UniProtKB/Swiss-Prot O14965: Variant p.Val174Met

Aurora kinase A
Gene: AURKA
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Variant information Variant position:

174 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 Valine (V) to Methionine (M) at position 174 (V174M, p.Val174Met). 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
Variant description:

In a metastatic melanoma sample; somatic mutation; constitutively enhanced kinase activity. Any additional useful information about the variant.

Sequence information Variant position:

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

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

QSKFILALKVLFKAQLEKAG V EHQLRREVEIQSHLRHPNIL 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                         QSKFILALKVLFKAQLEKAGVEHQLRREVEIQSHLRHPNIL

Mouse                         QSKFILALKVLFKTQLEKANVEHQLRREVEIQSHLRHPNIL

Rat                           QSKFILALKVLFKVQLEKAGVEHQLRREVEIQSHLRHPNIL

Pig                           QSKFILALKVLFKTQLEKAGVEHQLRREVEIQSHLRHPNIL

Bovine                        QSKFILALKVLFKAQLEKAGVEHQLRREVEIQSHLRHPNIL

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 – 403	Aurora kinase A
Domain	133 – 383	Protein kinase
Binding site	162 – 162
Mutagenesis	162 – 162	K -> R. Loss of kinase activity.
Mutagenesis	165 – 165	F -> A. Decreases the interaction with phosphatase type 1 isoforms.

Literature citations
A cancer-associated aurora A mutant is mislocalized and misregulated due to loss of interaction with TPX2.
Bibby R.A.; Tang C.; Faisal A.; Drosopoulos K.; Lubbe S.; Houlston R.; Bayliss R.; Linardopoulos S.;
J. Biol. Chem. 284:33177-33184(2009)
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 127-388 IN COMPLEX WITH ADP; CHARACTERIZATION OF VARIANTS ARG-155 AND MET-174; INTERACTION WITH TPX2; 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] ILE-31; LEU-50; VAL-57; ARG-155; MET-174 AND VAL-373;

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.