UniProtKB/Swiss-Prot P16234: Variant p.Val561Asp

Platelet-derived growth factor receptor alpha
Gene: PDGFRA
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Variant information Variant position:

561 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Valine (V) to Aspartate (D) at position 561 (V561D, p.Val561Asp). 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 hydrophobic (V) to medium size and acidic (D) 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 a GIST sample; constitutively activated kinase. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121908586 [ dbSNP | Ensembl ]

Sequence information Variant position:

561 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1089 The length of the canonical sequence.
Location on the sequence:

SLIVLVVIWKQKPRYEIRWR V IESISPDGHEYIYVDPMQLP 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                         SLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLP

Mouse                         SLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLP

Rat                           SLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLP

Chicken                       SLIVLVIIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLP

Xenopus laevis                SLIVLVIIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLP

Zebrafish                     SLIVLVIIWKQKPRYEIRWRVIESVSPDGHEYIYVDPMQLP

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	24 – 1089	Platelet-derived growth factor receptor alpha
Topological domain	550 – 1089	Cytoplasmic
Modified residue	572 – 572	Phosphotyrosine; by autocatalysis
Modified residue	574 – 574	Phosphotyrosine; by autocatalysis
Alternative sequence	219 – 1089	Missing. In isoform 2.
Mutagenesis	572 – 572	Y -> F. Abolishes interaction with SRC-family members and impairs internalization of the activated receptor; when associated with F-574.
Mutagenesis	574 – 574	Y -> F. Abolishes interaction with SRC-family members and impairs internalization of the activated receptor; when associated with F-572.
Beta strand	560 – 562

Literature citations
PDGFRA activating mutations in gastrointestinal stromal tumors.
Heinrich M.C.; Corless C.L.; Duensing A.; McGreevey L.; Chen C.J.; Joseph N.; Singer S.; Griffith D.J.; Haley A.; Town A.; Demetri G.D.; Fletcher C.D.; Fletcher J.A.;
Science 299:708-710(2003)
Cited for: FUNCTION IN PHOSPHORYLATION OF AKT1; MAP KINASES; STAT1 AND STAT3; INVOLVEMENT IN GIST; VARIANTS ASP-561; VAL-842; 842-ASP--HIS-845 DEL AND 845-HIS--PRO-448 DEL; CHARACTERIZATION OF VARIANTS ASP-561; VAL-842; 842-ASP--HIS-845 DEL AND 845-HIS--PRO-448 DEL; PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib.
Corless C.L.; Schroeder A.; Griffith D.; Town A.; McGreevey L.; Harrell P.; Shiraga S.; Bainbridge T.; Morich J.; Heinrich M.C.;
J. Clin. Oncol. 23:5357-5364(2005)
Cited for: INVOLVEMENT IN GIST; VARIANTS ASP-561; LYS-659; TYR-842; VAL-842; 842-ASP--HIS-845 DEL; 845-HIS--PRO-448 DEL AND CYS-849; CHARACTERIZATION OF VARIANTS ASP-561; LYS-659; TYR-842; VAL-842; 842-ASP--HIS-845 DEL; 845-HIS--PRO-448 DEL AND CYS-849; ACTIVITY REGULATION;

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.