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TYRP1 (tyrosinase-related protein 1)

Written2016-04Kunal Ray, Mainak Sengupta, Sampurna Ghosh
Academy of Scientific and Innovative Research (AcSIR), Campus at CSIR - Central Road Research Institute, Mathura Road, New Delhi - 110 025, kunalray@gmail.com (KR); University of Calcutta, Department of Genetics, 35, Ballygunge Circular Road, Kolkata - 700 019, sengupta.mainak@gmail.com); sampurna_ghosh@yahoo.in (MS, SG) India.

Abstract TYRP1 gene, having a chromosomal location of 9p23, encodes a melanosomal enzyme belonging to the tyrosinase family. TYRP1 catalyses oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid. TYRP1 is also thought to play a role in stabilizing tyrosinase and modulates its catalytic activity, in maintenance of melanosome structure, affecting melanocyte proliferation and melanocyte cell death. Defects in this gene cause oculocutaneous albinism type III; OCA III (also known as rufous oculocutaneous albinism).

(Note : for Links provided by Atlas : click)

Identity

Alias_namesTYRP
CAS2
Alias_symbol (synonym)GP75
CATB
TRP
b-PROTEIN
OCA3
HGNC (Hugo)
LocusID (NCBI) 7306
Atlas_Id 46370
Location 9p23  [Link to chromosome band 9p23]
Location_base_pair Starts at 12693386 and ends at 12710266 bp from pter ( according to hg19-Feb_2009)  [Mapping TYRP1.png]
 
  Cytogenetic band showing TYRP1 locus (Ref: http://www.genecards.org/cgi-bin/carddisp.pl?gene=TYRP1)

DNA/RNA

Description In Chromosome 9, the 24,852 bases long gene starts from12,685,439 bp from pter and ends at 12,710,290 bp from pter; Orientation: Plus strand. The gene contains 8 exons and spans ~24.8 kb of the genome.
Transcription The gene encodes a 2876 bp mRNA. This gene has been reported to have 7 transcripts (splice variants) of which 3 have been found to be protein coding (http://asia.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000107165;r=9:12685439-12710290). Microphthalmia-associated transcription factor (MITF) stimulates melanin synthesis by up-regulating expression of TYRP1 acting as a transcription factor.

Protein

Description The gene encodes a protein, containing 537 amino acids, of molecular mass 60724 Da; it is an enzyme needing Cu++ as cofactor (binds 2 copper ions per subunit).
Expression TYRP1 is mainly expressed in two cell types: (a) Melanocytes that are derived from neural crest cells colonizing within iris, cochlea, skin and choroids, and (b) Retinal pigment epithelial (RPE) cells that are derived from the optic cup. It has also been reported to be expressed in heart and ear (http://genatlas.medecine.univ-paris5.fr/fiche.php?symbol=TYRP1). Interestingly, expression of the gene in the following tissue types are evident by its existence in the corresponding cDNA libraries: brain, cerebrum, ear, embryonic tissue, eye, fetus, gastrointestinal tract, heart, kidney, mammary gland, nervous, retina, skin, stem cell and stomach (http://cgap.nci.nih.gov/Genes/GeneInfo?ORG=Hs&LLNO=7306).
Localisation TYRP1 is a melanosomal membrane protein.
Function TYRP1 acts a 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase converting DHICA to Indole 5,6-quinone carboxylic acid in the melanin biosynthesis pathway. It is also involved in maintaining the stability of tyrosinase protein, modulating its catalytic activity in eumelanin synthesis, in maintenance of melanosome structure and affects melanocyte proliferation and cell death.
Homology Interspecies: Homolog to murine brown locus. Intraspecies : Homolog to tyrosinase family of proteins comprising of TYR, TYRP1 and DCT (TYRP2)

Mutations

Germinal A small number of mutations in the TYRP1 gene have been found to cause oculocutaneous albinism III. Seventeen mutations have been reported in Albinism Database (http://www.ifpcs.org/albinism/oca3mut.html). It is to be noted that Albinism Database has been updated till 2009. OCA3 has been described primarily in dark-skinned people from Southern Africa. Affected individuals have reddish-brown skin, ginger or red hair, and hazel or brown irises. OCA3 or Rufous oculocutaneous albinism has been estimated to affect 1:8500 individuals in Africa; however, it is very rare in any other populations as per published literature.
Somatic Somatic mutations in TYRP1 have been identified in different cancers (https://dcc.icgc.org/genes/ENSG00000107165, http://cancer.sanger.ac.uk/cosmic/search?q=TYRP1), but no causality has been reported.

