Reviewed, UniProtKB/Swiss-Prot P14679 (TYRO_HUMAN)

Names and origin

Protein names

Recommended name:
    Tyrosinase
    EC=1.14.18.1
Alternative name(s):
    Monophenol monooxygenase
    Tumor rejection antigen AB
    SK29-AB
    LB24-AB

Gene names

Name:

TYR

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	529 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the rate-limiting conversions of tyrosine to DOPA, DOPA to DOPA-quinone and possibly 5,6-dihydroxyindole to indole-5,6 quinone.
Catalytic activity	L-tyrosine + L-dopa + O2 = L-dopa + dopaquinone + H2O.
Cofactor	Binds 2 copper ions per subunit.
Subcellular location	Melanosome membrane; Single-pass type I membrane protein. Ref.14 Ref.15
Induction	Increased expression after UV-B radiation.
Polymorphism	Genetic variations in TYR are associated with skin/hair/eye pigmentation type 3 (SHEP3) [MIM:601800]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair. Compound heterozygosity for the R402Q polymorphism and a mutant allele of TYR is a common cause of autosomal recessive ocular albinism. The R402Q polymorphism is also found in Waardenburg syndrome type II with ocular albinism (WS2-OA) in association with a deletion in the MITF gene.
Involvement in disease	Defects in TYR are the cause of oculocutaneous albinism type IA (OCA-IA) [MIM:203100]; also known as tyrosinase negative oculocutaneous albinism. OCA-IA is an autosomal recessive disorder characterized by absence of pigment in hair, skin and eyes. OCA-IA is characterized by complete lack of tyrosinase activity due to production of an inactive enzyme OCA-IA patients presents with the life-long absence of melanin pigment after birth and manifest increased sensitivity to ultraviolet radiation and to predisposition to skin cancer. Ref.16 Ref.17 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.30 Ref.31 Ref.33 Ref.35 Ref.36 Ref.37 Ref.38 Defects in TYR are the cause of oculocutaneous albinism type IB (OCA-IB) [MIM:606952]; also known as albinism yellow mutant type. OCA-IB is characterized by reduced activity of tyrosinase. OCA-IB patients have white hair at birth that rapidly turns yellow or blond. They manifest the development of minimal-to-moderate amounts of cutaneous and ocular pigment. Defects in TYR are the cause of oculocutaneous albinism type I temperature-sensitive (OCA-ITS) [MIM:606952]. OCA-ITS patients have white axillary and scalp hair and pigmented arm and leg hair.
Sequence similarities	Belongs to the tyrosinase family.

Ontologies

Keywords
Biological process	Melanin biosynthesis
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Albinism Deafness Disease mutation Waardenburg syndrome
Domain	Signal Transmembrane
Ligand	Copper Metal-binding
Molecular function	Monooxygenase Oxidoreductase Tumor antigen
PTM	Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	eye pigment biosynthetic process Traceable author statement. Source: ProtInc melanin biosynthetic process from tyrosine Traceable author statement. Source: ProtInc oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW visual perception Traceable author statement. Source: ProtInc
Cellular component	Golgi-associated vesicle Traceable author statement. Source: ProtInc integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lysosome Traceable author statement. Source: UniProtKB melanosome Inferred from sequence or structural similarity. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	copper ion binding Inferred from mutant phenotype. Source: UniProtKB monophenol monooxygenase activity Inferred from direct assay. Source: UniProtKB protein heterodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P14679-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P14679-2)

