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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P06746: Variant p.Lys289Met

DNA polymerase beta
Gene: POLB
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Variant information Variant position: help 289 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Lysine (K) to Methionine (M) at position 289 (K289M, p.Lys289Met). 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: help Change from large size and basic (K) to medium size and hydrophobic (M) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help Found in a colon cancer sample; uncertain significance; affects DNA-directed DNA polymerase activity resulting in nucleotide misincorporation in gapped DNA and decreased fidelity during DNA synthesis in base-excision repair; decreased affinity for gapped DNA; due to altered structure of the C-terminal region, the mutant enzyme in complex with DNA and dGTP does not undergo the open to closed conformational change that is necessary to assembly a catalytically competent active site. Any additional useful information about the variant.


Sequence information Variant position: help 289 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 335 The length of the canonical sequence.
Location on the sequence: help VLYFTGSDIFNKNMRAHALE K GFTINEYTIRPLGVTGVAGE 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         VLYFTGSDIFNKNMRAHALEKGFTINEYTIRPLGVTGVAGE

Mouse                         VLYFTGSDIFNKNMRAHALEKGFTINEYTIRPLGVTGVAGE

Rat                           VLYFTGSDIFNKNMRAHALEKGFTINEYTIRPLGVTGVAGE

Bovine                        VLYFTGSDIFNKNMRAHALEKGFTINEYTIRPLGVTGVAGE

Xenopus laevis                VLYFTGSDIFNKNMRTHALEKGFTLNEYTLRPLGVTGIAGE

Zebrafish                     VLYFTGSDIFNKNMRTHALEKGFTLNEYTIRPLGVTGVAGE

Sequence annotation in neighborhood: help 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 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.
Helix 276 – 289



Literature citations
Revealing an internal stabilization deficiency in the DNA polymerase beta K289M cancer variant through the combined use of chemical biology and X-ray crystallography.
Batra V.K.; Alnajjar K.S.; Sweasy J.B.; McKenna C.E.; Goodman M.F.; Wilson S.H.;
Biochemistry 59:955-963(2020)
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF WILD-TYPE AND VARIANT MET-289 IN COMPLEX WITH DNA AND DGTP; CHARACTERIZATION OF VARIANT MET-289; A DNA polymerase beta mutant from colon cancer cells induces mutations.
Lang T.; Maitra M.; Starcevic D.; Li S.X.; Sweasy J.B.;
Proc. Natl. Acad. Sci. U.S.A. 101:6074-6079(2004)
Cited for: VARIANT MET-289; CHARACTERIZATION OF VARIANT MET-289;
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.