ATM - Serine-protein kinase ATM - human protein (Function)
 
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ATM »  Serine-protein kinase ATM
 
Gene name:  ATM
Family name: PI3/PI4-kinase » ATM
Entry whose protein(s) existence is based on evidence at protein level
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1 298 1
GENE REF ISO

Function

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Overview 
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. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. Phosphorylates ATF2 which stimulates its function in DNA damage response.  
8
  • CuratedUniProtKB
GO molecular function 
1-phosphatidylinositol-3-kinase activitydefinition[GO:0016303]  
1
  • IMPUniProtKB
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
DNA bindingdefinition[GO:0003677]  
  • IEAUniProtKB KW
DNA-dependent protein kinase activitydefinition[GO:0004677]  
1
  • IDABHF-UCL
Histone serine kinase activitydefinition[GO:0035174] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
12
  • IPIIntAct
  • IPIUniProtKB
Protein complex bindingdefinition[GO:0032403]  
1
  • IDABHF-UCL
Protein dimerization activitydefinition[GO:0046983]  
1
  • IDABHF-UCL
Protein N-terminus bindingdefinition[GO:0047485]  
1
  • IDAUniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
3
  • IDAUniProtKB
  • IDABHF-UCL
GO biological process 
Brain developmentdefinition[GO:0007420] silver  
  • IEAOrtholog Compara
Cell cycle arrestdefinition[GO:0007050]  
1
  • IMPBHF-UCL
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
2
  • IMPUniProtKB
  • IMPBHF-UCL
Cellular response to gamma radiationdefinition[GO:0071480]  
1
  • IDABHF-UCL
DNA damage induced protein phosphorylationdefinition[GO:0006975]  
1
  • IDABHF-UCL
Heart developmentdefinition[GO:0007507] silver  
  • IEAOrtholog Compara
Histone mRNA catabolic processdefinition[GO:0071044]  
1
  • IDAUniProtKB
Histone-serine phosphorylationdefinition[GO:0035404] silver  
  • IEAOrtholog Compara
Intrinsic apoptotic signaling pathway in response to DNA damagedefinition[GO:0008630] silver  
  • IEAOrtholog Compara
Lipoprotein catabolic processdefinition[GO:0042159] silver  
  • IEAOrtholog Compara
Mitotic spindle assembly checkpointdefinition[GO:0007094]  
1
  • IMPUniProtKB
Negative regulation of B cell proliferationdefinition[GO:0030889]  
1
  • IMPUniProtKB
Neuron apoptotic processdefinition[GO:0051402] silver  
  • IEAOrtholog Compara
Oocyte developmentdefinition[GO:0048599] silver  
  • IEAOrtholog Compara
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • IDABHF-UCL
Phosphatidylinositol-3-phosphate biosynthetic processdefinition[GO:0036092]  
1
  • IMPGOC
Positive regulation of apoptotic processdefinition[GO:0043065]  
1
  • IMPUniProtKB
Positive regulation of DNA damage response, signal transduction by p53 class mediatordefinition[GO:0043517]  
1
  • IMPBHF-UCL
Positive regulation of neuron apoptotic processdefinition[GO:0043525] silver  
  • IEAOrtholog Compara
Pre-B cell allelic exclusiondefinition[GO:0002331]  
  • ISSOrtholog Curator
Protein autophosphorylationdefinition[GO:0046777]  
2
  • IDABHF-UCL
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Reciprocal meiotic recombinationdefinition[GO:0007131]  
1
  • TASPINC
Replicative senescencedefinition[GO:0090399]  
1
  • IMPBHF-UCL
Response to hypoxiadefinition[GO:0001666] silver  
  • IEAOrtholog Compara
Response to ionizing radiationdefinition[GO:0010212]  
2
  • IDAUniProtKB
  • IDABHF-UCL
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
Signal transduction involved in mitotic G2 DNA damage checkpointdefinition[GO:0072434]  
1
  • IMPBHF-UCL
Somitogenesisdefinition[GO:0001756] silver  
  • IEAOrtholog Compara
Telomere maintenancedefinition[GO:0000723] silver  
  • IEAInterPro 2 GO
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
2
  • CuratedUniProtKB
It is regulated in the following manner
Inhibited by wortmannin.  
1
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Apoptosis  hsa04210+472  
Cell cycle  hsa04110+472  
HTLV-I infection  hsa05166+472  
p53 signaling pathway  hsa04115+472  
According to Reactome, this protein belongs to the following pathways:
ATM mediated phosphorylation of repair proteins  REACT_1924  
ATM mediated response to DNA double-strand break  REACT_204  
Autodegradation of the E3 ubiquitin ligase COP1  REACT_20549  
DNA Damage/Telomere Stress Induced Senescence  REACT_169185  
G2/M DNA damage checkpoint  REACT_897  
Meiotic recombination  REACT_27271  
Recruitment of repair and signaling proteins to double-strand breaks  REACT_97  
Regulation of HSF1-mediated heat shock response  REACT_200780  
Regulation of the Fanconi anemia pathway  REACT_18265  
Stabilization of p53  REACT_309  
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A  REACT_1614  
 

Keywords

Biological process 
Cell cycle  definition   [KW-0131]
DNA damage  definition   [KW-0227]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links