UniProtKB/Swiss-Prot Q07912: Variant p.Glu346Lys

Activated CDC42 kinase 1
Gene: TNK2
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Variant information Variant position:

346 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 Glutamate (E) to Lysine (K) at position 346 (E346K, p.Glu346Lys). 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 acidic (E) to large size and basic (K) 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 endometrioid cancer sample; somatic mutation; undergoes autoactivation and causes phosphorylation on Y-284 leading to activation of AKT1; increased autophosphorylation at Y-284; increased function in phosphorylation of peptide substrates and WASP; no effect on catalytic activity itself as the purified kinase domain has activity in vitro comparable to wild-type protein; no effect on subcellular localization to perinuclear region. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs970946035 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

1038 The length of the canonical sequence.
Location on the sequence:

YGQEPWIGLNGSQILHKIDK E GERLPRPEDCPQDIYNVMVQ 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                         YGQEPWIGLNGSQILHKIDKEGERLPRPEDCPQDIYNVMVQ

Mouse                         YGQEPWIGLNGSQILHKIDKEGERLPRPEDCPQDIYNVMVQ

Rat                           YGQEPWIGLNGSQILHKIDKEGERLPRPEDCPQDIYNVMVQ

Bovine                        YGQEPWIGLNGSQILHKIDKEGERLPRPEDCPQDIYNVMVQ

Baker's yeast                 ---------SGNRISESV--------RDNSAP---------

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 – 1038	Activated CDC42 kinase 1
Domain	126 – 385	Protein kinase
Mutagenesis	365 – 365	V -> R. Increased autophosphorylation at Y-284.

Literature citations
Cancer-associated mutations activate the nonreceptor tyrosine kinase Ack1.
Prieto-Echaguee V.; Gucwa A.; Craddock B.P.; Brown D.A.; Miller W.T.;
J. Biol. Chem. 285:10605-10615(2010)
Cited for: FUNCTION; SUBCELLULAR LOCATION; VARIANTS LEU-34; GLN-99; LYS-346 AND ILE-409; CHARACTERIZATION OF VARIANTS LEU-34; GLN-99; LYS-346 AND ILE-409; MUTAGENESIS OF LEU-120; LEU-197 AND VAL-365; Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation.
Mahajan K.; Coppola D.; Challa S.; Fang B.; Chen Y.A.; Zhu W.; Lopez A.S.; Koomen J.; Engelman R.W.; Rivera C.; Muraoka-Cook R.S.; Cheng J.Q.; Schoenbrunn E.; Sebti S.M.; Earp H.S.; Mahajan N.P.;
PLoS ONE 5:E9646-E9646(2010)
Cited for: FUNCTION; CATALYTIC ACTIVITY; COFACTOR; INTERACTION WITH AKT1; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT LYS-346; PHOSPHORYLATION AT TYR-284; TISSUE SPECIFICITY; 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 LEU-34; ARG-71; GLN-99; TRP-99; MET-152; LYS-346; ILE-409; SER-507; LEU-725; GLN-748 AND HIS-1038;

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.