UniProtKB/SwissProt variant VAR

Variant information

Variant position:

835

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

Type of variant:

US

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:

From Aspartate (D) to Tyrosine (Y) at position 835 (D835Y, p.Asp835Tyr).

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 lymphoblastic leukemia patients and in acute myelogenous leukemia patients; somatic mutation; constitutively activated.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121913488 [ dbSNP | Ensembl ]

Sequence information

Variant position:

835

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

Protein sequence length:

993

The length of the canonical sequence.

Location on the sequence:

RNVLVTHGKVVKICDFGLAR D IMSDSNYVVRGNARLPVKWM

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                         RNVLVTHGKVVKICDFGLARDIMSDSNYVVRGNARLPVKWM

Mouse                         RNVLVTHGKVVKICDFGLARDILSDSSYVVRGNARLPVKWM

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.

Type	Positions	Description
Chain	27 – 993	Receptor-type tyrosine-protein kinase FLT3
Topological domain	564 – 993	Cytoplasmic
Domain	610 – 943	Protein kinase
Modified residue	842 – 842	Phosphotyrosine; by autocatalysis
Alternative sequence	807 – 847	Missing. In isoform 2.

Literature citations

Identification of novel FLT-3 Asp835 mutations in adult acute myeloid leukaemia.
Abu-Duhier F.M.; Goodeve A.C.; Wilson G.A.; Care R.S.; Peake I.R.; Reilly J.T.;
Br. J. Haematol. 113:983-988(2001)
Cited for: VARIANTS TYR-835 DEL; HIS-835 AND TYR-835; INVOLVEMENT IN AML;

Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies.
Yamamoto Y.; Kiyoi H.; Nakano Y.; Suzuki R.; Kodera Y.; Miyawaki S.; Asou N.; Kuriyama K.; Yagasaki F.; Shimazaki C.; Akiyama H.; Saito K.; Nishimura M.; Motoji T.; Shinagawa K.; Takeshita A.; Saito H.; Ueda R.; Ohno R.; Naoe T.;
Blood 97:2434-2439(2001)
Cited for: VARIANTS ASN-835; GLU-835; HIS-835; VAL-835 AND TYR-835; CHARACTERIZATION OF VARIANTS ASN-835; GLU-835; HIS-835; VAL-835 AND TYR-835; PHOSPHORYLATION; INVOLVEMENT IN AML;

FLT3 mutations in the activation loop of tyrosine kinase domain are frequently found in infant ALL with MLL rearrangements and pediatric ALL with hyperdiploidy.
Taketani T.; Taki T.; Sugita K.; Furuichi Y.; Ishii E.; Hanada R.; Tsuchida M.; Sugita K.; Ida K.; Hayashi Y.;
Blood 103:1085-1088(2004)
Cited for: VARIANTS GLU-835; HIS-835; TYR-835; ILE-836 DEL AND MET-836; FUNCTION IN ACTIVATION OF STAT5A AND/OR STAT5B; PHOSPHORYLATION; INVOLVEMENT IN AML;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P36888: Variant p.Asp835Tyr