Atlas of Genetics and Cytogenetics in Oncology and Haematology

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TYR (tyrosinase (oculocutaneous albinism IA))

Written2012-06Erin E Mendoza, Randy Burd
Department of Nutritional Sciences, University of Arizona, Tucson, AZ 85721, USA

(Note : for Links provided by Atlas : click)


Alias (NCBI)CMM8
HGNC Alias symbOCAIA
HGNC Alias nameoculocutaneous albinism IA
LocusID (NCBI) 7299
Atlas_Id 42738
Location 11q14.3  [Link to chromosome band 11q14]
Location_base_pair Starts at 89177875 and ends at 89295759 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping TYR.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
EFHB (3p24.3)::TYR (11q14.3)ME3 (11q14.2)::TYR (11q14.3)SLC4A7 (3p24.1)::TYR (11q14.3)
TYR (11q14.3)::MMP20 (11q22.2)TYR (11q14.3)::PICALM (11q14.2)TYR (11q14.3)::SLMAP (3p14.3)


  Diagram of Tyrosinase promoter region adapted from Ray et al. 2007. H5'URS(human 5' upstream regulatory sequence), TDE (Tyrosinase distal element), and TPE (Tyrosinase proximal element).
Description Gene encompasses 80 kb of DNA, 5 exons.
Transcription 2082 bp.
Pseudogene Tyrosinase Like Gene (TRYL 11p11.2) shares 98,55% sequence identity with the 3' region of Tyrosinase. The sequence similarity lies in exons IV and V and lacks exons I, II, and III (Chaki et al., 2005).


  Schematic of Tyrosinase Polypeptide adapted from Mashima 1994. SP (signal peptide), EGF (Epidermal growth factor)-like domain, CuA and CuB (Copper binding domains) and TM (transmembrane domain).
Description 529 amino acids; nascent protein is 60 kDa; Posttranslationally modified by glycosylation giving an 80 kDa protein. Contains an 18 amino acid long signal peptide, six N glycosylation sites, two copper binding sites (CuA and CuB) and a transmembrane domain (Mashima, 1994; Kosmadaki et al., 2010).
Expression Expressed mainly in neural crest derived melanocytes and is sorted into the melanosomes within the melanocyte. Tyrosinase is also found in retinal pigment epithelium cells (Hearing, 2011).
Localisation Transmembrane protein.
Function Tyrosinase catalyzes conversion of tyrosine to DOPA; the rate limiting step of melanin biosynthesis and subsequently DOPA to dopaquinone (Olivares et al., 2009).
  Tyrosinase catalyzes the conversion of tyrosine to DOPA in the rate-limiting step of melanin biosynthesis.
Homology The protein tyrosinase related protein 1 (TRP1) is a member of the tyrosinase protein family and utilizes copper as its cofactor. Its function in humans is not well elucidated but is thought to aid in maintaining tyrosinase catalytic activity and stability. It is also involved in maintaining melanosome structure as well as proliferation and cell death of melanocytes (Sarangarajan et al., 2000; Ghanem et al., 2011). Tyrosinase related protein 2 (TRP2), which is also known as DOPAchrome tautomerase catalyzes the conversion of DOPAchrome to 5,6-dihydroxy indole-2-carboxylic acid (DHICA). TRP2 binds 2 zinc ions as cofactors instead of copper (Olivares et al., 2001; Wan et al., 2011).


Germinal Partial or complete deletion of Tyrosinase leads to dysregulation of melanin synthesis within the melanosomes leading to oculocutaneous albinism (OCA1). The presence of non-pathologic polymorphisms results in variations in skin pigmentation. There are a total of 189 reported OCA1 mutations including 148 missense or nonsense, 23 small deletions, 8 small insertions, 2 insertion/deletion type 1, 1 complex rearrangement, and 7 splice site alterations (Ray et al., 2007; Ko et al., 2011).

