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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P11387: Variant p.Thr729Ala

DNA topoisomerase 1
Gene: TOP1
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Variant information Variant position: help 729 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Threonine (T) to Alanine (A) at position 729 (T729A, p.Thr729Ala). 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: help Change from medium size and polar (T) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 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: help In CPT-resistant lung cancer. Any additional useful information about the variant.


Sequence information Variant position: help 729 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 765 The length of the canonical sequence.
Location on the sequence: help EENKQIALGTSKLNYLDPRI T VAWCKKWGVPIEKIYNKTQR 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         EENKQIALGTSKLNYLDPRITVAWCKKWGVPIEKIYNKTQR

Mouse                         EENKQIALGTSKLNYLDPRITVAWCKKWGVPIEKIYNKTQR

Rat                           EENKQIALGTSKLNYLDPRITVAWCKKWGVPIEKIYNKTQR

Xenopus laevis                EENKQIALGTSKLNYLDPRISVAWCKKYGVPIEKIYNKTQR

Caenorhabditis elegans        DENKQIALGTSKLNYIDPRITVAWCKKFEVPLEKVFTKTHR

Drosophila                    DENKTIALGTSKLNYLDPRISVAWCKKHDVPIEKIFNKTQR

Slime mold                    DELKTVALGTSKINYLDPRITVAWCKKNKVPVDKIFTKSLR

Baker's yeast                 EENSQVSLGTSKINYIDPRLSVVFCKKYDVPIEKIFTKTLR

Fission yeast                 DENKTTALGTSKINYIDPRLTYSFSKREDVPIEKLFSKTIR

Sequence annotation in neighborhood: help 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 2 – 765 DNA topoisomerase 1
Domain 432 – 765 Topo IB-type catalytic
Active site 723 – 723 O-(3'-phospho-DNA)-tyrosine intermediate
Cross 712 – 712 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Mutagenesis 723 – 723 Y -> F. No change in CPT-induced clearing from nuclei.
Helix 726 – 735



Literature citations
Detection of topoisomerase I gene point mutation in CPT-11 resistant lung cancer cell line.
Kubota N.; Kanzawa F.; Nishio K.; Takeda Y.; Ohmori T.; Fujiwara Y.; Terashima Y.; Saijo N.;
Biochem. Biophys. Res. Commun. 188:571-577(1992)
Cited for: VARIANT CPT-RESISTANT LUNG CANCER ALA-729;
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.