ASCC3 encodes a large ATP-dependent superfamily II helicase that functions in distinct ASCC-containing complexes. In the nucleus, ASCC3 is the catalytic helicase subunit of the ALKBH3-associated ASCC DNA dealkylation repair complex, where it helps unwind alkylated duplex DNA and is recruited to alkylation-induced nuclear foci. In the cytosol, ASCC3/RQT2 is the ATPase subunit of the human ribosome quality control trigger complex with ASCC2 and TRIP4, where it promotes splitting of K63-ubiquitinated collided ribosomes to initiate ribosome-associated quality control. ASCC3 was also originally identified as a component of the ASC-1 transcription coactivator complex, but its best-supported mechanistic roles are DNA alkylation repair and stalled ribosome rescue.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003723 RNA binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: RNA binding is plausible for ASCC3 but is less specific than its characterized helicase/RQT roles. Reason: ASCC3 contacts nucleic acids in both the DNA repair and ribosome-rescue settings, and purified ASCC3 can bind ssRNA in vitro, but RNA binding alone does not capture the core ATP-dependent activities. Keep the annotation as contextual rather than using it as the main MF. Supporting Evidence: PMID:29144457 Purified ASCC3 bound to ssRNA in vitro |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization is well supported for the ASCC DNA alkylation repair role. Reason: ASCC3 was originally purified from HeLa nuclei as an ASC-1 complex subunit and later shown to form alkylation-induced nuclear foci with ALKBH3/ASCC repair machinery. This is a core location for the DNA repair arm of ASCC3 biology. Supporting Evidence: PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent PMID:12077347 ASC-1 exists as a steady-state complex associated with three polypeptides, P200, P100, and P50, in HeLa nuclei |
| GO:0043138 3'-5' DNA helicase activity | IBA GO_REF:0000033 | ACCEPT | Summary: ASCC3 3'-5' DNA helicase activity is directly supported and central to ALKBH3-coupled dealkylation repair. Reason: The ALKBH3-ASCC paper demonstrates that ASCC3 unwinds duplex DNA to produce the single-stranded substrate preferred by ALKBH3. This is the most specific molecular-function term for the nuclear DNA repair activity. Supporting Evidence: PMID:22055184 ASCC3 unwinds DNA to generate the single-stranded substrate needed for ALKBH3-mediated DNA repair PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent file:human/ASCC3/ASCC3-notes.md ASCC3 is a large ATP-dependent SF2 helicase with two well-supported functional contexts. |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MODIFY | Summary: The broad nucleic-acid binding annotation is directionally true but should be replaced by the specific DNA helicase activity. Reason: ASCC3 is a nucleic-acid-dependent ATPase/helicase, but the InterPro-derived term is too general. Direct evidence supports 3'-5' DNA helicase activity in ALKBH3-mediated repair. Proposed replacements: 3'-5' DNA helicase activity Supporting Evidence: PMID:22055184 ASCC3 unwinds DNA to generate the single-stranded substrate needed for ALKBH3-mediated DNA repair PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent file:human/ASCC3/ASCC3-notes.md ASCC3 is a large ATP-dependent SF2 helicase with two well-supported functional contexts. |
| GO:0004386 helicase activity | IEA GO_REF:0000117 | MODIFY | Summary: Generic helicase activity should be refined to ASCC3-specific DNA helicase and ATPase terms. Reason: ASCC3 is a helicase-family ATPase, but GOA already has stronger, more specific annotations for 3'-5' DNA helicase activity and ATP hydrolysis activity. The generic helicase term should not be the preferred assertion. Proposed replacements: 3'-5' DNA helicase activity ATP hydrolysis activity Supporting Evidence: PMID:22055184 ASCC3 unwinds DNA to generate the single-stranded substrate needed for ALKBH3-mediated DNA repair PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent file:human/ASCC3/ASCC3-notes.md ASCC3 is a large ATP-dependent SF2 helicase with two well-supported functional contexts. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP binding is consistent with ASCC3 helicase/ATPase function but is not the most informative MF annotation. Reason: ASCC3 uses ATP-dependent helicase activity in both DNA repair and hRQT ribosome splitting. ATP binding is true as a supporting property, but ATP hydrolysis activity and the specific biological processes carry the core functional meaning. Supporting Evidence: PMID:32579943 its loss phenocopies the loss of ZNF598. This activity of ASCC3 is dependent on its ATP-dependent helicase activities |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear localization is well supported for the ASCC DNA alkylation repair role. Reason: ASCC3 was originally purified from HeLa nuclei as an ASC-1 complex subunit and later shown to form alkylation-induced nuclear foci with ALKBH3/ASCC repair machinery. This is a core location for the DNA repair arm of ASCC3 biology. Supporting Evidence: PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent PMID:12077347 ASC-1 exists as a steady-state complex associated with three polypeptides, P200, P100, and P50, in HeLa nuclei |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: Cytosolic localization is supported by the ribosome-associated quality-control role. Reason: ASCC3 acts on cytosolic collided ribosomes as part of hRQT. Cytosol annotations are appropriate for the RQC arm of ASCC3, while nuclear annotations remain appropriate for the DNA repair arm. Supporting Evidence: PMID:32579943 ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the lead ribosome PMID:36302773 the trimeric hRQT complex-mediated subunit dissociation file:human/ASCC3/ASCC3-notes.md Conservative decision: retain the exact ribosome-rescue/RQC annotations and do not add a new ASCC3 annotation to `GO:0006515`. |
| GO:0016607 nuclear speck | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear speckle/foci localization is supported in the alkylation damage response context. Reason: ASCC3 and ASCC complex foci are linked to RNA polymerase II/splicing-associated nuclear regions after alkylation damage, and ASCC1 is described at nuclear speckle foci before damage. This is a supported subnuclear context for the repair complex rather than a separate enzymatic function. Supporting Evidence: PMID:29144457 ASCC foci co-localized with elongating (Ser2 phosphorylated) RNA polymerase II PMID:29997253 ASCC1 is present at nuclear speckle foci prior to damage |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000116 | ACCEPT | Summary: ATP hydrolysis activity is directly tied to ASCC3 helicase-dependent DNA repair and hRQT ribosome splitting. Reason: ASCC3 is an ATP-dependent helicase; RQC studies show ASCC3 ATPase activity is required for hRQT-mediated ribosome rescue, and DNA repair studies show ATP-dependent helicase activity in ASCC3. This is an informative core MF annotation. Supporting Evidence: PMID:32579943 This activity of ASCC3 is dependent on its ATP-dependent helicase activities PMID:32099016 The ATPase activity of ASCC3 and the ubiquitin-binding activity of ASCC2 are crucial for triggering |
| GO:0043138 3'-5' DNA helicase activity | IEA GO_REF:0000003 | ACCEPT | Summary: ASCC3 3'-5' DNA helicase activity is directly supported and central to ALKBH3-coupled dealkylation repair. Reason: The ALKBH3-ASCC paper demonstrates that ASCC3 unwinds duplex DNA to produce the single-stranded substrate preferred by ALKBH3. This is the most specific molecular-function term for the nuclear DNA repair activity. Supporting Evidence: PMID:22055184 ASCC3 unwinds DNA to generate the single-stranded substrate needed for ALKBH3-mediated DNA repair PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent file:human/ASCC3/ASCC3-notes.md ASCC3 is a large ATP-dependent SF2 helicase with two well-supported functional contexts. |
