UniProtKB/Swiss-Prot P07949 : Variant p.Val804Met
Proto-oncogene tyrosine-protein kinase receptor Ret
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Variant information
Variant position:
804
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
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:
804 (V804M, p.Val804Met).
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:
The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:
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).following page
Variant description:
Any additional useful information about the variant.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
804
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:
1114
The length of the canonical sequence.
Location on the sequence:
V EYAKYGSLRGFLRESRKVGP
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 HPHVIKLYGACSQDGPLLLIV EYAKYGSLRGFLRESRKVGP
Mouse HPHVIKLYGACSQDGPLLLIV EYAKYGSLRGFLRDSRKIGP
Rat HPHVIKLYGACSQDGPLLLIV EYAKYGSLRGFLRDSRKIGP
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
29 – 1114 Proto-oncogene tyrosine-protein kinase receptor Ret
Chain
708 – 1017 Soluble RET kinase fragment
Topological domain
658 – 1114 Cytoplasmic
Domain
724 – 1016 Protein kinase
Modified residue
806 – 806 Phosphotyrosine; by autocatalysis
Modified residue
809 – 809 Phosphotyrosine; by autocatalysis
Mutagenesis
708 – 1114 Missing. Loss of induced cell death, but increased cell aggregation.
Beta strand
801 – 805
Literature citations
Oncogenic RET kinase domain mutations perturb the autophosphorylation trajectory by enhancing substrate presentation in trans.
Plaza-Menacho I.; Barnouin K.; Goodman K.; Martinez-Torres R.J.; Borg A.; Murray-Rust J.; Mouilleron S.; Knowles P.; McDonald N.Q.;
Mol. Cell 53:738-751(2014)
Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 705-1013 IN COMPLEX WITH ADENOSINE; FUNCTION; CATALYTIC ACTIVITY; PHOSPHORYLATION AT TYR-687; TYR-826; TYR-900; TYR-905; TYR-981; TYR-1015; TYR-1029 AND TYR-1062; MUTAGENESIS OF GLU-734; LYS-758; ARG-912 AND ILE-913; VARIANT MEN2B THR-918; CHARACTERIZATION OF VARIANT MEN2B THR-918; VARIANT MTC MET-804; CHARACTERIZATION OF VARIANT MTC MET-804;
A GTG to ATG novel point mutation at codon 804 in exon 14 of the RET proto-oncogene in two families affected by familial medullary thyroid carcinoma.
Fattoruso O.; Quadro L.; Libroia A.; Verga U.; Lupoli G.; Cascone E.; Colantuoni V.;
Hum. Mutat. Suppl. 1:S167-S171(1998)
Cited for: VARIANT MTC MET-804;
A RET double mutation in the germline of a kindred with FMTC.
Bartsch D.K.; Hasse C.; Schug C.; Barth P.; Rothmund M.; Hoeppner W.;
Exp. Clin. Endocrinol. Diabetes 108:128-132(2000)
Cited for: VARIANTS MTC MET-804 AND LEU-844;
Drug resistance profiles of mutations in the RET kinase domain.
Liu X.; Shen T.; Mooers B.H.M.; Hilberg F.; Wu J.;
Br. J. Pharmacol. 175:3504-3515(2018)
Cited for: ACTIVITY REGULATION; VARIANTS ILE-730; VAL-730; LYS-732; ALA-738; ASN-806; VAL-807; ALA-810; SER-810; ILE-871 AND VAL-998; CHARACTERIZATION OF VARIANTS ILE-730; VAL-730; LYS-732; ALA-738; ASN-806; VAL-807; ALA-810; SER-810; ILE-871 AND VAL-998; VARIANTS MTC LEU-804; MET-804 AND THR-918; CHARACTERIZATION OF VARIANTS MTC LEU-804; MET-804 AND THR-918;
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.