The sequence of this isoform differs from the canonical sequence as follows:
     346-377: GFASPLTGIADASQSSMHNALHIYMNGTMSQV → EMGFLHVGWAGLKLLTSRDPPPWPPKMLGLQA
     378-529: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 529	511	Tyrosinase		PRO_0000035879
Regions
	Topological domain	19 – 476	458	Lumenal, melanosome Potential
	Transmembrane	477 – 497	21	Potential
	Topological domain	498 – 529	32	Cytoplasmic Potential
Sites
	Metal binding	180	1	Copper A By similarity
	Metal binding	202	1	Copper A By similarity
	Metal binding	211	1	Copper A By similarity
	Metal binding	363	1	Copper B By similarity
	Metal binding	367	1	Copper B By similarity
	Metal binding	390	1	Copper B By similarity
Amino acid modifications
	Glycosylation	86	1	N-linked (GlcNAc...) Potential
	Glycosylation	111	1	N-linked (GlcNAc...) Potential
	Glycosylation	161	1	N-linked (GlcNAc...) Potential
	Glycosylation	230	1	N-linked (GlcNAc...) Potential
	Glycosylation	337	1	N-linked (GlcNAc...) Potential
	Glycosylation	371	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	346 – 377	32	GFASP…TMSQV → EMGFLHVGWAGLKLLTSRDP PPWPPKMLGLQA in isoform 2.		VSP_006701
	Alternative sequence	378 – 529	152	Missing in isoform 2.		VSP_006702
	Natural variant	19	1	H → Q in OCA-IA.		VAR_007649
	Natural variant	21	1	P → S in OCA-IA. Ref.20		VAR_007650
	Natural variant	36	1	C → Y in OCA-IA. Ref.33		VAR_021683
	Natural variant	42	1	D → G in OCA-IA. dbSNP rs28940878. Ref.23		VAR_007651
	Natural variant	44	1	S → G in OCA-IA. Ref.38		VAR_021684
	Natural variant	44	1	S → R in OCA-IA. Ref.38		VAR_021685
	Natural variant	47	1	G → D in OCA-IA. Ref.26 Ref.36 Ref.38		VAR_007652
	Natural variant	47	1	G → V in OCA-IA. Ref.38		VAR_021686
	Natural variant	52	1	R → I in OCA-I.		VAR_007653
	Natural variant	55	1	C → Y in OCA-IA. dbSNP rs28940879. Ref.23 Ref.35		VAR_007654
	Natural variant	68	1	Q → H in OCA-IA. Ref.38		VAR_021687
	Natural variant	77	1	R → Q in OCA-IA. Ref.33 Ref.36 Ref.38		VAR_007655
	Natural variant	77	1	R → RR in OCA-IA. Ref.35		VAR_009236
	Natural variant	77	1	R → W in OCA-IA and OCA-IB. Ref.33		VAR_007656
	Natural variant	79	1	S → L in OCA-IA. Ref.38		VAR_021688
	Natural variant	80	1	W → R in OCA-IA.		VAR_007657
	Natural variant	81	1	P → L in OCA-IA. dbSNP rs28940876. Ref.17 Ref.33 Ref.38		VAR_007658
	Natural variant	89	1	C → R in OCA-IA. dbSNP rs28940877. Ref.21		VAR_007659
	Natural variant	97	1	G → R in OCA-IA. Ref.33		VAR_007660
	Natural variant	109	1	G → R in OCA-IA. Ref.36		VAR_021689
	Natural variant	134	1	F → C: dbSNP rs33955261.		VAR_034576
	Natural variant	142	1	K → N: dbSNP rs11545463.		VAR_042665
	Natural variant	152	1	P → S in OCA-IB. Ref.26		VAR_007925
	Natural variant	155	1	T → S in OCA-IA. Ref.38		VAR_021690
	Natural variant	176	1	F → I in OCA-IA. Ref.24		VAR_007661
	Natural variant	177	1	V → F in OCA-IA. Ref.38		VAR_021691
	Natural variant	179	1	M → L in OCA-IA. Ref.38		VAR_021692
	Natural variant	180	1	H → N in OCA-IA. Ref.38		VAR_021693
	Natural variant	192	1	S → Y Associated with SHEP3; light/dark skin. dbSNP rs1042602. Ref.16 Ref.33 Ref.38 Ref.7 Ref.11 Ref.39 Ref.40		VAR_007662
	Natural variant	199	1	D → N in OCA-IA. Ref.38		VAR_021694
	Natural variant	201	1	A → S in OCA-IA. Ref.38		VAR_021695
	Natural variant	205	1	P → T in OCA-IA. Ref.36		VAR_021696
	Natural variant	206	1	A → T in OCA-IA. dbSNP rs28940880. Ref.23		VAR_007663
	Natural variant	216	1	L → M in OCA-IA.		VAR_007664
	Natural variant	217	1	R → G in OCA-IA.		VAR_007665
	Natural variant	217	1	R → Q in OCA-IA. Ref.24 Ref.33		VAR_007667
	Natural variant	217	1	R → S in OCA-IA. Ref.38		VAR_021697