Implicated in

Entity Melanoma
Disease Highly aggressive neoplasma arising from melanocytes. Melanoma is responsible for the majority of skin cancer related deaths with a very high probability of metastasis. This neoplasm is greatly resistant to most conventional therapies. Due to the longevity of melanocytes, these cells are considered to have a greater mutagenic burden. This burden is also greater due to the position of melanocytes within the skin and their exposure to UV light. Tyrosinase enzymatic activity has been found to be associated with a better prognosis due to its association with functional activity of the tumor supressor p53. Tyrosinase-mediated melanin production signaled by p53 activation is a key protective response to UV damage (Flaherty, 2012; Gilcrest, 2011).
Oncogenesis Several environmental and genetic factors are involved in the complex process of melanocytic tumorigenesis. Melanin production involving tyrosinase as the rate-limiting step has been shown to protect keratinocytes from DNA damage and oxidative stress from ultra violet radiation; A low incidence of melanoma in darker skinned populations has been observed, indicating a photoprotective role of melanin (Kanavy, 2011).
Entity Oculocutaneous albinism 1A
Disease Autosomal recessive condition that results in partial or complete loss of tyrosinase activity. Complete loss of activity results in the absence of melanin in the skin and eyes and is classified as OCA1A and the presence of only reduced tyrosinase activity is classified as OCA1B. Complete loss of tyrosinase activity results in the total absence of melanin in the skin and hair. The iris in patients with OCA1A is light blue or gray and the retina lacks pigmentation as well. Tyrosinase null patients have greatly reduced visual acuity accompanied by nystagmus, strabismus, and usually photophobia (Ray et al., 2007). Patients with OCA1B present with varying levels of pigment. The hair in these patients is often yellow. The yellow color is a result of the pheomelanin synthesis. Dopaquinone has a high affinity for sulfhydryl compounds and produces pheomelanin as a result, causing yellow pigmentation. Patients with OCA1B often develop pigmentation in the cooler regions of the body, like the extremities (Chiang et al., 2008).
Prognosis Prognosis in patients is generally good with no system abnormalities other than the loss or reduction in pigmentation. Patients are advised to protect their skin from sun to prevent sunburn (Ray et al., 2007).
Oncogenesis Transcription of tyrosinase has been shown to increase with activation of the tumor suppressor p53, linking both to the tanning response following exposure to UV damage (Khlgatian et al., 2002 and Cui et al., 2007).


