ATR - Serine/threonine-protein kinase ATR - human protein (Function)
 
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ATR »  Serine/threonine-protein kinase ATR   [ EC 2.7.11.1 ]
 
Protein also known as:  Ataxia telangiectasia and Rad3-related protein.
Gene name:  ATR
Family name: PI3/PI4-kinase » ATM
Entry whose protein(s) existence is based on evidence at protein level
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1 288 3
GENE REF ISO

Function

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Overview 
Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at sites of DNA damage, thereby regulating DNA damage response mechanism. Required for FANCD2 ubiquitination. Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication.  
23
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
DNA bindingdefinition[GO:0003677]  
1
  • UniProtKB KW
MutLalpha complex bindingdefinition[GO:0032405]  
1
  • MGI
MutSalpha complex bindingdefinition[GO:0032407]  
1
  • MGI
Protein bindingdefinition[GO:0005515]  
5
  • IntAct
  • UniProtKB
Protein dimerization activitydefinition[GO:0046983]  
1
  • RefGenome
Protein kinase activitydefinition[GO:0004672]  
1
  • UniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • BHF-UCL
GO biological process 
Cell cycledefinition[GO:0007049]  
1
  • PINC
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
1
  • UniProtKB
Cellular response to gamma radiationdefinition[GO:0071480]  
1
  • BHF-UCL
Cellular response to UVdefinition[GO:0034644]  
1
  • BHF-UCL
DNA damage checkpointdefinition[GO:0000077]  
1
  • UniProtKB
Double-strand break repair via homologous recombinationdefinition[GO:0000724]  
1
  • RefGenome
Multicellular organismal developmentdefinition[GO:0007275]  
1
  • PINC
Negative regulation of DNA replicationdefinition[GO:0008156]  
1
  • UniProtKB
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • BHF-UCL
Positive regulation of DNA damage response, signal transduction by p53 class mediatordefinition[GO:0043517]  
1
  • BHF-UCL
Protein autophosphorylationdefinition[GO:0046777]  
1
  • BHF-UCL
Regulation of protein bindingdefinition[GO:0043393] silver  
1
  • Ortholog Compara
Replicative senescencedefinition[GO:0090399]  
1
  • BHF-UCL
Response to drugdefinition[GO:0042493] silver  
1
  • Ortholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
1
  • UniProtKB
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
1
  • UniProtKB
It requires the following cofactor
 Mn(2+)  
2
  • UniProtKB
It is regulated in the following manner
Activated by DNA and inhibited by BCR-ABL oncogene. Slightly activated by ATRIP. Inhibited by caffeine, wortmannin and LY294002.  
4
  • UniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Cell cycle  hsa04110+545  
Fanconi anemia pathway  hsa03460+545  
HTLV-I infection  hsa05166+545  
p53 signaling pathway  hsa04115+545  
According to Reactome, this protein belongs to the following pathways:
Activation of ATR in response to replication stress  REACT_6769  
G2/M DNA damage checkpoint  REACT_897  
Meiotic synapsis  REACT_75792  
Regulation of HSF1-mediated heat shock response  REACT_200780  
Regulation of the Fanconi anemia pathway  REACT_18265  
 

Keywords

Biological process 
DNA damage  definition   [KW-0227]
DNA repair  definition   [KW-0234]
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

Other
GeneWiki: Ataxia_telangiectasia_and_Rad3_related
GenomeRNAi: 545
PRO: PR:Q13535
Chemistry
GuidetoPHARMACOLOGY: 1935