	Natural variant	217	1	R → W in OCA-IA. Ref.20 Ref.33		VAR_007666
	Natural variant	217	1	Missing in OCA-IA.		VAR_007926
	Natural variant	227	1	Missing in OCA-IA.		VAR_021698
	Natural variant	236	1	W → L in OCA-IA. Ref.38		VAR_021699
	Natural variant	236	1	W → S in OCA-IA. Ref.33		VAR_021700
	Natural variant	239	1	R → W in OCA-IA. Ref.37		VAR_021701
	Natural variant	240	1	D → V in OCA-IA. Ref.38		VAR_021702
	Natural variant	243	1	K → T in OCA-IA. Ref.38		VAR_021703
	Natural variant	253	1	G → R in OCA-IA.		VAR_007668
	Natural variant	256	1	H → Y in OCA-IA. Ref.36 Ref.38		VAR_021704
	Natural variant	272	1	W → C in OCA-IA. Ref.33		VAR_021705
	Natural variant	275	1	V → F in OCA-IB. Ref.36 Ref.18		VAR_007669
	Natural variant	288	1	L → S in OCA-IA.		VAR_007927
	Natural variant	289	1	C → G in OCA-IA. Ref.35		VAR_009237
	Natural variant	289	1	C → R in OCA-IA. Ref.33 Ref.38		VAR_007670
	Natural variant	294	1	E → G in OCA-IA. Ref.33		VAR_021706
	Natural variant	294	1	E → K in OCA-IA/IB. Ref.26 Ref.33 Ref.36		VAR_007928
	Natural variant	299	1	R → H in OCA-IA. Ref.20 Ref.26 Ref.35		VAR_007671
	Natural variant	299	1	R → S in OCA-IB. Ref.35		VAR_007672
	Natural variant	308	1	R → T: dbSNP rs1042608.		VAR_011825
	Natural variant	312	1	L → V in OCA-I.		VAR_007673
	Natural variant	313	1	P → R in OCA-I.		VAR_007674
	Natural variant	318	1	V → E in OCA-IA. Ref.38		VAR_021707
	Natural variant	325	1	T → A in OCA-IB.		VAR_007675
	Natural variant	328	1	E → Q in OCA-IA. Ref.25		VAR_007929
	Natural variant	329	1	S → P in OCA-IA. Ref.38		VAR_021708
	Natural variant	332	1	M → T in OCA-IA. Ref.38		VAR_021709
	Natural variant	339	1	S → G in OCA-IA. Ref.36		VAR_007676
	Natural variant	340	1	F → L in OCA-I.		VAR_007677
	Natural variant	345	1	E → G in OCA-IA. Ref.38		VAR_021710
	Natural variant	346	1	G → E in OCA-IA.		VAR_007930
	Natural variant	355	1	A → E in OCA-IA.		VAR_007931
	Natural variant	355	1	A → P in OCA-IA and OCA-IB. Ref.33 Ref.36 Ref.38		VAR_007678
	Natural variant	361	1	S → R in OCA-IA. Ref.28		VAR_007932
	Natural variant	367	1	H → Y in OCA. Ref.27		VAR_007933
	Natural variant	370	1	M → T in OCA-IA. Ref.27		VAR_007934
	Natural variant	371	1	N → T in OCA-IA.		VAR_007679
	Natural variant	371	1	N → Y in OCA-IA. Ref.28 Ref.33		VAR_007935
	Natural variant	373	1	T → K in OCA-IA. Ref.16 Ref.26 Ref.33 Ref.36 Ref.38 Ref.27		VAR_007680
	Natural variant	378	1	Q → K in OCA-IA. Ref.38		VAR_021711
	Natural variant	380	1	S → P in OCA-IB.		VAR_007681
	Natural variant	382	1	N → K in OCA-IA.		VAR_007682
	Natural variant	383	1	D → N in OCA-IA. Ref.16 Ref.36 Ref.38		VAR_007683
	Natural variant	390	1	H → D in OCA-IB.		VAR_007684
	Natural variant	393	1	V → F in OCA-IA. Ref.38		VAR_007936
	Natural variant	395	1	S → N in OCA-IA.		VAR_007685
	Natural variant	395	1	S → R in OCA-IA. Ref.38		VAR_021712
	Natural variant	398	1	E → A in OCA-IA. Ref.38		VAR_021713
	Natural variant	398	1	E → V in OCA-IA. Ref.38		VAR_021714
	Natural variant	400	1	W → L in OCA-IA. Ref.35		VAR_009238
	Natural variant	402	1	R → G in OCA-IB.		VAR_007937
	Natural variant	402	1	R → L in OCA-IA. Ref.38		VAR_021715
	Natural variant	402	1	R → Q: dbSNP rs1126809. Ref.16 Ref.33 Ref.38 Ref.27 Ref.29		VAR_007686
	Natural variant	403	1	R → S in OCA-IA and OCA-IB. Ref.20 Ref.33 Ref.38		VAR_007687
	Natural variant	404	1	H → N in OCA-IA. Ref.38		VAR_021716
	Natural variant	404	1	H → P in OCA-I.		VAR_007688
	Natural variant	405	1	R → L in OCA-IA. Ref.38		VAR_021717
	Natural variant	406	1	P → L in OCA-IA and OCA-IB. Ref.33 Ref.38 Ref.18		VAR_007689
	Natural variant	408	1	Q → H in OCA-IA. Ref.38		VAR_021718
