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UniProtKB/Swiss-Prot P15056: Variant p.Val600Glu

Serine/threonine-protein kinase B-raf
Gene: BRAF
Chromosomal location: 7q34
Variant information

Variant position:  600
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Valine (V) to Glutamate (E) at position 600 (V600E, p.Val600Glu).
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 (V) to medium size and acidic (E)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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

Involvement in disease:  Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:12198537, ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:23263490, ECO:0000269|PubMed:24455489}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In CRC; also found in sarcoma, metastatic melanoma, ovarian serous carcinoma, pilocytic astrocytoma; somatic mutation; most common mutation; constitutive and elevated kinase activity; efficiently induces cell transformation; suppression of mutation in melanoma causes growth arrest and promotes apoptosis; loss of regulation by PMRT5.
Any additional useful information about the variant.

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



Sequence information

Variant position:  600
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  766
The length of the canonical sequence.

Location on the sequence:   NNIFLHEDLTVKIGDFGLAT  V KSRWSGSHQFEQLSGSILWM
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                         NNIFLHEDLTVKIGDFGLATVKSRWSGSHQFEQLSGSILWM

Mouse                         NNIFLHEDLTVKIGDFGLATVKSRWSGSHQFEQLSGSILWM

Chicken                       NNIFLHEDLTVKIGDFGLATVKSRWSGSHQFEQLSGSILWM

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.

TypePositionsDescription
Chain 2 – 766 Serine/threonine-protein kinase B-raf
Domain 457 – 717 Protein kinase
Turn 598 – 600


Literature citations

Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF.
Andreu-Perez P.; Esteve-Puig R.; de Torre-Minguela C.; Lopez-Fauqued M.; Bech-Serra J.J.; Tenbaum S.; Garcia-Trevijano E.R.; Canals F.; Merlino G.; Avila M.A.; Recio J.A.;
Sci. Signal. 4:RA58-RA58(2011)
Cited for: INTERACTION WITH PRMT5; METHYLATION AT ARG-671; CHARACTERIZATION OF VARIANT CRC GLU-600; MUTAGENESIS OF ARG-671;

Mutations of the BRAF gene in human cancer.
Davies H.; Bignell G.R.; Cox C.; Stephens P.; Edkins S.; Clegg S.; Teague J.; Woffendin H.; Garnett M.J.; Bottomley W.; Davis N.; Dicks E.; Ewing R.; Floyd Y.; Gray K.; Hall S.; Hawes R.; Hughes J.; Kosmidou V.; Menzies A.; Mould C.; Parker A.; Stevens C.; Watt S.; Hooper S.; Wilson R.; Jayatilake H.; Gusterson B.A.; Cooper C.; Shipley J.; Hargrave D.; Pritchard-Jones K.; Maitland N.; Chenevix-Trench G.; Riggins G.J.; Bigner D.D.; Palmieri G.; Cossu A.; Flanagan A.; Nicholson A.; Ho J.W.C.; Leung S.Y.; Yuen S.T.; Weber B.L.; Seigler H.F.; Darrow T.L.; Paterson H.; Marais R.; Marshall C.J.; Wooster R.; Stratton M.R.; Futreal P.A.;
Nature 417:949-954(2002)
Cited for: VARIANTS CANCER GLU-464; VAL-464; ALA-466; GLU-466; VAL-466; ALA-469; GLU-469; LYS-586; LEU-595; ARG-596; ARG-597; VAL-597; GLU-600 AND ASP-600; CHARACTERIZATION OF VARIANTS CANCER VAL-464; ALA-469; VAL-597 AND GLU-600;

Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status.
Rajagopalan H.; Bardelli A.; Lengauer C.; Kinzler K.W.; Vogelstein B.; Velculescu V.E.;
Nature 418:934-934(2002)
Cited for: VARIANTS CRC ILE-462; SER-463; GLU-464; GLU-600 AND GLU-601;

Suppression of BRAF(V599E) in human melanoma abrogates transformation.
Hingorani S.R.; Jacobetz M.A.; Robertson G.P.; Herlyn M.; Tuveson D.A.;
Cancer Res. 63:5198-5202(2003)
Cited for: CHARACTERIZATION OF VARIANT MELANOMA GLU-600;

The consensus coding sequences of human breast and colorectal cancers.
Sjoeblom T.; Jones S.; Wood L.D.; Parsons D.W.; Lin J.; Barber T.D.; Mandelker D.; Leary R.J.; Ptak J.; Silliman N.; Szabo S.; Buckhaults P.; Farrell C.; Meeh P.; Markowitz S.D.; Willis J.; Dawson D.; Willson J.K.V.; Gazdar A.F.; Hartigan J.; Wu L.; Liu C.; Parmigiani G.; Park B.H.; Bachman K.E.; Papadopoulos N.; Vogelstein B.; Kinzler K.W.; Velculescu V.E.;
Science 314:268-274(2006)
Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-600;

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] SER-301; ALA-469; VAL-469; SER-581; ARG-596; ARG-597; VAL-597 AND GLU-600;

Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas.
Palles C.; Cazier J.B.; Howarth K.M.; Domingo E.; Jones A.M.; Broderick P.; Kemp Z.; Spain S.L.; Guarino Almeida E.; Salguero I.; Sherborne A.; Chubb D.; Carvajal-Carmona L.G.; Ma Y.; Kaur K.; Dobbins S.; Barclay E.; Gorman M.; Martin L.; Kovac M.B.; Humphray S.; Lucassen A.; Holmes C.C.; Bentley D.; Donnelly P.; Taylor J.; Petridis C.; Roylance R.; Sawyer E.J.; Kerr D.J.; Clark S.; Grimes J.; Kearsey S.E.; Thomas H.J.; McVean G.; Houlston R.S.; Tomlinson I.;
Nat. Genet. 45:136-144(2013)
Cited for: VARIANT CRC GLU-600;

Evidence that GRIN2A mutations in melanoma correlate with decreased survival.
D'mello S.A.; Flanagan J.U.; Green T.N.; Leung E.Y.; Askarian-Amiri M.E.; Joseph W.R.; McCrystal M.R.; Isaacs R.J.; Shaw J.H.; Furneaux C.E.; During M.J.; Finlay G.J.; Baguley B.C.; Kalev-Zylinska M.L.;
Front. Oncol. 3:333-333(2014)
Cited for: VARIANT CRC GLU-600;

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.