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P40126

- TYRP2_HUMAN

UniProt

P40126 - TYRP2_HUMAN

Protein

L-dopachrome tautomerase

Gene

DCT

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 1 (01 Feb 1995)
      Previous versions | rss
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    Functioni

    Involved in regulating eumelanin and phaeomelanin levels.

    Catalytic activityi

    L-dopachrome = 5,6-dihydroxyindole-2-carboxylate.

    Cofactori

    Binds 2 zinc ions per subunit.By similarity

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi189 – 1891Zinc ABy similarity
    Metal bindingi211 – 2111Zinc ABy similarity
    Metal bindingi220 – 2201Zinc ABy similarity
    Metal bindingi369 – 3691Zinc BBy similarity
    Metal bindingi373 – 3731Zinc BBy similarity
    Metal bindingi396 – 3961Zinc BBy similarity

    GO - Molecular functioni

    1. copper ion binding Source: ProtInc
    2. dopachrome isomerase activity Source: UniProtKB
    3. oxidoreductase activity Source: InterPro

    GO - Biological processi

    1. cell development Source: Ensembl
    2. developmental pigmentation Source: Ensembl
    3. epidermis development Source: ProtInc
    4. melanin biosynthetic process from tyrosine Source: UniProtKB
    5. positive regulation of neuroblast proliferation Source: Ensembl
    6. ventricular zone neuroblast division Source: Ensembl

    Keywords - Molecular functioni

    Isomerase

    Keywords - Biological processi

    Melanin biosynthesis

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    UniPathwayiUPA00785.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    L-dopachrome tautomerase (EC:5.3.3.12)
    Short name:
    DCT
    Short name:
    DT
    Alternative name(s):
    L-dopachrome Delta-isomerase
    Tyrosinase-related protein 2
    Short name:
    TRP-2
    Short name:
    TRP2
    Gene namesi
    Name:DCT
    Synonyms:TYRP2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 13

    Organism-specific databases

    HGNCiHGNC:2709. DCT.

    Subcellular locationi

    Melanosome membrane 2 Publications; Single-pass type I membrane protein 2 Publications

    GO - Cellular componenti

    1. cytosol Source: UniProtKB
    2. integral component of membrane Source: ProtInc
    3. melanosome Source: UniProtKB
    4. melanosome membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA27179.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2323Sequence AnalysisAdd
    BLAST
    Chaini24 – 519496L-dopachrome tautomerasePRO_0000035892Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi170 – 1701N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi178 – 1781N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi237 – 2371N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi300 – 3001N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi342 – 3421N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi377 – 3771N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PaxDbiP40126.
    PRIDEiP40126.

    PTM databases

    PhosphoSiteiP40126.

    Expressioni

    Gene expression databases

    ArrayExpressiP40126.
    BgeeiP40126.
    CleanExiHS_DCT.
    GenevestigatoriP40126.

    Organism-specific databases

    HPAiCAB017634.
    HPA010743.
    HPA010800.

    Interactioni

    Subunit structurei

    Tyrosinase, TYRP1 and DCT/TYRP2 may form a multienzyme complex.By similarity

    Protein-protein interaction databases

    BioGridi108006. 1 interaction.
    STRINGi9606.ENSP00000392762.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4HX1X-ray1.80C180-188[»]
    ProteinModelPortaliP40126.
    SMRiP40126. Positions 210-459.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini24 – 472449Lumenal, melanosomeSequence AnalysisAdd
    BLAST
    Topological domaini494 – 51926CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei473 – 49321HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the tyrosinase family.Curated

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG301916.
    HOGENOMiHOG000118376.
    HOVERGENiHBG003553.
    InParanoidiP40126.
    KOiK01827.
    OMAiWPRKFFN.
    OrthoDBiEOG7TJ3HG.
    PhylomeDBiP40126.
    TreeFamiTF315865.

