UniProtKB/SwissProt variant VAR

Variant information

Variant position:

3003

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 Asparagine (N) to Aspartate (D) at position 3003 (N3003D, p.Asn3003Asp).

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 medium size and polar (N) to medium size and acidic (D)

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 AT; decreased protein abundance.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1137889 [ dbSNP | Ensembl ]

Sequence information

Variant position:

3003

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:

TLNADDQECKRNLSDIDQSF N KVAERVLMRLQEKLKGVEEG

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                         TLNADDQECKRNLSDIDQSFNKVAERVLMRLQEKLKGVEEG

Mouse                         TPNADDQECKQSLSDTDQSFNKVAERVLMRLQEKLKGVEEG

Pig                           TPRADDQECKRNLSDTDQSFNKVAERVLMRLQEKLKGVEEG

Caenorhabditis elegans        -----------------PSY--ISEMAIGRLREKLRGTDDG

Drosophila                    -----------------ESVNLVAQRALLLVQNKLDGREAG

Baker's yeast                 FDNVSKFISNNDRNENQESY-----RALKGVEEKLMGNG--

Fission yeast                 DASRDPKIQRNNVSGESE-----AERAILKVRQKLSST---

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	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

The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species.
Savitsky K.; Sfez S.; Tagle D.A.; Ziv Y.; Sartiel A.; Collins F.S.; Shiloh Y.; Rotman G.;
Hum. Mol. Genet. 4:2025-2032(1995)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANT AT ASP-3003;

The ATM gene and susceptibility to breast cancer: analysis of 38 breast tumors reveals no evidence for mutation.
Vorechovsky I.; Rasio D.; Luo L.; Monaco C.; Hammarstroem L.; Webster A.D.B.; Zaloudik J.; Barbanti-Brodano G.; James M.R.; Russo G.; Croce C.M.; Negrini M.;
Cancer Res. 56:2726-2732(1996)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]; VARIANT AT ASP-3003; VARIANTS CYS-49; ARG-1054; PHE-1420; ILE-2079 AND ALA-2287;

A single ataxia telangiectasia gene with a product similar to PI-3 kinase.
Savitsky K.; Bar-Shira A.; Gilad S.; Rotman G.; Ziv Y.; Vanagaite L.; Tagle D.A.; Smith S.; Uziel T.; Sfez S.; Ashkenazi M.; Pecker I.; Frydman M.; Harnik R.; Patanjali S.R.; Simmons A.; Clines G.A.; Sartiel A.; Gatti R.A.; Chessa L.; Sanal O.; Lavin M.F.; Jaspers N.G.J.; Taylor A.M.R.; Arlett C.F.; Miki T.; Weissman S.M.; Lovett M.; Collins F.S.; Shiloh Y.;
Science 268:1749-1753(1995)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1332-3056; VARIANTS 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 DEL; SER-2860 DEL AND ASP-3003;

Molecular and functional characterization of a cohort of Spanish patients with ataxia-telangiectasia.
Carranza D.; Vega A.K.; Torres-Rusillo S.; Montero E.; Martinez L.J.; Santamaria M.; Santos J.L.; Molina I.J.;
NeuroMolecular Med. 19:161-174(2017)
Cited for: VARIANTS AT VAL-323; PRO-1046; ARG-2023; SER-2068; ASP-2080; HIS-2627; LEU-2834 AND ASP-3003; CHARACTERIZATION OF VARIANTS AT VAL-323; PRO-1046; ARG-2023; SER-2068; ASP-2080; HIS-2627; LEU-2834 AND ASP-3003; PHOSPHORYLATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13315: Variant p.Asn3003Asp