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O75762

- TRPA1_HUMAN

UniProt

O75762 - TRPA1_HUMAN

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Protein
Transient receptor potential cation channel subfamily A member 1
Gene
TRPA1, ANKTM1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - 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. 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 regulationi

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

GO - Molecular functioni

  1. calcium channel activity Source: Ensembl
  2. channel activity Source: ProtInc
Complete GO annotation...

GO - Biological processi

  1. calcium ion transmembrane transport Source: Reactome
  2. detection of chemical stimulus involved in sensory perception of pain Source: Ensembl
  3. detection of mechanical stimulus involved in sensory perception of pain Source: Ensembl
  4. ion transmembrane transport Source: Reactome
  5. ion transport Source: ProtInc
  6. response to cold Source: Ensembl
  7. response to drug Source: Ensembl
  8. response to hydrogen peroxide Source: Ensembl
  9. response to pain Source: Ensembl
  10. thermoception Source: Ensembl
  11. transmembrane transport Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Ion channel

Keywords - Biological processi

Ion transport, Sensory transduction, Transport

Enzyme and pathway databases

ReactomeiREACT_169333. 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
ProteomesiUP000005640: Chromosome 8

Organism-specific databases

HGNCiHGNC:497. TRPA1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 719719Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei720 – 74021Helical; Name=1; Reviewed prediction
Add
BLAST
Topological domaini741 – 77232Extracellular Reviewed prediction
Add
BLAST
Transmembranei773 – 79321Helical; Name=2; Reviewed prediction
Add
BLAST
Topological domaini794 – 80512Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei806 – 82621Helical; Name=3; Reviewed prediction
Add
BLAST
Topological domaini827 – 8293Extracellular Reviewed prediction
Transmembranei830 – 85021Helical; Name=4; Reviewed prediction
Add
BLAST
Topological domaini851 – 87323Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei874 – 89421Helical; Name=5; Reviewed prediction
Add
BLAST
Topological domaini895 – 94046Extracellular Reviewed prediction
Add
BLAST
Transmembranei941 – 96121Helical; Name=6; Reviewed prediction
Add
BLAST
Topological domaini962 – 1119158Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: ProtInc
  2. plasma membrane Source: Reactome
  3. stereocilium bundle Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti855 – 8551N → 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 Publication
VAR_069737

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi615040. phenotype.
Orphaneti391389. Familial episodic pain syndrome with predominantly upper body involvement.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11191119Transient receptor potential cation channel subfamily A member 1
PRO_0000215369Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi192 ↔ 665Alternate By similarity
Disulfide bondi462 ↔ 665Alternate By similarity
Disulfide bondi608 ↔ 621Alternate By similarity
Disulfide bondi621 ↔ 665Alternate By similarity
Glycosylationi747 – 7471N-linked (GlcNAc...) Reviewed prediction
Glycosylationi753 – 7531N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO75762.
PRIDEiO75762.

PTM databases

PhosphoSiteiO75762.

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

ArrayExpressiO75762.
BgeeiO75762.
CleanExiHS_TRPA1.
GenevestigatoriO75762.

Organism-specific databases

HPAiHPA026630.

Interactioni

Subunit structurei

Homotetramer By similarity.

Protein-protein interaction databases

BioGridi114471. 2 interactions.
STRINGi9606.ENSP00000262209.

Structurei

3D structure databases

ProteinModelPortaliO75762.
SMRiO75762. Positions 41-640, 693-970.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati62 – 9231ANK 1
Add
BLAST
Repeati97 – 12630ANK 2
Add
BLAST
Repeati130 – 16031ANK 3
Add
BLAST
Repeati164 – 19330ANK 4
Add
BLAST
Repeati197 – 22630ANK 5
Add
BLAST
Repeati238 – 26730ANK 6
Add
BLAST
Repeati271 – 30131ANK 7
Add
BLAST
Repeati308 – 33730ANK 8
Add
BLAST
Repeati341 – 37030ANK 9
Add
BLAST
Repeati412 – 44130ANK 10
Add
BLAST
Repeati445 – 47430ANK 11
Add
BLAST
Repeati481 – 51030ANK 12
Add
BLAST
Repeati513 – 54230ANK 13
Add
BLAST
Repeati547 – 57630ANK 14
Add
BLAST
Repeati579 – 60931ANK 15
Add
BLAST

Sequence similaritiesi

Contains 15 ANK repeats.

