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UniProtKB/Swiss-Prot P08581: Variant p.Tyr1230His

Hepatocyte growth factor receptor
Gene: MET
Variant information

Variant position:  1230
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 Histidine (H) at position 1230 (Y1230H, p.Tyr1230His).
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 (H)
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:  Renal cell carcinoma papillary (RCCP) [MIM:605074]: A subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. {ECO:0000269|PubMed:10327054, ECO:0000269|PubMed:10417759, ECO:0000269|PubMed:10433944, ECO:0000269|PubMed:9140397, ECO:0000269|PubMed:9563489}. 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 RCCP; somatic mutation.
Any additional useful information about the variant.

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

Sequence information

Variant position:  1230
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
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

Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas.
Schmidt L.; Duh F.-M.; Chen F.; Kishida T.; Glenn G.; Choyke P.; Scherer S.W.; Zhuang Z.; Lubensky I.; Dean M.; Allikmets R.; Chidambaram A.; Bergerheim U.R.; Feltis J.T.; Casadevall C.; Zamarron A.; Bernues M.; Richard S.; Lips C.J.M.; Walther M.M.; Tsui L.-C.; Geil L.; Orcutt M.L.; Stackhouse T.; Lipan J.; Slife L.; Brauch H.; Decker J.; Niehans G.; Hughson M.D.; Moch H.; Storkel S.; Lerman M.I.; Linehan W.M.; Zbar B.;
Nat. Genet. 16:68-73(1997)
Cited for: VARIANTS RCCP THR-1131; LEU-1188; VAL-1195; ILE-1220; HIS-1228; ASN-1228; CYS-1230; HIS-1230 AND THR-1250; VARIANT VAL-320;

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.