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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P07949: Variant p.Val804Met

Proto-oncogene tyrosine-protein kinase receptor Ret
Gene: RET
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Variant information Variant position: help 804
Type of variant: help LP/P [Disclaimer]
Residue change: help From Valine (V) to Methionine (M) at position 804 (V804M, p.Val804Met).
Physico-chemical properties: help Similar physico-chemical property. Both residues are medium size and hydrophobic.
BLOSUM score: help 1
Variant description: help In MTC; familial form; faster autophosphorylation and activation, leading to enhanced activity; confers resistance to vandetanib, lenvatinib, cabozantinib and nintedanib inhibitors.
Other resources: help


Sequence information Variant position: help 804
Protein sequence length: help 1114
Location on the sequence: help HPHVIKLYGACSQDGPLLLI V EYAKYGSLRGFLRESRKVGP
Residue conservation: help
Human                         HPHVIKLYGACSQDGPLLLIVEYAKYGSLRGFLRESRKVGP

Mouse                         HPHVIKLYGACSQDGPLLLIVEYAKYGSLRGFLRDSRKIGP

Rat                           HPHVIKLYGACSQDGPLLLIVEYAKYGSLRGFLRDSRKIGP

Sequence annotation in neighborhood: help
TypePositionsDescription
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.