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Protein

5,6-dihydroxyindole-2-carboxylic acid oxidase

Gene

TYRP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid in the presence of bound Cu2+ ions (PubMed:28661582). May regulate or influence the type of melanin synthesized (PubMed:22556244, PubMed:16704458). Also to a lower extent, capable of hydroxylating tyrosine and producing melanin (By similarity).By similarity3 Publications1 Publication

Cofactori

Cu2+1 PublicationNote: Binds 2 copper ions per subunit (By similarity). Contains bound zinc ions after heterologous expression in insect cells, giving rise to a protein that lacks DHICA oxidase activity (PubMed:28661582).By similarity1 Publication

Enzyme regulationi

The activity depends critically on the nature of the bound metal ion. Catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) in the presence of bound Cu2+ ions, but lacks activity in the presence of bound Zn2+ ions.1 Publication

Pathwayi: melanin biosynthesis

This protein is involved in the pathway melanin biosynthesis, which is part of Pigment biosynthesis.3 Publications
View all proteins of this organism that are known to be involved in the pathway melanin biosynthesis and in Pigment biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi192Copper A1 Publication1
Metal bindingi215Copper A1 Publication1
Metal bindingi224Copper A1 Publication1
Metal bindingi377Copper B1 Publication1
Metal bindingi381Copper B1 Publication1
Metal bindingi404Copper B1 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionMonooxygenase, Oxidoreductase
Biological processMelanin biosynthesis
LigandCopper, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5662702. Melanin biosynthesis.
SIGNORiP17643.
UniPathwayiUPA00785.

Names & Taxonomyi

Protein namesi
Recommended name:
5,6-dihydroxyindole-2-carboxylic acid oxidase (EC:1.14.18.-1 Publication)
Short name:
DHICA oxidase
Alternative name(s):
Catalase B
Glycoprotein 751 Publication
Melanoma antigen gp751 Publication
Tyrosinase-related protein 11 Publication
Short name:
TRP1 Publication
Short name:
TRP-1
Short name:
TRP1
Gene namesi
Name:TYRP1
Synonyms:CAS21 Publication, TYRP, TYRRP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000107165.12.
HGNCiHGNC:12450. TYRP1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 477Lumenal, melanosomeSequence analysisAdd BLAST453
Transmembranei478 – 501HelicalSequence analysisAdd BLAST24
Topological domaini502 – 537CytoplasmicSequence analysisAdd BLAST36

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Albinism, oculocutaneous, 3 (OCA3)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in skin, hair, and eyes. Tyrosinase activity is normal and patients have only moderate reduction of pigment. The eyes present red reflex on transillumination of the iris, dilution of color of iris, nystagmus and strabismus. Darker-skinned individuals have bright copper-red coloration of the skin and hair.
See also OMIM:203290
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07259924A → T in OCA3. 1 PublicationCorresponds to variant dbSNP:rs61758405Ensembl.1
Natural variantiVAR_026828356R → Q in OCA3. 1 PublicationCorresponds to variant dbSNP:rs281865424Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi362Y → F: No effect; when associated with S-374 and V-391. 1 Publication1
Mutagenesisi374R → S: No effect; when associated with F-362 and V-391. 1 Publication1
Mutagenesisi391T → V: No effect; when associated with F-362 and S-374. 1 Publication1

Keywords - Diseasei

Albinism, Disease mutation

Organism-specific databases

DisGeNETi7306.
MalaCardsiTYRP1.
MIMi203290. phenotype.
612271. phenotype.
OpenTargetsiENSG00000107165.
Orphaneti79433. Oculocutaneous albinism type 3.
PharmGKBiPA37101.

Chemistry databases

ChEMBLiCHEMBL3712886.

Polymorphism and mutation databases

BioMutaiTYRP1.
DMDMi12644141.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Add BLAST24
ChainiPRO_000003588925 – 5375,6-dihydroxyindole-2-carboxylic acid oxidaseAdd BLAST513

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi30 ↔ 41Combined sources1 Publication
Disulfide bondi42 ↔ 65Combined sources1 Publication
Disulfide bondi56 ↔ 99Combined sources1 Publication
Glycosylationi96N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi101 ↔ 110Combined sources1 Publication
Glycosylationi104N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi113 ↔ 122Combined sources1 Publication
Glycosylationi181N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi258 ↔ 261Combined sources1 Publication
Disulfide bondi290 ↔ 303Combined sources1 Publication
Glycosylationi304N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Glycosylationi350N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Glycosylationi385N-linked (GlcNAc...) asparagineCombined sources1 Publication1

Post-translational modificationi

Glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP17643.
PeptideAtlasiP17643.
PRIDEiP17643.

