UniProtKB/Swiss-Prot Q9UGP5: Variant p.Arg438Trp

DNA polymerase lambda
Gene: POLL
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Variant information Variant position:

438 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 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.

Variant rs3730477 [ dbSNP | Ensembl ]

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.

Type	Positions	Description
Chain	1 – 575	DNA polymerase lambda
Binding site	427 – 427
Binding site	429 – 429
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.