| GO:0180022 RQC-trigger complex | IEA GO_REF:0000117 | ACCEPT | Summary: ASCC3 is a core subunit of the human RQC-trigger/hRQT complex. Reason: The original ASC-1 complex paper supports ASCC3/p200 complex membership, and later RQC papers establish the ASCC3-ASCC2-TRIP4 hRQT complex as the ribosome quality-control trigger. The term is therefore biologically correct, even when the older original reference alone is not sufficient for the modern RQC label. Supporting Evidence: PMID:32099016 The hRQT complex is composed of ASCC3, ASCC2, and TRIP4 PMID:36302773 the trimeric hRQT complex-mediated subunit dissociation |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: The interaction evidence is real but generic protein binding is not an informative ASCC3 molecular-function annotation. Reason: These rows reflect physical associations from targeted or large-scale interaction data. They are useful as support for ASCC/ALKBH3/hRQT complex biology when specific partners are considered, but the generic GO protein binding term should not be retained as a core MF for ASCC3. Supporting Evidence: file:human/ASCC3/ASCC3-notes.md Treat generic binding annotations conservatively. `protein binding` rows are interaction evidence but not informative molecular-function curation. |
| GO:0005515 protein binding | IPI PMID:29997253 RNA ligase-like domain in activating signal cointegrator 1 c... | MARK AS OVER ANNOTATED | Summary: The interaction evidence is real but generic protein binding is not an informative ASCC3 molecular-function annotation. Reason: These rows reflect physical associations from targeted or large-scale interaction data. They are useful as support for ASCC/ALKBH3/hRQT complex biology when specific partners are considered, but the generic GO protein binding term should not be retained as a core MF for ASCC3. Supporting Evidence: file:human/ASCC3/ASCC3-notes.md Treat generic binding annotations conservatively. `protein binding` rows are interaction evidence but not informative molecular-function curation. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: The interaction evidence is real but generic protein binding is not an informative ASCC3 molecular-function annotation. Reason: These rows reflect physical associations from targeted or large-scale interaction data. They are useful as support for ASCC/ALKBH3/hRQT complex biology when specific partners are considered, but the generic GO protein binding term should not be retained as a core MF for ASCC3. Supporting Evidence: file:human/ASCC3/ASCC3-notes.md Treat generic binding annotations conservatively. `protein binding` rows are interaction evidence but not informative molecular-function curation. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: The interaction evidence is real but generic protein binding is not an informative ASCC3 molecular-function annotation. Reason: These rows reflect physical associations from targeted or large-scale interaction data. They are useful as support for ASCC/ALKBH3/hRQT complex biology when specific partners are considered, but the generic GO protein binding term should not be retained as a core MF for ASCC3. Supporting Evidence: file:human/ASCC3/ASCC3-notes.md Treat generic binding annotations conservatively. `protein binding` rows are interaction evidence but not informative molecular-function curation. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosolic localization is supported by the ribosome-associated quality-control role. Reason: ASCC3 acts on cytosolic collided ribosomes as part of hRQT. Cytosol annotations are appropriate for the RQC arm of ASCC3, while nuclear annotations remain appropriate for the DNA repair arm. Supporting Evidence: PMID:32579943 ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the lead ribosome PMID:36302773 the trimeric hRQT complex-mediated subunit dissociation file:human/ASCC3/ASCC3-notes.md Conservative decision: retain the exact ribosome-rescue/RQC annotations and do not add a new ASCC3 annotation to `GO:0006515`. |
| GO:0072344 rescue of stalled cytosolic ribosome | TAS Reactome:R-HSA-9948299 | ACCEPT | Summary: Rescue of stalled cytosolic ribosomes is the PN-relevant core process for ASCC3/hRQT. Reason: ASCC3 acts in the hRQT/RQC-trigger complex to split ubiquitinated collided ribosomes, allowing downstream RQC. This exact GO term is the conservative PN projection target and is already present in GOA. Supporting Evidence: PMID:32579943 ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the lead ribosome PMID:36302773 the trimeric hRQT complex-mediated subunit dissociation file:human/ASCC3/ASCC3-notes.md Conservative decision: retain the exact ribosome-rescue/RQC annotations and do not add a new ASCC3 annotation to `GO:0006515`. Reactome:R-HSA-9948300 splits stalled 80S K63-polyubiquitinated ribosomes into 60S subunits and K63-polyubiquitinated 40S subunits |