	Natural variant	409	1	E → D in OCA-IA. Ref.38		VAR_021719
	Natural variant	416	1	A → S in OCA-IA. Ref.38		VAR_021720
	Natural variant	417	1	P → H in OCA-IA. Ref.38		VAR_021721
	Natural variant	419	1	G → R in OCA-IA. Ref.23 Ref.25 Ref.33 Ref.38		VAR_007690
	Natural variant	422	1	R → Q in OCA-ITS and OCA-IA. Ref.33 Ref.38 Ref.22		VAR_007691
	Natural variant	424	1	S → F in OCA-IA. Ref.38		VAR_021722
	Natural variant	426	1	M → K in OCA-IA. Ref.38		VAR_021723
	Natural variant	427	1	V → G in OCA-IA. Ref.38		VAR_021724
	Natural variant	431	1	P → L in OCA-IA. Ref.25		VAR_007938
	Natural variant	434	1	R → I in OCA-IA. Ref.38		VAR_021725
	Natural variant	435	1	N → D in OCA-IA. Ref.38		VAR_021726
	Natural variant	439	1	F → V in OCA-IA. Ref.33		VAR_021727
	Natural variant	444	1	D → G in OCA-IA. Ref.38		VAR_021728
	Natural variant	446	1	G → S in OCA-IA. Ref.20 Ref.33 Ref.36		VAR_007692
	Natural variant	448	1	D → N in OCA-IA and OCA-IB. Ref.20 Ref.33 Ref.38		VAR_007693
Experimental info
	Sequence conflict	42 – 45	4	DRSP → TGV in AAA61241. Ref.2
	Sequence conflict	179	1	M → I in CAA68756. Ref.4
	Sequence conflict	373 – 378	6	TMSQVQ → HVPGT in AAA61241. Ref.2
	Sequence conflict	495	1	L → P in AAA61241. Ref.2
	Sequence conflict	495	1	L → P in AAA61244. Ref.2
	Sequence conflict	520 – 523	4	DYHS → GLPQ Ref.2
	Sequence conflict	525 – 528	4	YQSH → VSEPFIKGLGNRVGPKSPDL TLTQSNVQVPENICWYFL Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1993. Version 3. Checksum: 67211A91608A59E1	FASTA	529	60,393
	10 20 30 40 50 60 MLLAVLYCLL WSFQTSAGHF PRACVSSKNL MEKECCPPWS GDRSPCGQLS GRGSCQNILL 70 80 90 100 110 120 SNAPLGPQFP FTGVDDRESW PSVFYNRTCQ CSGNFMGFNC GNCKFGFWGP NCTERRLLVR 130 140 150 160 170 180 RNIFDLSAPE KDKFFAYLTL AKHTISSDYV IPIGTYGQMK NGSTPMFNDI NIYDLFVWMH 190 200 210 220 230 240 YYVSMDALLG GSEIWRDIDF AHEAPAFLPW HRLFLLRWEQ EIQKLTGDEN FTIPYWDWRD 250 260 270 280 290 300 AEKCDICTDE YMGGQHPTNP NLLSPASFFS SWQIVCSRLE EYNSHQSLCN GTPEGPLRRN 310 320 330 340 350 360 PGNHDKSRTP RLPSSADVEF CLSLTQYESG SMDKAANFSF RNTLEGFASP LTGIADASQS 370 380 390 400 410 420 SMHNALHIYM NGTMSQVQGS ANDPIFLLHH AFVDSIFEQW LRRHRPLQEV YPEANAPIGH 430 440 450 460 470 480 NRESYMVPFI PLYRNGDFFI SSKDLGYDYS YLQDSDPDSF QDYIKSYLEQ ASRIWSWLLG 490 500 510 520 AAMVGAVLTA LLAGLVSLLC RHKRKQLPEE KQPLLMEKED YHSLYQSHL
	Isoform 2. Checksum: E4E415B71C60359B	FASTA	377	42,914
	10 20 30 40 50 60 MLLAVLYCLL WSFQTSAGHF PRACVSSKNL MEKECCPPWS GDRSPCGQLS GRGSCQNILL 70 80 90 100 110 120 SNAPLGPQFP FTGVDDRESW PSVFYNRTCQ CSGNFMGFNC GNCKFGFWGP NCTERRLLVR 130 140 150 160 170 180 RNIFDLSAPE KDKFFAYLTL AKHTISSDYV IPIGTYGQMK NGSTPMFNDI NIYDLFVWMH 190 200 210 220 230 240 YYVSMDALLG GSEIWRDIDF AHEAPAFLPW HRLFLLRWEQ EIQKLTGDEN FTIPYWDWRD 250 260 270 280 290 300 AEKCDICTDE YMGGQHPTNP NLLSPASFFS SWQIVCSRLE EYNSHQSLCN GTPEGPLRRN 310 320 330 340 350 360 PGNHDKSRTP RLPSSADVEF CLSLTQYESG SMDKAANFSF RNTLEEMGFL HVGWAGLKLL 370 TSRDPPPWPP KMLGLQA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Organization and nucleotide sequences of the human tyrosinase gene and a truncated tyrosinase-related segment." Giebel L.B., Strunk K.M., Spritz R.A. Genomics 9:435-445(1991) [PubMed: 1903356] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[2]	"Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus." Kwon B.S., Haq A.K., Pomerantz S.H., Halaban R. Proc. Natl. Acad. Sci. U.S.A. 84:7473-7477(1987) [PubMed: 2823263] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	Erratum Kwon B.S., Haq A.K., Pomerantz S.H., Halaban R. Proc. Natl. Acad. Sci. U.S.A. 85:6352-6352(1988) Cited for: SEQUENCE REVISION TO 384-398.
