Details for: TYRP1

Gene ID: 7306

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: TYRP1

Ensembl ID: ENSG00000107165

Description: tyrosinase related protein 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • melanocyte CL0000148
    CSI 13.83
    rCSI 10.24%
    PRS 99.84
  • choroid plexus epithelial cell CL0000706
    CSI 8.9
    rCSI 14.58%
    PRS 99.88
  • retinal pigment epithelial cell CL0002586
    CSI 8.87
    rCSI 17.61%
    PRS 99.87
  • exhausted T cell CL0011025
    CSI 1.06
    rCSI 18%
    PRS 99.8

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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  • Node Size: Proportional to Target Cell CSI magnitude
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  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [TYRP1](/details-gene/7306) (Tyrosinase Related Protein 1) is a protein-coding gene located on chromosome 9p23. It encodes a glycoprotein, also known as gp75, which functions as a 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase involved in the melanin biosynthesis pathway. Structurally, it is an integral melanosomal membrane protein that contains a binuclear zinc active site critical for its enzymatic function ([Link](https://doi.org/10.1002/anie.201704616)). Reflecting its central role in pigmentation, [TYRP1](/details-gene/7306) is most significantly expressed in [melanocytes](/details-cell/CL0000148) and other pigmented cells, such as [retinal pigment epithelial cells](/details-cell/CL0002586). Mutations in this gene are clinically associated with oculocutaneous albinism, specifically OCA3 ([115501](https://omim.org/entry/115501)), and have also been linked to variations in hair color in certain populations ([Link](https://doi.org/10.1126/science.1217849)). ## Cellular Roles and Expression Landscape The expression profile of [TYRP1](/details-gene/7306) underscores its highly specialized function in pigmentation. **Overall**, the gene shows paramount significance in cells of the melanocytic lineage. It is the top marker for [melanocytes](/details-cell/CL0000148) (CSI: 13.83), consistent with its role as a key enzyme in melanin synthesis. High significance is also observed in other pigmented or specialized secretory epithelial tissues, including the [choroid plexus epithelial cell](/details-cell/CL0000706) (CSI: 8.90) and the [retinal pigment epithelial cell](/details-cell/CL0002586) (CSI: 8.87), which are crucial for eye function and pigmentation. The specificity of [TYRP1](/details-gene/7306) expression is highlighted by the sharp decrease in its significance in other cell types. For example, its relatively low CSI score in immune cells like the [exhausted T cell](/details-cell/CL0011025) (CSI: 1.06) suggests its primary role is confined to a specific set of tissues and is not a general cellular maintenance protein. This restricted expression pattern makes it a defining marker for cells involved in melanin production. ## Pathways and Molecular Function The functional annotations for [TYRP1](/details-gene/7306) align closely with its established role in pigmentation. It is a key component of the [Melanin biosynthetic process](/details-ontology/GO:0042438) and is involved in [Melanocyte differentiation](/details-ontology/GO:0030318) and [Melanosome organization](/details-ontology/GO:0032438). Its localization is primarily within the [Melanosome](/details-ontology/GO:0042470) and specifically the [Melanosome membrane](/details-ontology/GO:0033162), which is the site of melanin synthesis and storage. From a molecular standpoint, [TYRP1](/details-gene/7306) exhibits [Oxidoreductase activity](/details-ontology/GO:0016491) and [Tyrosinase activity](/details-ontology/GO:0004503), which are essential for catalyzing steps in the melanin synthesis pathway. Its function is also dependent on [Metal ion binding](/details-ontology/GO:0046872), specifically zinc, which is critical for its catalytic center ([Link](https://doi.org/10.1002/anie.201704616)). Reactome pathway analysis further confirms its role, placing it within the [Melanin biosynthesis](/details-pathway/R-HSA-5662702) pathway and highlighting its regulation through [Mitf-m-dependent gene expression](/details-pathway/R-HSA-9856651), a master regulator of melanocyte development and function. ## Research Directions Given that [TYRP1](/details-gene/7306) is a well-known melanoma antigen ([Link](https://doi.org/10.1084/jem.171.4.1375)), research should focus on its role in melanoma pathophysiology and its potential as a therapeutic target. **Proposed Hypotheses:** 1. The enzymatic activity of [TYRP1](/details-gene/7306) in melanoma cells contributes to tumor progression not only through pigmentation but also by modulating intracellular oxidative stress, thereby providing a survival advantage. 2. In non-classical cell types like the [choroid plexus epithelial cell](/details-cell/CL0000706), [TYRP1](/details-gene/7306) may have a secondary, non-pigmentary function related to metal ion transport or detoxification, leveraging its metal-binding capabilities to maintain homeostasis at the blood-cerebrospinal fluid barrier. **Experimental Approach:** To test the hypothesis that [TYRP1](/details-gene/7306) modulates oxidative stress to promote melanoma survival, one could employ a CRISPR-Cas9 knockout strategy in a panel of human melanoma cell lines with high endogenous [TYRP1](/details-gene/7306) expression. Following gene ablation, key experiments would include: (i) assessing changes in basal and induced levels of reactive oxygen species (ROS) using fluorescent probes like DCFDA; (ii) measuring cell viability and apoptosis rates after challenging the cells with pro-oxidant chemotherapeutic agents (e.g., dacarbazine) or H2O2; and (iii) performing metabolomic analysis to identify alterations in redox-related pathways. **Therapeutic Potential:** [TYRP1](/details-gene/7306) represents a highly attractive therapeutic target for melanoma. Its expression is largely restricted to melanocytes and melanoma cells, minimizing the potential for on-target, off-tumor toxicity. As a cell surface glycoprotein, it is readily accessible to antibody-based therapies. Therefore, [TYRP1](/details-gene/7306) is a promising candidate for the development of antibody-drug conjugates (ADCs) or for use as a target antigen in CAR-T cell therapies. The therapeutic strategy would focus on targeted killing of melanoma cells that express [TYRP1](/details-gene/7306).

