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UniProtKB/Swiss-Prot Q9UGP5: Variant p.Arg438Trp

DNA polymerase lambda
Gene: POLL
Variant information

Variant position:  438
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Arginine (R) to Tryptophan (W) at position 438 (R438W, p.Arg438Trp).
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 large size and aromatic (W)
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:  Changed DNA polymerase activity characterized by decreased fidelity and unchanged polymerization capacity; changed function in DNA double-strand break repair by non-homologous end joining and homologous recombination; no effect on 5'-deoxyribose-5-phosphate lyase activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  438
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  575
The length of the canonical sequence.

Location on the sequence:   YRRGKATCGDVDVLITHPDG  R SHRGIFSRLLDSLRQEGFLT
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                         YRRGKATCGDVDVLITHPDGRSHRGIFSRLLDSLRQEGFLT

Mouse                         YRRGKMTCGDVDVLITHPDGRSHRGIFSCLLDSLRQQGFLT

Rat                           FRRGKVTCGDVDVLITHPDGRSHQGIFSPLLDSLRQQGFLT

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.

TypePositionsDescription
Chain 1 – 575 DNA polymerase lambda
Metal binding 427 – 427 Manganese
Metal binding 429 – 429 Manganese
Mutagenesis 427 – 427 D -> A. Loss of polymerase activity; when associated with A-429.
Mutagenesis 429 – 429 D -> A. Loss of polymerase activity; when associated with A-427.
Beta strand 435 – 438


Literature citations

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT TRP-438;

Characterization of a natural mutator variant of human DNA polymerase lambda which promotes chromosomal instability by compromising NHEJ.
Terrados G.; Capp J.P.; Canitrot Y.; Garcia-Diaz M.; Bebenek K.; Kirchhoff T.; Villanueva A.; Boudsocq F.; Bergoglio V.; Cazaux C.; Kunkel T.A.; Hoffmann J.S.; Blanco L.;
PLoS ONE 4:E7290-E7290(2009)
Cited for: FUNCTION; CATALYTIC ACTIVITY; VARIANT TRP-438; CHARACTERIZATION OF VARIANT TRP-438; MUTAGENESIS OF ASP-427 AND ASP-429;

The R438W polymorphism of human DNA polymerase lambda triggers cellular sensitivity to camptothecin by compromising the homologous recombination repair pathway.
Capp J.P.; Boudsocq F.; Bergoglio V.; Trouche D.; Cazaux C.; Blanco L.; Hoffmann J.S.; Canitrot Y.;
Carcinogenesis 31:1742-1747(2010)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT TRP-438;

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.