| GO:0005634 nucleus | EXP PMID:29144457 A ubiquitin-dependent signalling axis specific for ALKBH-med... | ACCEPT | Summary: Nuclear localization is well supported for the ASCC DNA alkylation repair role. Reason: ASCC3 was originally purified from HeLa nuclei as an ASC-1 complex subunit and later shown to form alkylation-induced nuclear foci with ALKBH3/ASCC repair machinery. This is a core location for the DNA repair arm of ASCC3 biology. Supporting Evidence: PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent PMID:12077347 ASC-1 exists as a steady-state complex associated with three polypeptides, P200, P100, and P50, in HeLa nuclei |
| GO:0016607 nuclear speck | EXP PMID:29144457 A ubiquitin-dependent signalling axis specific for ALKBH-med... | ACCEPT | Summary: Nuclear speckle/foci localization is supported in the alkylation damage response context. Reason: ASCC3 and ASCC complex foci are linked to RNA polymerase II/splicing-associated nuclear regions after alkylation damage, and ASCC1 is described at nuclear speckle foci before damage. This is a supported subnuclear context for the repair complex rather than a separate enzymatic function. Supporting Evidence: PMID:29144457 ASCC foci co-localized with elongating (Ser2 phosphorylated) RNA polymerase II PMID:29997253 ASCC1 is present at nuclear speckle foci prior to damage |
| GO:0016607 nuclear speck | EXP PMID:29997253 RNA ligase-like domain in activating signal cointegrator 1 c... | ACCEPT | Summary: Nuclear speckle/foci localization is supported in the alkylation damage response context. Reason: ASCC3 and ASCC complex foci are linked to RNA polymerase II/splicing-associated nuclear regions after alkylation damage, and ASCC1 is described at nuclear speckle foci before damage. This is a supported subnuclear context for the repair complex rather than a separate enzymatic function. Supporting Evidence: PMID:29144457 ASCC foci co-localized with elongating (Ser2 phosphorylated) RNA polymerase II PMID:29997253 ASCC1 is present at nuclear speckle foci prior to damage |
| GO:0016887 ATP hydrolysis activity | TAS Reactome:R-HSA-9948300 | ACCEPT | Summary: ATP hydrolysis activity is directly tied to ASCC3 helicase-dependent DNA repair and hRQT ribosome splitting. Reason: ASCC3 is an ATP-dependent helicase; RQC studies show ASCC3 ATPase activity is required for hRQT-mediated ribosome rescue, and DNA repair studies show ATP-dependent helicase activity in ASCC3. This is an informative core MF annotation. Supporting Evidence: PMID:32579943 This activity of ASCC3 is dependent on its ATP-dependent helicase activities PMID:32099016 The ATPase activity of ASCC3 and the ubiquitin-binding activity of ASCC2 are crucial for triggering |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9948291 | ACCEPT | Summary: Cytosolic localization is supported by the ribosome-associated quality-control role. Reason: ASCC3 acts on cytosolic collided ribosomes as part of hRQT. Cytosol annotations are appropriate for the RQC arm of ASCC3, while nuclear annotations remain appropriate for the DNA repair arm. Supporting Evidence: PMID:32579943 ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the lead ribosome PMID:36302773 the trimeric hRQT complex-mediated subunit dissociation file:human/ASCC3/ASCC3-notes.md Conservative decision: retain the exact ribosome-rescue/RQC annotations and do not add a new ASCC3 annotation to `GO:0006515`. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9948300 | ACCEPT | Summary: Cytosolic localization is supported by the ribosome-associated quality-control role. Reason: ASCC3 acts on cytosolic collided ribosomes as part of hRQT. Cytosol annotations are appropriate for the RQC arm of ASCC3, while nuclear annotations remain appropriate for the DNA repair arm. Supporting Evidence: PMID:32579943 ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the lead ribosome PMID:36302773 the trimeric hRQT complex-mediated subunit dissociation file:human/ASCC3/ASCC3-notes.md Conservative decision: retain the exact ribosome-rescue/RQC annotations and do not add a new ASCC3 annotation to `GO:0006515`. |