Implicated in

Note
Entity Melanoma
Note TYRP1 expression has been found to be significantly correlated with distant metastasis-free survival (DMFS), overall survival and Breslow thickness in melanoma patients (F Journe et al., 2011). Polymorphisms in 3'UTR of TYRP1 mRNA: rs683 and rs910 have been found to affect TYRP1 mRNA regulation by miR-155 and its subsequent translation into protein (El Hajj P et al., 2015). These SNPs have been hypothesized to render TYRP1 expression nonsusceptible to miR-155 activity and disclose a prognostic value for TYRP1 protein in a subgroup of melanoma patients. TYRP1 SNP rs1408799 has been found to be associated with melanoma risk (OR, 0.77; 95% CI, 0.60-0.98) (Nan H et al., 2009).
  

Bibliography

SNPs at miR-155 binding sites of TYRP1 explain discrepancy between mRNA and protein and refine TYRP1 prognostic value in melanoma
El Hajj P, Gilot D, Migault M, Theunis A, van Kempen LC, Salés F, Fayyad-Kazan H, Badran B, Larsimont D, Awada A, Bachelot L, Galibert MD, Ghanem G, Journe F
Br J Cancer 2015 Jun 30;113(1):91-8
PMID 26068396
 
TYRP1 mRNA expression in melanoma metastases correlates with clinical outcome
Journe F, Id Boufker H, Van Kempen L, Galibert MD, Wiedig M, Salès F, Theunis A, Nonclercq D, Frau A, Laurent G, Awada A, Ghanem G
Br J Cancer 2011 Nov 22;105(11):1726-32
PMID 22045183
 
Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians
Nan H, Kraft P, Hunter DJ, Han J
Int J Cancer 2009 Aug 15;125(4):909-17
PMID 19384953
 

Citation

This paper should be referenced as such :
Ray K, Sengupta M, Ghosh S
TYRP1 (tyrosinase-related protein 1);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/TYRP1ID46370ch9p23.html


