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O75762 (TRPA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:TRPA1
Synonyms:ANKTM1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1119 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function. Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes. Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana. Not involved in menthol sensation. 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.

Enzyme regulation

Inhibited by ruthenium red, a potent blocker of TRPV channels By similarity.

Subunit structure

Homotetramer By similarity.

Subcellular location

Membrane; Multi-pass membrane protein Probable.

Tissue specificity

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

Post-translational modification

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

Involvement in disease

Episodic pain syndrome, familial, 1 (FEPS1) [MIM:615040]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3

Sequence similarities

Belongs to the transient receptor (TC 1.A.4) family. [View classification]

Contains 15 ANK repeats.

Ontologies

Keywords
   Biological processIon transport
Sensory transduction
Transport
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainANK repeat
Repeat
Transmembrane
Transmembrane helix
   Molecular functionIon channel
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcalcium ion transmembrane transport

Traceable author statement. Source: Reactome

detection of chemical stimulus involved in sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

detection of mechanical stimulus involved in sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

ion transmembrane transport

Traceable author statement. Source: Reactome

ion transport

Traceable author statement Ref.1. Source: ProtInc

response to cold

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

response to pain

Inferred from electronic annotation. Source: Ensembl

thermoception

Inferred from electronic annotation. Source: Ensembl

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentintegral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

stereocilium bundle

Inferred from electronic annotation. Source: Ensembl

   Molecular_functioncalcium channel activity

Inferred from electronic annotation. Source: Ensembl

channel activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11191119Transient receptor potential cation channel subfamily A member 1
PRO_0000215369

Regions

Topological domain1 – 719719Cytoplasmic Potential
Transmembrane720 – 74021Helical; Name=1; Potential
Topological domain741 – 77232Extracellular Potential
Transmembrane773 – 79321Helical; Name=2; Potential
Topological domain794 – 80512Cytoplasmic Potential
Transmembrane806 – 82621Helical; Name=3; Potential
Topological domain827 – 8293Extracellular Potential
Transmembrane830 – 85021Helical; Name=4; Potential
Topological domain851 – 87323Cytoplasmic Potential
Transmembrane874 – 89421Helical; Name=5; Potential
Topological domain895 – 94046Extracellular Potential
Transmembrane941 – 96121Helical; Name=6; Potential
Topological domain962 – 1119158Cytoplasmic Potential
Repeat62 – 9231ANK 1
Repeat97 – 12630ANK 2
Repeat130 – 16031ANK 3
Repeat164 – 19330ANK 4
Repeat197 – 22630ANK 5
Repeat238 – 26730ANK 6
Repeat271 – 30131ANK 7
Repeat308 – 33730ANK 8
Repeat341 – 37030ANK 9
Repeat412 – 44130ANK 10
Repeat445 – 47430ANK 11
Repeat481 – 51030ANK 12
Repeat513 – 54230ANK 13
Repeat547 – 57630ANK 14
Repeat579 – 60931ANK 15

Amino acid modifications

Glycosylation7471N-linked (GlcNAc...) Potential
Glycosylation7531N-linked (GlcNAc...) Potential
Disulfide bond192 ↔ 665Alternate By similarity
Disulfide bond462 ↔ 665Alternate By similarity
Disulfide bond608 ↔ 621Alternate By similarity
Disulfide bond621 ↔ 665Alternate By similarity

Natural variations

Natural variant31R → C. Ref.1
Corresponds to variant rs13268757 [ dbSNP | Ensembl ].
VAR_020660
Natural variant581R → T. Ref.1
Corresponds to variant rs16937976 [ dbSNP | Ensembl ].
VAR_047471
Natural variant1791E → K.
Corresponds to variant rs920829 [ dbSNP | Ensembl ].
VAR_020661
Natural variant1861K → N. Ref.1
Corresponds to variant rs7819749 [ dbSNP | Ensembl ].
VAR_020662
Natural variant8551N → 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. Ref.3
VAR_069737
Natural variant10181H → R.
Corresponds to variant rs959976 [ dbSNP | Ensembl ].
VAR_020663

Sequences

Sequence LengthMass (Da)Tools
O75762 [UniParc].

Last modified November 30, 2010. Version 3.
Checksum: 283BF31BC77CF71B

FASTA1,119127,501
        10         20         30         40         50         60 
MKRSLRKMWR PGEKKEPQGV VYEDVPDDTE DFKESLKVVF EGSAYGLQNF NKQKKLKRCD 

        70         80         90        100        110        120 
DMDTFFLHYA AAEGQIELME KITRDSSLEV LHEMDDYGNT PLHCAVEKNQ IESVKFLLSR 

       130        140        150        160        170        180 
GANPNLRNFN MMAPLHIAVQ GMNNEVMKVL LEHRTIDVNL EGENGNTAVI IACTTNNSEA 

       190        200        210        220        230        240 
LQILLKKGAK PCKSNKWGCF PIHQAAFSGS KECMEIILRF GEEHGYSRQL HINFMNNGKA 

       250        260        270        280        290        300 
TPLHLAVQNG DLEMIKMCLD NGAQIDPVEK GRCTAIHFAA TQGATEIVKL MISSYSGSVD 

       310        320        330        340        350        360 
IVNTTDGCHE TMLHRASLFD HHELADYLIS VGADINKIDS EGRSPLILAT ASASWNIVNL 

       370        380        390        400        410        420 
LLSKGAQVDI KDNFGRNFLH LTVQQPYGLK NLRPEFMQMQ QIKELVMDED NDGCTPLHYA 