| GO:0005634 nucleus | IDA PMID:29997253 RNA ligase-like domain in activating signal cointegrator 1 c... | ACCEPT | Summary: Nuclear localization is well supported for the ASCC DNA alkylation repair role. Reason: ASCC3 was originally purified from HeLa nuclei as an ASC-1 complex subunit and later shown to form alkylation-induced nuclear foci with ALKBH3/ASCC repair machinery. This is a core location for the DNA repair arm of ASCC3 biology. Supporting Evidence: PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent PMID:12077347 ASC-1 exists as a steady-state complex associated with three polypeptides, P200, P100, and P50, in HeLa nuclei |
| GO:0006260 DNA replication | NAS PMID:29997253 RNA ligase-like domain in activating signal cointegrator 1 c... | REMOVE | Summary: The cited ASCC damage-response evidence does not support a general DNA replication role for ASCC3. Reason: ASCC3 participates in ALKBH3-mediated alkylation repair and forms repair foci in cell-cycle contexts, but the cited ASCC1/ASCC paper supports repair-complex regulation rather than DNA replication. This annotation appears to overinterpret ComplexPortal context. Supporting Evidence: PMID:29997253 ASCC1 interacts with the ASCC complex through the ASCC3 helicase subunit PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent |
| GO:0006307 DNA alkylation repair | NAS PMID:29997253 RNA ligase-like domain in activating signal cointegrator 1 c... | ACCEPT | Summary: DNA alkylation repair is a directly supported core ASCC3 function. Reason: ASCC3 unwinds alkylated duplex DNA and supports ALKBH3-dependent DNA dealkylation repair. Later studies show alkylation-specific nuclear recruitment of the ASCC repair complex. Supporting Evidence: PMID:22055184 ASCC3 unwinds DNA to generate the single-stranded substrate needed for ALKBH3-mediated DNA repair PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent file:human/ASCC3/ASCC3-notes.md ASCC3 is a large ATP-dependent SF2 helicase with two well-supported functional contexts. |
| GO:0032790 ribosome disassembly | NAS PMID:32099016 Identification of a novel trigger complex that facilitates r... | ACCEPT | Summary: Ribosome disassembly is directly supported by hRQT/ASCC biochemical and cell-based studies. Reason: ASCC3-containing ASCC/hRQT disassembles ubiquitinated collided ribosomes in an ATP-dependent reaction, which is the mechanistic core of ASCC3 in RQC. Supporting Evidence: PMID:32579943 ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the lead ribosome PMID:36302773 hRQT-driven splitting of ribosomes collided on endogenous XBP1u and poly(A) staller mRNAs |
| GO:1990116 ribosome-associated ubiquitin-dependent protein catabolic process | NAS PMID:32099016 Identification of a novel trigger complex that facilitates r... | ACCEPT | Summary: ASCC3 is upstream in ribosome-associated ubiquitin-dependent nascent-chain quality control. Reason: ASCC3/hRQT splits stalled, ubiquitinated ribosomes and thereby produces the subunit/nascent-chain intermediates that enter RQC-associated ubiquitin-dependent protein degradation. The term is broader than the immediate splitting event but is supported as the pathway context. Supporting Evidence: PMID:32099016 Ribosome stalling triggers the ribosome-associated quality control (RQC) pathway PMID:32579943 60S-peptidyl-tRNAs are substrates for RQC factors that trigger nascent polypeptide ubiquitination and degradation |
| GO:1990391 DNA repair complex | IPI PMID:29997253 RNA ligase-like domain in activating signal cointegrator 1 c... | ACCEPT | Summary: ASCC3 is a subunit of the ASCC DNA alkylation repair complex. Reason: The ASCC1/ASCC2/ASCC3 complex is repeatedly supported in the alkylation repair literature and is recruited with ALKBH3 to alkylation-induced nuclear foci. Supporting Evidence: PMID:29997253 ASCC1 interacts with the ASCC complex through the ASCC3 helicase subunit PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent |
| GO:0016887 ATP hydrolysis activity | IDA PMID:32579943 The ASC-1 Complex Disassembles Collided Ribosomes. | ACCEPT | Summary: ATP hydrolysis activity is directly tied to ASCC3 helicase-dependent DNA repair and hRQT ribosome splitting. Reason: ASCC3 is an ATP-dependent helicase; RQC studies show ASCC3 ATPase activity is required for hRQT-mediated ribosome rescue, and DNA repair studies show ATP-dependent helicase activity in ASCC3. This is an informative core MF annotation. Supporting Evidence: PMID:32579943 This activity of ASCC3 is dependent on its ATP-dependent helicase activities PMID:32099016 The ATPase activity of ASCC3 and the ubiquitin-binding activity of ASCC2 are crucial for triggering |
| GO:0016887 ATP hydrolysis activity | IDA PMID:36302773 A distinct mammalian disome collision interface harbors K63-... | ACCEPT | Summary: ATP hydrolysis activity is directly tied to ASCC3 helicase-dependent DNA repair and hRQT ribosome splitting. Reason: ASCC3 is an ATP-dependent helicase; RQC studies show ASCC3 ATPase activity is required for hRQT-mediated ribosome rescue, and DNA repair studies show ATP-dependent helicase activity in ASCC3. This is an informative core MF annotation. Supporting Evidence: PMID:32579943 This activity of ASCC3 is dependent on its ATP-dependent helicase activities PMID:32099016 The ATPase activity of ASCC3 and the ubiquitin-binding activity of ASCC2 are crucial for triggering |
| GO:0022626 cytosolic ribosome | IDA PMID:36302773 A distinct mammalian disome collision interface harbors K63-... | ACCEPT | Summary: ASCC3 is active on cytosolic ribosomes during hRQT-mediated RQC initiation. Reason: The RQC studies directly place ASCC3/hRQT on collided cytosolic ribosomes and show that ASCC3 ATPase activity drives subunit dissociation. Supporting Evidence: PMID:32579943 ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the lead ribosome PMID:36302773 the trimeric hRQT complex-mediated subunit dissociation file:human/ASCC3/ASCC3-notes.md Conservative decision: retain the exact ribosome-rescue/RQC annotations and do not add a new ASCC3 annotation to `GO:0006515`. |
| GO:0032790 ribosome disassembly | IDA PMID:32579943 The ASC-1 Complex Disassembles Collided Ribosomes. | ACCEPT | Summary: Ribosome disassembly is directly supported by hRQT/ASCC biochemical and cell-based studies. Reason: ASCC3-containing ASCC/hRQT disassembles ubiquitinated collided ribosomes in an ATP-dependent reaction, which is the mechanistic core of ASCC3 in RQC. Supporting Evidence: PMID:32579943 ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the lead ribosome PMID:36302773 hRQT-driven splitting of ribosomes collided on endogenous XBP1u and poly(A) staller mRNAs |
| GO:0032790 ribosome disassembly | IDA PMID:36302773 A distinct mammalian disome collision interface harbors K63-... | ACCEPT | Summary: Ribosome disassembly is directly supported by hRQT/ASCC biochemical and cell-based studies. Reason: ASCC3-containing ASCC/hRQT disassembles ubiquitinated collided ribosomes in an ATP-dependent reaction, which is the mechanistic core of ASCC3 in RQC. Supporting Evidence: PMID:32579943 ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the lead ribosome PMID:36302773 hRQT-driven splitting of ribosomes collided on endogenous XBP1u and poly(A) staller mRNAs |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:32579943 The ASC-1 Complex Disassembles Collided Ribosomes. | ACCEPT | Summary: Rescue of stalled cytosolic ribosomes is the PN-relevant core process for ASCC3/hRQT. Reason: ASCC3 acts in the hRQT/RQC-trigger complex to split ubiquitinated collided ribosomes, allowing downstream RQC. This exact GO term is the conservative PN projection target and is already present in GOA. Supporting Evidence: PMID:32579943 ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the lead ribosome PMID:36302773 the trimeric hRQT complex-mediated subunit dissociation file:human/ASCC3/ASCC3-notes.md Conservative decision: retain the exact ribosome-rescue/RQC annotations and do not add a new ASCC3 annotation to `GO:0006515`. Reactome:R-HSA-9948300 splits stalled 80S K63-polyubiquitinated ribosomes into 60S subunits and