[4]	"Induction of pigmentation in mouse fibroblasts by expression of human tyrosinase cDNA." Bouchard B., Fuller B.B., Vijayasaradhi S., Houghton A.N. J. Exp. Med. 169:2029-2042(1989) [PubMed: 2499655] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Melanoma.
[5]	"A single base insertion in the putative transmembrane domain of the tyrosinase gene as a cause for tyrosinase-negative oculocutaneous albinism." Chintamaneni C.D., Halaban R., Kobayashi Y., Witkop C.J., Kwon B.S. Proc. Natl. Acad. Sci. U.S.A. 88:5272-5276(1991) [PubMed: 1711223] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]	"The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas." Brichard V., van Pel A., Woelfel T., Woelfel C., de Plaen E., Lethe B.G., Coulie P., Boon T. J. Exp. Med. 178:489-495(1993) [PubMed: 8340755] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1). Tissue: Melanoma and T-cell.
[7]	"The tyrosinase gene in gorillas and the albinism of 'Snowflake'." Martinez-Arias R., Comas D., Andres A., Abello M.-T., Domingo-Roura X., Bertranpetit J. Pigment Cell Res. 13:467-470(2000) [PubMed: 11153699] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANT TYR-192.
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Skin.
[9]	"Characteristic sequences in the upstream region of the human tyrosinase gene." Kikuchi H., Miura H., Yamamoto H., Takeuchi T., Dei T., Watanabe M. Biochim. Biophys. Acta 1009:283-286(1989) [PubMed: 2480811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-272. Tissue: Liver.
[10]	"Functional analysis of the cDNA encoding human tyrosinase precursor." Takeda A., Tomita Y., Okinaga S., Tagami H., Shibahara S. Biochem. Biophys. Res. Commun. 162:984-990(1989) [PubMed: 2504160] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-32.
[11]	"Molecular phylogenetics and the origins of placental mammals." Murphy W.J., Eizirik E., Johnson W.E., Zhang Y.-P., Ryder O.A., O'Brien S.J. Nature 409:614-618(2001) [PubMed: 11214319] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 54-195, VARIANT TYR-192.
[12]	"Molecular basis of type I (tyrosinase-related) oculocutaneous albinism: mutations and polymorphisms of the human tyrosinase gene." Oetting W.S., King R.A. Hum. Mutat. 2:1-6(1993) [PubMed: 8477259] [Abstract] Cited for: REVIEW ON OCA VARIANTS.
[13]	"Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism." Oetting W.S., King R.A. Hum. Mutat. 13:99-115(1999) [PubMed: 10094567] [Abstract] Cited for: REVIEW ON OCA-I VARIANTS.
[14]	"Proteomic analysis of early melanosomes: identification of novel melanosomal proteins." Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., Appella E. J. Proteome Res. 2:69-79(2003) [PubMed: 12643545] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[15]	"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes." Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F. J. Proteome Res. 5:3135-3144(2006) [PubMed: 17081065] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[16]	"Detection of mutations in the tyrosinase gene in a patient with type IA oculocutaneous albinism." Spritz R.A., Strunk K.M., Giebel L.B., King R.A. N. Engl. J. Med. 322:1724-1728(1990) [PubMed: 2342539] [Abstract] Cited for: VARIANTS OCA-IA LYS-373 AND ASN-383, VARIANTS TYR-192 AND GLN-402.
[17]	"A frequent tyrosinase gene mutation in classic, tyrosinase-negative (type IA) oculocutaneous albinism." Giebel L.B., Strunk K.M., King R.A., Hanifin J.M., Spritz R.A. Proc. Natl. Acad. Sci. U.S.A. 87:3255-3258(1990) [PubMed: 1970634] [Abstract] Cited for: VARIANT OCA-IA LEU-81.
