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Protein

Tyrosinase

Gene

Tyr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reactions leading to melanin production from tyrosine. In addition to hydroxylating tyrosine to DOPA (3,4-dihydroxyphenylalanine), also catalyzes the oxidation of DOPA to DOPA-quinone, and possibly the oxidation of DHI (5,6-dihydroxyindole) to indole-5,6 quinone (PubMed:2494997, PubMed:2517217, PubMed:1537333).3 Publications

Catalytic activityi

2 L-dopa + O2 = 2 dopaquinone + 2 H2O.1 Publication
L-tyrosine + O2 = dopaquinone + H2O.1 Publication

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi180Copper ABy similarity1
Metal bindingi202Copper ABy similarity1
Metal bindingi211Copper ABy similarity1
Metal bindingi363Copper BBy similarity1
Metal bindingi367Copper BBy similarity1
Metal bindingi390Copper BBy similarity1

GO - Molecular functioni

  • copper ion binding Source: MGI
  • monophenol monooxygenase activity Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • cell proliferation Source: MGI
  • melanin biosynthetic process Source: MGI
  • pigmentation Source: MGI
  • response to cAMP Source: Ensembl
  • response to UV Source: Ensembl
  • response to vitamin D Source: Ensembl
  • thymus development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Biological processi

Melanin biosynthesis

Keywords - Ligandi

Copper, Metal-binding

Enzyme and pathway databases

BRENDAi1.14.18.1. 3474.
ReactomeiR-MMU-5662702. Melanin biosynthesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosinase (EC:1.14.18.1)
Alternative name(s):
Albino locus protein
Monophenol monooxygenase
Gene namesi
Name:Tyr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:98880. Tyr.

Subcellular locationi

  • Melanosome membrane By similarity; Single-pass type I membrane protein By similarity
  • Melanosome 1 Publication

  • Note: Proper trafficking to melanosome is regulated by SGSM2, ANKRD27, RAB9A, RAB32 and RAB38.1 Publication

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 476Lumenal, melanosomeSequence analysisAdd BLAST458
Transmembranei477 – 497HelicalSequence analysisAdd BLAST21
Topological domaini498 – 533CytoplasmicSequence analysisAdd BLAST36

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytosol Source: Ensembl
  • integral component of membrane Source: UniProtKB
  • melanosome Source: UniProtKB
  • melanosome membrane Source: UniProtKB-SubCell
  • nucleus Source: Ensembl
  • perinuclear region of cytoplasm Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Defects in Tyr result in various forms of albinism. Himalayan strain tyrosinase is temperature-sensitive.

Keywords - Diseasei

Albinism, Disease mutation

Chemistry databases

ChEMBLiCHEMBL5346.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000003588019 – 533TyrosinaseAdd BLAST515

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi86N-linked (GlcNAc...)Sequence analysis1
Glycosylationi111N-linked (GlcNAc...)Sequence analysis1
Glycosylationi161N-linked (GlcNAc...)Sequence analysis1
Glycosylationi230N-linked (GlcNAc...)Sequence analysis1
Glycosylationi337N-linked (GlcNAc...)Sequence analysis1
Glycosylationi371N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP11344.
PRIDEiP11344.

PTM databases

PhosphoSitePlusiP11344.

Expressioni

Gene expression databases

BgeeiENSMUSG00000004651.
CleanExiMM_TYR.
ExpressionAtlasiP11344. baseline and differential.
GenevisibleiP11344. MM.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
Tyrp1P071472EBI-821603,EBI-821614

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi204394. 7 interactors.
IntActiP11344. 1 interactor.
STRINGi10090.ENSMUSP00000004770.

Chemistry databases

BindingDBiP11344.

Structurei

3D structure databases

ProteinModelPortaliP11344.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi503 – 508Poly-Lys6

Sequence similaritiesi

Belongs to the tyrosinase family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IEZU. Eukaryota.
ENOG410Y42I. LUCA.
GeneTreeiENSGT00500000044790.
HOGENOMiHOG000118376.
HOVERGENiHBG003553.
InParanoidiP11344.
KOiK00505.
OMAiEEYNSHQ.
OrthoDBiEOG091G03YR.
PhylomeDBiP11344.
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. 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.

