TYRP1 (tyrosinase-related protein 1)

2016-04-01 Kunal Ray , Mainak Sengupta , Sampurna Ghosh Affiliation

Identity

HGNC

TYRP1

LOCATION

9p23

IMAGE

LEGEND

Cytogenetic band showing TYRP1 locus (Ref: http://www.genecards.org/cgi-bin/carddisp.pl?gene=TYRP1)

LOCUSID

7306

ALIAS

CAS2,CATB,GP75,OCA3,TRP,TRP1,TYRP,b-PROTEIN

FUSION GENES

Show Gene Fusions

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.

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

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)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Tyrosine metabolism	KEGG	ko00350
Melanogenesis	KEGG	ko04916
Tyrosine metabolism	KEGG	hsa00350
Melanogenesis	KEGG	hsa04916
Metabolic pathways	KEGG	hsa01100
Metabolism	REACTOME	R-HSA-1430728
Metabolism of amino acids and derivatives	REACTOME	R-HSA-71291
Melanin biosynthesis	REACTOME	R-HSA-5662702

Protein levels (Protein atlas)

Not detected

Low

Medium

High

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/js/haematological-explorer/humanGenome