    Family and domain databases

    Gene3Di1.10.1280.10. 1 hit.
    InterProiIPR002227. Tyrosinase_Cu-bd.
    IPR008922. Unchr_di-copper_centre.
    [Graphical view]
    PfamiPF00264. Tyrosinase. 1 hit.
    [Graphical view]
    PRINTSiPR00092. TYROSINASE.
    SUPFAMiSSF48056. SSF48056. 1 hit.
    PROSITEiPS00497. TYROSINASE_1. 1 hit.
    PS00498. TYROSINASE_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P40126-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSPLWWGFLL SCLGCKILPG AQGQFPRVCM TVDSLVNKEC CPRLGAESAN    50
    VCGSQQGRGQ CTEVRADTRP WSGPYILRNQ DDRELWPRKF FHRTCKCTGN 100
    FAGYNCGDCK FGWTGPNCER KKPPVIRQNI HSLSPQEREQ FLGALDLAKK 150
    RVHPDYVITT QHWLGLLGPN GTQPQFANCS VYDFFVWLHY YSVRDTLLGP 200
    GRPYRAIDFS HQGPAFVTWH RYHLLCLERD LQRLIGNESF ALPYWNFATG 250
    RNECDVCTDQ LFGAARPDDP TLISRNSRFS SWETVCDSLD DYNHLVTLCN 300
    GTYEGLLRRN QMGRNSMKLP TLKDIRDCLS LQKFDNPPFF QNSTFSFRNA 350
    LEGFDKADGT LDSQVMSLHN LVHSFLNGTN ALPHSAANDP IFVVLHSFTD 400
    AIFDEWMKRF NPPADAWPQE LAPIGHNRMY NMVPFFPPVT NEELFLTSDQ 450
    LGYSYAIDLP VSVEETPGWP TTLLVVMGTL VALVGLFVLL AFLQYRRLRK 500
    GYTPLMETHL SSKRYTEEA 519
    Length:519
    Mass (Da):59,145
    Last modified:February 1, 1995 - v1
    Checksum:iAFDDF21768002A89
    GO
    Isoform 2 (identifier: P40126-2) [UniParc]FASTAAdd to Basket

    Also known as: TRP-2-6b

    The sequence of this isoform differs from the canonical sequence as follows:
         393-393: V → VVISNRLLYNATTNILEHVRKEKATKELPSLHVL

    Show »
    Length:552
    Mass (Da):62,929
    Checksum:iF2B047A524167DD3
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei393 – 3931V → VVISNRLLYNATTNILEHVR KEKATKELPSLHVL in isoform 2. 1 PublicationVSP_043581

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D17547 mRNA. Translation: BAA04484.1.
    L18967 mRNA. Translation: AAA20870.1.
    S69231 mRNA. Translation: AAC60627.1.
    DQ902581 mRNA. Translation: ABI73976.1.
    AL139318 Genomic DNA. Translation: CAC19460.1.
    BC028311 mRNA. Translation: AAH28311.1.
    L38953 Genomic DNA. Translation: AAC41925.1.
    D28767 Genomic DNA. Translation: BAA05956.1.
    CCDSiCCDS45060.1. [P40126-2]
    CCDS9470.1. [P40126-1]
    PIRiS43510. YRHUR2.
    RefSeqiNP_001123361.1. NM_001129889.1. [P40126-2]
    NP_001913.2. NM_001922.3. [P40126-1]
    UniGeneiHs.301865.

    Genome annotation databases

    EnsembliENST00000377028; ENSP00000366227; ENSG00000080166. [P40126-1]
    ENST00000446125; ENSP00000392762; ENSG00000080166. [P40126-2]
    GeneIDi1638.
    KEGGihsa:1638.
    UCSCiuc001vlv.4. human. [P40126-1]
    uc010afh.3. human. [P40126-2]

    Polymorphism databases

    DMDMi731026.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D17547 mRNA. Translation: BAA04484.1 .
    L18967 mRNA. Translation: AAA20870.1 .
    S69231 mRNA. Translation: AAC60627.1 .
    DQ902581 mRNA. Translation: ABI73976.1 .
    AL139318 Genomic DNA. Translation: CAC19460.1 .
    BC028311 mRNA. Translation: AAH28311.1 .
    L38953 Genomic DNA. Translation: AAC41925.1 .
    D28767 Genomic DNA. Translation: BAA05956.1 .
    CCDSi CCDS45060.1. [P40126-2 ]
    CCDS9470.1. [P40126-1 ]
    PIRi S43510. YRHUR2.
    RefSeqi NP_001123361.1. NM_001129889.1. [P40126-2 ]
    NP_001913.2. NM_001922.3. [P40126-1 ]
    UniGenei Hs.301865.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4HX1 X-ray 1.80 C 180-188 [» ]
    ProteinModelPortali P40126.
    SMRi P40126. Positions 210-459.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108006. 1 interaction.
    STRINGi 9606.ENSP00000392762.

