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Protein

5,6-dihydroxyindole-2-carboxylic acid oxidase

Gene

TYRP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Caution

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

Activity 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

  • acetoacetic acid metabolic process Source: Ensembl
  • melanin biosynthetic process Source: Reactome
  • melanin metabolic process Source: GO_Central
  • melanocyte differentiation Source: GO_Central
  • melanosome organization Source: GO_Central
  • positive regulation of melanin biosynthetic process Source: CACAO

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-5662702 Melanin biosynthesis
SIGNORiP17643
UniPathwayi
UPA00785

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
MIMi115501 gene
neXtProtiNX_P17643

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:rs61758405EnsemblClinVar.1
Natural variantiVAR_026828356R → Q in OCA3. 1 PublicationCorresponds to variant dbSNP:rs281865424EnsemblClinVar.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
ProteomicsDBi53498

PTM databases

iPTMnetiP17643
PhosphoSitePlusiP17643

Expressioni

Tissue specificityi

Pigment cells.

Gene expression databases

BgeeiENSG00000107165 Expressed in 144 organ(s), highest expression level in pigmented layer of retina
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, 2 interactors
MINTiP17643
STRINGi9606.ENSP00000373570

Structurei

Secondary structure

1537
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiWRVVCES
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, 1 hit
PROSITEiView protein in PROSITE
PS00497 TYROSINASE_1, 1 hit
PS00498 TYROSINASE_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7EQI3E7EQI3_HUMAN
5,6-dihydroxyindole-2-carboxylic ac...
TYRP1
247Annotation score:
C9JZ52C9JZ52_HUMAN
5,6-dihydroxyindole-2-carboxylic ac...
TYRP1
102Annotation score:

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:rs61758405EnsemblClinVar.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:rs387907171EnsemblClinVar.1
Natural variantiVAR_026827326R → H. Corresponds to variant dbSNP:rs16929374EnsemblClinVar.1
Natural variantiVAR_026828356R → Q in OCA3. 1 PublicationCorresponds to variant dbSNP:rs281865424EnsemblClinVar.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

Cross-referencesi

Web resourcesi

Mutations of the TYRP1 gene

Retina International's Scientific Newsletter

Albinism database (ADB)

TYRP1 mutations

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

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[»]
5M8SX-ray2.20A/B/C/D25-470[»]
5M8TX-ray2.35A/B/C/D25-470[»]
ProteinModelPortaliP17643
SMRiP17643
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113156, 7 interactors
IntActiP17643, 2 interactors
MINTiP17643
STRINGi9606.ENSP00000373570

Chemistry databases

ChEMBLiCHEMBL3712886

PTM databases

iPTMnetiP17643
PhosphoSitePlusiP17643

Polymorphism and mutation databases

BioMutaiTYRP1
DMDMi12644141

Proteomic databases

PaxDbiP17643
PeptideAtlasiP17643
PRIDEiP17643
ProteomicsDBi53498

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7306
DisGeNETi7306
EuPathDBiHostDB:ENSG00000107165.12
GeneCardsiTYRP1
HGNCiHGNC:12450 TYRP1
HPAiCAB002520
HPA000937
MalaCardsiTYRP1
MIMi115501 gene
203290 phenotype
612271 phenotype
neXtProtiNX_P17643
OpenTargetsiENSG00000107165
Orphaneti79433 Oculocutaneous albinism type 3
PharmGKBiPA37101
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayi
UPA00785

ReactomeiR-HSA-5662702 Melanin biosynthesis
SIGNORiP17643

Miscellaneous databases

GeneWikiiTYRP1
GenomeRNAii7306
PROiPR:P17643
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000107165 Expressed in 144 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_TYRP1
ExpressionAtlasiP17643 baseline and differential
GenevisibleiP17643 HS

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, 1 hit
PROSITEiView protein in PROSITE
PS00497 TYROSINASE_1, 1 hit
PS00498 TYROSINASE_2, 1 hit
ProtoNetiSearch...

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 7, 2018
This is version 184 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

Keywords - Technical termi

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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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