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UniProtKB/Swiss-Prot P10721: Variant p.Asp816Tyr

Mast/stem cell growth factor receptor Kit
Gene: KIT
Chromosomal location: 4q11-q12
Variant information

Variant position:  816
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
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 Aspartate (D) to Tyrosine (Y) at position 816 (D816Y, p.Asp816Tyr).
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 acidic (D) to large size and aromatic (Y)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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

Variant description:  In acute myeloid leukemia, mastocytosis and a germ cell tumor of the testis; somatic mutation; constitutively activated.
Any additional useful information about the variant.

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

Sequence information

Variant position:  816
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  976
The length of the canonical sequence.

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.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.










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.

Chain 26 – 976 Mast/stem cell growth factor receptor Kit
Topological domain 546 – 976 Cytoplasmic
Domain 589 – 937 Protein kinase
Metal binding 797 – 797 Magnesium
Metal binding 810 – 810 Magnesium
Binding site 796 – 796 ATP
Modified residue 821 – 821 Phosphoserine
Modified residue 823 – 823 Phosphotyrosine; by autocatalysis
Alternative sequence 414 – 976 Missing. In isoform 3.
Mutagenesis 823 – 823 Y -> F. No decrease in activity. Leads to autophosphorylation at Tyr-900.

Literature citations

c-kit activating mutations and mast cell proliferation in human leukemia.
Beghini A.; Larizza L.; Cairoli R.; Morra E.;
Blood 92:701-702(1998)

Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis.
Longley B.J. Jr.; Metcalfe D.D.; Tharp M.; Wang X.; Tyrrell L.; Lu S.-Z.; Heitjan D.; Ma Y.;
Proc. Natl. Acad. Sci. U.S.A. 96:1609-1614(1999)

Sequence analysis of the protein kinase gene family in human testicular germ-cell tumors of adolescents and adults.
Bignell G.; Smith R.; Hunter C.; Stephens P.; Davies H.; Greenman C.; Teague J.; Butler A.; Edkins S.; Stevens C.; O'meara S.; Parker A.; Avis T.; Barthorpe S.; Brackenbury L.; Buck G.; Clements J.; Cole J.; Dicks E.; Edwards K.; Forbes S.; Gorton M.; Gray K.; Halliday K.; Harrison R.; Hills K.; Hinton J.; Jones D.; Kosmidou V.; Laman R.; Lugg R.; Menzies A.; Perry J.; Petty R.; Raine K.; Shepherd R.; Small A.; Solomon H.; Stephens Y.; Tofts C.; Varian J.; Webb A.; West S.; Widaa S.; Yates A.; Gillis A.J.M.; Stoop H.J.; van Gurp R.J.H.L.M.; Oosterhuis J.W.; Looijenga L.H.J.; Futreal P.A.; Wooster R.; Stratton M.R.;
Genes Chromosomes Cancer 45:42-46(2006)
Cited for: VARIANTS TYR-816; LYS-822 AND PRO-829;

Patterns of somatic mutation in human cancer genomes.
Greenman C.; Stephens P.; Smith R.; Dalgliesh G.L.; Hunter C.; Bignell G.; Davies H.; Teague J.; Butler A.; Stevens C.; Edkins S.; O'Meara S.; Vastrik I.; Schmidt E.E.; Avis T.; Barthorpe S.; Bhamra G.; Buck G.; Choudhury B.; Clements J.; Cole J.; Dicks E.; Forbes S.; Gray K.; Halliday K.; Harrison R.; Hills K.; Hinton J.; Jenkinson A.; Jones D.; Menzies A.; Mironenko T.; Perry J.; Raine K.; Richardson D.; Shepherd R.; Small A.; Tofts C.; Varian J.; Webb T.; West S.; Widaa S.; Yates A.; Cahill D.P.; Louis D.N.; Goldstraw P.; Nicholson A.G.; Brasseur F.; Looijenga L.; Weber B.L.; Chiew Y.-E.; DeFazio A.; Greaves M.F.; Green A.R.; Campbell P.; Birney E.; Easton D.F.; Chenevix-Trench G.; Tan M.-H.; Khoo S.K.; Teh B.T.; Yuen S.T.; Leung S.Y.; Wooster R.; Futreal P.A.; Stratton M.R.;
Nature 446:153-158(2007)
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ILE-532; LEU-541; SER-691; ASN-715; ASN-737; TRP-804; TYR-816; LYS-822 AND PRO-829;

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.