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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. May regulate or influence the type of melanin synthesized. Also to a lower extent, capable of hydroxylating tyrosine and producing melanin.By similarity

Cofactori

Cu2+By similarityNote: Binds 2 copper ions per subunit.By similarity

Pathwayi: melanin biosynthesis

This protein is involved in the pathway melanin biosynthesis, which is part of Pigment biosynthesis.
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 ABy similarity1
Metal bindingi215Copper ABy similarity1
Metal bindingi224Copper ABy similarity1
Metal bindingi377Copper BBy similarity1
Metal bindingi381Copper BBy similarity1
Metal bindingi404Copper BBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Biological processi

Melanin biosynthesis

Keywords - Ligandi

Copper, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS02976-MONOMER.
ReactomeiR-HSA-5662702. Melanin biosynthesis.
UniPathwayiUPA00785.

Names & Taxonomyi

Protein namesi
Recommended name:
5,6-dihydroxyindole-2-carboxylic acid oxidase (EC:1.14.18.-)
Short name:
DHICA oxidase
Alternative name(s):
Catalase B
Glycoprotein 75
Melanoma antigen gp75
Tyrosinase-related protein 1
Short name:
TRP
Short name:
TRP-1
Short name:
TRP1
Gene namesi
Name:TYRP1
Synonyms:CAS2, TYRP, TYRRP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:12450. TYRP1.

Subcellular locationi

  • Melanosome membrane By similarity; Single-pass type I membrane protein By similarity
  • Melanosome By similarity

  • Note: Located to mature stage III and IV melanosomes and apposed endosomal tubular membranes. Transported to pigmented melanosomes by the BLOC-1 complex. Proper trafficking to melanosome is regulated by SGSM2, ANKRD27, RAB9A, RAB32 and RAB38.By similarity

Topology

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

GO - Cellular componenti

  • clathrin-coated endocytic vesicle membrane Source: UniProtKB
  • endosome membrane Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • melanosome Source: UniProtKB
  • melanosome membrane Source: UniProtKB
Complete GO annotation...

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 rs61758405dbSNPEnsembl.1
Natural variantiVAR_026828356R → Q in OCA3. 1 PublicationCorresponds to variant rs281865424dbSNPEnsembl.1

Keywords - Diseasei

Albinism, Disease mutation

Organism-specific databases

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

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
Glycosylationi96N-linked (GlcNAc...)Sequence analysis1
Glycosylationi104N-linked (GlcNAc...)Sequence analysis1
Glycosylationi181N-linked (GlcNAc...)Sequence analysis1
Glycosylationi304N-linked (GlcNAc...)Sequence analysis1
Glycosylationi350N-linked (GlcNAc...)Sequence analysis1
Glycosylationi385N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Glycosylated.By similarity

Keywords - PTMi

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

Binary interactionsi

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113156. 6 interactors.
IntActiP17643. 1 interactor.
MINTiMINT-1784675.
STRINGi9606.ENSP00000373570.

Structurei

3D structure databases

ProteinModelPortaliP17643.
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.
InterProiIPR015559. DiOHindole_carboxylic_A_Oxase.
IPR002227. Tyrosinase_Cu-bd.
IPR008922. Unchr_di-copper_centre.
[Graphical view]
PANTHERiPTHR11474:SF3. PTHR11474:SF3. 2 hits.
PfamiPF00264. Tyrosinase. 1 hit.
[Graphical view]
PRINTSiPR00092. TYROSINASE.
SUPFAMiSSF48056. SSF48056. 2 hits.
PROSITEiPS00497. TYROSINASE_1. 1 hit.
PS00498. TYROSINASE_2. 1 hit.
[Graphical view]

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 (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 rs61758405dbSNPEnsembl.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 rs387907171dbSNPEnsembl.1
Natural variantiVAR_026827326R → H.Corresponds to variant rs16929374dbSNPEnsembl.1
Natural variantiVAR_026828356R → Q in OCA3. 1 PublicationCorresponds to variant rs281865424dbSNPEnsembl.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

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

ProteinModelPortaliP17643.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113156. 6 interactors.
IntActiP17643. 1 interactor.
MINTiMINT-1784675.
STRINGi9606.ENSP00000373570.

PTM databases

iPTMnetiP17643.
PhosphoSitePlusiP17643.

Polymorphism and mutation databases

BioMutaiTYRP1.
DMDMi12644141.

Proteomic databases

PaxDbiP17643.
PeptideAtlasiP17643.
PRIDEiP17643.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7306.
DisGeNETi7306.
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.
OMAiTCHCNGN.
OrthoDBiEOG091G03YR.
PhylomeDBiP17643.
TreeFamiTF315865.

Enzyme and pathway databases

UniPathwayiUPA00785.
BioCyciZFISH:HS02976-MONOMER.
ReactomeiR-HSA-5662702. Melanin biosynthesis.

Miscellaneous databases

GeneWikiiTYRP1.
GenomeRNAii7306.
PROiP17643.
SOURCEiSearch...

Gene expression databases

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

Family and domain databases

Gene3Di1.10.1280.10. 1 hit.
InterProiIPR015559. DiOHindole_carboxylic_A_Oxase.
IPR002227. Tyrosinase_Cu-bd.
IPR008922. Unchr_di-copper_centre.
[Graphical view]
PANTHERiPTHR11474:SF3. PTHR11474:SF3. 2 hits.
PfamiPF00264. Tyrosinase. 1 hit.
[Graphical view]
PRINTSiPR00092. TYROSINASE.
SUPFAMiSSF48056. SSF48056. 2 hits.
PROSITEiPS00497. TYROSINASE_1. 1 hit.
PS00498. TYROSINASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTYRP1_HUMAN
AccessioniPrimary (citable) accession number: P17643
Secondary accession number(s): P78468
, P78469, Q13721, Q15679
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: January 11, 2001
Last modified: November 30, 2016
This is version 169 of the entry and version 2 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, 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.