Keywords - Domaini

ANK repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0666.
HOGENOMiHOG000044486.
HOVERGENiHBG059027.
InParanoidiO75762.
KOiK04984.
OMAiWLAYGFR.
PhylomeDBiO75762.
TreeFamiTF317264.

Family and domain databases

Gene3Di1.25.40.20. 4 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR005821. Ion_trans_dom.
[Graphical view]
PfamiPF00023. Ank. 10 hits.
PF00520. Ion_trans. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 14 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 2 hits.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 9 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O75762-1 [UniParc]FASTAAdd to Basket

« Hide

MKRSLRKMWR PGEKKEPQGV VYEDVPDDTE DFKESLKVVF EGSAYGLQNF     50
NKQKKLKRCD DMDTFFLHYA AAEGQIELME KITRDSSLEV LHEMDDYGNT 100
PLHCAVEKNQ IESVKFLLSR GANPNLRNFN MMAPLHIAVQ GMNNEVMKVL 150
LEHRTIDVNL EGENGNTAVI IACTTNNSEA LQILLKKGAK PCKSNKWGCF 200
PIHQAAFSGS KECMEIILRF GEEHGYSRQL HINFMNNGKA TPLHLAVQNG 250
DLEMIKMCLD NGAQIDPVEK GRCTAIHFAA TQGATEIVKL MISSYSGSVD 300
IVNTTDGCHE TMLHRASLFD HHELADYLIS VGADINKIDS EGRSPLILAT 350
ASASWNIVNL LLSKGAQVDI KDNFGRNFLH LTVQQPYGLK NLRPEFMQMQ 400
QIKELVMDED NDGCTPLHYA CRQGGPGSVN NLLGFNVSIH SKSKDKKSPL 450
HFAASYGRIN TCQRLLQDIS DTRLLNEGDL HGMTPLHLAA KNGHDKVVQL 500
LLKKGALFLS DHNGWTALHH ASMGGYTQTM KVILDTNLKC TDRLDEDGNT 550
ALHFAAREGH AKAVALLLSH NADIVLNKQQ ASFLHLALHN KRKEVVLTII 600
RSKRWDECLK IFSHNSPGNK CPITEMIEYL PECMKVLLDF CMLHSTEDKS 650
CRDYYIEYNF KYLQCPLEFT KKTPTQDVIY EPLTALNAMV QNNRIELLNH 700
PVCKEYLLMK WLAYGFRAHM MNLGSYCLGL IPMTILVVNI KPGMAFNSTG 750
IINETSDHSE ILDTTNSYLI KTCMILVFLS SIFGYCKEAG QIFQQKRNYF 800
MDISNVLEWI IYTTGIIFVL PLFVEIPAHL QWQCGAIAVY FYWMNFLLYL 850
QRFENCGIFI VMLEVILKTL LRSTVVFIFL LLAFGLSFYI LLNLQDPFSS 900
PLLSIIQTFS MMLGDINYRE SFLEPYLRNE LAHPVLSFAQ LVSFTIFVPI 950
VLMNLLIGLA VGDIAEVQKH ASLKRIAMQV ELHTSLEKKL PLWFLRKVDQ 1000
KSTIVYPNKP RSGGMLFHIF CFLFCTGEIR QEIPNADKSL EMEILKQKYR 1050
LKDLTFLLEK QHELIKLIIQ KMEIISETED DDSHCSFQDR FKKEQMEQRN 1100
SRWNTVLRAV KAKTHHLEP 1119
Length:1,119
Mass (Da):127,501
Last modified:November 30, 2010 - v3
Checksum:i283BF31BC77CF71B
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti3 – 31R → C.1 Publication
Corresponds to variant rs13268757 [ dbSNP | Ensembl ].
VAR_020660
Natural varianti58 – 581R → T.1 Publication
Corresponds to variant rs16937976 [ dbSNP | Ensembl ].
VAR_047471
Natural varianti179 – 1791E → K.
Corresponds to variant rs920829 [ dbSNP | Ensembl ].
VAR_020661
Natural varianti186 – 1861K → N.1 Publication
Corresponds to variant rs7819749 [ dbSNP | Ensembl ].
VAR_020662
Natural varianti855 – 8551N → 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 Publication
VAR_069737
Natural varianti1018 – 10181H → R.
Corresponds to variant rs959976 [ dbSNP | Ensembl ].
VAR_020663

