UniProtKB/Swiss-Prot P06746: Variant p.Leu22Pro

DNA polymerase beta
Gene: POLB
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Variant information Variant position:

22 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 Leucine (L) to Proline (P) at position 22 (L22P, p.Leu22Pro). 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:

-3 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; loss of function in base-excision repair; decreased DNA-directed DNA polymerase activity; loss of 5'-dRP lyase activity; lower affinity for gapped DNA. Any additional useful information about the variant.

Sequence information Variant position:

22 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:

SKRKAPQETLNGGITDMLTE L ANFEKNVSQAIHKYNAYRKA 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                         SKRKAPQETLNGGITDMLTELANFEKNVSQAIHKYNAYRKA

Mouse                         SKRKAPQETLNGGITDMLVELANFEKNVSQAIHKYNAYRKA

Rat                           SKRKAPQETLNGGITDMLVELANFEKNVSQAIHKYNAYRKA

Bovine                        SKRKAPQETLNGGITDMLTELANFEKNVNQAIHKYNAYRKA

Xenopus laevis                SKRKAPQESPNEGITDFLVELANYERNVNRAIHKYNAYRKA

Zebrafish                     SKRKAPQESLNEGITDFLVELANYERNVNRAIHKYNAYRKA

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
Cross	41 – 41	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis	25 – 25	F -> W. No effect on 5'-dRP lyase activity. Decreased ssDNA binding.
Mutagenesis	34 – 34	H -> G. Decreased 5'-dRP lyase activity. Decreased ssDNA binding.
Mutagenesis	35 – 35	K -> A. Decreased 5'-dRP lyase activity. Decreased ssDNA binding. Loss of 5'-dRP lyase activity; when associated with A-68 and A-72. Decreased ssDNA binding; when associated with A-68 and A-72. No effect on structure shown by circular dichroism.
Mutagenesis	35 – 35	K -> Q. Reduces 5'-dRP lyase activity slightly.
Mutagenesis	35 – 35	K -> R. No effect on 5'-dRP lyase activity.
Mutagenesis	39 – 39	Y -> F. No effect on 5'-dRP lyase activity.
Mutagenesis	39 – 39	Y -> Q. Abolishes DNA polymerase and 5'-dRP lyase activity.
Mutagenesis	41 – 41	K -> R. Abolishes ubiquitination; when associated with R-61 and R-81.
Helix	13 – 28

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 Leu22Pro tumor-associated variant of DNA polymerase beta is dRP lyase deficient.
Dalal S.; Chikova A.; Jaeger J.; Sweasy J.B.;
Nucleic Acids Res. 36:411-422(2008)
Cited for: CHARACTERIZATION OF VARIANT PRO-22;

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.