UniProtKB/Swiss-Prot Q13315: Variant p.Lys3018Asn

Serine-protein kinase ATM
Gene: ATM
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Variant information Variant position:

3018 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 Asparagine (N) at position 3018 (K3018N, p.Lys3018Asn). 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 polar (N) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

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:

In B-cell chronic lymphocytic leukemia. Any additional useful information about the variant.

Sequence information Variant position:

3018 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

3056 The length of the canonical sequence.
Location on the sequence:

IDQSFNKVAERVLMRLQEKL K GVEEGTVLSVGGQVNLLIQQ 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                         IDQSFNKVAERVLMRLQEKLKGVEEGTV--LSVGGQVNLLIQQ

Mouse                         TDQSFNKVAERVLMRLQEKLKGVEEGTV--LSVGGQVNLLI

Pig                           TDQSFNKVAERVLMRLQEKLKGVEEGTV--LSVGGQVNFLI

Caenorhabditis elegans        --PSY--ISEMAIGRLREKLRGTDDGVTA-QSSNLQIRRLL

Drosophila                    --ESVNLVAQRALLLVQNKLDGREAGTMGDSNVEAQVERLI

Baker's yeast                 NQESY-----RALKGVEEKLMGNG------LSVESSVQDLI

Fission yeast                 ESE-----AERAILKVRQKLSST-------LSVEASVGELI

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	2 – 3056	Serine-protein kinase ATM
Modified residue	3016 – 3016	N6-acetyllysine
Mutagenesis	3016 – 3016	K -> Q. Mimics acetylation, preventing dephosphorylation and subsequent ATM deactivation during the late stage of DNA damage response.
Mutagenesis	3016 – 3016	K -> R. Loss of DNA damage-inducible acetylation. Retains constitutive kinase activity, but blocks DNA damage-induced kinase activation. Disrupts dimer and abolishes S-1981 autophosphorylation.
Mutagenesis	3018 – 3018	K -> R. Retains DNA damage-inducible acetylation and S-1981 autophosphorylation.

Literature citations
Somatic ATM mutations indicate a pathogenic role of ATM in B-cell chronic lymphocytic leukemia.
Schaffner C.; Stilgenbauer S.; Rappold G.A.; Doehner H.; Lichter P.;
Blood 94:748-753(1999)
Cited for: POSSIBLE INVOLVEMENT IN BCLL AND MCL; VARIANTS ASN-1853; VAL-1853; ARG-1953; LYS-2418 INS; PRO-2420; GLY-2423; HIS-3008 AND ASN-3018;

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.