Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Atm. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Atm
  • participates in the following biological processes:
    • DNA repair ^[12]
    • protein phosphorylation ^[12]
  • performs the following molecular functions:
    • protein kinase activity ^[12]
  • is located in the following cellular components:
    • spindle ^[7]
• The gene product of Atm has been shown to bind to the gene products of Eef1e1. ^[10]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Atm
  • participates in the following biological processes:
    • DNA damage checkpoint ^[16]
    • DNA repair ^{[13, 14]}
    • female gamete generation ^[2]
    • intrinsic apoptotic signaling pathway in response to DNA damage ^{[6, 9]}
    • negative regulation of apoptotic process ^[8]
    • pre-B cell allelic exclusion ^[5]
• Researchers have inferred, based on genetic interactions, that the gene product of Atm
  • participates in the following biological processes:
    • brain development based on interactions with Prkdc ^[4]
    • heart development based on interactions with Prkdc ^[4]
    • intrinsic apoptotic signaling pathway in response to DNA damage based on interactions with Brca2 ^[3]
    • lipoprotein catabolic process based on interactions with Apoe ^[15]
    • neuron apoptotic process based on interactions with Lig4 ^[11]
    • positive regulation of neuron apoptotic process based on interactions with Bax, Lig4 ^{[1, 9]}
    • response to ionizing radiation based on interactions with Bax ^[1]
    • somitogenesis based on interactions with Prkdc ^[4]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Atm:
  • participates in the following biological processes:
    • cell cycle arrest
    • cellular response to gamma radiation
    • DNA damage induced protein phosphorylation
    • G2/M transition DNA damage checkpoint
    • histone mRNA catabolic process
    • histone phosphorylation
    • histone-serine phosphorylation
    • mitotic cell cycle spindle assembly checkpoint
    • negative regulation of B cell proliferation
    • peptidyl-serine phosphorylation
    • phosphatidylinositol-3-phosphate biosynthetic process
    • positive regulation of apoptotic process
    • positive regulation of DNA damage response, signal transduction by p53 class mediator
    • protein autophosphorylation
    • regulation of cell cycle
    • replicative senescence
    • response to DNA damage stimulus
    • response to hypoxia
    • response to ionizing radiation
  • performs the following molecular functions:
    • 1-phosphatidylinositol-3-kinase activity
    • DNA-dependent protein kinase activity
    • histone serine kinase activity
    • protein complex binding
    • protein dimerization activity
    • protein N-terminus binding
    • protein serine/threonine kinase activity
  • is located in the following cellular components:
    • cytoplasm
    • nucleus

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Summary text based on GO annotations supported by structural data

• Atm encodes a protein or proteins that contain the following InterPro domains: Armadillo-type fold, ATM/Tel1, Phosphatidylinositol 3-/4-kinase, catalytic domain, Phosphatidylinositol 3/4-kinase, conserved site, PIK-related kinase, PIK-related kinase, FAT, PIK-related kinase, FATC, Protein kinase-like domain, Telomere-length maintenance and DNA damage repair, indicating that the gene product:
  • participates in the following biological processes:
    • telomere maintenance
  • performs the following molecular functions:
    • phosphotransferase activity, alcohol group as acceptor
    • transferase activity, transferring phosphorus-containing groups

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Atm indicates that it:
  • participates in the following biological processes:
    • cell cycle
    • phosphorylation
  • performs the following molecular functions:
    • ATP binding
    • DNA binding
    • kinase activity
    • nucleotide binding
    • transferase activity
  • is located in the following cellular components:
    • cytoplasmic vesicle

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References

1. Chong MJ et al. (2000) Atm and Bax cooperate in ionizing radiation-induced apoptosis in the central nervous system. Proc Natl Acad Sci U S A, 97:889-94. (PubMed:10639175)
2. Di Giacomo M et al. (2005) Distinct DNA-damage-dependent and -independent responses drive the loss of oocytes in recombination-defective mouse mutants. Proc Natl Acad Sci U S A, 102:737-42. (PubMed:15640358)
3. Frappart PO et al. (2007) BRCA2 is required for neurogenesis and suppression of medulloblastoma. EMBO J, 26:2732-42. (PubMed:17476307)
4. Gladdy RA et al. (2006) p53-Independent apoptosis disrupts early organogenesis in embryos lacking both ataxia-telangiectasia mutated and Prkdc. Mol Cancer Res, 4:311-8. (PubMed:16687486)
5. Hewitt SL et al. (2009) RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci. Nat Immunol, 10:655-64. (PubMed:19448632)
6. Lee Y et al. (2000) Defective neurogenesis resulting from DNA ligase IV deficiency requires Atm Genes Dev, 14:2576-80. (PubMed:11040211)
7. Liu J et al. (2004) Serine-threonine kinases and transcription factors active in signal transduction are detected at high levels of phosphorylation during mitosis in preimplantation embryos and trophoblast stem cells. Reproduction, 128:643-654. (PubMed:15509711)
8. Morita Y et al. (2001) Caspase-2 deficiency prevents programmed germ cell death resulting from cytokine insufficiency but not meiotic defects caused by loss of ataxia telangiectasia-mutated (Atm) gene function. Cell Death Differ, 8:614-20. (PubMed:11536012)
9. Orii KE et al. (2006) Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development. Proc Natl Acad Sci U S A, 103:10017-22. (PubMed:16777961)
10. Park BJ et al. (2005) The haploinsufficient tumor suppressor p18 upregulates p53 via interactions with ATM/ATR. Cell, 120:209-21. (PubMed:15680327)
11. Sekiguchi J et al. (2001) Genetic interactions between ATM and the nonhomologous end-joining factors in genomic stability and development. Proc Natl Acad Sci U S A, 98:3243-8. (PubMed:11248063)
12. Sengupta S et al. (2004) Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. J Cell Biol, 166:801-13. (PubMed:15364958)
13. Shima N et al. (2004) The Mouse Genomic Instability Mutation chaos1 Is an Allele of Polq That Exhibits Genetic Interaction with Atm. Mol Cell Biol, 24:10381-9. (PubMed:15542845)
14. Stern N et al. (2002) Accumulation of DNA damage and reduced levels of nicotine adenine dinucleotide in the brains of Atm-deficient mice. J Biol Chem, 277:602-8. (PubMed:11679583)
15. Wu D et al. (2005) Heterozygous mutation of ataxia-telangiectasia mutated gene aggravates hypercholesterolemia in apoE-deficient mice. J Lipid Res, 46:1380-7. (PubMed:15863839)
16. Yuan L et al. (2003) DNA damage-induced G2/M checkpoint in SV40 large T antigen-immortalized embryonic fibroblast cells requires SHP-2 tyrosine phosphatase. J Biol Chem, 278:42812-20. (PubMed:12937170)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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