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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P10721: Variant p.Asp816Tyr

Mast/stem cell growth factor receptor Kit
Gene: KIT
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Variant information Variant position: help 816 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change: help 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: help 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: help -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: help In MASTSYS and MASTC; also found in acute myeloid leukemia and a germ cell tumor of the testis; somatic mutation; constitutively activated. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 816 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 976 The length of the canonical sequence.
Location on the sequence: help RNILLTHGRITKICDFGLAR D IKNDSNYVVKGNARLPVKWM 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         RNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWM

                              RNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWM

Mouse                         RNILLTHGRITKICDFGLARDIRNDSNYVVKGNARLPVKWM

Pig                           RNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWM

Bovine                        RNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWM

Goat                          RNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWM

Cat                           RNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWM

Chicken                       RNILLTHGRITKICDFGLARDIRNDSNYVVKGNARLPVKWM

Xenopus laevis                RNILLTHGRITKICDFGLARDIRNDSNYVVKGNARLPVKWM

Sequence annotation in neighborhood: help 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 26 – 976 Mast/stem cell growth factor receptor Kit
Topological domain 546 – 976 Cytoplasmic
Domain 589 – 937 Protein kinase
Binding site 796 – 796
Binding site 797 – 797
Binding site 810 – 810
Modified residue 821 – 821 Phosphoserine
Modified residue 823 – 823 Phosphotyrosine; by autocatalysis
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)
Cited for: VARIANT ACUTE MYELOID LEUKEMIA TYR-816; 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)
Cited for: VARIANTS MASTSYS VAL-816 AND TYR-816; VARIANTS MASTC PHE-816 AND LYS-839; CHARACTERIZATION OF VARIANTS MASTSYS VAL-816 AND TYR-816; CHARACTERIZATION OF VARIANTS MASTC PHE-816 AND LYS-839; INVOLVEMENT IN MASTSYS AND MASTC; 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; Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations.
Bodemer C.; Hermine O.; Palmerini F.; Yang Y.; Grandpeix-Guyodo C.; Leventhal P.S.; Hadj-Rabia S.; Nasca L.; Georgin-Lavialle S.; Cohen-Akenine A.; Launay J.M.; Barete S.; Feger F.; Arock M.; Catteau B.; Sans B.; Stalder J.F.; Skowron F.; Thomas L.; Lorette G.; Plantin P.; Bordigoni P.; Lortholary O.; de Prost Y.; Moussy A.; Sobol H.; Dubreuil P.;
J. Invest. Dermatol. 130:804-815(2010)
Cited for: VARIANT LEU-541; VARIANTS MASTC ILE-816; TYR-816 AND VAL-816; CHARACTERIZATION OF VARIANTS MASTC ILE-816; TYR-816 AND VAL-816;
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.