UniProtKB/Swiss-Prot P08581: Variant p.Met1250Ile

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 1250 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 Methionine (M) to Isoleucine (I) at position 1250 (M1250I, p.Met1250Ile). 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: Similar physico-chemical property. Both residues are medium size and hydrophobic. 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 HCC. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs121913676 [ dbSNP | Ensembl ]

Sequence information

Variant position: 1250 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 1390 The length of the canonical sequence.
Location on the sequence: YDKEYYSVHNKTGAKLPVKW M ALESLQTQKFTTKSDVWSFG 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.

Type	Positions	Description
Chain	25 – 1390	Hepatocyte growth factor receptor
Topological domain	956 – 1390	Cytoplasmic
Domain	1078 – 1345	Protein kinase
Region	1212 – 1390	Interaction with RANBP9
Modified residue	1230 – 1230	Phosphotyrosine
Modified residue	1234 – 1234	Phosphotyrosine; by autocatalysis
Modified residue	1235 – 1235	Phosphotyrosine; by autocatalysis
Alternative sequence	765 – 1390	Missing. In isoform 3.
Mutagenesis	1234 – 1234	Y -> F. Complete loss of kinase activity and of ligand-induced ubiquitination. Alters interaction with PTPN1 and PTPN2. Loss of interaction with PTPN1 and PTPN2; when associated with F-1235.
Mutagenesis	1235 – 1235	Y -> F. Complete loss of kinase activity. Alters interaction with PTPN1 and PTPN2. Loss of interaction with PTPN1 and PTPN2; when associated with F-1234.

Literature citations

Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas.
Park W.S.; Dong S.M.; Kim S.Y.; Na E.Y.; Shin M.S.; Pi J.H.; Kim B.J.; Bae J.H.; Hong Y.K.; Lee K.S.; Lee S.H.; Yoo N.J.; Jang J.J.; Pack S.; Zhuang Z.; Schmidt L.; Zbar B.; Lee J.Y.;
Cancer Res. 59:307-310(1999)
Cited for: VARIANTS HCC ILE-1173; ARG-1244 AND ILE-1250;