[18]	"Tyrosinase gene mutations associated with type IB ('yellow') oculocutaneous albinism." Giebel L.B., Tripathi R.K., Strunk K.M., Hanifin J.M., Jackson C.E., King R.A., Spritz R.A. Am. J. Hum. Genet. 48:1159-1167(1991) [PubMed: 1903591] [Abstract] Cited for: VARIANTS OCA-IB PHE-275 AND LEU-406.
[19]	Erratum Giebel L.B., Tripathi R.K., Strunk K.M., Hanifin J.M., Jackson C.E., King R.A., Spritz R.A. Am. J. Hum. Genet. 49:696-696(1991)
[20]	"Tyrosinase gene mutations in type I (tyrosinase-deficient) oculocutaneous albinism define two clusters of missense substitutions." Tripathi R.K., Strunk K.M., Giebel L.B., Weleber R.G., Spritz R.A. Am. J. Med. Genet. 43:865-871(1992) [PubMed: 1642278] [Abstract] Cited for: VARIANTS OCA-IA SER-21; TRP-217; HIS-299; SER-403; SER-446 AND ASN-448.
[21]	"Homozygous tyrosinase gene mutation in an American black with tyrosinase-negative (type IA) oculocutaneous albinism." Spritz R.A., Strunk K.M., Hsieh C.-L., Sekhon G.S., Francke U. Am. J. Hum. Genet. 48:318-324(1991) [PubMed: 1899321] [Abstract] Cited for: VARIANT OCA-IA ARG-89.
[22]	"A tyrosinase gene missense mutation in temperature-sensitive type I oculocutaneous albinism. A human homologue to the Siamese cat and the Himalayan mouse." Giebel L.B., Tripathi R.K., King R.A., Spritz R.A. J. Clin. Invest. 87:1119-1122(1991) [PubMed: 1900309] [Abstract] Cited for: VARIANT OCA-ITS GLN-422.
[23]	"Non-random distribution of missense mutations within the human tyrosinase gene in type I (tyrosinase-related) oculocutaneous albinism." King R.A., Mentink M.M., Oetting W.S. Mol. Biol. Med. 8:19-29(1991) [PubMed: 1943686] [Abstract] Cited for: VARIANTS OCA-IA GLY-42; TYR-55; THR-206 AND ARG-419.
[24]	"Molecular analysis of type I-A (tyrosinase negative) oculocutaneous albinism." Oetting W.S., King R.A. Hum. Genet. 90:258-262(1992) [PubMed: 1487241] [Abstract] Cited for: VARIANTS OCA-IA ILE-176 AND GLN-217.
[25]	"Mutations of the tyrosinase gene in Indo-Pakistani patients with type I (tyrosinase-deficient) oculocutaneous albinism (OCA)." Tripathi R.K., Bundey S., Musarella M.A., Droetto S., Strunk K.M., Holmes S.A., Spritz R.A. Am. J. Hum. Genet. 53:1173-1179(1993) [PubMed: 7902671] [Abstract] Cited for: VARIANTS OCA-IA GLN-328; ARG-419 AND LEU-431.
[26]	"Mutations of the tyrosinase gene in patients with oculocutaneous albinism from various ethnic groups in Israel." Gershoni-Baruch R., Rosenmann A., Droetto S., Holmes S.A., Tripathi R.K., Spritz R.A. Am. J. Hum. Genet. 54:586-594(1994) [PubMed: 8128955] [Abstract] Cited for: VARIANTS OCA-IA ASP-47; CYS-217 DEL; HIS-299 AND LYS-373, VARIANTS OCA-IB SER-152 AND LYS-294.
[27]	"Initiation codon mutation of the tyrosinase gene as a cause of human albinism." Breimer L.H., Winder A.F., Jay B., Jay M. Clin. Chim. Acta 227:17-22(1994) [PubMed: 7955413] [Abstract] Cited for: VARIANTS OCA TYR-367; THR-370 AND LYS-373, VARIANT GLN-402.
[28]	"Diagnosis of oculocutaneous albinism with molecular analysis." Summers C.G., Oetting W.S., King R.A. Am. J. Ophthalmol. 121:724-726(1996) [PubMed: 8644824] [Abstract] Cited for: VARIANTS OCA-IA ARG-361 AND TYR-371.
[29]	"Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA)." Morell R., Spritz R.A., Ho L., Pierpont J., Guo W., Friedman T.B., Asher J.H. Jr. Hum. Mol. Genet. 6:659-664(1997) [PubMed: 9158138] [Abstract] Cited for: VARIANT GLN-402.
[30]	"Novel mutations of the tyrosinase (TYR) gene in type I oculocutaneous albinism (OCA1)." Spritz R.A., Oh J., Fukai K., Holmes S.A., Ho L., Chitayat D., France T.D., Musarella M.A., Orlow S.J., Schnur R.E., Weleber R.G., Levin A.V. Hum. Mutat. 10:171-174(1997) [PubMed: 9259202] [Abstract] Cited for: VARIANTS OCA-IA AND OCA-IB.