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y10601 mRNA. Translation: CAA71610.1.
AC022867 Genomic DNA. No translation available.
CCDSiCCDS34908.1.
RefSeqiNP_015628.2. NM_007332.2.
UniGeneiHs.716816.

Genome annotation databases

EnsembliENST00000262209; ENSP00000262209; ENSG00000104321.
GeneIDi8989.
KEGGihsa:8989.
UCSCiuc003xza.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Protein Spotlight

The power behind pain - Issue 82 of May 2007

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y10601 mRNA. Translation: CAA71610.1 .
AC022867 Genomic DNA. No translation available.
CCDSi CCDS34908.1.
RefSeqi NP_015628.2. NM_007332.2.
UniGenei Hs.716816.

3D structure databases

ProteinModelPortali O75762.
SMRi O75762. Positions 41-640, 693-970.
ModBasei Search...

Protein-protein interaction databases

BioGridi 114471. 2 interactions.
STRINGi 9606.ENSP00000262209.

Chemistry

BindingDBi O75762.
ChEMBLi CHEMBL6007.
DrugBanki DB00825. Menthol.
GuidetoPHARMACOLOGYi 485.

Protein family/group databases

TCDBi 1.A.4.6.3. the transient receptor potential ca(2+) channel (trp-cc) family.

PTM databases

PhosphoSitei O75762.

Proteomic databases

PaxDbi O75762.
PRIDEi O75762.

Protocols and materials databases

DNASUi 8989.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000262209 ; ENSP00000262209 ; ENSG00000104321 .
GeneIDi 8989.
KEGGi hsa:8989.
UCSCi uc003xza.3. human.

Organism-specific databases

CTDi 8989.
GeneCardsi GC08M072983.
H-InvDB HIX0034373.
HIX0124652.
HGNCi HGNC:497. TRPA1.
HPAi HPA026630.
MIMi 604775. gene.
615040. phenotype.
neXtProti NX_O75762.
Orphaneti 391389. Familial episodic pain syndrome with predominantly upper body involvement.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0666.
HOGENOMi HOG000044486.
HOVERGENi HBG059027.
InParanoidi O75762.
KOi K04984.
OMAi WLAYGFR.
PhylomeDBi O75762.
TreeFami TF317264.

Enzyme and pathway databases

Reactomei REACT_169333. TRP channels.

Miscellaneous databases

GenomeRNAii 8989.
NextBioi 33711.
PROi O75762.
SOURCEi Search...

Gene expression databases

ArrayExpressi O75762.
Bgeei O75762.
CleanExi HS_TRPA1.
Genevestigatori O75762.

Family and domain databases

Gene3Di 1.25.40.20. 4 hits.
InterProi IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR005821. Ion_trans_dom.
[Graphical view ]
Pfami PF00023. Ank. 10 hits.
PF00520. Ion_trans. 1 hit.
[Graphical view ]
PRINTSi PR01415. ANKYRIN.
SMARTi SM00248. ANK. 14 hits.
[Graphical view ]
SUPFAMi SSF48403. SSF48403. 2 hits.
PROSITEi PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 9 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. Cited for: VARIANT FEPS1 SER-855, CHARACTERIZATION OF VARIANT FEPS1 SER-855.

Entry informationi

Entry nameiTRPA1_HUMAN
AccessioniPrimary (citable) accession number: O75762
Secondary accession number(s): A6NIN6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: November 30, 2010
Last modified: September 3, 2014
This is version 114 of the entry and version 3 of the sequence. [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

Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3

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