UniProtKB/Swiss-Prot P51530: Variant p.Lys227Glu

DNA replication ATP-dependent helicase/nuclease DNA2
Gene: DNA2
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Variant information Variant position:

227 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

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:

From Lysine (K) to Glutamate (E) at position 227 (K227E, p.Lys227Glu). 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 (K) to medium size and acidic (E) 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 PEOA6; uncertain significance; the mutant protein has significantly reduced nuclease and helicase activity; consistent with a loss of function mutation. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs760412883 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

1060 The length of the canonical sequence.
Location on the sequence:

KQEVEDYLPSFCKWAGDFMH K NTSTDFPQMQLSLPSDNSKD 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                         KQEVEDYLPSFCK----WAGDFMHKNTSTDFPQMQLSLPSDNSKD

Mouse                         LCEVEEYLPSFSK----WAEDFMRKGPSSEFPQMQLSLPSD

Rat                           RCEVEEYLPSFSK----WADEFMHKGTKAEFPQMHLSLPSD

Bovine                        KQEVEEYLPSFSK----WAGDFMHKHTSTDFPQMQLSLPSD

Chicken                       MQEIEEYLPSFFK----WTEDFVRNPANQN--KMQLKLPSE

Xenopus laevis                MGEIQEYLPSLSK----WATDFMTHPLNQQ--QINRTKSTA

Xenopus tropicalis            MGEVQEYLPSFAK----WAIDFMTHPLNQH--QINVTRPTA

Baker's yeast                 QYVKELVMKEHAENILYFVNKFVSKSNYGCYTSI------S

Fission yeast                 REELDARLPLLKS----IVERYLI----------------S

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 – 1060	DNA replication ATP-dependent helicase/nuclease DNA2
Region	81 – 519	Nuclease activity

Literature citations
Mutations in DNA2 link progressive myopathy to mitochondrial DNA instability.
Ronchi D.; Di Fonzo A.; Lin W.; Bordoni A.; Liu C.; Fassone E.; Pagliarani S.; Rizzuti M.; Zheng L.; Filosto M.; Ferro M.T.; Ranieri M.; Magri F.; Peverelli L.; Li H.; Yuan Y.C.; Corti S.; Sciacco M.; Moggio M.; Bresolin N.; Shen B.; Comi G.P.;
Am. J. Hum. Genet. 92:293-300(2013)
Cited for: VARIANTS PEOA6 HIS-198; GLU-227 AND ILE-637; CHARACTERIZATION OF VARIANTS PEOA6 HHIS-198; GLU-227 AND ILE-637;

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.