Genular Protein ID: 767227494

Symbol: TYRP1_HUMAN

Name: 5,6-dihydroxyindole-2-carboxylic acid oxidase

UniProtKB Accession Codes:

P17643 P78468 P78469 Q13721 Q15679

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 12 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 1 ExpressionAtlas 1 GO 15 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 4 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 9 PDBsum 9 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 1 Rhea 2 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 2111010

Title: Nucleotide sequence of the cDNA encoding human tyrosinase-related protein.

PubMed ID: 2111010

DOI: 10.1093/nar/18.9.2807

PubMed ID: 1906272

Title: Mapping the human CAS2 gene, the homologue of the mouse brown (b) locus, to human chromosome 9p22-pter.

PubMed ID: 1906272

DOI: 10.1016/0006-291x(91)91803-k

PubMed ID: 9434945

Title: Complete sequence and polymorphism study of the human TYRP1 gene encoding tyrosinase-related protein 1.

PubMed ID: 9434945

DOI: 10.1007/s003359900678

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8530077

Title: Chromosomal structure of the human TYRP1 and TYRP2 loci and comparison of the tyrosinase-related protein gene family.

PubMed ID: 8530077

DOI: 10.1006/geno.1995.1211

PubMed ID: 1575733

Title: Downstream region of the human tyrosinase-related protein gene enhances its promoter activity.

PubMed ID: 1575733

DOI: 10.1016/0006-291x(92)90627-w

PubMed ID: 2324688

Title: The melanoma antigen gp75 is the human homologue of the mouse b (brown) locus gene product.

PubMed ID: 2324688

DOI: 10.1084/jem.171.4.1375

PubMed ID: 1945866

Title: Human tyrosinase-like protein (TYRL) carboxy terminus: closer homology with the mouse protein than previously reported.

PubMed ID: 1945866

DOI: 10.1093/nar/19.20.5803

PubMed ID: 1693779

Title: Murine and human b locus pigmentation genes encode a glycoprotein (gp75) with catalase activity.

PubMed ID: 1693779

DOI: 10.1073/pnas.87.12.4809

PubMed ID: 9758418

Title: Human tyrosinase related protein-1 (TRP-1) does not function as a DHICA oxidase activity in contrast to murine TRP-1.

PubMed ID: 9758418

DOI: 10.1111/j.1600-0625.1998.tb00324.x

PubMed ID: 12643545

Title: Proteomic analysis of early melanosomes: identification of novel melanosomal proteins.

PubMed ID: 12643545

DOI: 10.1021/pr025562r

PubMed ID: 17081065

Title: Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.

PubMed ID: 17081065

DOI: 10.1021/pr060363j

PubMed ID: 28661582

Title: Structure of Human Tyrosinase Related Protein1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis.

PubMed ID: 28661582

DOI: 10.1002/anie.201704616

PubMed ID: 22556244

Title: Melanesian blond hair is caused by an amino acid change in TYRP1.

PubMed ID: 22556244

DOI: 10.1126/science.1217849

PubMed ID: 16704458

Title: Oculocutaneous albinism with TYRP1 gene mutations in a Caucasian patient.

PubMed ID: 16704458

DOI: 10.1111/j.1600-0749.2006.00298.x

PubMed ID: 23504663

Title: DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics.

PubMed ID: 23504663

DOI: 10.1002/humu.22315

Sequence Information:

  • Length: 537
  • Mass: 60724
  • Checksum: 1051CEEF52908CCA
  • Sequence:
    • MSAPKLLSLG CIFFPLLLFQ QARAQFPRQC ATVEALRSGM CCPDLSPVSG PGTDRCGSSS 
GRGRCEAVTA DSRPHSPQYP HDGRDDREVW PLRFFNRTCH CNGNFSGHNC GTCRPGWRGA 
ACDQRVLIVR RNLLDLSKEE KNHFVRALDM AKRTTHPLFV IATRRSEEIL GPDGNTPQFE 
NISIYNYFVW THYYSVKKTF LGVGQESFGE VDFSHEGPAF LTWHRYHLLR LEKDMQEMLQ 
EPSFSLPYWN FATGKNVCDI CTDDLMGSRS NFDSTLISPN SVFSQWRVVC DSLEDYDTLG 
TLCNSTEDGP IRRNPAGNVA RPMVQRLPEP QDVAQCLEVG LFDTPPFYSN STNSFRNTVE 
GYSDPTGKYD PAVRSLHNLA HLFLNGTGGQ THLSPNDPIF VLLHTFTDAV FDEWLRRYNA 
DISTFPLENA PIGHNRQYNM VPFWPPVTNT EMFVTAPDNL GYTYEIQWPS REFSVPEIIA 
IAVVGALLLV ALIFGTASYL IRARRSMDEA NQPLLTDQYQ CYAEEYEKLQ NPNQSVV