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UniProtKB/Swiss-Prot P08581: Variant p.Pro991Ser

Hepatocyte growth factor receptor
Gene: MET
Variant information

Variant position:  991
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 Proline (P) to Serine (S) at position 991 (P991S, p.Pro991Ser).
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 (P) to small size and polar (S)
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 gastric cancer; prolonged tyrosine phosphorylation in response to HGF/SF; transforming activity in athymic nude mice.
Any additional useful information about the variant.

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

Sequence information

Variant position:  991
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1390
The length of the canonical sequence.

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.

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.

Chain 25 – 1390 Hepatocyte growth factor receptor
Topological domain 956 – 1390 Cytoplasmic
Site 1003 – 1003 Required for ligand-induced CBL-mediated ubiquitination
Modified residue 977 – 977 Phosphothreonine
Modified residue 990 – 990 Phosphoserine
Modified residue 997 – 997 Phosphoserine
Modified residue 1000 – 1000 Phosphoserine
Modified residue 1003 – 1003 Phosphotyrosine
Alternative sequence 765 – 1390 Missing. In isoform 3.

Literature citations

A novel germ line juxtamembrane Met mutation in human gastric cancer.
Lee J.-H.; Han S.-U.; Cho H.; Jennings B.; Gerrard B.; Dean M.; Schmidt L.; Zbar B.; Vande Woude G.F.V.;
Oncogene 19:4947-4953(2000)

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.