Atm

Symbol: Atm
Name: Ataxia telangiectasia mutated homolog (human)
Entrez gene ID: 11920
Ensembl gene ID: ENSMUSG00000034218
Species: Mouse (Taxid: 10090)

Functional description:
Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism. Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, RAD9 and DCLRE1C. May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Binds DNA ends. Plays a role in replication-dependent histone mRNA degradation. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. [UniProt]

Observation:

Atm-deficient mice are viable, retarded in growth, infertile (male produce no mature sperm and female no gametes), display neurological dysfunction, and exhibit severe defects in T cell maturation while going on to develop thymomas [8917548; 8689683]. The majority of mutant mice rapidly develop thymic lymphomas and die before 4 months of age [8843194].

Cells of Atm(-/-) mice exhibit slow growth also in culture and premature senescence, telomeres are extensively shortened in multiple tissues [8689683].

Mice mutant for Atm and Terc display progressive multi-organ system compromise and features of accelerated aging [12540856].



Interventions:
  • Atm knockout

  • Assays: Organismal Lifespan

    Classification:
  • Aging Associated
  • Aging-Suppressor
  • Negative Aging-Suppressor
  • Cancer-Related
  • Tumor-Suppressor


  • References:
  • 8843194: Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma.
  • 8917548: Pleiotropic defects in ataxia-telangiectasia protein-deficient mice.
  • 12540856: Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing.
  • 8689683: Atm-deficient mice: a paradigm of ataxia telangiectasia.


  • Aging Relevance Analysis/Source:
  • GenAge
  • GenDR

  • Homologs
  • ATM (9606)
  • ATM (9598)
  • ATM (9615)
  • ATM (9913)
  • Atm (10090)
  • Atm (10116)
  • ATM (9031)
  • LOC100331343 (7955)

  • Inparanoids
  • ENSRNOP00000045529 (10116)
  • YBL088C (4932)
  • SPCC23B6.03c (4896)
  • ENSMUSP00000113388 (10090)
  • ENSMUSP00000113388 (10090)
  • ENSMUSP00000113388 (10090)



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