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


External links

Nomenclature
HGNC (Hugo)TYRP1   12450
Cards
AtlasTYRP1ID46370ch9p23
Entrez_Gene (NCBI)TYRP1  7306  tyrosinase-related protein 1
AliasesCAS2; CATB; GP75; OCA3; 
TRP; TRP1; TYRP; b-PROTEIN
GeneCards (Weizmann)TYRP1
Ensembl hg19 (Hinxton)ENSG00000107165 [Gene_View]  chr9:12693386-12710266 [Contig_View]  TYRP1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000107165 [Gene_View]  chr9:12693386-12710266 [Contig_View]  TYRP1 [Vega]
ICGC DataPortalENSG00000107165
TCGA cBioPortalTYRP1
AceView (NCBI)TYRP1
Genatlas (Paris)TYRP1
WikiGenes7306
SOURCE (Princeton)TYRP1
Genetics Home Reference (NIH)TYRP1
Genomic and cartography
GoldenPath hg19 (UCSC)TYRP1  -     chr9:12693386-12710266 +  9p23   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)TYRP1  -     9p23   [Description]    (hg38-Dec_2013)
EnsemblTYRP1 - 9p23 [CytoView hg19]  TYRP1 - 9p23 [CytoView hg38]
Mapping of homologs : NCBITYRP1 [Mapview hg19]  TYRP1 [Mapview hg38]
OMIM115501   203290   612271   
Gene and transcription
Genbank (Entrez)AK297887 AL600654 BC052608 CD679533 CR407683
RefSeq transcript (Entrez)NM_000550
RefSeq genomic (Entrez)NC_000009 NC_018920 NG_011705 NT_008413 NW_004929342
Consensus coding sequences : CCDS (NCBI)TYRP1
Cluster EST : UnigeneHs.270279 [ NCBI ]
CGAP (NCI)Hs.270279
Alternative Splicing GalleryENSG00000107165
Gene ExpressionTYRP1 [ NCBI-GEO ]   TYRP1 [ EBI - ARRAY_EXPRESS ]   TYRP1 [ SEEK ]   TYRP1 [ MEM ]
Gene Expression Viewer (FireBrowse)TYRP1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7306
GTEX Portal (Tissue expression)TYRP1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP17643   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP17643  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP17643
Splice isoforms : SwissVarP17643
Catalytic activity : Enzyme1.14.18.- [ Enzyme-Expasy ]   1.14.18.-1.14.18.- [ IntEnz-EBI ]   1.14.18.- [ BRENDA ]   1.14.18.- [ KEGG ]   
PhosPhoSitePlusP17643
Domaine pattern : Prosite (Expaxy)TYROSINASE_1 (PS00497)    TYROSINASE_2 (PS00498)   
Domains : Interpro (EBI)DiOHindole_carboxylic_A_Oxase    Tyrosinase_Cu-bd    Unchr_di-copper_centre   
Domain families : Pfam (Sanger)Tyrosinase (PF00264)   
Domain families : Pfam (NCBI)pfam00264   
Conserved Domain (NCBI)TYRP1
DMDM Disease mutations7306
Blocks (Seattle)TYRP1
SuperfamilyP17643
Human Protein AtlasENSG00000107165
Peptide AtlasP17643
HPRD00283
IPIIPI00015913   IPI00930372   IPI00479738   IPI00947481   
Protein Interaction databases
DIP (DOE-UCLA)P17643
IntAct (EBI)P17643
FunCoupENSG00000107165
BioGRIDTYRP1
STRING (EMBL)TYRP1
ZODIACTYRP1
Ontologies - Pathways
QuickGOP17643
Ontology : AmiGOcopper ion binding  protein binding  endosome membrane  integral component of membrane  oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, another compound as one donor, and incorporation of one atom of oxygen  melanocyte differentiation  clathrin-coated endocytic vesicle membrane  melanosome organization  melanosome membrane  melanin biosynthetic process  melanosome  protein homodimerization activity  acetoacetic acid metabolic process  protein heterodimerization activity  positive regulation of melanin biosynthetic process  oxidation-reduction process  
Ontology : EGO-EBIcopper ion binding  protein binding  endosome membrane  integral component of membrane  oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, another compound as one donor, and incorporation of one atom of oxygen  melanocyte differentiation  clathrin-coated endocytic vesicle membrane  melanosome organization  melanosome membrane  melanin biosynthetic process  melanosome  protein homodimerization activity  acetoacetic acid metabolic process  protein heterodimerization activity  positive regulation of melanin biosynthetic process  oxidation-reduction process  
Pathways : KEGGTyrosine metabolism    Melanogenesis   
NDEx NetworkTYRP1
Atlas of Cancer Signalling NetworkTYRP1
Wikipedia pathwaysTYRP1
Orthology - Evolution
OrthoDB7306
GeneTree (enSembl)ENSG00000107165
Phylogenetic Trees/Animal Genes : TreeFamTYRP1
HOVERGENP17643
HOGENOMP17643
Homologs : HomoloGeneTYRP1
Homology/Alignments : Family Browser (UCSC)TYRP1
Gene fusions - Rearrangements
Fusion : MitelmanACO1/TYRP1 [9p21.1/9p23]  [t(9;9)(p21;p23)]  
Fusion : MitelmanRALGPS1/TYRP1 [9q33.3/9p23]  [t(9;9)(p23;q33)]  
Fusion: TCGAACO1 9p21.1 TYRP1 9p23 BRCA
Fusion: TCGAC9orf150 TYRP1 9p23 BRCA
Fusion: TCGARALGPS1 9q33.3 TYRP1 9p23 BRCA
Fusion Cancer (Beijing)ZMYND8 [20q13.12]  -  TYRP1 [9p23]  [FUSC003807]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTYRP1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TYRP1
dbVarTYRP1
ClinVarTYRP1
1000_GenomesTYRP1 
Exome Variant ServerTYRP1
ExAC (Exome Aggregation Consortium)TYRP1 (select the gene name)
Genetic variants : HAPMAP7306
Genomic Variants (DGV)TYRP1 [DGVbeta]
DECIPHER (Syndromes)9:12693386-12710266  ENSG00000107165
CONAN: Copy Number AnalysisTYRP1 
Mutations
ICGC Data PortalTYRP1 
TCGA Data PortalTYRP1 
Broad Tumor PortalTYRP1
OASIS PortalTYRP1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTYRP1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDTYRP1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Mendelian genes
BioMutasearch TYRP1
DgiDB (Drug Gene Interaction Database)TYRP1
DoCM (Curated mutations)TYRP1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TYRP1 (select a term)
intoGenTYRP1
NCG5 (London)TYRP1
Cancer3DTYRP1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM115501    203290    612271   
Orphanet11459   
MedgenTYRP1
Genetic Testing Registry TYRP1
NextProtP17643 [Medical]
TSGene7306
GENETestsTYRP1
Huge Navigator TYRP1 [HugePedia]
snp3D : Map Gene to Disease7306
BioCentury BCIQTYRP1
ClinGenTYRP1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7306
Chemical/Pharm GKB GenePA37101
Clinical trialTYRP1
Miscellaneous
canSAR (ICR)TYRP1 (select the gene name)
Probes
Litterature
PubMed80 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTYRP1
EVEXTYRP1
GoPubMedTYRP1
iHOPTYRP1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Nov 18 20:04:03 CET 2016

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