    PTM databases

    PhosphoSitei P40126.

    Polymorphism databases

    DMDMi 731026.

    Proteomic databases

    PaxDbi P40126.
    PRIDEi P40126.

    Protocols and materials databases

    DNASUi 1638.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000377028 ; ENSP00000366227 ; ENSG00000080166 . [P40126-1 ]
    ENST00000446125 ; ENSP00000392762 ; ENSG00000080166 . [P40126-2 ]
    GeneIDi 1638.
    KEGGi hsa:1638.
    UCSCi uc001vlv.4. human. [P40126-1 ]
    uc010afh.3. human. [P40126-2 ]

    Organism-specific databases

    CTDi 1638.
    GeneCardsi GC13M095091.
    HGNCi HGNC:2709. DCT.
    HPAi CAB017634.
    HPA010743.
    HPA010800.
    MIMi 191275. gene.
    neXtProti NX_P40126.
    PharmGKBi PA27179.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG301916.
    HOGENOMi HOG000118376.
    HOVERGENi HBG003553.
    InParanoidi P40126.
    KOi K01827.
    OMAi WPRKFFN.
    OrthoDBi EOG7TJ3HG.
    PhylomeDBi P40126.
    TreeFami TF315865.

    Enzyme and pathway databases

    UniPathwayi UPA00785 .

    Miscellaneous databases

    GeneWikii Dopachrome_tautomerase.
    GenomeRNAii 1638.
    NextBioi 6730.
    PROi P40126.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P40126.
    Bgeei P40126.
    CleanExi HS_DCT.
    Genevestigatori P40126.

    Family and domain databases

    Gene3Di 1.10.1280.10. 1 hit.
    InterProi IPR002227. Tyrosinase_Cu-bd.
    IPR008922. Unchr_di-copper_centre.
    [Graphical view ]
    Pfami PF00264. Tyrosinase. 1 hit.
    [Graphical view ]
    PRINTSi PR00092. TYROSINASE.
    SUPFAMi SSF48056. SSF48056. 1 hit.
    PROSITEi PS00497. TYROSINASE_1. 1 hit.
    PS00498. TYROSINASE_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning and functional analysis of a cDNA coding for human DOPAchrome tautomerase/tyrosinase-related protein-2."
      Yokoyama K., Suzuki H., Yasumoto K.I., Tomita Y., Shibahara S.
      Biochim. Biophys. Acta 1217:317-321(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "Sequence of the human dopachrome tautomerase-encoding TRP-2 cDNA."
      Cassady J.L., Sturm R.A.
      Gene 143:295-298(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "Molecular characterization of a human tyrosinase-related-protein-2 cDNA. Patterns of expression in melanocytic cells."
      Bouchard B., del Marmol V., Jackson I.J., Cherif D., Dubertret L.
      Eur. J. Biochem. 219:127-134(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    4. "Pre-existing immunity to tyrosinase-related protein (TRP)-2, a new TRP-2 isoform, and the NY-ESO-1 melanoma antigen in a patient with a dramatic response to immunotherapy."
      Khong H.T., Rosenberg S.A.
      J. Immunol. 168:951-956(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
      Tissue: Melanoma.
    5. "The DNA sequence and analysis of human chromosome 13."
      Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.
      , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
      Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Mammary gland.
    7. "Chromosomal structure of the human TYRP1 and TYRP2 loci and comparison of the tyrosinase-related protein gene family."
      Sturm R.A., O'Sullivan B.J., Box N.F., Smith A.G., Smit S.E., Puttick E.R.J., Parsons P.G., Dunn I.S.
      Genomics 29:24-34(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-98.
      Tissue: Liver.
    8. "Cloning of the human DOPAchrome tautomerase/tyrosinase-related protein 2 gene and identification of two regulatory regions required for its pigment cell-specific expression."
      Yokoyama K., Yasumoto K.I., Suzuki H., Shibahara S.
      J. Biol. Chem. 269:27080-27087(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-98.
      Tissue: Liver.
    9. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
      Tissue: Melanoma.
    10. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
      Tissue: Melanoma.

    Entry informationi

    Entry nameiTYRP2_HUMAN
    AccessioniPrimary (citable) accession number: P40126
    Secondary accession number(s): Q09GT4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: February 1, 1995
    Last modified: October 1, 2014
    This is version 139 of the entry and version 1 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 13
      Human chromosome 13: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3