Relation Results

Summary

Name ATR
Full Name Serine/threonine-protein kinase ATR
Synonyms Ataxia telangiectasia and Rad3-related protein, FRAP-related protein 1 | FRP1
Primary ID Q13535
Links - -
Type protein
Relations 67
Pathways DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
Function Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), ...
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Type: Score: Layout: SPV 
0.3490.7060.7920.7980.20.5930.7390.4960.360.20.7430.4690.2570.3790.9250.7540.7830.5170.6540.2820.4180.8570.5330.20.8770.670.20.20.3130.4320.8590.5440.6120.5940.2510.7220.70.3940.3070.3510.5580.650.20.2790.8130.481ATRCREB1MCM2WRNBRCA1MCCFANCATP53XPAPARP1SIAH1ATMXRCC3KIFC1E2F1CHEK1RPA2NBNMDM2DBF4KMT2APOLHRAD17SMARCAL1USP28ATRIPFANCD2AKAP12ZDHHC13PRKDCCCAR2CHEK2WDHD1RBBP8ABL1MUTYHMCM4DNA_damageCDKN2AUSP20CDS1MCM6BRCA1-B complexNEK1PI4K2ATOPBP1XPC

Modifications Tables

Relations

Regulator
Mechanism
target
score
+ down-regulates img/direct_inhibition.png phosphorylation CREB1 0.349
Identifier Residue Sequence Organism Cell Line
SIGNOR-124060 Ser107 SVDSVTDsQKRREIL Homo sapiens
pmid sentence
Atm phosphorylated creb in vitro and in vivo in response to ionizing radiation (ir) and h(2)o(2) on a stress-inducible domain. Ir-induced phosphorylation of creb correlated with a decrease in creb transactivation potential and reduced interaction between creb and its transcriptional coactivator, creb-binding protein (cbp). A creb mutant containing ala substitutions at atm phosphorylation sites displayed enhanced transactivation potentialit is, therefore, likely that atm and atr regulate creb phosphorylation collectively in response to stress stimuli.
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ img/unknown.png phosphorylation MCM2 0.706
Identifier Residue Sequence Organism Cell Line
SIGNOR-126363 Ser108 DVEELTAsQREAAER Homo sapiens
pmid sentence
Atm phosphorylates mcm3 on s535 in response to ionizing radiation. Second, atr phosphorylates mcm2 on s108 in response to multiple forms of dna damage and stalling of replication forksthe functional consequences of mcm2 s108 and mcm3 s535 phosphorylation are not clear
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation WRN 0.792
Identifier Residue Sequence Organism Cell Line
SIGNOR-277187 Ser1141 PEKAYSSsQPVISAQ Homo sapiens HeLa Cell
pmid sentence
A serine residue, S1141, in WRN is phosphorylated in vivo by the ATR kinase in response to replication stress. ATR-mediated WRN S1141 phosphorylation leads to ubiquitination of WRN, facilitating the reversible interaction of WRN with perturbed replication forks and subsequent degradation of WRN.
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png phosphorylation WRN 0.792
Identifier Residue Sequence Organism Cell Line
SIGNOR-278159 Ser1141 PEKAYSSsQPVISAQ Homo sapiens
pmid sentence
Importantly, ATR-mediated phosphorylation targets Werner syndrome protein for ubiquitination and degradation.|WRN is phosphorylated at serine 1141 by ATR in response to replication-associated DSBs A. WRN is heavily phosphorylated at S1141 in response to CPT treatment of cells.
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation BRCA1 0.798
Identifier Residue Sequence Organism Cell Line
SIGNOR-250581 Ser1143 PMGSSHAsQVCSETP Homo sapiens HEK-293T Cell
pmid sentence
Of the four potential phosphoacceptor sites in the BRCA1 (1005–1313) fragment (Ser 1143, Ser 1239, Ser 1280, Ser 1298), Ala substitutions at two sites, Ser 1143 and Ser 1280, reduced the in vitro phosphorylation of GST–BRCA1 (1005–1313) by ATR, whereas substitution of Ser 1239 or Ser 1298 with Ala had little or no effect (Fig. 2C; data not shown). A Ser 1143/Ser 1280 double mutant was a poor substrate for ATR, suggesting that these are the two major in vitro phosphorylation sites on this BRCA1 fragment. | Together, these results demonstrate that ATR and BRCA1 are components of the same genotoxic stress-responsive pathway, and that ATR directly phosphorylates BRCA1 in response to damaged DNA or stalled DNA replication.
