Homo sapiens Protein: ATR
InnateDB Protein IDBP-59525.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol ATR
Protein Name ataxia telangiectasia and Rad3 related
Synonyms FCTCS; FRP1; MEC1; SCKL; SCKL1;
Species Homo sapiens
Ensembl Protein ENSP00000343741
InnateDB Gene IDBG-59521 (ATR)
Protein Structure
UniProt Annotation
Function 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. {ECO:0000269PubMed:10597277, ECO:0000269PubMed:10608806, ECO:0000269PubMed:10859164, ECO:0000269PubMed:11114888, ECO:0000269PubMed:11418864, ECO:0000269PubMed:11673449, ECO:0000269PubMed:11721054, ECO:0000269PubMed:11865061, ECO:0000269PubMed:12526805, ECO:0000269PubMed:12791985, ECO:0000269PubMed:12814551, ECO:0000269PubMed:14657349, ECO:0000269PubMed:14729973, ECO:0000269PubMed:14742437, ECO:0000269PubMed:15210935, ECO:0000269PubMed:15314022, ECO:0000269PubMed:15496423, ECO:0000269PubMed:16260606, ECO:0000269PubMed:21144835, ECO:0000269PubMed:9427750, ECO:0000269PubMed:9636169, ECO:0000269PubMed:9925639}.
Subcellular Localization Nucleus {ECO:0000269PubMed:11114888, ECO:0000269PubMed:11721054, ECO:0000269PubMed:11865061, ECO:0000269PubMed:12814551, ECO:0000269PubMed:14871897, ECO:0000269PubMed:16260606, ECO:0000269PubMed:18283122, ECO:0000269PubMed:8843195}. Nucleus, PML body {ECO:0000250}. Chromosome {ECO:0000250}. Note=Depending on the cell type, it can also be found in PML nuclear bodies. Recruited to chromatin during S-phase. Redistributes to discrete nuclear foci upon DNA damage, hypoxia or replication fork stalling.
Disease Associations Seckel syndrome 1 (SCKL1) [MIM:210600]: A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation. {ECO:0000269PubMed:12640452}. Note=The disease is caused by mutations affecting the gene represented in this entry.Cutaneous telangiectasia and cancer syndrome, familial (FCTCS) [MIM:614564]: A disease characterized by cutaneous telangiectases in infancy with patchy alopecia over areas of affected skin, thinning of the lateral eyebrows, and mild dental and nail anomalies. Affected individuals are at increased risk of developing oropharyngeal cancer, and other malignancies have been reported as well. {ECO:0000269PubMed:22341969}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Tissue Specificity Ubiquitous, with highest expression in testis. Isoform 2 is found in pancreas, placenta and liver but not in heart, testis and ovary. {ECO:0000269PubMed:11470508, ECO:0000269PubMed:8610130, ECO:0000269PubMed:8843195}.
Number of Interactions This gene and/or its encoded proteins are associated with 125 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.
Experimentally validated
Total 125 [view]
Protein-Protein 121 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 4 [view]
Predicted by orthology
Total 5 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003677 DNA binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0005488 binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0016773 phosphotransferase activity, alcohol group as acceptor
GO:0032405 MutLalpha complex binding
GO:0032407 MutSalpha complex binding
Biological Process
GO:0000077 DNA damage checkpoint
GO:0006260 DNA replication
GO:0006281 DNA repair
GO:0006468 protein phosphorylation
GO:0006974 cellular response to DNA damage stimulus
GO:0007049 cell cycle
GO:0007275 multicellular organismal development
GO:0008156 negative regulation of DNA replication
GO:0018105 peptidyl-serine phosphorylation
GO:0034644 cellular response to UV
GO:0042493 response to drug
GO:0043393 regulation of protein binding
GO:0043517 positive regulation of DNA damage response, signal transduction by p53 class mediator
GO:0046777 protein autophosphorylation
GO:0071480 cellular response to gamma radiation
GO:0090399 replicative senescence
Cellular Component
GO:0001741 XY body
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0016605 PML body
Protein Structure and Domains
InterPro IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
IPR003151 PIK-related kinase, FAT
IPR003152 PIK-related kinase, FATC
IPR011009 Protein kinase-like domain
IPR012993 UME
IPR014009 PIK-related kinase
IPR016024 Armadillo-type fold
IPR021133 HEAT, type 2
PFAM PF00454
Post-translational Modifications
SwissProt Q13535
PhosphoSite PhosphoSite-Q13535
UniProt Splice Variant
Entrez Gene 545
UniGene Hs.271791
RefSeq NP_001175
OMIM 601215
HPRD 08369
EMBL AB208847 AF325699 U49844 U76308 Y09077
GenPept AAC50405 AAC50929 AAK26749 BAD92084 CAA70298