UniProtKB/Swiss-Prot P11388: Variant p.Arg450Gln

DNA topoisomerase 2-alpha
Gene: TOP2A
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Variant information Variant position:

450 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 Glutamine (Q) at position 450 (R450Q, p.Arg450Gln). 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 polar (Q) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

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:

In teniposide (VM-26) resistant cells. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs746765101 [ dbSNP | Ensembl ]

Sequence information Variant position:

450 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1531 The length of the canonical sequence.
Location on the sequence:

VKHNRIKGIPKLDDANDAGG R NSTECTLILTEGDSAKTLAV 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                         VKHNRIKGIPKLDDANDAGGRNSTECTLILTEGDSAKTLAV

Mouse                         VKHTKIKGIPKLDDANDAGSRNSTECTLILTEGDSAKTLAV

Rat                           VKHNRIKGIPKLDDANDAGSRNSAECTLILTEGDSAKTLAV

Pig                           VKHNRIKGIPKLDDANDAGGRNSTECTLILTEGDSAKTLAV

Chicken                       VKHTKIKGVPKLDDANDAGSKNSIDCTLILTEGDSAKTLAV

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 – 1531	DNA topoisomerase 2-alpha
Binding site	461 – 461
Cross	440 – 440	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Cross	466 – 466	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Mutagenesis	461 – 461	E -> AC. Impairs bending of target DNA. Strongly reduced DNA cleavage.

Literature citations
Expression of a mutant DNA topoisomerase II in CCRF-CEM human leukemic cells selected for resistance to teniposide.
Bugg B.Y.; Danks M.K.; Beck W.T.; Suttle D.P.;
Proc. Natl. Acad. Sci. U.S.A. 88:7654-7658(1991)
Cited for: VARIANT TENIPOSIDE-RESISTANT GLN-450;

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.