PTM databases

iPTMnetiP17643.
PhosphoSitePlusiP17643.

Expressioni

Tissue specificityi

Pigment cells.

Gene expression databases

BgeeiENSG00000107165.
CleanExiHS_TYRP1.
ExpressionAtlasiP17643. baseline and differential.
GenevisibleiP17643. HS.

Organism-specific databases

HPAiCAB002520.
HPA000937.

Interactioni

Subunit structurei

Monomer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
GIPC1O149083EBI-7900408,EBI-373132

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113156. 7 interactors.
IntActiP17643. 1 interactor.
MINTiMINT-1784675.
STRINGi9606.ENSP00000373570.

Structurei

Secondary structure

1537
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni28 – 30Combined sources3
Helixi33 – 38Combined sources6
Beta strandi44 – 46Combined sources3
Beta strandi48 – 50Combined sources3
Turni51 – 54Combined sources4
Turni56 – 61Combined sources6
Beta strandi62 – 67Combined sources6
Turni86 – 94Combined sources9
Beta strandi96 – 101Combined sources6
Beta strandi105 – 107Combined sources3
Turni119 – 122Combined sources4
Beta strandi128 – 130Combined sources3
Helixi133 – 135Combined sources3
Helixi138 – 153Combined sources16
Beta strandi157 – 164Combined sources8
Helixi166 – 168Combined sources3
Beta strandi174 – 176Combined sources3
Beta strandi179 – 183Combined sources5
Helixi184 – 196Combined sources13
Beta strandi203 – 205Combined sources3
Beta strandi213 – 217Combined sources5
Helixi220 – 239Combined sources20
Turni263 – 266Combined sources4
Beta strandi271 – 273Combined sources3
Helixi282 – 285Combined sources4
Helixi293 – 299Combined sources7
Helixi322 – 324Combined sources3
Helixi330 – 336Combined sources7
Helixi355 – 360Combined sources6
Helixi376 – 383Combined sources8
Helixi387 – 389Combined sources3
Turni391 – 393Combined sources3
Helixi394 – 396Combined sources3
Helixi399 – 417Combined sources19
Turni418 – 420Combined sources3
Helixi422 – 424Combined sources3
Beta strandi427 – 431Combined sources5
Helixi449 – 452Combined sources4
Helixi456 – 459Combined sources4
Beta strandi460 – 464Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5M8LX-ray2.35A/B/C/D25-470[»]
5M8MX-ray2.65A/B/C/D25-470[»]
5M8NX-ray2.60A/B/C/D25-470[»]
5M8OX-ray2.50A/B/C/D25-470[»]
5M8PX-ray2.80A/B/C/D25-470[»]
5M8QX-ray2.85A/B/C/D25-470[»]
5M8RX-ray2.40A/B/C/D25-470[»]
5M8TX-ray2.35A/B/C/D25-470[»]
ProteinModelPortaliP17643.
SMRiP17643.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the tyrosinase family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IEEB. Eukaryota.
ENOG410XSJD. LUCA.
GeneTreeiENSGT00500000044790.
HOGENOMiHOG000118376.
HOVERGENiHBG003553.
InParanoidiP17643.
KOiK00506.
OMAiTCHCNGN.
OrthoDBiEOG091G03YR.
PhylomeDBiP17643.
TreeFamiTF315865.

Family and domain databases

Gene3Di1.10.1280.10. 1 hit.
InterProiView protein in InterPro
IPR002227. Tyrosinase_Cu-bd.
IPR008922. Unchr_di-copper_centre.
PfamiView protein in Pfam
PF00264. Tyrosinase. 1 hit.
PRINTSiPR00092. TYROSINASE.
SUPFAMiSSF48056. SSF48056. 2 hits.
PROSITEiView protein in PROSITE
PS00497. TYROSINASE_1. 1 hit.
PS00498. TYROSINASE_2. 1 hit.

