UniProtKB/Swiss-Prot O14757: Variant p.Val312Met

Serine/threonine-protein kinase Chk1
Gene: CHEK1
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Variant information Variant position:

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

LB/B 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 Valine (V) to Methionine (M) at position 312 (V312M, p.Val312Met). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. 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
Other resources:

Links to websites of interest for the variant.

Variant rs34097480 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

KHIQSNLDFSPVNSASSEEN V KYSSSQPEPRTGLSLWDTSP 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                         KHIQSNLDFSPVNSAS------SEENVKYSSSQPEP----------RTGLSLWDTSP

Mouse                         KHIHSNLDFSPVNNGS------SEETVKFSSSQPEP-----

Rat                           KHIHSNLDFSPINSGS------SEENVKFSSSQPEP-----

Chicken                       KHIRSDTDFSPVKSAL------GEDKASYSTSQPEP-----

Xenopus laevis                KQIRSDIDISHFSH--------SEEKTALSSTQPEP-----

Caenorhabditis elegans        LKRARN----------------NDENI--TCTQQAE-----

Drosophila                    QRLQSS---AHLSNGL------DDSISRNYCSQPMPTMRSD

Baker's yeast                 KKLFSHLKVSLSNENYLKFTQDTNSNNRYISTQPIG-----

Fission yeast                 SRLMLKLRI-------------DLDKPRLASSRASQ-----

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 – 476	Serine/threonine-protein kinase Chk1
Region	270 – 327	Disordered
Compositional bias	281 – 327	Polar residues
Modified residue	296 – 296	Phosphoserine
Modified residue	301 – 301	Phosphoserine
Modified residue	317 – 317	Phosphoserine; by ATM and ATR
Modified residue	331 – 331	Phosphoserine
Mutagenesis	317 – 317	S -> A. Abrogates interaction with RAD51; when associated with A-345. Reduces phosphorylation and impairs activation by hydroxyurea and ionizing radiation. Abrogates nuclear retention upon checkpoint activation. Impairs interaction with FBXO6.
Mutagenesis	317 – 317	S -> E. Enhances interaction with RAD51; when associated with E-345.

Literature citations
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] VAL-223 AND MET-312;

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.