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O75762

- TRPA1_HUMAN

UniProt

O75762 - TRPA1_HUMAN

Protein

Transient receptor potential cation channel subfamily A member 1

Gene

TRPA1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 115 (01 Oct 2014)
      Sequence version 3 (30 Nov 2010)
      Previous versions | rss
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    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.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

    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

    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

    GO - Cellular componenti

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

    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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 1PRO_0000215369Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi192 ↔ 665AlternateBy similarity
    Disulfide bondi462 ↔ 665AlternateBy similarity
    Disulfide bondi608 ↔ 621AlternateBy similarity
    Disulfide bondi621 ↔ 665AlternateBy similarity
    Glycosylationi747 – 7471N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi753 – 7531N-linked (GlcNAc...)Sequence Analysis

    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 719719CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini741 – 77232ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini794 – 80512CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini827 – 8293ExtracellularSequence Analysis
    Topological domaini851 – 87323CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini895 – 94046ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini962 – 1119158CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei720 – 74021Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei773 – 79321Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei806 – 82621Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei830 – 85021Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei874 – 89421Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei941 – 96121Helical; Name=6Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

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

    Sequence similaritiesi

    Contains 15 ANK repeats.PROSITE-ProRule annotation

    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...
    MobiDBi 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

    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: October 1, 2014
    This is version 115 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