UniProtKB/Swiss-Prot P06746: Variant p.Glu295Lys

DNA polymerase beta
Gene: POLB
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Variant information Variant position:

295 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 295 (E295K, p.Glu295Lys). 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:

Found in a gastric cancer sample; uncertain significance; dominant negative variant; induces cellular transformation when expressed in mouse cells; results in loss of function in base-excision repair; loss of DNA-directed DNA polymerase activity; retains 5'-dRP lyase activity; does not affect DNA binding. Any additional useful information about the variant.

Sequence information Variant position:

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

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

SDIFNKNMRAHALEKGFTIN E YTIRPLGVTGVAGEPLPVDS 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                         SDIFNKNMRAHALEKGFTINEYTIRPLGVTGVAGEPLPVDS

Mouse                         SDIFNKNMRAHALEKGFTINEYTIRPLGVTGVAGEPLPVDS

Rat                           SDIFNKNMRAHALEKGFTINEYTIRPLGVTGVAGEPLPVDS

Bovine                        SDIFNKNMRAHALEKGFTINEYTIRPLGVTGVAGEPLPVDS

Xenopus laevis                SDIFNKNMRTHALEKGFTLNEYTLRPLGVTGIAGEPLPIDS

Zebrafish                     SDIFNKNMRTHALEKGFTLNEYTIRPLGVTGVAGEPLLVDS

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 – 335	DNA polymerase beta
Mutagenesis	285 – 285	H -> D. Affects DNA-directed DNA polymerase activity; contrary to wild-type enzyme, the mutant efficiently extends mispaired termini in gapped DNA. No effect on secondary structure shown by circular dichroism.
Mutagenesis	288 – 288	E -> K. Changed DNA-directed DNA polymerase activity; in complex with the DNA template and the incoming dNTP, it assumes a close conformation faster than wild-type POLB and exhibits a slower rate of nucleotide release. Results in decreased fidelity on one-base-gapped DNA and increased mutation frequency at A-T base pairs. No effect on secondary structure shown by circular dichroism. No effect on thermal stability.

Literature citations
Functional mutation of DNA polymerase beta found in human gastric cancer--inability of the base excision repair in vitro.
Iwanaga A.; Ouchida M.; Miyazaki K.; Hori K.; Mukai T.;
Mutat. Res. 435:121-128(1999)
Cited for: VARIANTS PRO-22; CYS-39; ASN-160; ARG-239; ASP-294 AND LYS-295; CHARACTERIZATION OF VARIANT LYS-295; FUNCTION; The E295K DNA polymerase beta gastric cancer-associated variant interferes with base excision repair and induces cellular transformation.
Lang T.; Dalal S.; Chikova A.; DiMaio D.; Sweasy J.B.;
Mol. Cell. Biol. 27:5587-5596(2007)
Cited for: CHARACTERIZATION OF VARIANT LYS-295; FUNCTION;

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.