ATRIP (ATR-interacting protein) is the obligate regulatory partner of the checkpoint kinase ATR. It forms a stable ATR-ATRIP heterodimer, and ATR and ATRIP are mutually required for each other's stability. Its N-terminal checkpoint recruitment domain binds RPA coated on single-stranded DNA, bringing ATR to stalled replication forks and resected DNA breaks. A TopBP1-interacting region is needed for TopBP1 to activate ATR. ATRIP is therefore essential for ATR-CHK1 checkpoint signalling in response to replication stress and DNA damage, and PRP19-dependent RPA ubiquitination promotes its accumulation at damage sites. Biallelic ATRIP mutation causes a Seckel syndrome-like disorder.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000077 DNA damage checkpoint signaling | IEA GO_REF:0000002 | ACCEPT | Summary: DNA damage checkpoint signaling (IEA). ATRIP is required for ATR checkpoint signalling. It targets ATR-ATRIP to RPA-coated ssDNA and contains the TopBP1-interacting region needed for TopBP1 to activate ATR. ATRIP knockdown abolishes checkpoint responses. Core process. Reason: [PMID:11721054 "Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage."] [PMID:12791985 "The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA."] [PMID:18519640 "Here, we show that ATRIP contains a TopBP1-interacting region that is necessary for the association of TopBP1 and ATR, for TopBP1-mediated activation of ATR, and for cells to survive and recover DNA synthesis following replication stress."] Supporting Evidence: PMID:11721054 Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage. PMID:12791985 The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA. PMID:18519640 Here, we show that ATRIP contains a TopBP1-interacting region that is necessary for the association of TopBP1 and ATR, for TopBP1-mediated activation of ATR, and for cells to survive and recover DNA synthesis following replication stress. |
| GO:0000077 DNA damage checkpoint signaling | TAS PMID:14657349 MSH2 and ATR form a signaling module and regulate two branch... | ACCEPT | Summary: DNA damage checkpoint signaling (TAS). ATRIP is required for ATR checkpoint signalling. It targets ATR-ATRIP to RPA-coated ssDNA and contains the TopBP1-interacting region needed for TopBP1 to activate ATR. ATRIP knockdown abolishes checkpoint responses. Core process. Reason: [PMID:11721054 "Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage."] [PMID:12791985 "The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA."] [PMID:18519640 "Here, we show that ATRIP contains a TopBP1-interacting region that is necessary for the association of TopBP1 and ATR, for TopBP1-mediated activation of ATR, and for cells to survive and recover DNA synthesis following replication stress."] Supporting Evidence: PMID:11721054 Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage. PMID:12791985 The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA. PMID:18519640 Here, we show that ATRIP contains a TopBP1-interacting region that is necessary for the association of TopBP1 and ATR, for TopBP1-mediated activation of ATR, and for cells to survive and recover DNA synthesis following replication stress. |
| GO:0005515 protein binding | IPI PMID:14657349 MSH2 and ATR form a signaling module and regulate two branch... | REMOVE | Summary: Protein binding (IPI) with MSH2, from an MSH2-ATR signalling study. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:17686975 Reconstitution of a human ATR-mediated checkpoint response t... | MODIFY | Summary: Protein binding (IPI) with ATR, from an in vitro reconstitution of ATR checkpoint signalling. ATRIP is the obligate regulatory partner of the ATR kinase: the two form a stable heterodimer and stabilize each other. Protein kinase binding is the informative term. Reason: [file:human/ATRIP/ATRIP-uniprot.txt "CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The"] [file:human/ATRIP/ATRIP-uniprot.txt "CC heterodimer binds the RPA complex and is then recruited to single-"] [PMID:11721054 "Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage."] [PMID:11721054 "Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways."] Proposed replacements: protein kinase binding Supporting Evidence: file:human/ATRIP/ATRIP-uniprot.txt CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The file:human/ATRIP/ATRIP-uniprot.txt CC heterodimer binds the RPA complex and is then recruited to single- PMID:11721054 Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage. PMID:11721054 Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways. |
| GO:0005515 protein binding | IPI PMID:19889979 Functional genomic screens identify CINP as a genome mainten... | MODIFY | Summary: Protein binding (IPI) with ATR, from a functional-genomics study of CINP. ATRIP is the obligate regulatory partner of the ATR kinase: the two form a stable heterodimer and stabilize each other. Protein kinase binding is the informative term. Reason: [file:human/ATRIP/ATRIP-uniprot.txt "CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The"] [file:human/ATRIP/ATRIP-uniprot.txt "CC heterodimer binds the RPA complex and is then recruited to single-"] [PMID:11721054 "Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage."] [PMID:11721054 "Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways."] Proposed replacements: protein kinase binding Supporting Evidence: file:human/ATRIP/ATRIP-uniprot.txt CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The file:human/ATRIP/ATRIP-uniprot.txt CC heterodimer binds the RPA complex and is then recruited to single- PMID:11721054 Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage. PMID:11721054 Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways. |