[31]	"Mutations of the human tyrosinase gene associated with tyrosinase related oculocutaneous albinism (OCA1)." Oetting W.S., Fryer J.P., King R.A. Hum. Mutat. 12:433-434(1998) [PubMed: 10671066] [Abstract] Cited for: VARIANTS OCA-IA AND OCA-IB.
[32]	Erratum Oetting W.S., Fryer J.P., King R.A. Hum. Mutat. 13:83-83(1999)
[33]	"Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population." Passmore L.A., Kaesmann-Kellner B., Weber B.H.F. Hum. Genet. 105:200-210(1999) [PubMed: 10987646] [Abstract] Cited for: VARIANTS OCA-IA TYR-36; GLN-77; TRP-77; LEU-81; ARG-97; GLN-217; TRP-217; SER-236; CYS-272; ARG-289; GLY-294; LYS-294; PRO-355; TYR-371; LYS-373; LEU-406; ARG-419; GLN-422; VAL-439; SER-446 AND ASN-448, VARIANT OCA-IB SER-403, VARIANTS TYR-192 AND GLN-402.
[34]	Erratum Passmore L.A., Kaesmann-Kellner B., Weber B.H.F. Hum. Genet. 108:208-208(2001)
[35]	"Insertion/deletion mutations of type I oculocutaneous albinism in Chinese patients from Taiwan." Tsai C.-H., Tsai F.-J., Wu J.-Y., Lin S.-P., Chang J.-G., Yang C.-F., Lee C.-C. Hum. Mutat. 14:542-542(1999) [PubMed: 10571953] [Abstract] Cited for: VARIANTS OCA-IA TYR-55; ARG-77 INS; GLY-289; HIS-299; SER-299 AND LEU-400.
[36]	"Mutation analysis of the tyrosinase gene in oculocutaneous albinism." Camand O., Marchant D., Boutboul S., Pequignot M., Odent S., Dollfus H., Sutherland J., Levin A., Menasche M., Marsac C., Dufier J.-L., Heon E., Abitbol M. Hum. Mutat. 17:352-352(2001) [PubMed: 11295837] [Abstract] Cited for: VARIANTS OCA-IA ASP-47; GLN-77; ARG-109; THR-205; TYR-256; PHE-275; LYS-294; GLY-339; PRO-355; LYS-373; ASN-383 AND SER-446.
[37]	"A novel mutation of the tyrosinase gene causing oculocutaneous albinism type 1 (OCA1)." Nakamura E., Miyamura Y., Matsunaga J., Kano Y., Dakeishi-Hara M., Tanita M., Kono M., Tomita Y. J. Dermatol. Sci. 28:102-105(2002) [PubMed: 11858948] [Abstract] Cited for: VARIANT OCA-IA TRP-239.
[38]	"Detection of 53 novel DNA variations within the tyrosinase gene and accumulation of mutations in 17 patients with albinism." Opitz S., Kaesmann-Kellner B., Kaufmann M., Schwinger E., Zuehlke C. Hum. Mutat. 23:630-631(2004) [PubMed: 15146472] [Abstract] Cited for: VARIANTS OCA-IA ARG-44; GLY-44; ASP-47; VAL-47; HIS-68; GLN-77; LEU-79; LEU-81; SER-155; PHE-177; LEU-179; ASN-180; ASN-199; SER-201; SER-217; LEU-236; VAL-240; THR-243; TYR-256; ARG-289; GLU-318; PRO-329; THR-332; GLY-345; PRO-355; LYS-373; LYS-378; ASN-383; PHE-393; ARG-395; VAL-398; ALA-398; LEU-402; SER-403; ASN-404; LEU-405; LEU-406; HIS-408; ASP-409; SER-416; HIS-417; ARG-419; GLN-422; PHE-424; LYS-426; GLY-427; ILE-434; ASP-435; GLY-444 AND ASN-448, VARIANTS TYR-192 AND GLN-402.
[39]	"A genomewide association study of skin pigmentation in a South Asian population." Stokowski R.P., Pant P.V.K., Dadd T., Fereday A., Hinds D.A., Jarman C., Filsell W., Ginger R.S., Green M.R., van der Ouderaa F.J., Cox D.R. Am. J. Hum. Genet. 81:1119-1132(2007) [PubMed: 17999355] [Abstract] Cited for: VARIANT TYR-192, ASSOCIATION WITH SHEP3.
[40]	"Genetic determinants of hair, eye and skin pigmentation in Europeans." Sulem P., Gudbjartsson D.F., Stacey S.N., Helgason A., Rafnar T., Magnusson K.P., Manolescu A., Karason A., Palsson A., Thorleifsson G., Jakobsdottir M., Steinberg S., Palsson S., Jonasson F., Sigurgeirsson B., Thorisdottir K., Ragnarsson R., Benediktsdottir K.R. , Aben K.K., Kiemeney L.A., Olafsson J.H., Gulcher J., Kong A., Thorsteinsdottir U., Stefansson K. Nat. Genet. 39:1443-1452(2007) [PubMed: 17952075] [Abstract] Cited for: VARIANT TYR-192, ASSOCIATION WITH SHEP3.
+	Additional computationally mapped references.