Determination of variants in the 3'-region of the tyrosinase gene requires locus specific amplification.
Chaki M, Mukhopadhyay A, Ray K.
Hum Mutat. 2005 Jul;26(1):53-8.
PMID 15895460
A new hypothesis of OCA1B.
Chiang PW, Drautz JM, Tsai AC, Spector E, Clericuzio CL.
Am J Med Genet A. 2008 Nov 15;146A(22):2968-70.
PMID 18925668
Central role of p53 in the suntan response and pathologic hyperpigmentation.
Cui R, Widlund HR, Feige E, Lin JY, Wilensky DL, Igras VE, D'Orazio J, Fung CY, Schanbacher CF, Granter SR, Fisher DE.
Cell. 2007 Mar 9;128(5):853-64.
PMID 17350573
Targeting metastatic melanoma.
Flaherty KT.
Annu Rev Med. 2012;63:171-83. Epub 2011 Oct 27. (REVIEW)
PMID 22034865
Tyrosinase related protein 1 (TYRP1/gp75) in human cutaneous melanoma.
Ghanem G, Fabrice J.
Mol Oncol. 2011 Apr;5(2):150-5. Epub 2011 Feb 3. (REVIEW)
PMID 21324755
Molecular aspects of tanning.
Gilchrest BA.
J Invest Dermatol. 2011 Nov 17;131(E1):E14-7. (REVIEW)
PMID 22094400
Determination of melanin synthetic pathways.
Hearing VJ.
J Invest Dermatol. 2011 Nov 17;131(E1):E8-E11. (REVIEW)
PMID 22094404
Ultraviolet radiation and melanoma.
Kanavy HE, Gerstenblith MR.
Semin Cutan Med Surg. 2011 Dec;30(4):222-8. (REVIEW)
PMID 22123420
Tyrosinase gene expression is regulated by p53.
Khlgatian MK, Hadshiew IM, Asawanonda P, Yaar M, Eller MS, Fujita M, Norris DA, Gilchrest BA.
J Invest Dermatol. 2002 Jan;118(1):126-32.
PMID 11851885
Mutation spectrum of the TYR and SLC45A2 genes in patients with oculocutaneous albinism.
Ko JM, Yang JA, Jeong SY, Kim HJ.
Mol Med Report. 2012 Apr;5(4):943-8. doi: 10.3892/mmr.2012.764. Epub 2012 Jan 25.
PMID 22294196
Recent progresses in understanding pigmentation.
Kosmadaki MG, Naif A, Hee-Young P.
G Ital Dermatol Venereol. 2010 Feb;145(1):47-55. (REVIEW)
PMID 20197745
Molecular and biological control of melanogenesis through tyrosinase genes and intrinsic and extrinsic regulatory factors.
Mishima Y.
Pigment Cell Res. 1994 Dec;7(6):376-87. (REVIEW)
PMID 7761345
New insights into the active site structure and catalytic mechanism of tyrosinase and its related proteins.
Olivares C, Solano F.
Pigment Cell Melanoma Res. 2009 Dec;22(6):750-60. Epub 2009 Sep 7. (REVIEW)
PMID 19735457
Tyrosinase and ocular diseases: some novel thoughts on the molecular basis of oculocutaneous albinism type 1.
Ray K, Chaki M, Sengupta M.
Prog Retin Eye Res. 2007 Jul;26(4):323-58. Epub 2007 Jan 17. (REVIEW)
PMID 17355913
Mutant alleles at the brown locus encoding tyrosinase-related protein-1 (TRP-1) affect proliferation of mouse melanocytes in culture.
Sarangarajan R, Zhao Y, Babcock G, Cornelius J, Lamoreux ML, Boissy RE.
Pigment Cell Res. 2000 Oct;13(5):337-44.
PMID 11041210
A second tyrosinase-related protein, TRP-2, is a melanogenic enzyme termed DOPAchrome tautomerase.
Tsukamoto K, Jackson IJ, Urabe K, Montague PM, Hearing VJ.
EMBO J. 1992 Feb;11(2):519-26.
PMID 1537333
Regulation of melanocyte pivotal transcription factor MITF by some other transcription factors.
Wan P, Hu Y, He L.
Mol Cell Biochem. 2011 Aug;354(1-2):241-6. Epub 2011 Apr 26. (REVIEW)
PMID 21519923


This paper should be referenced as such :
Mendoza, EE ; Burd, R
TYR (tyrosinase (oculocutaneous albinism IA))
Atlas Genet Cytogenet Oncol Haematol. 2012;16(12):918-920.
Free journal version : [ pdf ]   [ DOI ]

Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Oculocutaneous Albinism

External links


HGNC (Hugo)TYR   12442
Atlas Explorer : (Salamanque)TYR
Entrez_Gene (NCBI)TYR    tyrosinase
AliasesATN; CMM8; OCA1; OCA1A; 
GeneCards (Weizmann)TYR
Ensembl hg19 (Hinxton)ENSG00000077498 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000077498 [Gene_View]  ENSG00000077498 [Sequence]  chr11:89177875-89295759 [Contig_View]  TYR [Vega]
ICGC DataPortalENSG00000077498
TCGA cBioPortalTYR
Genatlas (Paris)TYR
SOURCE (Princeton)TYR
Genetics Home Reference (NIH)TYR
Genomic and cartography
GoldenPath hg38 (UCSC)TYR  -     chr11:89177875-89295759 +  11q14.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TYR  -     11q14.3   [Description]    (hg19-Feb_2009)
GoldenPathTYR - 11q14.3 [CytoView hg19]  TYR - 11q14.3 [CytoView hg38]
Genome Data Viewer NCBITYR [Mapview hg19]  
OMIM203100   601800   606933   606952   
Gene and transcription
Genbank (Entrez)AB775899 AB775900 AB775901 BC027179 BU736025
RefSeq transcript (Entrez)NM_000372
Consensus coding sequences : CCDS (NCBI)TYR
Gene ExpressionTYR [ NCBI-GEO ]   TYR [ EBI - ARRAY_EXPRESS ]   TYR [ SEEK ]   TYR [ MEM ]
Gene Expression Viewer (FireBrowse)TYR [ Firebrowse - Broad ]
GenevisibleExpression of TYR in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7299
GTEX Portal (Tissue expression)TYR
Human Protein AtlasENSG00000077498-TYR [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP14679   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP14679  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP14679
Catalytic activity : Enzyme1.14.18.1 [ Enzyme-Expasy ] [ IntEnz-EBI ] [ BRENDA ] [ KEGG ]   [ MEROPS ]
Domaine pattern : Prosite (Expaxy)TYROSINASE_1 (PS00497)    TYROSINASE_2 (PS00498)   
Domains : Interpro (EBI)Tyrosinase_Cu-bd    Unchr_di-copper_centre   
Domain families : Pfam (Sanger)Tyrosinase (PF00264)   
Domain families : Pfam (NCBI)pfam00264   
Conserved Domain (NCBI)TYR
AlphaFold pdb e-kbP14679   
Human Protein Atlas [tissue]ENSG00000077498-TYR [tissue]
Protein Interaction databases
IntAct (EBI)P14679
Ontologies - Pathways
Ontology : AmiGOtyrosinase activity  tyrosinase activity  copper ion binding  protein binding  nucleus  cytoplasm  lysosome  Golgi-associated vesicle  cytosol  melanin biosynthetic process from tyrosine  eye pigment biosynthetic process  visual perception  cell population proliferation  response to UV  response to blue light  integral component of membrane  melanosome membrane  response to vitamin D  melanin biosynthetic process  melanin biosynthetic process  melanosome  identical protein binding  protein homodimerization activity  intracellular membrane-bounded organelle  pigmentation  perinuclear region of cytoplasm  thymus development  response to cAMP  
Ontology : EGO-EBItyrosinase activity  tyrosinase activity  copper ion binding  protein binding  nucleus  cytoplasm  lysosome  Golgi-associated vesicle  cytosol  melanin biosynthetic process from tyrosine  eye pigment biosynthetic process  visual perception  cell population proliferation  response to UV  response to blue light  integral component of membrane  melanosome membrane  response to vitamin D  melanin biosynthetic process  melanin biosynthetic process  melanosome  identical protein binding  protein homodimerization activity  intracellular membrane-bounded organelle  pigmentation  perinuclear region of cytoplasm  thymus development  response to cAMP  
REACTOMEP14679 [protein]
REACTOME PathwaysR-HSA-5662702 [pathway]   
NDEx NetworkTYR
Atlas of Cancer Signalling NetworkTYR
Wikipedia pathwaysTYR
Orthology - Evolution
GeneTree (enSembl)ENSG00000077498
Phylogenetic Trees/Animal Genes : TreeFamTYR
Homologs : HomoloGeneTYR
Homology/Alignments : Family Browser (UCSC)TYR
Gene fusions - Rearrangements
Fusion : MitelmanSLC4A7::TYR [3p24.1/11q14.3]  
Fusion : MitelmanTYR::MMP20 [11q14.3/11q22.2]  
Fusion : FusionGDB1.14.18.1   
Fusion : FusionHubABTB2--TYR    EFHB--TYR    ME3--TYR    SLC4A7--TYR    TYR--MMP20    TYR--PICALM    TYR--SET    TYR--SLMAP   
Fusion : QuiverTYR
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTYR [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TYR
Exome Variant ServerTYR
GNOMAD BrowserENSG00000077498
Varsome BrowserTYR
ACMGTYR variants
Genomic Variants (DGV)TYR [DGVbeta]
DECIPHERTYR [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTYR 
ICGC Data PortalTYR 
TCGA Data PortalTYR 
Broad Tumor PortalTYR
OASIS PortalTYR [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTYR  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DTYR
Mutations and Diseases : HGMDTYR
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)TYR
DoCM (Curated mutations)TYR
CIViC (Clinical Interpretations of Variants in Cancer)TYR
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM203100    601800    606933    606952   
Orphanet220    22110    22111    11460    11457   
Genetic Testing Registry TYR
NextProtP14679 [Medical]
Target ValidationTYR
Huge Navigator TYR [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDTYR
Pharm GKB GenePA37095
Clinical trialTYR
DataMed IndexTYR
PubMed214 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Jan 20 14:19:51 CET 2022

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