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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

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).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
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 – 719719CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei720 – 74021Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini741 – 77232ExtracellularSequence AnalysisAdd
BLAST
Transmembranei773 – 79321Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini794 – 80512CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei806 – 82621Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini827 – 8293ExtracellularSequence Analysis
Transmembranei830 – 85021Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini851 – 87323CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei874 – 89421Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini895 – 94046ExtracellularSequence AnalysisAdd
BLAST
Transmembranei941 – 96121Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini962 – 1119158CytoplasmicSequence AnalysisAdd
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.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

BgeeiO75762.
CleanExiHS_TRPA1.
ExpressionAtlasiO75762. baseline and differential.
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...

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.
GeneTreeiENSGT00770000120568.
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

        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

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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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 GC08M072932.
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.
GeneTreei ENSGT00770000120568.
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

Bgeei O75762.
CleanExi HS_TRPA1.
ExpressionAtlasi O75762. baseline and differential.
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: November 26, 2014
This is version 117 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