Human Gene ATR (ENST00000350721.9) from GENCODE V44
Description: Homo sapiens ATR serine/threonine kinase (ATR), transcript variant 1, mRNA. (from RefSeq NM_001184) RefSeq Summary (NM_001184): The protein encoded by this gene is a serine/threonine kinase and DNA damage sensor, activating cell cycle checkpoint signaling upon DNA stress. The encoded protein can phosphorylate and activate several proteins involved in the inhibition of DNA replication and mitosis, and can promote DNA repair, recombination, and apoptosis. This protein is also important for fragile site stability and centrosome duplication. Defects in this gene are a cause of Seckel syndrome 1. [provided by RefSeq, Aug 2017]. Gencode Transcript: ENST00000350721.9 Gencode Gene: ENSG00000175054.16 Transcript (Including UTRs) Position: hg38 chr3:142,449,235-142,578,733 Size: 129,499 Total Exon Count: 47 Strand: - Coding Region Position: hg38 chr3:142,449,429-142,578,704 Size: 129,276 Coding Exon Count: 47
ID:ATR_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase ATR; EC=2.7.11.1; AltName: Full=Ataxia telangiectasia and Rad3-related protein; AltName: Full=FRAP-related protein 1; 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Manganese. ENZYME REGULATION: Activated by DNA and inhibited by BCR-ABL oncogene. Slightly activated by ATRIP. Inhibited by caffeine, wortmannin and LY294002. SUBUNIT: Interacts with ATRIP (By similarity). Forms an heterodimer with ATRIP. Binds to DNA, and to UV-damaged DNA with higher affinity. Interacts with RAD17, MSH2 and HDAC2. Present in a complex containing ATRIP and RPA-coated single-stranded DNA. Present in a complex containing CHD4 and HDAC2. Interacts with BCR-ABL after genotoxic stress. Interacts with EEF1E1. This interaction is enhanced by UV irradiation. Interacts with CLSPN and CEP164. Interacts with TELO2 and TTI1. INTERACTION: O43156:TTI1; NbExp=2; IntAct=EBI-968983, EBI-1055680; SUBCELLULAR LOCATION: Nucleus. Nucleus, PML body (By similarity). 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. TISSUE SPECIFICITY: Ubiquitous, with highest expression in testis. Isoform 2 is found in pancreas, placenta and liver but not in heart, testis and ovary. PTM: Phosphorylated; autophosphorylates in vitro. DISEASE: Defects in ATR are a cause of Seckel syndrome type 1 (SCKL1) [MIM:210600]. SCKL1 is a rare autosomal recessive disorder characterized by growth retardation, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance. DISEASE: Defects in ATR are the cause of 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. SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily. SIMILARITY: Contains 1 FAT domain. SIMILARITY: Contains 1 FATC domain. SIMILARITY: Contains 2 HEAT repeats. SIMILARITY: Contains 1 PI3K/PI4K domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ATR";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13535
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000077 DNA damage checkpoint GO:0006260 DNA replication GO:0006281 DNA repair GO:0006974 cellular response to DNA damage stimulus GO:0007275 multicellular organism development GO:0008156 negative regulation of DNA replication GO:0016310 phosphorylation GO:0018105 peptidyl-serine phosphorylation GO:0032212 positive regulation of telomere maintenance via telomerase GO:0034644 cellular response to UV GO:0036297 interstrand cross-link repair GO:0042493 response to drug GO:0043517 positive regulation of DNA damage response, signal transduction by p53 class mediator GO:0046777 protein autophosphorylation GO:0070198 protein localization to chromosome, telomeric region GO:0071480 cellular response to gamma radiation GO:0090399 replicative senescence GO:0097694 establishment of RNA localization to telomere GO:0097695 establishment of macromolecular complex localization to telomere GO:1900034 regulation of cellular response to heat GO:1904884 positive regulation of telomerase catalytic core complex assembly
LF385524 - JP 2014500723-A/193027: Polycomb-Associated Non-Coding RNAs. MA621101 - JP 2018138019-A/193027: Polycomb-Associated Non-Coding RNAs. U76308 - Human protein kinase ATR mRNA, complete cds. Y09077 - H.sapiens mRNA for atr gene. U49844 - Human FRAP-related protein (FRP1) mRNA, complete cds. BC172404 - Synthetic construct Homo sapiens clone IMAGE:100069098, MGC:199109 ataxia telangiectasia and Rad3 related (ATR) mRNA, encodes complete protein. LF208585 - JP 2014500723-A/16088: Polycomb-Associated Non-Coding RNAs. MA444162 - JP 2018138019-A/16088: Polycomb-Associated Non-Coding RNAs. AB208847 - Homo sapiens mRNA for ataxia telangiectasia and Rad3 related protein variant protein. JD109963 - Sequence 90987 from Patent EP1572962. AK131535 - Homo sapiens cDNA FLJ16765 fis, clone BRAWH3011637. JD026114 - Sequence 7138 from Patent EP1572962. JD033999 - Sequence 15023 from Patent EP1572962. AK307402 - Homo sapiens cDNA, FLJ97350.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04110 - Cell cycle hsa04115 - p53 signaling pathway
Reactome (by CSHL, EBI, and GO)
Protein Q13535 (Reactome details) participates in the following event(s):
R-HSA-912450 ATR Kinase is recruited to unsynapsed regions R-HSA-176250 Binding of ATR-ATRIP to the RPA-ssDNA complex R-HSA-5684875 Binding of ATR:ATRIP to RPA at resected DNA DSBs R-HSA-6788385 The complex of ATR and ATRIP is recruited to ICL-DNA R-HSA-5686657 ERCC1:XPF cleaves flaps generated by SSA R-HSA-5693561 RAD51 binds BRCA2 at resected DNA DSBs R-HSA-6788392 ATR phosphorylates RPA2, FANCI, FANCD2 and FANCM at ICL-DNA R-HSA-5685011 ATR activation at DNA DSBs R-HSA-176116 Recruitment and activation of Chk1 R-HSA-176298 Activation of claspin R-HSA-912470 ATR phosphorylates Histone H2A.X at unsynapsed regions R-HSA-3371567 DBC1 is phosphorylated by ATM/ART R-HSA-5685156 ATR phosphorylates RPA2 R-HSA-5684887 Activation of CHEK1 at resected DNA DSBs R-HSA-5684882 CHEK1 is recruited to resected DNA DSBs R-HSA-5693580 Association of RAD52 with the RPA complex at resected DNA DSBs R-HSA-6799332 ATR phosphorylates TP53 R-HSA-5693564 Association of RAD51 with RAD52:DNA double-strand break ends R-HSA-5686642 RAD52 promotes single strand annealing at resected DNA DSBs R-HSA-1221632 Meiotic synapsis R-HSA-176187 Activation of ATR in response to replication stress R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-6783310 Fanconi Anemia Pathway R-HSA-5685938 HDR through Single Strand Annealing (SSA) R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes R-HSA-1500620 Meiosis R-HSA-69481 G2/M Checkpoints R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-73894 DNA Repair R-HSA-5693579 Homologous DNA Pairing and Strand Exchange R-HSA-69473 G2/M DNA damage checkpoint R-HSA-3371453 Regulation of HSF1-mediated heat shock response R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-1474165 Reproduction R-HSA-1640170 Cell Cycle R-HSA-69620 Cell Cycle Checkpoints R-HSA-5693538 Homology Directed Repair R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-3371556 Cellular response to heat stress R-HSA-212436 Generic Transcription Pathway R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-2262752 Cellular responses to stress R-HSA-73857 RNA Polymerase II Transcription R-HSA-5633007 Regulation of TP53 Activity R-HSA-8953897 Cellular responses to external stimuli R-HSA-74160 Gene expression (Transcription)
US Server
