UniProtKB/Swiss-Prot P04049: Variant p.Ser259Ala

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

259 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Serine (S) to Alanine (A) at position 259 (S259A, p.Ser259Ala). 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 small size and polar (S) 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 an ovarian serous carcinoma sample; somatic mutation; increased ERK activation. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs3730271 [ dbSNP | Ensembl ]

Sequence information Variant position:

259 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

648 The length of the canonical sequence.
Location on the sequence:

TFNTSSPSSEGSLSQRQRST S TPNVHMVSTTLPVDSRMIED 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                         TFNTSSPSSEGS------LSQRQRSTSTPNVHMVSTTLPVDSRMIED

Mouse                         TFNTSSPSSEGS------LSQRQRSTSTPNVHMVSTTLHVD

Rat                           TFNTSSPSSEGS------LSQRQRSTSTPNVHMVSTTLPVD

Bovine                        TFSASSPSSEGS------LSQRQRSTSTPNVHMVSATLPVD

Chicken                       TFNTSNPSSEGT------LSQRQRSTSTPNVHMVSTTMPVD

Xenopus laevis                SFSTPSPVSECS------LSQRQRSTSTPNVHMVSTTMAVD

Fission yeast                 DFHSETIQSLESHYKLNQVGEKEYSTI-SDLCFSKGNLFLY

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	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
A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity.
Rodriguez-Viciana P.; Oses-Prieto J.; Burlingame A.; Fried M.; McCormick F.;
Mol. Cell 22:217-230(2006)
Cited for: IDENTIFICATION IN A COMPLEX WITH PP1CA; PPP1CB; PPP1CC; SHOC2 AND MRAS; PHOSPHORYLATION AT SER-259; CHARACTERIZATION OF VARIANT ALA-259; Patterns of somatic mutation in human cancer genomes.
Greenman C.; Stephens P.; Smith R.; Dalgliesh G.L.; Hunter C.; Bignell G.; Davies H.; Teague J.; Butler A.; Stevens C.; Edkins S.; O'Meara S.; Vastrik I.; Schmidt E.E.; Avis T.; Barthorpe S.; Bhamra G.; Buck G.; Choudhury B.; Clements J.; Cole J.; Dicks E.; Forbes S.; Gray K.; Halliday K.; Harrison R.; Hills K.; Hinton J.; Jenkinson A.; Jones D.; Menzies A.; Mironenko T.; Perry J.; Raine K.; Richardson D.; Shepherd R.; Small A.; Tofts C.; Varian J.; Webb T.; West S.; Widaa S.; Yates A.; Cahill D.P.; Louis D.N.; Goldstraw P.; Nicholson A.G.; Brasseur F.; Looijenga L.; Weber B.L.; Chiew Y.-E.; DeFazio A.; Greaves M.F.; Green A.R.; Campbell P.; Birney E.; Easton D.F.; Chenevix-Trench G.; Tan M.-H.; Khoo S.K.; Teh B.T.; Yuen S.T.; Leung S.Y.; Wooster R.; Futreal P.A.; Stratton M.R.;
Nature 446:153-158(2007)
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ALA-259 AND HIS-335;

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.