Identifier Residue Sequence Organism Cell Line
SIGNOR-250582 Ser1280 QVILAKAsQEHHLSE Homo sapiens HEK-293T Cell
pmid sentence
Of the four potential phosphoacceptor sites in the BRCA1 (1005–1313) fragment (Ser 1143, Ser 1239, Ser 1280, Ser 1298), Ala substitutions at two sites, Ser 1143 and Ser 1280, reduced the in vitro phosphorylation of GST–BRCA1 (1005–1313) by ATR, whereas substitution of Ser 1239 or Ser 1298 with Ala had little or no effect (Fig. 2C; data not shown). A Ser 1143/Ser 1280 double mutant was a poor substrate for ATR, suggesting that these are the two major in vitro phosphorylation sites on this BRCA1 fragment. | Together, these results demonstrate that ATR and BRCA1 are components of the same genotoxic stress-responsive pathway, and that ATR directly phosphorylates BRCA1 in response to damaged DNA or stalled DNA replication.
Identifier Residue Sequence Organism Cell Line
SIGNOR-106432 Ser1387 EDCSGLSsQSDILTT Homo sapiens Lymphoblastoid Cell Line
pmid sentence
Brca1 is phosphorylated at ser-1423 and ser-1524 after ir and uv;however, ser-1387 is specifically phosphorylated after ir, and ser-1457 is predominantly phosphorylated after uv.atr controls brca1 phosphorylation in vivo. Taken together, our results support a model in which atm and atr act in parallel but somewhat overlapping pathways of dna damage signaling but respond primarily to different types of dna lesion.
Identifier Residue Sequence Organism Cell Line
SIGNOR-106436 Ser1423 AVLEQHGsQPSNSYP Homo sapiens Lymphoblastoid Cell Line
pmid sentence
Brca1 is phosphorylated at ser-1423 and ser-1524 after ir and uv;however, ser-1387 is specifically phosphorylated after ir, and ser-1457 is predominantly phosphorylated after uv.atr controls brca1 phosphorylation in vivo. Taken together, our results support a model in which atm and atr act in parallel but somewhat overlapping pathways of dna damage signaling but respond primarily to different types of dna lesion.
Identifier Residue Sequence Organism Cell Line
SIGNOR-106440 Ser1457 SEKAVLTsQKSSEYP Homo sapiens Lymphoblastoid Cell Line
pmid sentence
Brca1 is phosphorylated at ser-1423 and ser-1524 after ir and uv;however, ser-1387 is specifically phosphorylated after ir, and ser-1457 is predominantly phosphorylated after uv.atr controls brca1 phosphorylation in vivo. Taken together, our results support a model in which atm and atr act in parallel but somewhat overlapping pathways of dna damage signaling but respond primarily to different types of dna lesion.
Identifier Residue Sequence Organism Cell Line
SIGNOR-250583 Thr1394 SQSDILTtQQRDTMQ Homo sapiens HEK-293T Cell
pmid sentence
Although no single mutation eliminated the GST–BRCA1 (1314–1863) electrophoretic mobility shift, a quadruple mutant (GST–BRCA14A) containing Ala substitutions at Ser 1387, Thr 1394, Ser 1423, and Ser 1457 showed no alteration in electrophoretic mobility after phosphorylation by ATR-containing immune complexes (Fig.2D). The total incorporation of 32Pi into the GST–BRCA14Asubstrate was reduced by 70% relative to that obtained with wild-type GST–BRCA1 (1314–1863), suggesting that these four residues account for most, but not all of the phosphorylation sites in this fragment. | Together, these results demonstrate that ATR and BRCA1 are components of the same genotoxic stress-responsive pathway, and that ATR directly phosphorylates BRCA1 in response to damaged DNA or stalled DNA replication.