P11344-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFLAVLYCLL WSFQISDGHF PRACASSKNL LAKECCPPWM GDGSPCGQLS
60 70 80 90 100
GRGSCQDILL SSAPSGPQFP FKGVDDRESW PSVFYNRTCQ CSGNFMGFNC
110 120 130 140 150
GNCKFGFGGP NCTEKRVLIR RNIFDLSVSE KNKFFSYLTL AKHTISSVYV
160 170 180 190 200
IPTGTYGQMN NGSTPMFNDI NIYDLFVWMH YYVSRDTLLG GSEIWRDIDF
210 220 230 240 250
AHEAPGFLPW HRLFLLLWEQ EIRELTGDEN FTVPYWDWRD AENCDICTDE
260 270 280 290 300
YLGGRHPENP NLLSPASFFS SWQIICSRSE EYNSHQVLCD GTPEGPLLRN
310 320 330 340 350
PGNHDKAKTP RLPSSADVEF CLSLTQYESG SMDRTANFSF RNTLEGFASP
360 370 380 390 400
LTGIADPSQS SMHNALHIFM NGTMSQVQGS ANDPIFLLHH AFVDSIFEQW
410 420 430 440 450
LRRHRPLLEV YPEANAPIGH NRDSYMVPFI PLYRNGDFFI TSKDLGYDYS
460 470 480 490 500
YLQESDPGFY RNYIEPYLEQ ASRIWPWLLG AALVGAVIAA ALSGLSSRLC
510 520 530
LQKKKKKKQP QEERQPLLMD KDDYHSLLYQ SHL
Length:533
Mass (Da):60,606
Last modified:May 29, 2007 - v3
Checksum:iA4C109A97CBD5D6A
GO

Sequence cautioni

The sequence BAA00079 differs from that shown.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti40M → I in AAA37806 (PubMed:2567165).Curated1
Sequence conflicti197D → Q in AAA37806 (PubMed:2567165).Curated1
Sequence conflicti264S → I in CAA31273 (PubMed:3141148).Curated1
Sequence conflicti346G → V in AAA40516 (PubMed:3134020).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti103C → S in albino mice. 3 Publications1
Natural varianti420H → R in strain: Himalayan. 1 Publication1
Natural varianti482A → T in chinchilla mice. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D00440 mRNA. Translation: BAA00341.1.
D00131 mRNA. Translation: BAA00079.1. Sequence problems.
M20234 mRNA. Translation: AAA40516.1.
X12782 mRNA. Translation: CAA31273.1.
M26729 mRNA. Translation: AAA37806.1.
M24560 mRNA. Translation: AAA40517.1.
D00439 Genomic DNA. Translation: BAA00340.1.
X51743 Genomic DNA. Translation: CAA36033.1.
CCDSiCCDS52304.1.
PIRiA27711. YRMSCS.
RefSeqiNP_035791.1. NM_011661.5.
UniGeneiMm.238127.

Genome annotation databases

EnsembliENSMUST00000004770; ENSMUSP00000004770; ENSMUSG00000004651.
GeneIDi22173.
KEGGimmu:22173.
UCSCiuc009ifo.1. mouse.

Cross-referencesi

Web resourcesi

Protein Spotlight

Snowy stardom - Issue 49 of August 2004

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D00440 mRNA. Translation: BAA00341.1.
D00131 mRNA. Translation: BAA00079.1. Sequence problems.
M20234 mRNA. Translation: AAA40516.1.
X12782 mRNA. Translation: CAA31273.1.
M26729 mRNA. Translation: AAA37806.1.
M24560 mRNA. Translation: AAA40517.1.
D00439 Genomic DNA. Translation: BAA00340.1.
X51743 Genomic DNA. Translation: CAA36033.1.
CCDSiCCDS52304.1.
PIRiA27711. YRMSCS.
RefSeqiNP_035791.1. NM_011661.5.
UniGeneiMm.238127.

3D structure databases

ProteinModelPortaliP11344.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204394. 7 interactors.
IntActiP11344. 1 interactor.
STRINGi10090.ENSMUSP00000004770.

Chemistry databases

BindingDBiP11344.
ChEMBLiCHEMBL5346.

PTM databases

PhosphoSitePlusiP11344.

Proteomic databases

PaxDbiP11344.
PRIDEiP11344.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000004770; ENSMUSP00000004770; ENSMUSG00000004651.
GeneIDi22173.
KEGGimmu:22173.
UCSCiuc009ifo.1. mouse.

Organism-specific databases

CTDi7299.
MGIiMGI:98880. Tyr.

Phylogenomic databases

eggNOGiENOG410IEZU. Eukaryota.
ENOG410Y42I. LUCA.
GeneTreeiENSGT00500000044790.
HOGENOMiHOG000118376.
HOVERGENiHBG003553.
InParanoidiP11344.
KOiK00505.
OMAiEEYNSHQ.
OrthoDBiEOG091G03YR.
PhylomeDBiP11344.
TreeFamiTF315865.

Enzyme and pathway databases

BRENDAi1.14.18.1. 3474.
ReactomeiR-MMU-5662702. Melanin biosynthesis.

Miscellaneous databases

PROiP11344.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000004651.
CleanExiMM_TYR.
ExpressionAtlasiP11344. baseline and differential.
GenevisibleiP11344. MM.

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. 2 hits.
PROSITEiPS00497. TYROSINASE_1. 1 hit.
PS00498. TYROSINASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTYRO_MOUSE
AccessioniPrimary (citable) accession number: P11344
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: May 29, 2007
Last modified: November 2, 2016
This is version 167 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  3. 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.