KAKTHHLEP
Length:1,119
Mass (Da):127,501
Last modified:November 30, 2010 - v3
Checksum:i283BF31BC77CF71B
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YAW0H0YAW0_HUMAN
Transient receptor potential cation...
TRPA1
916Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0206603R → C1 PublicationCorresponds to variant dbSNP:rs13268757Ensembl.1
Natural variantiVAR_04747158R → T1 PublicationCorresponds to variant dbSNP:rs16937976Ensembl.1
Natural variantiVAR_020661179E → K. Corresponds to variant dbSNP:rs920829Ensembl.1
Natural variantiVAR_020662186K → N1 PublicationCorresponds to variant dbSNP:rs7819749Ensembl.1
Natural variantiVAR_069737855N → S in FEPS1; 5-fold increase in inward current when stimulated by the agonist cinnamaldehyde compared to wild-type at normal neuronal resting potential; consistent with a gain of function mutation. 1 PublicationCorresponds to variant dbSNP:rs398123010EnsemblClinVar.1
Natural variantiVAR_0206631018H → R. Corresponds to variant dbSNP:rs959976Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y10601 mRNA Translation: CAA71610.1
AC022867 Genomic DNA No translation available.
CCDSiCCDS34908.1
RefSeqiNP_015628.2, NM_007332.2
XP_011515927.1, XM_011517625.2
XP_016869435.1, XM_017013946.1
UniGeneiHs.716816

Genome annotation databases

EnsembliENST00000262209; ENSP00000262209; ENSG00000104321
GeneIDi8989
KEGGihsa:8989
UCSCiuc003xza.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Protein Spotlight

The power behind pain - Issue 82 of May 2007

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y10601 mRNA Translation: CAA71610.1
AC022867 Genomic DNA No translation available.
CCDSiCCDS34908.1
RefSeqiNP_015628.2, NM_007332.2
XP_011515927.1, XM_011517625.2
XP_016869435.1, XM_017013946.1
UniGeneiHs.716816

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3J9Pelectron microscopy4.24A/B/C/D2-1119[»]
ProteinModelPortaliO75762
SMRiO75762
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114471, 2 interactors
DIPiDIP-61520N
IntActiO75762, 2 interactors
MINTiO75762
STRINGi9606.ENSP00000262209

Chemistry databases

BindingDBiO75762
ChEMBLiCHEMBL6007
DrugBankiDB00825 Menthol
GuidetoPHARMACOLOGYi485

Protein family/group databases

TCDBi1.A.4.6.3 the transient receptor potential ca(2+) channel (trp-cc) family

PTM databases

iPTMnetiO75762
PhosphoSitePlusiO75762

Polymorphism and mutation databases

BioMutaiTRPA1

Proteomic databases

PaxDbiO75762
PeptideAtlasiO75762
PRIDEiO75762
ProteomicsDBi50181

Protocols and materials databases

DNASUi8989
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262209; ENSP00000262209; ENSG00000104321
GeneIDi8989
KEGGihsa:8989
UCSCiuc003xza.4 human

Organism-specific databases

CTDi8989
DisGeNETi8989
EuPathDBiHostDB:ENSG00000104321.10
GeneCardsiTRPA1
H-InvDBiHIX0034373
HIX0124652
HGNCiHGNC:497 TRPA1
MalaCardsiTRPA1
MIMi604775 gene
615040 phenotype
neXtProtiNX_O75762
OpenTargetsiENSG00000104321
Orphaneti391389 Familial episodic pain syndrome with predominantly upper body involvement
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0510 Eukaryota
COG0666 LUCA
GeneTreeiENSGT00920000149074
HOGENOMiHOG000044486
HOVERGENiHBG059027
InParanoidiO75762
KOiK04984
OMAiYYIEYNF
OrthoDBiEOG091G01BG
PhylomeDBiO75762
TreeFamiTF317264

Enzyme and pathway databases

ReactomeiR-HSA-3295583 TRP channels

Miscellaneous databases

GenomeRNAii8989
PROiPR:O75762
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104321 Expressed in 104 organ(s), highest expression level in oocyte
CleanExiHS_TRPA1
ExpressionAtlasiO75762 baseline and differential
GenevisibleiO75762 HS

Family and domain databases

CDDicd00204 ANK, 4 hits
Gene3Di1.25.40.20, 4 hits
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR005821 Ion_trans_dom
IPR030288 TRPA1/painless
PANTHERiPTHR24190 PTHR24190, 1 hit
PfamiView protein in Pfam
PF12796 Ank_2, 6 hits
PF00520 Ion_trans, 1 hit
PRINTSiPR01415 ANKYRIN
SMARTiView protein in SMART
SM00248 ANK, 14 hits
SUPFAMiSSF48403 SSF48403, 2 hits
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 9 hits
ProtoNetiSearch...

Entry informationi

Entry nameiTRPA1_HUMAN
AccessioniPrimary (citable) accession number: O75762
Secondary accession number(s): A6NIN6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: November 30, 2010
Last modified: September 12, 2018
This is version 149 of the entry and version 3 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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