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UniProtKB/Swiss-Prot Q13315: Variant p.Arg3008Cys

Serine-protein kinase ATM
Gene: ATM
Variant information

Variant position:  3008
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Arginine (R) to Cysteine (C) at position 3008 (R3008C, p.Arg3008Cys).
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 (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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 AT; also found in T-prolymphocytic leukemia and mantle cell lymphoma; lack of phosphorylation of target proteins.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.

Sequence information

Variant position:  3008
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  3056
The length of the canonical sequence.

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.




Caenorhabditis elegans        ------------PSY--ISEMAIGRLREKLRGTDDGVTA-Q

Drosophila                    ------------ESVNLVAQRALLLVQNKLDGREAGTMGDS

Baker's yeast                 KFISNNDRNENQESY-----RALKGVEEKLMGNG------L

Fission yeast                 PKIQRNNVSGESE-----AERAILKVRQKLSST-------L

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.

Chain 2 – 3056 Serine-protein kinase ATM
Modified residue 2996 – 2996 Phosphoserine
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.
Helix 3001 – 3018

Literature citations

Biallelic mutations in the ATM gene in T-prolymphocytic leukemia.
Stilgenbauer S.; Schaffner C.; Litterst A.; Liebisch P.; Gilad S.; Bar-Shira A.; James M.R.; Lichter P.; Doehner H.;
Nat. Med. 3:1155-1159(1997)

Strategies for mutational analysis of the large multiexon ATM gene using high-density oligonucleotide arrays.
Hacia J.G.; Sun B.; Hunt N.; Edgemon K.; Mosbrook D.; Robbins C.; Fodor S.P.A.; Tagle D.A.; Collins F.S.;
Genome Res. 8:1245-1258(1998)
Cited for: VARIANTS 2855-ARG-ILE-2856 AND CYS-3008; VARIANT VAL-1853;

ATM is usually rearranged in T-cell prolymphocytic leukaemia.
Yuille M.A.R.; Coignet L.J.A.; Abraham S.M.; Yaqub F.; Luo L.; Matutes E.; Brito-Babapulle V.; Vorechovsky I.; Dyer M.J.S.; Catovsky D.;
Oncogene 16:789-796(1998)
Cited for: VARIANTS TPLL GLY-2139; VAL-2890 AND CYS-3008;

Mutations at the ataxia-telangiectasia locus and clinical phenotypes of A-T patients.
Li A.; Swift M.;
Am. J. Med. Genet. 92:170-177(2000)
Cited for: VARIANTS AT GLU-224; VAL-323; PRO-1420; CYS-2218; 2546-SER--ILE-2548 DEL; GLN-2625; CYS-2832; 2855-ARG-ILE-2856 AND CYS-3008; VARIANTS VAL-1853 AND ILE-2438;

Mantle cell lymphoma is characterized by inactivation of the ATM gene.
Schaffner C.; Idler I.; Stilgenbauer S.; Doehner H.; Lichter P.;
Proc. Natl. Acad. Sci. U.S.A. 97:2773-2778(2000)
Cited for: VARIANTS MCL LYS-2418 INS; GLY-2423 AND CYS-3008;

Modeling ATM mutant proteins from missense changes confirms retained kinase activity.
Barone G.; Groom A.; Reiman A.; Srinivasan V.; Byrd P.J.; Taylor A.M.;
Hum. Mutat. 30:1222-1230(2009)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS AT LEU-292; PRO-1465; ILE-1743; THR-2274; GLY-2424; 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 DEL; ASP-2554; GLY-2668; CYS-2827; 2855-SER-VAL-2856 DELINS ARG-ILE AND CYS-3008; CHARACTERIZATION OF VARIANTS VAL-546; ARG-1054; ILE-1322; ARG-1691; CYS-1961 AND SER-2765; VARIANT ILE-1322; MUTAGENESIS OF LYS-1807; VAL-1941; TYR-2019; GLU-2039; LEU-2338; SER-2394; LEU-2452; SER-2685; PRO-2699; ASP-2708 AND GLN-2730;

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.