TYRP1 (tyrosinase-related protein 1)
2016-04-01 Kunal Ray , Mainak Sengupta , Sampurna Ghosh AffiliationIdentity
HGNC
LOCATION
9p23
IMAGE
LEGEND
Cytogenetic band showing TYRP1 locus (Ref: http://www.genecards.org/cgi-bin/carddisp.pl?gene=TYRP1)
LOCUSID
ALIAS
CAS2,CATB,GP75,OCA3,TRP,TRP1,TYRP,b-PROTEIN
FUSION GENES
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).
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.
Proteins
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.
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
Entity name
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 3UTR 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).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 26068396 | 2015 | SNPs at miR-155 binding sites of TYRP1 explain discrepancy between mRNA and protein and refine TYRP1 prognostic value in melanoma. | El Hajj P et al |
| 22045183 | 2011 | TYRP1 mRNA expression in melanoma metastases correlates with clinical outcome. | Journe F et al |
| 19384953 | 2009 | Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians. | Nan H et al |
Other Information
Locus ID:
NCBI: 7306
MIM: 115501
HGNC: 12450
Ensembl: ENSG00000107165
Variants:
dbSNP: 7306
ClinVar: 7306
TCGA: ENSG00000107165
COSMIC: TYRP1
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000107165 | ENST00000381136 | E7EQI3 |
| ENSG00000107165 | ENST00000388918 | P17643 |
| ENSG00000107165 | ENST00000473763 | C9JZ52 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 33305505 | 2021 | Human TYRP1: Two functions for a single gene? | 11 |
| 33314655 | 2021 | Evaluation of the effect of narrow band-ultraviolet B on the expression of tyrosinase, TYRP-1, and TYRP-2 mRNA in vitiligo skin and their correlations with clinical improvement: A retrospective study. | 4 |
| 33811629 | 2021 | Association of TYRP1 with hypoxia and its correlation with patient outcome in uveal melanoma. | 4 |
| 34107850 | 2021 | Identification of TYR, TYRP1, DCT and LARP7 as related biomarkers and immune infiltration characteristics of vitiligo via comprehensive strategies. | 13 |
| 34638544 | 2021 | Tyrp1 Mutant Variants Associated with OCA3: Computational Characterization of Protein Stability and Ligand Binding. | 5 |
| 33305505 | 2021 | Human TYRP1: Two functions for a single gene? | 11 |
| 33314655 | 2021 | Evaluation of the effect of narrow band-ultraviolet B on the expression of tyrosinase, TYRP-1, and TYRP-2 mRNA in vitiligo skin and their correlations with clinical improvement: A retrospective study. | 4 |
| 33811629 | 2021 | Association of TYRP1 with hypoxia and its correlation with patient outcome in uveal melanoma. | 4 |
| 34107850 | 2021 | Identification of TYR, TYRP1, DCT and LARP7 as related biomarkers and immune infiltration characteristics of vitiligo via comprehensive strategies. | 13 |
| 34638544 | 2021 | Tyrp1 Mutant Variants Associated with OCA3: Computational Characterization of Protein Stability and Ligand Binding. | 5 |
| 31947795 | 2020 | Protein Stability and Functional Characterization of Intra-Melanosomal Domain of Human Recombinant Tyrosinase-Related Protein 1. | 8 |
| 32915910 | 2020 | Association between brown eye colour in rs12913832:GG individuals and SNPs in TYR, TYRP1, and SLC24A4. | 10 |
| 31947795 | 2020 | Protein Stability and Functional Characterization of Intra-Melanosomal Domain of Human Recombinant Tyrosinase-Related Protein 1. | 8 |
| 32915910 | 2020 | Association between brown eye colour in rs12913832:GG individuals and SNPs in TYR, TYRP1, and SLC24A4. | 10 |
| 31077632 | 2019 | The TYRP1-mediated protection of human tyrosinase activity does not involve stable interactions of tyrosinase domains. | 14 |
Citation
Kunal Ray ; Mainak Sengupta ; Sampurna Ghosh
TYRP1 (tyrosinase-related protein 1)
Atlas Genet Cytogenet Oncol Haematol. 2016-04-01
Online version: http://atlasgeneticsoncology.org/gene/46370/tyrp1-(tyrosinase-related-protein-1)
