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UniProtKB/Swiss-Prot P08514: Variant p.Ser957Leu

Integrin alpha-IIb
Gene: ITGA2B
Variant information

Variant position:  957
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 Serine (S) to Leucine (L) at position 957 (S957L, p.Ser957Leu).
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 small size and polar (S) to medium size and hydrophobic (L)
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:  Glanzmann thrombasthenia (GT) [MIM:273800]: A common inherited disease of platelet aggregation. It is characterized by mucocutaneous bleeding of mild-to-moderate severity. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb-IIIa complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the GPIIb-IIIa complex at reduced levels, have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. {ECO:0000269|PubMed:10607701, ECO:0000269|PubMed:11798398, ECO:0000269|PubMed:12083483, ECO:0000269|PubMed:12181054, ECO:0000269|PubMed:12424194, ECO:0000269|PubMed:12506038, ECO:0000269|PubMed:15099289, ECO:0000269|PubMed:15219201, ECO:0000269|PubMed:17018384, ECO:0000269|PubMed:20020534, ECO:0000269|PubMed:7508443, ECO:0000269|PubMed:7706461, ECO:0000269|PubMed:8282784, ECO:0000269|PubMed:8704171, ECO:0000269|PubMed:9215749, ECO:0000269|PubMed:9473221, ECO:0000269|PubMed:9722314, ECO:0000269|PubMed:9734640, ECO:0000269|PubMed:9763559, ECO:0000269|PubMed:9920835}. 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 GT; severe type 1 phenotype; the mutation prevented normal ITGA2B/ITGB3 complex expression on the cell surface; the mutation may interfere with correct folding of the protein.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  957
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1039
The length of the canonical sequence.

Location on the sequence:   LAFLWLPSLYQRPLDQFVLQ  S HAWFNVSSLPYAVPPLSLPR
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                         LAFLWLPSLYQRPLDQFVLQSHAWFNVSSLPYAVPPLSLPR

Mouse                         QVMLGLSSLRQRPQEQFVLQSHAWFNVSSLPYSVPVVSLPS

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 32 – 1039 Integrin alpha-IIb
Chain 891 – 1039 Integrin alpha-IIb light chain, form 1
Chain 903 – 1039 Integrin alpha-IIb light chain, form 2
Topological domain 32 – 993 Extracellular
Glycosylation 962 – 962 N-linked (GlcNAc...) asparagine
Alternative sequence 910 – 1039 SCDSAPCTVVQCDLQEMARGQRAMVTVLAFLWLPSLYQRPLDQFVLQSHAWFNVSSLPYAVPPLSLPRGEAQVWTQLLRALEERAIPIWWVLVGVLGGLLLLTILVLAMWKVGFFKRNRPPLEEDDEEGE -> VSRLSGLWPGLPGTHGAEGMGGGRGVRVCCGPLWATLGPWEHFK. In isoform 3.
Alternative sequence 948 – 981 Missing. In isoform 2.
Beta strand 952 – 965


Literature citations

AlphaIIbbeta3 integrin: new allelic variants in Glanzmann thrombasthenia, effects on ITGA2B and ITGB3 mRNA splicing, expression, and structure-function.
Jallu V.; Dusseaux M.; Panzer S.; Torchet M.F.; Hezard N.; Goudemand J.; de Brevern A.G.; Kaplan C.;
Hum. Mutat. 31:237-246(2010)
Cited for: VARIANTS GT THR-405; THR-596; ARG-705; PRO-778; PHE-934; LEU-957; MET-982 AND THR-989; CHARACTERIZATION OF VARIANTS GT PHE-934 AND LEU-957;

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.