TYR

Protein identityUniProt · HPA

UniProt accession

P14679

Gene

TYR

Ensembl

ENSG00000077498

Chromosome

11

Canonical length

529 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted membrane proteins, Transporters

Subcellular location

Vesicles

OverviewNCBI Gene

The enzyme encoded by this gene catalyzes the first 2 steps, and at least 1 subsequent step, in the conversion of tyrosine to melanin. The enzyme has both tyrosine hydroxylase and dopa oxidase catalytic activities, and requires copper for function. Mutations in this gene result in oculocutaneous albinism, and nonpathologic polymorphisms result in skin pigmentation variation. The human genome contains a pseudogene similar to the 3' half of this gene. [provided by RefSeq, Oct 2008]

Canonical amino-acid sequenceUniProt

529 residues, UniProt reviewed canonical sequence.

>P14679|TYR
     1  MLLAVLYCLL WSFQTSAGHF PRACVSSKNL MEKECCPPWS GDRSPCGQLS GRGSCQNILL
    61  SNAPLGPQFP FTGVDDRESW PSVFYNRTCQ CSGNFMGFNC GNCKFGFWGP NCTERRLLVR
   121  RNIFDLSAPE KDKFFAYLTL AKHTISSDYV IPIGTYGQMK NGSTPMFNDI NIYDLFVWMH
   181  YYVSMDALLG GSEIWRDIDF AHEAPAFLPW HRLFLLRWEQ EIQKLTGDEN FTIPYWDWRD
   241  AEKCDICTDE YMGGQHPTNP NLLSPASFFS SWQIVCSRLE EYNSHQSLCN GTPEGPLRRN
   301  PGNHDKSRTP RLPSSADVEF CLSLTQYESG SMDKAANFSF RNTLEGFASP LTGIADASQS
   361  SMHNALHIYM NGTMSQVQGS ANDPIFLLHH AFVDSIFEQW LRRHRPLQEV YPEANAPIGH
   421  NRESYMVPFI PLYRNGDFFI SSKDLGYDYS YLQDSDPDSF QDYIKSYLEQ ASRIWSWLLG
   481  AAMVGAVLTA LLAGLVSLLC RHKRKQLPEE KQPLLMEKED YHSLYQSHL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TYR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

30 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TYR.

Disease | AllUniProt

Conditions TYR is implicated in, by any mechanism.

• Albinism, oculocutaneous, 1A (OCA1A) MIM:203100
• Albinism, oculocutaneous, 1B (OCA1B) MIM:606952

Disease | GeneticClinVar

312 pathogenic / likely-pathogenic of 835 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Oculocutaneous albinism type 1A
• SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN
• Oculocutaneous albinism type 1B
• Oculocutaneous albinism
• TYR-related disorder

Disease | ImmuneIEDB

Conditions an epitope on TYR was assayed in.

• melanoma T cell
• skin melanoma T cell
• vitiligo T cell
• autoimmune uveitis T cell
• myeloid leukemia T cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against TYR are reported. Each links to that disease's full target list.

• Vitiligo 11
• Melanoma 6

ReferencesPubMed · IEDB

Publications for TYR from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.96

gnomAD pLI

0

gnomAD missense Z

-1.95

DepMap mean gene effect

0.04

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell population proliferation
• eye pigment biosynthetic process
• melanin biosynthetic process
• melanin biosynthetic process from tyrosine
• pigmentation
• response to blue light
• response to cAMP
• response to UV
• response to vitamin D
• thymus development
• visual perception

Molecular functions

• copper ion binding
• identical protein binding
• protein homodimerization activity
• tyrosinase activity

Cellular components

• cytoplasm
• Golgi-associated vesicle
• lysosome
• melanosome
• melanosome membrane
• perinuclear region of cytoplasm

Protein domainsUniProt · Pfam · InterPro

• Tyrosinase copper-binding domain
• Di-copper centre-containing domain superfamily
• Tyrosinase and Hemocyanin
• Common central domain of tyrosinase

KeywordsUniProt

• Albinism
• Copper
• Deafness
• Glycoprotein
• Melanin biosynthesis
• Membrane
• Metal-binding
• Monooxygenase
• Oxidoreductase
• Signal
• Transmembrane
• Transmembrane helix
• Tumor antigen
• Waardenburg syndrome