UniProtKB/Swiss-Prot P06746: Variant p.Arg149Ile

DNA polymerase beta
Gene: POLB
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Variant information Variant position:

149 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Arginine (R) to Isoleucine (I) at position 149 (R149I, p.Arg149Ile). 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 large size and basic (R) to medium size and hydrophobic (I) 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:

Decreased DNA-directed DNA polymerase activity; does not affect secondary structure as shown by circular dichroism. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs779188078 [ dbSNP | Ensembl ]

Sequence information Variant position:

149 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:

EDKLNHHQRIGLKYFGDFEK R IPREEMLQMQDIVLNEVKKV 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                         EDKLNHHQRIGLKYFGDFEKRIPREEMLQMQDIVLNEVKKV

Mouse                         EDKLNHHQRIGLKYFEDFEKRIPREEMLQMQDIVLNEIKKV

Rat                           EDKLNHHQRIGLKYFEDFEKRIPREEMLQMQDIVLNEVKKL

Bovine                        EDKLNHHQRIGLKYFEDFEKRIPREEMLQMQDIVLSEVKKV

Xenopus laevis                EHKLNHHQKIGLKHFDDFEKRIPRKEMLQMQEIILDKVNNL

Zebrafish                     EHKLNHHQQIGLKYFEEFEKRIPRSEMQKMEALILKELDIV

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
Binding site	149 – 149
Binding site	149 – 149
Binding site	149 – 149
Binding site	149 – 149
Modified residue	152 – 152	Omega-N-methylarginine; by PRMT6
Mutagenesis	152 – 152	R -> C. Severely decreased function in base-excision repair. Severely decreased DNA-directed DNA polymerase activity. No effect on 5'-dRP lyase activity. No effect on DNA binding. No effect on structure shown by circular dichroism. No effect on interaction with APEX1, FEN1 and PCNA.
Mutagenesis	152 – 152	R -> K. Slight effect. Abolishes methylation by PRMT6 and impairs the polymerase activity; when associated with K-83.

Literature citations
Human Polbeta natural polymorphic variants G118V and R149I affects substrate binding and catalysis.
Kladova O.A.; Tyugashev T.E.; Mikushina E.S.; Soloviev N.O.; Kuznetsov N.A.; Novopashina D.S.; Kuznetsova A.A.;
Int. J. Mol. Sci. 24:0-0(2023)
Cited for: VARIANTS VAL-118 AND ILE-149; CHARACTERIZATION OF VARIANTS VAL-118 AND ILE-149;

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.