Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P04049: Variant p.Asp486Gly

RAF proto-oncogene serine/threonine-protein kinase
Gene: RAF1
Feedback?
Variant information Variant position: help 486 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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: help From Aspartate (D) to Glycine (G) at position 486 (D486G, p.Asp486Gly). 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: help Change from medium size and acidic (D) to glycine (G) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In NS5. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 486 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 648 The length of the canonical sequence.
Location on the sequence: help HRDMKSNNIFLHEGLTVKIG D FGLATVKSRWSGSQQVEQPT 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         HRDMKSNNIFLHEGLTVKIGDFGLATVKSR------WSGSQQVEQPT

Mouse                         HRDMKSNNIFLHEGLTVKIGDFGLATVKSR------WSGSQ

Rat                           HRDMKSNNIFLHEGLTVKIGDFGLATVKSR------WSGSQ

Bovine                        HRDMKSNNIFLHEGLTVKIGDFGLATVKSR------WSGSQ

Chicken                       HRDMKSNNIFLHEGLTVKIGDFGLATVKSR------WSGSQ

Xenopus laevis                HRDMKSNNIFLHEGLTVKIGDFGLATVKTR------WSGSQ

Fission yeast                 TSSGTDNQTFVWDS---RKPDKPLSLLKHGKTKMIHFDGAN
Sequence annotation in neighborhood: help 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.
TypePositionsDescription
Chain 1 – 648 RAF proto-oncogene serine/threonine-protein kinase
Domain 349 – 609 Protein kinase
Active site 468 – 468 Proton acceptor
Modified residue 471 – 471 Phosphoserine
Modified residue 491 – 491 Phosphothreonine
Modified residue 494 – 494 Phosphoserine
Modified residue 499 – 499 Phosphoserine; by PKC
Mutagenesis 491 – 491 T -> D. Increased kinase activity but can still be inhibited by PPP5C; when associated with D-494.
Mutagenesis 494 – 494 S -> D. Increased kinase activity but can still be inhibited by PPP5C; when associated with D-491.



Literature citations
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
Pandit B.; Sarkozy A.; Pennacchio L.A.; Carta C.; Oishi K.; Martinelli S.; Pogna E.A.; Schackwitz W.; Ustaszewska A.; Landstrom A.; Bos J.M.; Ommen S.R.; Esposito G.; Lepri F.; Faul C.; Mundel P.; Lopez Siguero J.P.; Tenconi R.; Selicorni A.; Rossi C.; Mazzanti L.; Torrente I.; Marino B.; Digilio M.C.; Zampino G.; Ackerman M.J.; Dallapiccola B.; Tartaglia M.; Gelb B.D.;
Nat. Genet. 39:1007-1012(2007)
Cited for: VARIANTS NS5 SER-256; PHE-259; ARG-260; LEU-261; SER-261; ASN-486; GLY-486; ILE-491; ARG-491 AND THR-612; VARIANT HYPERTROPHIC CARDIOMYOPATHY ILE-260; VARIANTS LPRD2 LEU-257 AND VAL-613; VARIANT NS5 LEU-257; CHARACTERIZATION OF VARIANTS NS5 SER-261; ASN-486 AND ILE-491; CHARACTERIZATION OF VARIANT LPRD2 VAL-613; CATALYTIC ACTIVITY;
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.