UniProtKB/Swiss-Prot P10721: Variant p.Asp816His

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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Aspartate (D) to Histidine (H) at position 816 (D816H, p.Asp816His).
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 medium size and polar (H)
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

Variant description:  In a testicular tumor; seminoma; 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.

Location on the sequence:   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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         RNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWM

Mouse                         RNILLTHGRITKICDFGLARDIRNDSNYVVKGNARLPVKWM

Pig                           RNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWM

Bovine                        RNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWM

Goat                          RNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWM

Cat                           RNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWM

Dog                           RNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWM

Chicken                       RNILLTHGRITKICDFGLARDIRNDSNYVVKGNARLPVKWM

Xenopus laevis                RNILLTHGRITKICDFGLARDIRNDSNYVVKGNARLPVKWM

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 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

Function of activation loop tyrosine phosphorylation in the mechanism of c-Kit auto-activation and its implication in sunitinib resistance.
DiNitto J.P.; Deshmukh G.D.; Zhang Y.; Jacques S.L.; Coli R.; Worrall J.W.; Diehl W.; English J.M.; Wu J.C.;
J. Biochem. 147:601-609(2010)
Cited for: PHOSPHORYLATION AT TYR-547; TYR-553; TYR-703; TYR-721; TYR-730; TYR-823 AND TYR-900; IDENTIFICATION BY MASS SPECTROMETRY; MUTAGENESIS OF TYR-823; CHARACTERIZATION OF VARIANT HIS-816;

KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients.
Gajiwala K.S.; Wu J.C.; Christensen J.; Deshmukh G.D.; Diehl W.; DiNitto J.P.; English J.M.; Greig M.J.; He Y.A.; Jacques S.L.; Lunney E.A.; McTigue M.; Molina D.; Quenzer T.; Wells P.A.; Yu X.; Zhang Y.; Zou A.; Emmett M.R.; Marshall A.G.; Zhang H.M.; Demetri G.D.;
Proc. Natl. Acad. Sci. U.S.A. 106:1542-1547(2009)
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 544-935 IN COMPLEX WITH SUNITINIB; CATALYTIC ACTIVITY; AUTOPHOSPHORYLATION; CHARACTERIZATION OF VARIANTS HIS-816 AND VAL-816; ENZYME REGULATION;

Activating c-kit gene mutations in human germ cell tumors.
Tian Q.; Frierson H.F. Jr.; Krystal G.W.; Moskaluk C.A.;
Am. J. Pathol. 154:1643-1647(1999)
Cited for: VARIANT HIS-816; CHARACTERIZATION OF VARIANT HIS-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.