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UniProtKB/Swiss-Prot P04049: Variant p.Pro261Ala

RAF proto-oncogene serine/threonine-protein kinase
Gene: RAF1
Variant information

Variant position:  261
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Proline (P) to Alanine (A) at position 261 (P261A, p.Pro261Ala).
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 medium size and hydrophobic (P) to small size and hydrophobic (A)
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 NS5; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type.
Any additional useful information about the variant.

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

Sequence information

Variant position:  261
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  648
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.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.








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 1 – 648 RAF proto-oncogene serine/threonine-protein kinase
Region 220 – 334 Disordered
Compositional bias 222 – 269 Polar residues
Modified residue 252 – 252 Phosphoserine
Modified residue 259 – 259 Phosphoserine; by PKA, PKC and PKB/AKT1
Modified residue 268 – 268 Phosphothreonine; by autocatalysis
Modified residue 269 – 269 Phosphothreonine; by PKA
Alternative sequence 278 – 278 E -> ENNNLSASPRAWSRRFCLRGR. In isoform 2.

Literature citations

Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
Razzaque M.A.; Nishizawa T.; Komoike Y.; Yagi H.; Furutani M.; Amo R.; Kamisago M.; Momma K.; Katayama H.; Nakagawa M.; Fujiwara Y.; Matsushima M.; Mizuno K.; Tokuyama M.; Hirota H.; Muneuchi J.; Higashinakagawa T.; Matsuoka R.;
Nat. Genet. 39:1013-1017(2007)
Cited for: VARIANTS NS5 LEU-257; ALA-261; SER-261; ALA-263 AND VAL-613; CHARACTERIZATION OF VARIANTS NS5 LEU-257; ALA-261; SER-261; ALA-263 AND VAL-613;

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.