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UniProtKB/Swiss-Prot P14679: Variant p.Thr373Lys

Tyrosinase
Gene: TYR
Variant information

Variant position:  373
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Threonine (T) to Lysine (K) at position 373 (T373K, p.Thr373Lys).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (T) to large size and basic (K)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Albinism, oculocutaneous, 1A (OCA1A) [MIM:203100]: An autosomal recessive disorder in which the biosynthesis of melanin pigment is absent in skin, hair, and eyes. It is characterized by complete lack of tyrosinase activity due to production of an inactive enzyme. Patients present with a life-long absence of melanin pigment after birth, and manifest increased sensitivity to ultraviolet radiation with predisposition to skin cancer. Visual anomalies include decreased acuity, nystagmus, strabismus and photophobia. {ECO:0000269|PubMed:10571953, ECO:0000269|PubMed:10671066, ECO:0000269|PubMed:10987646, ECO:0000269|PubMed:11295837, ECO:0000269|PubMed:11858948, ECO:0000269|PubMed:1487241, ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1642278, ECO:0000269|PubMed:1899321, ECO:0000269|PubMed:1943686, ECO:0000269|PubMed:1970634, ECO:0000269|PubMed:22981120, ECO:0000269|PubMed:2342539, ECO:0000269|PubMed:23504663, ECO:0000269|PubMed:24934919, ECO:0000269|PubMed:7902671, ECO:0000269|PubMed:7955413, ECO:0000269|PubMed:8128955, ECO:0000269|PubMed:8644824, ECO:0000269|PubMed:9259202}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In OCA1A.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  373
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  529
The length of the canonical sequence.

Location on the sequence:   GIADASQSSMHNALHIYMNG  T MSQVQGSANDPIFLLHHAFV
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 19 – 529 Tyrosinase
Topological domain 19 – 476 Lumenal, melanosome
Metal binding 363 – 363 Copper B
Metal binding 367 – 367 Copper B
Metal binding 390 – 390 Copper B
Glycosylation 371 – 371 N-linked (GlcNAc...) asparagine
Alternative sequence 346 – 377 GFASPLTGIADASQSSMHNALHIYMNGTMSQV -> EMGFLHVGWAGLKLLTSRDPPPWPPKMLGLQA. In isoform 2.


Literature citations

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)
Cited for: VARIANTS OCA1A LYS-373 AND ASN-383; VARIANTS TYR-192 AND GLN-402;

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)
Cited for: VARIANTS OCA1A ASP-47; CYS-217 DEL; HIS-299 AND LYS-373; VARIANTS OCA1B SER-152 AND LYS-294;

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)
Cited for: VARIANTS OCA1A TYR-367; THR-370 AND LYS-373; VARIANT GLN-402;

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)
Cited for: VARIANTS OCA1A 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 OCA1B SER-403; VARIANTS TYR-192 AND GLN-402;

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)
Cited for: VARIANTS OCA1A 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;

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)
Cited for: VARIANTS OCA1A 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;

DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics.
Simeonov D.R.; Wang X.; Wang C.; Sergeev Y.; Dolinska M.; Bower M.; Fischer R.; Winer D.; Dubrovsky G.; Balog J.Z.; Huizing M.; Hart R.; Zein W.M.; Gahl W.A.; Brooks B.P.; Adams D.R.;
Hum. Mutat. 34:827-835(2013)
Cited for: VARIANTS OCA1A LEU-50; TRP-77; PHE-275; TRP-298; VAL-355; HIS-364; LYS-373; ALA-384 AND ASP-490;

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