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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P18858: Variant p.Arg641Leu

DNA ligase 1
Gene: LIG1
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Variant information Variant position: help 641 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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 Arginine (R) to Leucine (L) at position 641 (R641L, p.Arg641Leu). 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 large size and basic (R) to medium size and hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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 IMD96; results in decreased repair response to DNA damage as shown by rescue assays in LIG1-deficient cells; severely reduced DNA ligase activity; 2-fold decrease of affinity for DNA; 5-fold increase of affiniy for Mg2+. Any additional useful information about the variant.


Sequence information Variant position: help 641 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 919 The length of the canonical sequence.
Location on the sequence: help EAVAWDREKKQIQPFQVLTT R KRKEVDASEIQVQVCLYAFD 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                         EAVAWDREKKQIQPFQVLTTRKRKEVDASEIQVQVCLYAFD

Mouse                         EAVAWDREKKQIQPFQVLTTRKRKEVDASEIQVQVCLYAFD

Rat                           EAVAWDREKKQIQPFQVLTTRKRKEVDASEIQVQVCLYAFD

Xenopus laevis                EAVAGDAEKKQIQPFQVLTTRKRKDVDASEIKVQVCVYAFD

Caenorhabditis elegans        EVVAID-EAGLILPFQVLSTRKRKNA-TDDNGVKVVVFLFD

Drosophila                    EIVAWDVERKQILPFQVLSTRKRKNVDIEEIKVQVCVYIFD

Slime mold                    EAVAFDAATKKILSFQVLSTRARKSVQLSQIKVPVCVFAFD

Baker's yeast                 EAVAWDKDQGKILPFQVLSTRKRKDVELNDVKVKVCLFAFD

Fission yeast                 EAVGWDRDENKILPFQKLATRKRKDVKIGDIKVRACLFAFD
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 1 – 919 DNA ligase 1
Binding site 621 – 621
Binding site 621 – 621
Mutagenesis 641 – 641 R -> A. Severely reduced DNA ligase activity.
Mutagenesis 642 – 642 K -> A. No effect on DNA ligase activity.
Mutagenesis 643 – 643 R -> A. No effect on DNA ligase activity.
Mutagenesis 644 – 644 K -> A. No effect on DNA ligase activity.



Literature citations
Biallelic mutations in DNA ligase 1 underlie a spectrum of immune deficiencies.
Maffucci P.; Chavez J.; Jurkiw T.J.; O'Brien P.J.; Abbott J.K.; Reynolds P.R.; Worth A.; Notarangelo L.D.; Felgentreff K.; Cortes P.; Boisson B.; Radigan L.; Cobat A.; Dinakar C.; Ehlayel M.; Ben-Omran T.; Gelfand E.W.; Casanova J.L.; Cunningham-Rundles C.;
J. Clin. Invest. 128:5489-5504(2018)
Cited for: VARIANT LEU-529; CHARACTERIZATION OF VARIANTS HIS-409; LEU-529 AND MET-753; VARIANTS IMD96 LYS-566; LEU-641 AND TRP-771; CHARACTERIZATION OF VARIANTS IMD96 LYS-566; LEU-641 AND TRP-771; INVOLVEMENT IN IMD96; FUNCTION; MUTAGENESIS OF LYS-568; ASP-600; ARG-641; LYS-642; ARG-643 AND LYS-644;
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.