| GO:0005515 protein binding | IPI PMID:19889979 Functional genomic screens identify CINP as a genome mainten... | REMOVE | Summary: Protein binding (IPI) with CINP, from a functional-genomics study of CINP. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:20616048 Reconstitution of RPA-covered single-stranded DNA-activated ... | MODIFY | Summary: Protein binding (IPI) with ATR, from a reconstitution of RPA-ssDNA-activated ATR signalling. ATRIP is the obligate regulatory partner of the ATR kinase: the two form a stable heterodimer and stabilize each other. Protein kinase binding is the informative term. Reason: [file:human/ATRIP/ATRIP-uniprot.txt "CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The"] [file:human/ATRIP/ATRIP-uniprot.txt "CC heterodimer binds the RPA complex and is then recruited to single-"] [PMID:11721054 "Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage."] [PMID:11721054 "Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways."] Proposed replacements: protein kinase binding Supporting Evidence: file:human/ATRIP/ATRIP-uniprot.txt CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The file:human/ATRIP/ATRIP-uniprot.txt CC heterodimer binds the RPA complex and is then recruited to single- PMID:11721054 Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage. PMID:11721054 Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways. |
| GO:0005515 protein binding | IPI PMID:20930849 Cyclin-dependent kinase 9-cyclin K functions in the replicat... | REMOVE | Summary: Protein binding (IPI) with CDK9, from a CDK9-cyclin K replication-stress study. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:23144622 Identification of the first ATRIP-deficient patient and nove... | MODIFY | Summary: Protein binding (IPI) with ATR, from the first ATRIP-deficient patient report. ATRIP is the obligate regulatory partner of the ATR kinase: the two form a stable heterodimer and stabilize each other. Protein kinase binding is the informative term. Reason: [file:human/ATRIP/ATRIP-uniprot.txt "CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The"] [file:human/ATRIP/ATRIP-uniprot.txt "CC heterodimer binds the RPA complex and is then recruited to single-"] [PMID:11721054 "Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage."] [PMID:11721054 "Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways."] Proposed replacements: protein kinase binding Supporting Evidence: file:human/ATRIP/ATRIP-uniprot.txt CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The file:human/ATRIP/ATRIP-uniprot.txt CC heterodimer binds the RPA complex and is then recruited to single- PMID:11721054 Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage. PMID:11721054 Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with POLR1C, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with SPRY2, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with MOS, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with SCG2, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with MX2, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with TASOR2, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with C1orf94, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with FAM156A, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with LNX1, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with METTL21A, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with PCTK1, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with CCDC28B, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with CINP, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with MID2, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with CDC23, from the HI-II-14 Y2H map. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:29170278 A mitosis-specific and R loop-driven ATR pathway promotes fa... | REMOVE | Summary: Protein binding (IPI) with CENPF, from a mitotic R-loop ATR pathway study. This partner is not part of the core ATR-ATRIP recruitment and activation mechanism captured elsewhere in this review. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:29170278 A mitosis-specific and R loop-driven ATR pathway promotes fa... | MODIFY | Summary: Protein binding (IPI) with ATR, from a mitotic R-loop ATR pathway study. ATRIP is the obligate regulatory partner of the ATR kinase: the two form a stable heterodimer and stabilize each other. Protein kinase binding is the informative term. Reason: [file:human/ATRIP/ATRIP-uniprot.txt "CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The"] [file:human/ATRIP/ATRIP-uniprot.txt "CC heterodimer binds the RPA complex and is then recruited to single-"] [PMID:11721054 "Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage."] [PMID:11721054 "Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways."] Proposed replacements: protein kinase binding Supporting Evidence: file:human/ATRIP/ATRIP-uniprot.txt CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The file:human/ATRIP/ATRIP-uniprot.txt CC heterodimer binds the RPA complex and is then recruited to single- PMID:11721054 Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage. PMID:11721054 Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Protein binding (IPI) with ATR, from the BioPlex network. ATRIP is the obligate regulatory partner of the ATR kinase: the two form a stable heterodimer and stabilize each other. Protein kinase binding is the informative term. Reason: [file:human/ATRIP/ATRIP-uniprot.txt "CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The"] [file:human/ATRIP/ATRIP-uniprot.txt "CC heterodimer binds the RPA complex and is then recruited to single-"] [PMID:11721054 "Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage."] [PMID:11721054 "Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways."] Proposed replacements: protein kinase binding Supporting Evidence: file:human/ATRIP/ATRIP-uniprot.txt CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The file:human/ATRIP/ATRIP-uniprot.txt CC heterodimer binds the RPA complex and is then recruited to single- PMID:11721054 Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage. PMID:11721054 Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nucleus (IEA). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005634 nucleus | NAS PMID:11721054 ATR and ATRIP: partners in checkpoint signaling. | ACCEPT | Summary: Nucleus (NAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasm (IDA). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-176116 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'Recruitment and activation of Chk1'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-176250 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'Binding of ATR-ATRIP to the RPA-ssDNA complex'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-176298 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'Activation of claspin'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684875 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'Binding of ATR:ATRIP to RPA at resected DNA DSBs'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684882 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'CHEK1 is recruited to resected DNA DSBs'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684887 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'Activation of CHEK1 at resected DNA DSBs'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685011 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'ATR activation at DNA DSBs'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685156 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'ATR phosphorylates RPA2'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686642 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'RAD52 promotes single strand annealing at resected DNA DSBs'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686657 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'ERCC1:XPF cleaves flaps generated by SSA'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686663 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'Completion of SSA'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693561 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'RAD51 binds BRCA2 at resected DNA DSBs'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693564 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'Association of RAD51 with RAD52:DNA double-strand break ends'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693580 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'Association of RAD52 with the RPA complex at resected DNA DSBs'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6788385 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'The complex of ATR and ATRIP is recruited to ICL-DNA'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6788392 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'ATR phosphorylates RPA2, FANCI, FANCD2 and FANCM at ICL-DNA'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6799332 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'ATR phosphorylates TP53'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9709571 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'BRCA2 mutants with BRC defects or a defect in the C-terminal RAD51 binding site do not bind RAD51'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9980006 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'ERCC1:XPF binds DNA DSBs with annealed 3' ssDNA overhangs and displaced flaps generated by SSA'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9980021 | ACCEPT | Summary: Nucleoplasm (TAS). ATRIP is nuclear and concentrates at intranuclear foci after DNA damage or replication stress. Reactome event: 'LIG1 binds SSA sites'. Accepted. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. |
| GO:0006281 DNA repair | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: DNA repair (IBA). ATRIP's role is in checkpoint signalling: it recruits and activates ATR, which then phosphorylates repair and checkpoint substrates. Repair is a downstream consequence rather than a step ATRIP performs. Kept as non-core. Reason: [PMID:12791985 "The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA."] [PMID:18519640 "Here, we show that ATRIP contains a TopBP1-interacting region that is necessary for the association of TopBP1 and ATR, for TopBP1-mediated activation of ATR, and for cells to survive and recover DNA synthesis following replication stress."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002408403 SUPPORTS TRANSFER ATRIP family node seeded by fly mus304; repair-defective phenotypes reflect checkpoint function. Supporting Evidence: PMID:12791985 The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA. PMID:18519640 Here, we show that ATRIP contains a TopBP1-interacting region that is necessary for the association of TopBP1 and ATR, for TopBP1-mediated activation of ATR, and for cells to survive and recover DNA synthesis following replication stress. |
| GO:0070310 ATR-ATRIP complex | IEA GO_REF:0000107 | ACCEPT | Summary: ATR-ATRIP complex (IEA, mouse ortholog projection). ATRIP forms a stable heterodimer with ATR, and the two are mutually dependent for stable expression. Core. Reason: [file:human/ATRIP/ATRIP-uniprot.txt "CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The"] [PMID:11721054 "Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage."] [PMID:11721054 "Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways."] Supporting Evidence: file:human/ATRIP/ATRIP-uniprot.txt CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The PMID:11721054 Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage. PMID:11721054 Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways. |