Publications: 6 Organism: Homo Sapiens
Pathways:DNA repair in cancer, Cell cycle: G2/M phase transition
+ up-regulates activity img/direct-activation.png phosphorylation MCC 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-273514 Ser118 SELRSELsQSQHEVN Homo sapiens HCT-116 Cell
pmid sentence
MCC is phosphorylated at the ATM/ATR consensus sites Ser118 and Ser120.  Finally, mutation of S118/120 to alanine did not affect MCC nuclear shuttling following UV but did impair MCC G2/M checkpoint activity.
Identifier Residue Sequence Organism Cell Line
SIGNOR-273515 Ser120 LRSELSQsQHEVNED Homo sapiens HCT-116 Cell
pmid sentence
MCC is phosphorylated at the ATM/ATR consensus sites Ser118 and Ser120.  Finally, mutation of S118/120 to alanine did not affect MCC nuclear shuttling following UV but did impair MCC G2/M checkpoint activity.
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation FANCA 0.593
Identifier Residue Sequence Organism Cell Line
SIGNOR-182953 Ser1449 AAPDADLsQEPHLF Homo sapiens
pmid sentence
The s1449a mutant failed to completely correct a variety of fa-associated phenotypes. The dna damage response is coordinated by phosphorylation events initiated by apical kinases atm (ataxia telangectasia mutated) and atr (atm and rad3-related), and atr is essential for proper fa pathway function. Serine 1449 is in a consensus atm/atr site
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation TP53 0.739
Identifier Residue Sequence Organism Cell Line
SIGNOR-115134 Ser15 PSVEPPLsQETFSDL Homo sapiens
pmid sentence
Nhibition of atr kinase activity substantially reduces hypoxia-induced phosphorylation of p53 protein on serine 15 as well as p53 protein accumulation.
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ up-regulates activity img/direct-activation.png phosphorylation XPA 0.496
Identifier Residue Sequence Organism Cell Line
SIGNOR-250584 Ser173 VKKNPHHsQWGDMKL Homo sapiens A-549 Cell
pmid sentence
Defects in ATR-dependent XPA phosphorylation increases the cell sensitivity to UV irradiation. | The XPA-deficient cells complemented with XPA-S196A mutant, in which Ser196 was substituted with an alanine, displayed significantly higher UV sensitivity compared with the XPA cells complemented with wild-type XPA. Moreover, substitution of Ser196 with aspartic acid for mimicking the phosphorylation of XPA increased the cell survival to UV irradiation.
Identifier Residue Sequence Organism Cell Line
SIGNOR-258985 Ser196 RSLEVWGsQEALEEA Homo sapiens
pmid sentence
ATR mediated phosphorylation of XPA on S196 enhances cAMP-mediated optimization of NER, and is promoted by SIRT1-mediated deacetylation of XPA on K63, K67 and K215.
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PARP1 0.36
Identifier Residue Sequence Organism Cell Line
SIGNOR-278506 Ser179 FRPEYSAsQLKGFSL Homo sapiens
pmid sentence
Specifically, ATR binds to and phosphorylates PARP1 at Ser179 after the ionophore treatments.|These data suggest that the phosphorylation of S179 is necessary and sufficient for ATR inhibition of PARP1 PARylation activity.
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ down-regulates activity img/direct_inhibition.png phosphorylation PARP1 0.36
Identifier Residue Sequence Organism Cell Line
SIGNOR-277551 Ser179 FRPEYSAsQLKGFSL Homo sapiens A-549 Cell
pmid sentence
Specifically, ATR binds to and phosphorylates PARP1 at Ser179 after the ionophore treatments. This site-specific phosphorylation inactivates PARP1, inhibiting ionophore-induced necrosis.
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ down-regulates activity img/direct_inhibition.png phosphorylation SIAH1 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-276167 Ser19 GTSKCPPsQRVPALT Homo sapiens HEK-293T Cell
pmid sentence
We have also demonstrated that DNA damage triggers disruption of the HIPK2-Siah-1 complex, resulting in HIPK2 stabilization and activation. Disruption of the HIPK2-Siah-1 complex is mediated by the ATM/ATR pathway and involves ATM/ATR-dependent phosphorylation of Siah-1 at Ser 19.
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation XPA 0.496
Identifier Residue Sequence Organism Cell Line
SIGNOR-145190 Ser196 RSLEVWGsQEALEEA Homo sapiens
pmid sentence
Atr was the major kinase responsible for the cellular phosphorylation of xpa following uv irradiation / we propose that the phosphorylation of xpa by atr checkpoint may positively regulate ner activity and thus may facilitate the cells to recover from ner-related dna damages.
Identifier Residue Sequence Organism Cell Line
SIGNOR-199802 Ser196 RSLEVWGsQEALEEA Homo sapiens
pmid sentence
Atr phosphorylates xpa. at serine 196. Atr-mediated xpa phosphorylation enhances xpa stability by inhibiting herc2-mediated ubiquitination and subsequent degradation.
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ATM 0.743
Identifier Residue Sequence Organism Cell Line
SIGNOR-150870 Ser1981 SLAFEEGsQSTTISS Homo sapiens
pmid sentence
Atr-dependent phosphorylation and activation of atm in response to uv treatment or replication fork stalling. Here, we show that atm phosphorylation at ser1981, a characterised autophosphorylation site, is atr-dependent and atm-independent following replication fork stalling or uv treatment
Publications: 1 Organism: Homo Sapiens
Pathways:DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ up-regulates activity img/direct-activation.png phosphorylation XRCC3 0.469
Identifier Residue Sequence Organism Cell Line
SIGNOR-262666 Ser225 PFRCEFDsQASAPRA Homo sapiens
pmid sentence
HXRCC3 S225 phosphorylation is mediated by ATR via an ATM-dependent signaling pathway. These data clearly indicate that ATR mediates the late activation of XRCC3 following DSB accumulation.
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation KIFC1 0.257
Identifier Residue Sequence Organism Cell Line
SIGNOR-277296 Ser26 RPLIKAPsQLPLSGS Homo sapiens MDA-MB-231 Cell
pmid sentence
 ATM and ATR kinases phosphorylate KIFC1-S26 during DNA-damage conditions.KIFC1 was stabilized upon phosphorylation and thus promoted centrosome clustering, CIN, and tumor recurrence both in vivo and in vitro.
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation E2F1 0.379
Identifier Residue Sequence Organism Cell Line
SIGNOR-109420 Ser31 ALRLLDSsQIVIISA Mus musculus Thymocyte
pmid sentence
These results thus suggest that this serine 31 residue is indeed an atm/atr phosphorylation site and in fact is the major site for atm/atr-mediated phosphorylation within e2f1. Thus, it is possible that the atm/atr-mediated phosphorylation inhibits the binding and function of skp2 and thus prevents the normal degradation of e2f1
Publications: 1 Organism: Mus Musculus
Pathways:Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition
+ up-regulates img/direct-activation.png phosphorylation CHEK1 0.925
Identifier Residue Sequence Organism Cell Line
SIGNOR-134712 Ser317 ENVKYSSsQPEPRTG Homo sapiens
pmid sentence
Atr activation typically leads to chk1 phosphorylation and activation. In response to genotoxic stress, chk1 is phosphorylated on serines 317 (s317) and 345 (s345) by the ataxia-telangiectasia-related (atr) protein kinase.
Identifier Residue Sequence Organism Cell Line
SIGNOR-134716 Ser345 LVQGISFsQPTCPDH Homo sapiens
pmid sentence
Atr activation typically leads to chk1 phosphorylation and activation. In response to genotoxic stress, chk1 is phosphorylated on serines 317 (s317) and 345 (s345) by the ataxia-telangiectasia-related (atr) protein kinase.
Publications: 2 Organism: Homo Sapiens
Pathways:DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G2/M phase transition
+ img/unknown.png phosphorylation RPA2 0.754
Identifier Residue Sequence Organism Cell Line
SIGNOR-188666 Ser33 GFGSPAPsQAEKKSR Homo sapiens
pmid sentence
Atr phosphorylates s33 in response to replication stress
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation NBN 0.783
Identifier Residue Sequence Organism Cell Line
SIGNOR-155214 Ser343 TTPGPSLsQGVSVDE Homo sapiens
pmid sentence
We demonstrate that mrn and atr/atr-interacting protein (trip) interact with each other, and the forkhead-associated/breast cancer c-terminal domains (fha/brct) of nbs1 play a significant role in mediating this interaction. Mutations in the fha/brct domains do not prevent atr activation but specifically impair atr-mediated nbs1 phosphorylation at ser-343, which results in a defect in the s-phase checkpoint.
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.517
Identifier Residue Sequence Organism Cell Line
SIGNOR-119546 Ser407 SSSIIYSsQEDVKEF Homo sapiens NCI-H1299 Cell
pmid sentence
We found that a major kinase responsible for s407 phosphorylation is atrs407 phosphorylation of mdm2 by atr reduces mdm2-dependent export of p53 from nuclei to cytoplasm.
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ down-regulates img/direct_inhibition.png phosphorylation DBF4 0.654
Identifier Residue Sequence Organism Cell Line
SIGNOR-177805 Ser502 FSTDNSGsQPKQKSD Homo sapiens
pmid sentence
Dbf4/cdc7 (dbf4-dependent kinase (ddk)) is activated at the onset of s-phase, and its kinase activity is required for dna replication initiation from each origin. We identified novel atm/atr phosphorylation sites on dbf4 and showed that atm/atr-mediated phosphorylation of dbf4 is critical for the intra-s-phase checkpoint to inhibit dna replication.
Identifier Residue Sequence Organism Cell Line
SIGNOR-177809 Ser539 GLITINSsQEHLTVQ Homo sapiens
pmid sentence
Dbf4/cdc7 (dbf4-dependent kinase (ddk)) is activated at the onset of s-phase, and its kinase activity is required for dna replication initiation from each origin. We identified novel atm/atr phosphorylation sites on dbf4 and showed that atm/atr-mediated phosphorylation of dbf4 is critical for the intra-s-phase checkpoint to inhibit dna replication.
Identifier Residue Sequence Organism Cell Line
SIGNOR-177813 Thr449 DDIRQNFtQLPLHKN Homo sapiens
pmid sentence
Dbf4/cdc7 (dbf4-dependent kinase (ddk)) is activated at the onset of s-phase, and its kinase activity is required for dna replication initiation from each origin. We identified novel atm/atr phosphorylation sites on dbf4 and showed that atm/atr-mediated phosphorylation of dbf4 is critical for the intra-s-phase checkpoint to inhibit dna replication.
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation KMT2A 0.282
Identifier Residue Sequence Organism Cell Line
SIGNOR-25151 Ser516 VHPPLPIsQSPENES Homo sapiens
pmid sentence
Mll is phosphorylated at serine 516 by atr in response to genotoxic stress in the s phase, which disrupts its interaction with, and hence its degradation by, the scf(skp2) e3 ligase, leading to its accumulation.
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation POLH 0.418
Identifier Residue Sequence Organism Cell Line
SIGNOR-171290 Ser601 EMDLAHNsQSMHASS Homo sapiens
pmid sentence
Atr-mediated phosphorylation of dna polymerase _ is needed for efficient recovery from uv damage. We show that, after uv irradiation, pol_ becomes phosphorylated at ser601 by the ataxia-telangiectasia mutated and rad3-related (atr) kinase. Atr-dependent phosphorylation of pol_ is necessary to restore normal survival and postreplication repair
Publications: 1 Organism: Homo Sapiens
Pathways:DNA repair in cancer
+ up-regulates activity img/direct-activation.png phosphorylation RAD17 0.857
Identifier Residue Sequence Organism Cell Line
SIGNOR-111248 Ser646 ETWSLPLsQNSASEL Homo sapiens HeLa Cell
pmid sentence
Here we demonstrate that atr but not atm phosphorylates the human rad17 (hrad17) checkpoint protein on ser(635) and ser(645) in vitro.The rfc-related checkpoint protein rad17, a phosphorylation substrate of atr, is critical for atr-mediated checkpoint signaling and cell survival.
Identifier Residue Sequence Organism Cell Line
SIGNOR-111252 Ser656 SASELPAsQPQPFSA Homo sapiens
pmid sentence
Here we demonstrate that atr but not atm phosphorylates the human rad17 (hrad17) checkpoint protein on ser(635) and ser(645) in vitro.The rfc-related checkpoint protein rad17, a phosphorylation substrate of atr, is critical for atr-mediated checkpoint signaling and cell survival.
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation SMARCAL1 0.533
Identifier Residue Sequence Organism Cell Line
SIGNOR-273516 Ser652 RLKSDVLsQLPAKQR Homo sapiens HEK-293 Cell
pmid sentence
ATR phosphorylates SMARCAL1 on S652, thereby limiting its fork regression activities and preventing aberrant fork processing. Thus, phosphorylation of SMARCAL1 is one mechanism by which ATR prevents fork collapse, promotes the completion of DNA replication, and maintains genome integrity.
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation USP28 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-275850 Ser67 DERVKEPsQDTVATE
pmid sentence
Here we report that the deubiquitylase USP28 is recruited to sites of DNA damage in cisplatin-treated cells. ATR phosphorylates USP28 and increases its enzymatic activity.|Representative immunoblots of n = 3. C Immunoblotting of total and phosphorylated USP28 at serine 67 and 714 in A431 cells exposed to indicated concentrations of CPPD for 6 h.
Identifier Residue Sequence Organism Cell Line
SIGNOR-275851 Ser714 ESSTNSSsQDYSTSQ
pmid sentence
Here we report that the deubiquitylase USP28 is recruited to sites of DNA damage in cisplatin-treated cells. ATR phosphorylates USP28 and increases its enzymatic activity.|Representative immunoblots of n = 3. C Immunoblotting of total and phosphorylated USP28 at serine 67 and 714 in A431 cells exposed to indicated concentrations of CPPD for 6 h.
Publications: 2
+ up-regulates img/direct-activation.png phosphorylation ATRIP 0.877
Identifier Residue Sequence Organism Cell Line
SIGNOR-129469 Ser68 EELDTLAsQALSQCP Homo sapiens
pmid sentence
When dna is damaged, the atr-atrip complex is recruited to chromatin and is activated to transduce the checkpoint signal, but the precise kinase activation mechanism remains unknown. Here, we show that atrip is phosphorylated in an atr-dependent manner after genotoxic stimuli. The serine 68 and 72 residues are important for the phosphorylation in vivo and are required exclusively for direct modification by atr in vitro.
Identifier Residue Sequence Organism Cell Line
SIGNOR-129473 Ser72 TLASQALsQCPAAAR Homo sapiens
pmid sentence
When dna is damaged, the atr-atrip complex is recruited to chromatin and is activated to transduce the checkpoint signal, but the precise kinase activation mechanism remains unknown. Here, we show that atrip is phosphorylated in an atr-dependent manner after genotoxic stimuli. The serine 68 and 72 residues are important for the phosphorylation in vivo and are required exclusively for direct modification by atr in vitro.
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation FANCD2 0.67
Identifier Residue Sequence Organism Cell Line
SIGNOR-149305 Ser717 KDGGPVTsQESGQKL Homo sapiens
pmid sentence
In the present study, we identify two novel dna damage-inducible phosphorylation sites on fancd2, threonine 691 and serine 717. Atr phosphorylates fancd2 on these two sites, thereby promoting fancd2 monoubiquitination and enhancing cellular resistance to dna cross-linking agents
Identifier Residue Sequence Organism Cell Line
SIGNOR-149309 Thr691 YGLEEYDtQDGIAIN Homo sapiens
pmid sentence
In the present study, we identify two novel dna damage-inducible phosphorylation sites on fancd2, threonine 691 and serine 717. Atr phosphorylates fancd2 on these two sites, thereby promoting fancd2 monoubiquitination and enhancing cellular resistance to dna cross-linking agents
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation AKAP12 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-278292 Ser732 TDGILAGsQEHDPGQ Homo sapiens
pmid sentence
The expression of either ATR-KD or the addition of the ATR kinase inhibitor VE-821 to ATR-WT expressing cells caused AKAP12 to be retained within the cytoplasm.|With UV damage, ATR phosphorylates AKAP12 at S732 which stimulates nuclear translocation of an AKAP12\u2013ATR-pS435 complex that results in enhanced 5\u2032 strand incision of NER.
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ZDHHC13 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-273517 Ser8 MEGPGLGsQCRNHSH Mus musculus Melanocyte
pmid sentence
Collectively these results suggest that ZDHHC13 phosphorylation by ATR following UVB irradiation promotes its interaction with MC1R to stimulate MC1R palmitoylation.
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png phosphorylation PRKDC 0.313
Identifier Residue Sequence Organism Cell Line
SIGNOR-148722 Thr2609 LTPMFVEtQASQGTL Homo sapiens
pmid sentence
Finally, in vitro atr-mediated phosphorylation at the t2609 cluster was further confirmed by western blot analysis using phosphospecific antibodies against t2647 (fig. ?(Fig.7e),7e), suggesting that dna-pkcs could be the direct target of atr kinase.
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ up-regulates activity img/direct-activation.png phosphorylation CCAR2 0.432
Identifier Residue Sequence Organism Cell Line
SIGNOR-267662 Thr454 AAEAAPPtQEAQGET Homo sapiens
pmid sentence
 Here, we report that, in human cell lines, DNA damage triggered the phosphorylation of DBC1 on Thr454 by ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia and Rad3-related) kinases. Phosphorylated DBC1 bound to and inhibited SIRT1, resulting in the dissociation of the SIRT1-p53 complex and stimulating p53 acetylation and p53-dependent cell death. 
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CHEK2 0.859
Identifier Residue Sequence Organism Cell Line
SIGNOR-81442 Thr68 SSLETVStQELYSIP Homo sapiens HEK-293 Cell
pmid sentence
Atm- and rad3-related also phosphorylates thr68 in addition to thr26 and ser50, which are not phosphorylated to a significant extent by atm in vitro.Substitution of thr68 with ala reduced the extent of phosphorylation and activation of chk2 in response to ir
Publications: 1 Organism: Homo Sapiens
Pathways:DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ up-regulates activity img/direct-activation.png phosphorylation WDHD1 0.544
Identifier Residue Sequence Organism Cell Line
SIGNOR-262664 Thr826 KAAELTAtQVEEEEE Homo sapiens HCT-116 Cell
pmid sentence
And-1 is phosphorylated at T826 by ATR following replication stress, and this phosphorylation is required for And-1 to accumulate at the damage sites, where And-1 promotes the interaction between Claspin and Chk1, thereby stimulating efficient Chk1 activation by ATR.
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RBBP8 0.612
Identifier Residue Sequence Organism Cell Line
SIGNOR-200245 Thr859 WEVGFPStQTCMERG Homo sapiens
pmid sentence
Characterization of this site using phospho-specific antibodies and mutational analysis reveals that it is phosphorylated by atr and is required for binding of ctip to chromatin and subsequent processive resection.
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ATR 0.594
Identifier Residue Sequence Organism Cell Line
SIGNOR-167632 Tyr291 DTDQLKLyEEPLSKL Homo sapiens
pmid sentence
C-abl can phosphorylate atr on y291 and y310 and this phosphorylation appears to have a positive role in atr activation under genotoxic stress.
Identifier Residue Sequence Organism Cell Line
SIGNOR-167636 Tyr310 FPFEAEAyRNIEPVY Homo sapiens
pmid sentence
C-abl can phosphorylate atr on y291 and y310 and this phosphorylation appears to have a positive role in atr activation under genotoxic stress.
Publications: 2 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ up-regulates img/direct-activation.png phosphorylation BRCA1 0.798
Identifier Residue Sequence Organism Cell Line
SIGNOR-201050 Homo sapiens
pmid sentence
The phosphorylation of atr and atm substrates, chk1, chk2, h2ax, and brca1 was significantly reduced or abrogated in mutant cells.
Publications: 1 Organism: Homo Sapiens
Pathways:DNA repair in cancer, Cell cycle: G2/M phase transition
+ up-regulates img/direct-activation.png binding ATR 0.251
Identifier Residue Sequence Organism Cell Line
SIGNOR-173966 Homo sapiens HEK-293 Cell
pmid sentence
Binding of myh directly participates in atr and topbp1 activation in dna damage signaling, leading to apoptosis.
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MCM4 0.722
Identifier Residue Sequence Organism Cell Line
SIGNOR-169412 Homo sapiens
pmid sentence
Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6.
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png ATR 0.7
Identifier Residue Sequence Organism Cell Line
SIGNOR-242609 Homo sapiens
pmid sentence
the ATM-Chk2 and ATR-Chk1 pathways, which are activated by DNA double-strand breaks (DSBs) and single-stranded DNA respectively.
Publications: 1 Organism: Homo Sapiens
Pathways:DNA repair in cancer, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ up-regulates activity img/direct-activation.png phosphorylation ATR 0.394
Identifier Residue Sequence Organism Cell Line
SIGNOR-134781 Homo sapiens
pmid sentence
Regulation of NF-kappaB and p53 through activation of ATR and Chk1 by the ARF tumour suppressorInduction of ATR activity in Hs68 E2F1ER cells by endogenous ARF.
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation USP20 0.307
Identifier Residue Sequence Organism Cell Line
SIGNOR-272822 Homo sapiens HEK-293 Cell
pmid sentence
USP20 phosphorylation by ATR is important for its stabilization and checkpoint activation
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png CDS1 0.351
Identifier Residue Sequence Organism Cell Line
SIGNOR-130187 Homo sapiens
pmid sentence
The pikk kinases serve as transducers of the damege signel, ultimately phosphorylating and activating the downstream effector kinases: checkpoint kinases 1 and 2.
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MCM6 0.558
Identifier Residue Sequence Organism Cell Line
SIGNOR-169450 Homo sapiens
pmid sentence
Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6.
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding ATR 0.65
Identifier Residue Sequence Organism Cell Line
SIGNOR-263231 Homo sapiens U2-OS Cell
pmid sentence
These results establish that TopBP1 can activate both Xenopus and human ATR. Furthermore, these experiments provide conclusive evidence that the kinase activity that is induced by TopBP1 is intrinsic to the ATR protein itself and is not due to a kinase that associates with ATR.
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding ATR 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-275841
pmid sentence
It was reported that NEK1 associates with ATR/ATRIP and primes it for activation in response to a variety of genotoxic agents
Publications: 1
+ down-regulates img/indirect_inhibition.png PI4K2A 0.279
Identifier Residue Sequence Organism Cell Line
SIGNOR-159933 Homo sapiens
pmid sentence
Plk1 itself is negatively regulated by the ddr in an atm/atr-dependent manner.
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding ATR 0.813
Identifier Residue Sequence Organism Cell Line
SIGNOR-263232 Homo sapiens U2-OS Cell
pmid sentence
These results establish that TopBP1 can activate both Xenopus and human ATR. Furthermore, these experiments provide conclusive evidence that the kinase activity that is induced by TopBP1 is intrinsic to the ATR protein itself and is not due to a kinase that associates with ATR.
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation USP20 0.307
Identifier Residue Sequence Organism Cell Line
SIGNOR-278393 Homo sapiens
pmid sentence
On the other hand, USP20 is phosphorylated by ATR, which disrupts the interaction between USP20 and HERC2, resulting in USP20 stabilization.|USP20 phosphorylation by ATR is important for its stabilization and checkpoint activation.
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding XPC 0.481
Identifier Residue Sequence Organism Cell Line
SIGNOR-201112 Homo sapiens
pmid sentence
Atrand atm physically interacted with xpc and promptly localized to the uv damage sites.
Publications: 1 Organism: Homo Sapiens
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