Browse ATR

Summary
SymbolATR
NameATR serine/threonine kinase
Aliases SCKL; SCKL1; MEC1; MEC1, mitosis entry checkpoint 1, homolog (S. cerevisiae); ataxia telangiectasia and Rad3 ......
Chromosomal Location3q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Nucleus Nucleus, PML body Chromosome 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.
Domain PF02259 FAT domain
PF02260 FATC domain
PF00454 Phosphatidylinositol 3- and 4-kinase
PF08064 UME (NUC010) domain
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.

> Gene Ontology
 
Biological Process GO:0000075 cell cycle checkpoint
GO:0000077 DNA damage checkpoint
GO:0000723 telomere maintenance
GO:0006260 DNA replication
GO:0006275 regulation of DNA replication
GO:0006278 RNA-dependent DNA biosynthetic process
GO:0006403 RNA localization
GO:0007004 telomere maintenance via telomerase
GO:0007568 aging
GO:0007569 cell aging
GO:0008156 negative regulation of DNA replication
GO:0009266 response to temperature stimulus
GO:0009314 response to radiation
GO:0009408 response to heat
GO:0009411 response to UV
GO:0009416 response to light stimulus
GO:0010212 response to ionizing radiation
GO:0010332 response to gamma radiation
GO:0010833 telomere maintenance via telomere lengthening
GO:0018105 peptidyl-serine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0022613 ribonucleoprotein complex biogenesis
GO:0022618 ribonucleoprotein complex assembly
GO:0030330 DNA damage response, signal transduction by p53 class mediator
GO:0031570 DNA integrity checkpoint
GO:0032200 telomere organization
GO:0032204 regulation of telomere maintenance
GO:0032206 positive regulation of telomere maintenance
GO:0032210 regulation of telomere maintenance via telomerase
GO:0032212 positive regulation of telomere maintenance via telomerase
GO:0032844 regulation of homeostatic process
GO:0032846 positive regulation of homeostatic process
GO:0033044 regulation of chromosome organization
GO:0034502 protein localization to chromosome
GO:0034605 cellular response to heat
GO:0034644 cellular response to UV
GO:0036297 interstrand cross-link repair
GO:0042493 response to drug
GO:0042770 signal transduction in response to DNA damage
GO:0043516 regulation of DNA damage response, signal transduction by p53 class mediator
GO:0043517 positive regulation of DNA damage response, signal transduction by p53 class mediator
GO:0044089 positive regulation of cellular component biogenesis
GO:0046777 protein autophosphorylation
GO:0051052 regulation of DNA metabolic process
GO:0051053 negative regulation of DNA metabolic process
GO:0051054 positive regulation of DNA metabolic process
GO:0051236 establishment of RNA localization
GO:0060249 anatomical structure homeostasis
GO:0070198 protein localization to chromosome, telomeric region
GO:0071214 cellular response to abiotic stimulus
GO:0071478 cellular response to radiation
GO:0071479 cellular response to ionizing radiation
GO:0071480 cellular response to gamma radiation
GO:0071482 cellular response to light stimulus
GO:0071826 ribonucleoprotein complex subunit organization
GO:0071897 DNA biosynthetic process
GO:0072331 signal transduction by p53 class mediator
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:1901796 regulation of signal transduction by p53 class mediator
GO:1901798 positive regulation of signal transduction by p53 class mediator
GO:1904356 regulation of telomere maintenance via telomere lengthening
GO:1904358 positive regulation of telomere maintenance via telomere lengthening
GO:1904868 telomerase catalytic core complex assembly
GO:1904882 regulation of telomerase catalytic core complex assembly
GO:1904884 positive regulation of telomerase catalytic core complex assembly
GO:1905323 telomerase holoenzyme complex assembly
GO:2000278 regulation of DNA biosynthetic process
GO:2000573 positive regulation of DNA biosynthetic process
GO:2001020 regulation of response to DNA damage stimulus
GO:2001022 positive regulation of response to DNA damage stimulus
GO:2001252 positive regulation of chromosome organization
Molecular Function GO:0004674 protein serine/threonine kinase activity
GO:0032404 mismatch repair complex binding
GO:0032405 MutLalpha complex binding
GO:0032407 MutSalpha complex binding
Cellular Component GO:0000781 chromosome, telomeric region
GO:0000784 nuclear chromosome, telomeric region
GO:0016604 nuclear body
GO:0016605 PML body
GO:0044454 nuclear chromosome part
GO:0098687 chromosomal region
> KEGG and Reactome Pathway
 
KEGG hsa03460 Fanconi anemia pathway
hsa04110 Cell cycle
hsa04115 p53 signaling pathway
Reactome R-HSA-176187: Activation of ATR in response to replication stress
R-HSA-1640170: Cell Cycle
R-HSA-69620: Cell Cycle Checkpoints
R-HSA-3371556: Cellular response to heat stress
R-HSA-2262752: Cellular responses to stress
R-HSA-5693532: DNA Double-Strand Break Repair
R-HSA-73894: DNA Repair
R-HSA-6783310: Fanconi Anemia Pathway
R-HSA-69481: G2/M Checkpoints
R-HSA-69473: G2/M DNA damage checkpoint
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-5693567: HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
R-HSA-5685942: HDR through Homologous Recombination (HRR)
R-HSA-5685938: HDR through Single Strand Annealing (SSA)
R-HSA-5693579: Homologous DNA Pairing and Strand Exchange
R-HSA-5693538: Homology Directed Repair
R-HSA-1500620: Meiosis
R-HSA-1221632: Meiotic synapsis
R-HSA-5693616: Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-5693607: Processing of DNA double-strand break ends
R-HSA-3371453: Regulation of HSF1-mediated heat shock response
R-HSA-5633007: Regulation of TP53 Activity
R-HSA-6804756: Regulation of TP53 Activity through Phosphorylation
R-HSA-6796648: TP53 Regulates Transcription of DNA Repair Genes
R-HSA-3700989: Transcriptional Regulation by TP53
Summary
SymbolATR
NameATR serine/threonine kinase
Aliases SCKL; SCKL1; MEC1; MEC1, mitosis entry checkpoint 1, homolog (S. cerevisiae); ataxia telangiectasia and Rad3 ......
Chromosomal Location3q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between ATR and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.
Summary
SymbolATR
NameATR serine/threonine kinase
Aliases SCKL; SCKL1; MEC1; MEC1, mitosis entry checkpoint 1, homolog (S. cerevisiae); ataxia telangiectasia and Rad3 ......
Chromosomal Location3q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of ATR in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell logFC: -2.32; FDR: 0.02150 Resistant to T cell-mediated killing
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolATR
NameATR serine/threonine kinase
Aliases SCKL; SCKL1; MEC1; MEC1, mitosis entry checkpoint 1, homolog (S. cerevisiae); ataxia telangiectasia and Rad3 ......
Chromosomal Location3q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of ATR in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0980.734
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.2610.79
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0220.977
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.2020.529
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.0830.97
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.3520.901
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1740.644
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.2120.891
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.1670.921
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.1510.905
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 28-0.0580.975
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0630.172
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of ATR in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 41407.1-7.11
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277318.58.210.30.161
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 01407.1-7.11
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275918.58.5100.275
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.85.9-1.11
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91622.212.59.70.602
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 592011.18.91
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 472514.310.71
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 111307.7-7.71
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 51208.3-8.31
Summary
SymbolATR
NameATR serine/threonine kinase
Aliases SCKL; SCKL1; MEC1; MEC1, mitosis entry checkpoint 1, homolog (S. cerevisiae); ataxia telangiectasia and Rad3 ......
Chromosomal Location3q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ATR. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolATR
NameATR serine/threonine kinase
Aliases SCKL; SCKL1; MEC1; MEC1, mitosis entry checkpoint 1, homolog (S. cerevisiae); ataxia telangiectasia and Rad3 ......
Chromosomal Location3q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ATR. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ATR.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolATR
NameATR serine/threonine kinase
Aliases SCKL; SCKL1; MEC1; MEC1, mitosis entry checkpoint 1, homolog (S. cerevisiae); ataxia telangiectasia and Rad3 ......
Chromosomal Location3q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ATR. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolATR
NameATR serine/threonine kinase
Aliases SCKL; SCKL1; MEC1; MEC1, mitosis entry checkpoint 1, homolog (S. cerevisiae); ataxia telangiectasia and Rad3 ......
Chromosomal Location3q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of ATR expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolATR
NameATR serine/threonine kinase
Aliases SCKL; SCKL1; MEC1; MEC1, mitosis entry checkpoint 1, homolog (S. cerevisiae); ataxia telangiectasia and Rad3 ......
Chromosomal Location3q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between ATR and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolATR
NameATR serine/threonine kinase
Aliases SCKL; SCKL1; MEC1; MEC1, mitosis entry checkpoint 1, homolog (S. cerevisiae); ataxia telangiectasia and Rad3 ......
Chromosomal Location3q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting ATR collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.