       430        440        450        460        470        480 
CRQGGPGSVN NLLGFNVSIH SKSKDKKSPL HFAASYGRIN TCQRLLQDIS DTRLLNEGDL 

       490        500        510        520        530        540 
HGMTPLHLAA KNGHDKVVQL LLKKGALFLS DHNGWTALHH ASMGGYTQTM KVILDTNLKC 

       550        560        570        580        590        600 
TDRLDEDGNT ALHFAAREGH AKAVALLLSH NADIVLNKQQ ASFLHLALHN KRKEVVLTII 

       610        620        630        640        650        660 
RSKRWDECLK IFSHNSPGNK CPITEMIEYL PECMKVLLDF CMLHSTEDKS CRDYYIEYNF 

       670        680        690        700        710        720 
KYLQCPLEFT KKTPTQDVIY EPLTALNAMV QNNRIELLNH PVCKEYLLMK WLAYGFRAHM 

       730        740        750        760        770        780 
MNLGSYCLGL IPMTILVVNI KPGMAFNSTG IINETSDHSE ILDTTNSYLI KTCMILVFLS 

       790        800        810        820        830        840 
SIFGYCKEAG QIFQQKRNYF MDISNVLEWI IYTTGIIFVL PLFVEIPAHL QWQCGAIAVY 

       850        860        870        880        890        900 
FYWMNFLLYL QRFENCGIFI VMLEVILKTL LRSTVVFIFL LLAFGLSFYI LLNLQDPFSS 

       910        920        930        940        950        960 
PLLSIIQTFS MMLGDINYRE SFLEPYLRNE LAHPVLSFAQ LVSFTIFVPI VLMNLLIGLA 

       970        980        990       1000       1010       1020 
VGDIAEVQKH ASLKRIAMQV ELHTSLEKKL PLWFLRKVDQ KSTIVYPNKP RSGGMLFHIF 

      1030       1040       1050       1060       1070       1080 
CFLFCTGEIR QEIPNADKSL EMEILKQKYR LKDLTFLLEK QHELIKLIIQ KMEIISETED 

      1090       1100       1110 
DDSHCSFQDR FKKEQMEQRN SRWNTVLRAV KAKTHHLEP 

« Hide

References

« Hide 'large scale' references
[1]"An ankyrin-like protein with transmembrane domains is specifically lost after oncogenic transformation of human fibroblasts."
Jaquemar D., Schenker T., Trueb B.
J. Biol. Chem. 274:7325-7333(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANTS CYS-3; THR-58 AND ASN-186.
Tissue: Lung.
[2]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome."
Kremeyer B., Lopera F., Cox J.J., Momin A., Rugiero F., Marsh S., Woods C.G., Jones N.G., Paterson K.J., Fricker F.R., Villegas A., Acosta N., Pineda-Trujillo N.G., Ramirez J.D., Zea J., Burley M.W., Bedoya G., Bennett D.L., Wood J.N., Ruiz-Linares A.
Neuron 66:671-680(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FEPS1 SER-855, CHARACTERIZATION OF VARIANT FEPS1 SER-855.
+Additional computationally mapped references.

Web resources

Protein Spotlight

The power behind pain - Issue 82 of May 2007

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y10601 mRNA. Translation: CAA71610.1.
AC022867 Genomic DNA. No translation available.
RefSeqNP_015628.2. NM_007332.2.
UniGeneHs.716816.

3D structure databases

ProteinModelPortalO75762.
SMRO75762. Positions 35-699.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114471. 2 interactions.
STRING9606.ENSP00000262209.

Chemistry

BindingDBO75762.
ChEMBLCHEMBL6007.
DrugBankDB00825. Menthol.
GuidetoPHARMACOLOGY485.

Protein family/group databases

TCDB1.A.4.6.3. the transient receptor potential ca(2+) channel (trp-cc) family.

PTM databases

PhosphoSiteO75762.

Proteomic databases

PaxDbO75762.
PRIDEO75762.

Protocols and materials databases

DNASU8989.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262209; ENSP00000262209; ENSG00000104321.
GeneID8989.
KEGGhsa:8989.
UCSCuc003xza.3. human.

Organism-specific databases

CTD8989.
GeneCardsGC08M072983.
H-InvDBHIX0034373.
HIX0124652.
HGNCHGNC:497. TRPA1.
HPAHPA026630.
MIM604775. gene.
615040. phenotype.
neXtProtNX_O75762.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0666.
HOGENOMHOG000044486.
HOVERGENHBG059027.
InParanoidO75762.
KOK04984.
OMAWLAYGFR.
PhylomeDBO75762.
TreeFamTF317264.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressO75762.
BgeeO75762.
CleanExHS_TRPA1.
GenevestigatorO75762.

Family and domain databases

Gene3D1.25.40.20. 4 hits.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR005821. Ion_trans_dom.
[Graphical view]
PfamPF00023. Ank. 10 hits.
PF00520. Ion_trans. 1 hit.
[Graphical view]
PRINTSPR01415. ANKYRIN.
SMARTSM00248. ANK. 14 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 2 hits.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 9 hits.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi8989.
NextBio33711.
PROO75762.
SOURCESearch...

Entry information

Entry nameTRPA1_HUMAN
AccessionPrimary (citable) accession number: O75762
Secondary accession number(s): A6NIN6
Entry history
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: November 30, 2010
Last modified: April 16, 2014
This is version 111 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM