Home  |  Contact

UniProtKB/Swiss-Prot P16234: Variant p.Tyr555Cys

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

Variant position:  555
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
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 Tyrosine (Y) to Cysteine (C) at position 555 (Y555C, p.Tyr555Cys).
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 large size and aromatic (Y) to medium size and polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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

Involvement in disease:  GIST-plus syndrome (GISTPS) [MIM:175510]: A disorder characterized by multiple mesenchymal tumors of the gastrointestinal tract, including gastrointestinal stromal tumor, inflammatory fibroid polyps, and fibroid tumors. Additional features are coarse facies and skin, broad hands and feet, and premature tooth loss. GISTPS is an autosomal dominant disease with incomplete penetrance. Gastrointestinal stromal tumor and inflammatory fibroid polyps may also occur in isolation. {ECO:0000269|PubMed:14699510, ECO:0000269|PubMed:17087943, ECO:0000269|PubMed:25975287}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In GISTPS; increased platelet-derived growth factor alpha-receptor activity; constitutively activated kinase.
Any additional useful information about the variant.



Sequence information

Variant position:  555
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:   LVIVIISLIVLVVIWKQKPR  Y EIRWRVIESISPDGHEYIYV
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                         LVIVIISLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYV

Mouse                         LVIVIVSLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYV

Rat                           LVIVIVSLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYV

Chicken                       LVIVIISLIVLVIIWKQKPRYEIRWRVIESISPDGHEYIYV

Xenopus laevis                LVIVIISLIVLVIIWKQKPRYEIRWRVIESISPDGHEYIYV

Zebrafish                     LVIVIISLIVLVIIWKQKPRYEIRWRVIESVSPDGHEYIYV

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 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.


Literature citations

Intestinal neurofibromatosis is a subtype of familial GIST and results from a dominant activating mutation in PDGFRA.
de Raedt T.; Cools J.; Debiec-Rychter M.; Brems H.; Mentens N.; Sciot R.; Himpens J.; de Wever I.; Schoeffski P.; Marynen P.; Legius E.;
Gastroenterology 131:1907-1912(2006)
Cited for: VARIANT GISTPS CYS-555; CHARACTERIZATION OF VARIANT GISTPS CYS-555; FUNCTION;

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.