Sequencei

Sequence statusi: Complete.

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

P17643-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSAPKLLSLG CIFFPLLLFQ QARAQFPRQC ATVEALRSGM CCPDLSPVSG
60 70 80 90 100
PGTDRCGSSS GRGRCEAVTA DSRPHSPQYP HDGRDDREVW PLRFFNRTCH
110 120 130 140 150
CNGNFSGHNC GTCRPGWRGA ACDQRVLIVR RNLLDLSKEE KNHFVRALDM
160 170 180 190 200
AKRTTHPLFV IATRRSEEIL GPDGNTPQFE NISIYNYFVW THYYSVKKTF
210 220 230 240 250
LGVGQESFGE VDFSHEGPAF LTWHRYHLLR LEKDMQEMLQ EPSFSLPYWN
260 270 280 290 300
FATGKNVCDI CTDDLMGSRS NFDSTLISPN SVFSQWRVVC DSLEDYDTLG
310 320 330 340 350
TLCNSTEDGP IRRNPAGNVA RPMVQRLPEP QDVAQCLEVG LFDTPPFYSN
360 370 380 390 400
STNSFRNTVE GYSDPTGKYD PAVRSLHNLA HLFLNGTGGQ THLSPNDPIF
410 420 430 440 450
VLLHTFTDAV FDEWLRRYNA DISTFPLENA PIGHNRQYNM VPFWPPVTNT
460 470 480 490 500
EMFVTAPDNL GYTYEIQWPS REFSVPEIIA IAVVGALLLV ALIFGTASYL
510 520 530
IRARRSMDEA NQPLLTDQYQ CYAEEYEKLQ NPNQSVV
Length:537
Mass (Da):60,724
Last modified:January 11, 2001 - v2
Checksum:i1051CEEF52908CCA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti395 – 396PN → SQ in CAA35820 (PubMed:2324688).Curated2
Sequence conflicti526 – 537YEKLQ…NQSVV → RI in CAA35785 (PubMed:2111010).CuratedAdd BLAST12
Sequence conflicti526 – 537YEKLQ…NQSVV → RI (PubMed:1906272).CuratedAdd BLAST12

Polymorphismi

Genetic variants in TYRP1 define the skin/hair/eye pigmentation variation locus 11 (SHEP11) [MIMi:612271] and are responsible for variability in hair color linked to chromosome 9p23 in Melanesians. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07259924A → T in OCA3. 1 PublicationCorresponds to variant dbSNP:rs61758405Ensembl.1
Natural variantiVAR_06817693R → C Polymorphism associated with blond hair in individuals from the Solomon Islands; rare or absent outside of Oceania. 1 PublicationCorresponds to variant dbSNP:rs387907171Ensembl.1
Natural variantiVAR_026827326R → H. Corresponds to variant dbSNP:rs16929374Ensembl.1
Natural variantiVAR_026828356R → Q in OCA3. 1 PublicationCorresponds to variant dbSNP:rs281865424Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X51420 mRNA. Translation: CAA35785.1.
AF001295 Genomic DNA. Translation: AAC15468.1.
L38952 Genomic DNA. Translation: AAC41924.1.
D83059 Genomic DNA. Translation: BAA11759.1.
BC052608 mRNA. Translation: AAH52608.1.
X51455 mRNA. Translation: CAA35820.1.
X60955 Genomic DNA. Translation: CAA43288.1.
CCDSiCCDS34990.1.
PIRiS09999. YRHUB6.
RefSeqiNP_000541.1. NM_000550.2.
UniGeneiHs.270279.

Genome annotation databases

EnsembliENST00000388918; ENSP00000373570; ENSG00000107165.
GeneIDi7306.
KEGGihsa:7306.
UCSCiuc003zkv.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTYRP1_HUMAN
AccessioniPrimary (citable) accession number: P17643
Secondary accession number(s): P78468
, P78469, Q13721, Q15679
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: January 11, 2001
Last modified: November 22, 2017
This is version 177 of the entry and version 2 of the sequence. See 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

Caution

The precise function of this protein in melanin biosynthesis is still under debate.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families