Web resources

Mutations of the TYR gene

Retina International's Scientific Newsletter

Albinism database (ADB)

TYR mutations

GeneReviews

Protein Spotlight

Snowy stardom - Issue 49 of August 2004

Wikipedia

Tyrosinase entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	M27160 mRNA. Translation: AAB37227.1. M63239 , M63235, M63236, M63237, M63238 Genomic DNA. Translation: AAA61242.1. J03581 mRNA. Translation: AAA61241.1. Different initiation. Y00819 mRNA. Translation: CAA68756.1. Different initiation. U01873 mRNA. Translation: AAB60319.1. Sequence problems. M74314 mRNA. Translation: AAA61244.1. X16073 Genomic DNA. Translation: CAA34205.1. AF237811 , AF237807, AF237808, AF237809, AF237810 Genomic DNA. Translation: AAK00805.1. BC027179 mRNA. Translation: AAH27179.1. AY012019 Genomic DNA. Translation: AAG38762.1.
IPI	IPI00027286. IPI00218270.
PIR	YRHU1. A38444.
RefSeq	NP_000363.1.
UniGene	Hs.503555
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	P14679.
PTM databases
PhosphoSite	P14679.
Proteomic databases
PRIDE	P14679.
Genome annotation databases
Ensembl	ENST00000263321; ENSP00000263321; ENSG00000077498; Homo sapiens. [Genome view]
GeneID	7299.
KEGG	hsa:7299.
UCSC	uc001pcs.1. human.
Organism-specific databases
CTD	7299.
GeneCards	GC11P088550.
H-InvDB	HIX0010011.
HGNC	HGNC:12442. TYR.
HPA	CAB000079.
MIM	103470. phenotype. 203100. phenotype. 601800. phenotype. 606933. gene. 606952. phenotype.
Orphanet	1000. Albinism ocular - late onset sensorineural deafness. 55. Oculocutaneous albinism. 895. Waardenburg syndrome type 2.
PharmGKB	PA37095.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P14679.
OMA	FSFRNTL.
Enzyme and pathway databases
BRENDA	1.14.18.1. 247.
Gene expression databases
ArrayExpress	P14679.
Bgee	P14679.
CleanEx	HS_TYR.
Genevestigator	P14679.
GermOnline	ENSG00000077498. Homo sapiens.
Family and domain databases
InterPro	IPR008922. Di-copper_centre. IPR002227. Tyrosinase. [Graphical view]
Gene3D	G3DSA:1.10.1280.10. Di-copper_centre. 1 hit.
Pfam	PF00264. Tyrosinase. 1 hit. [Graphical view]
PRINTS	PR00092. TYROSINASE.
PROSITE	PS00497. TYROSINASE_1. 1 hit. PS00498. TYROSINASE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00548. Azelaic Acid. DB01055. Mimosine. DB00157. NADH.
NextBio	28547.
SOURCE	Search...

Entry information

Entry name

TYRO_HUMAN

Accession

Primary (citable) accession number: P14679
Secondary accession number(s): Q15675 , Q15676, Q15680, Q8TAK4, Q9BYY0, Q9BZX1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	July 1, 1993
Last modified:	November 3, 2009
This is version 122 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.