| GO:0070310 ATR-ATRIP complex | IPI PMID:11721054 ATR and ATRIP: partners in checkpoint signaling. | ACCEPT | Summary: ATR-ATRIP complex (IPI). ATRIP forms a stable heterodimer with ATR, and the two are mutually dependent for stable expression. Core. Reason: [file:human/ATRIP/ATRIP-uniprot.txt "CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The"] [PMID:11721054 "Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage."] [PMID:11721054 "Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways."] Supporting Evidence: file:human/ATRIP/ATRIP-uniprot.txt CC -!- SUBUNIT: Interacts with ATR (By similarity). Heterodimer with ATR. The PMID:11721054 Small interfering RNA directed against ATRIP caused the loss of both ATRIP and ATR expression and the loss of checkpoint responses to DNA damage. PMID:11721054 Thus, ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways. |
| GO:0070530 K63-linked polyubiquitin modification-dependent protein binding | IDA PMID:24332808 PRP19 transforms into a sensor of RPA-ssDNA after DNA damage... | KEEP AS NON CORE | Summary: K63-linked polyubiquitin modification-dependent protein binding (IDA). The curator's assay is in the full text, which is not cached. The abstract shows that PRP19, an RPA-ssDNA-sensing ubiquitin ligase, promotes ATRIP accumulation at damage sites. ATRIP recognition of PRP19-dependent K63 chains on RPA is a plausible mechanism. Accepted, deferring to the curator; non-core relative to direct RPA-ssDNA binding. Reason: [PMID:24332808 "PRP19 facilitates the accumulation of ATRIP, the regulatory partner of the ataxia telangiectasia mutated and Rad3-related (ATR) kinase, at DNA damage sites."] Supporting Evidence: PMID:24332808 PRP19 facilitates the accumulation of ATRIP, the regulatory partner of the ataxia telangiectasia mutated and Rad3-related (ATR) kinase, at DNA damage sites. |
| GO:2000779 regulation of double-strand break repair | NAS PMID:11721054 ATR and ATRIP: partners in checkpoint signaling. | KEEP AS NON CORE | Summary: Regulation of double-strand break repair (NAS). ATR-ATRIP signalling regulates repair by phosphorylating repair factors at resected breaks, one of several outputs of the checkpoint signalling this review treats as core. As a statement about one downstream output, it is kept as non-core. Reason: [PMID:12791985 "The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA."] Supporting Evidence: PMID:12791985 The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA. |
| GO:0090734 site of DNA damage | IDA PMID:11721054 ATR and ATRIP: partners in checkpoint signaling. | NEW | Summary: Site of DNA damage (NEW, IDA). ATRIP localizes with ATR to intranuclear foci after DNA damage or replication inhibition (UniProt: redistributes to discrete nuclear foci on damage), and it is recruited through binding RPA-coated ssDNA. Comparator: ATR carries this term by IDA in QuickGO. Reason: [PMID:11721054 "ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication."] [file:human/ATRIP/ATRIP-uniprot.txt "CC ECO:0000269|PubMed:18283122}. Note=Redistributes to discrete nuclear"] [PMID:12791985 "The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA."] Supporting Evidence: PMID:11721054 ATR and ATRIP both localize to intranuclear foci after DNA damage or inhibition of replication. file:human/ATRIP/ATRIP-uniprot.txt CC ECO:0000269|PubMed:18283122}. Note=Redistributes to discrete nuclear PMID:12791985 The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:12791985 Sensing DNA damage through ATRIP recognition of RPA-ssDNA co... | NEW | Summary: Protein-macromolecule adaptor activity (NEW, IDA). ATRIP is the subunit that links the ATR kinase to its activating platform. RPA stimulates ATRIP binding to ssDNA, and ATRIP's binding to RPA-coated ssDNA lets the ATR-ATRIP complex associate with DNA and phosphorylate DNA-bound Rad17. A separate ATRIP region recruits TopBP1 to activate ATR. ATRIP's own binding to naked ssDNA is contested, so the bridging adaptor term is used rather than ssDNA binding. Reason: [PMID:12791985 "In vitro, RPA stimulates the binding of ATRIP to ssDNA."] [PMID:12791985 "The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA."] [PMID:18519640 "Here, we show that ATRIP contains a TopBP1-interacting region that is necessary for the association of TopBP1 and ATR, for TopBP1-mediated activation of ATR, and for cells to survive and recover DNA synthesis following replication stress."] Supporting Evidence: PMID:12791985 In vitro, RPA stimulates the binding of ATRIP to ssDNA. PMID:12791985 The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA. PMID:18519640 Here, we show that ATRIP contains a TopBP1-interacting region that is necessary for the association of TopBP1 and ATR, for TopBP1-mediated activation of ATR, and for cells to survive and recover DNA synthesis following replication stress. |
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Download this section (compressed HTML)Q: Should ATRIP's direct binding to RPA-coated ssDNA be captured as an MF (for example single-stranded DNA binding, or a specific RPA-complex binding term), given that yeast Ddc2/Lcd1 carries damaged DNA binding by IDA?
Experiment: Measure binding of purified ATRIP N-terminal domain to RPA-ssDNA versus free ssDNA by fluorescence anisotropy, with checkpoint-recruitment-domain mutants, to define its direct DNA-binding contribution.
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