K63-polyubiquitinated 40S subunits |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:36302773 A distinct mammalian disome collision interface harbors K63-... | ACCEPT | Summary: Rescue of stalled cytosolic ribosomes is the PN-relevant core process for ASCC3/hRQT. Reason: ASCC3 acts in the hRQT/RQC-trigger complex to split ubiquitinated collided ribosomes, allowing downstream RQC. This exact GO term is the conservative PN projection target and is already present in GOA. Supporting Evidence: PMID:32579943 ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the lead ribosome PMID:36302773 the trimeric hRQT complex-mediated subunit dissociation file:human/ASCC3/ASCC3-notes.md Conservative decision: retain the exact ribosome-rescue/RQC annotations and do not add a new ASCC3 annotation to `GO:0006515`. Reactome:R-HSA-9948300 splits stalled 80S K63-polyubiquitinated ribosomes into 60S subunits and K63-polyubiquitinated 40S subunits |
| GO:0072344 rescue of stalled cytosolic ribosome | IMP PMID:32099016 Identification of a novel trigger complex that facilitates r... | ACCEPT | Summary: Rescue of stalled cytosolic ribosomes is the PN-relevant core process for ASCC3/hRQT. Reason: ASCC3 acts in the hRQT/RQC-trigger complex to split ubiquitinated collided ribosomes, allowing downstream RQC. This exact GO term is the conservative PN projection target and is already present in GOA. Supporting Evidence: PMID:32579943 ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the lead ribosome PMID:36302773 the trimeric hRQT complex-mediated subunit dissociation file:human/ASCC3/ASCC3-notes.md Conservative decision: retain the exact ribosome-rescue/RQC annotations and do not add a new ASCC3 annotation to `GO:0006515`. Reactome:R-HSA-9948300 splits stalled 80S K63-polyubiquitinated ribosomes into 60S subunits and K63-polyubiquitinated 40S subunits |
| GO:1990116 ribosome-associated ubiquitin-dependent protein catabolic process | IMP PMID:32099016 Identification of a novel trigger complex that facilitates r... | ACCEPT | Summary: ASCC3 is upstream in ribosome-associated ubiquitin-dependent nascent-chain quality control. Reason: ASCC3/hRQT splits stalled, ubiquitinated ribosomes and thereby produces the subunit/nascent-chain intermediates that enter RQC-associated ubiquitin-dependent protein degradation. The term is broader than the immediate splitting event but is supported as the pathway context. Supporting Evidence: PMID:32099016 Ribosome stalling triggers the ribosome-associated quality control (RQC) pathway PMID:32579943 60S-peptidyl-tRNAs are substrates for RQC factors that trigger nascent polypeptide ubiquitination and degradation |
| GO:0005829 cytosol | IDA PMID:28757607 Ubiquitination of stalled ribosome triggers ribosome-associa... | ACCEPT | Summary: Cytosolic localization is supported by the ribosome-associated quality-control role. Reason: ASCC3 acts on cytosolic collided ribosomes as part of hRQT. Cytosol annotations are appropriate for the RQC arm of ASCC3, while nuclear annotations remain appropriate for the DNA repair arm. Supporting Evidence: PMID:32579943 ASCC acts on ubiquitinated collided ribosomes to selectively disassemble the lead ribosome PMID:36302773 the trimeric hRQT complex-mediated subunit dissociation file:human/ASCC3/ASCC3-notes.md Conservative decision: retain the exact ribosome-rescue/RQC annotations and do not add a new ASCC3 annotation to `GO:0006515`. |
| GO:0180022 RQC-trigger complex | IDA PMID:12077347 Novel transcription coactivator complex containing activatin... | ACCEPT | Summary: ASCC3 is a core subunit of the human RQC-trigger/hRQT complex. Reason: The original ASC-1 complex paper supports ASCC3/p200 complex membership, and later RQC papers establish the ASCC3-ASCC2-TRIP4 hRQT complex as the ribosome quality-control trigger. The term is therefore biologically correct, even when the older original reference alone is not sufficient for the modern RQC label. Supporting Evidence: PMID:32099016 The hRQT complex is composed of ASCC3, ASCC2, and TRIP4 PMID:36302773 the trimeric hRQT complex-mediated subunit dissociation |
| GO:0005634 nucleus | IDA PMID:12077347 Novel transcription coactivator complex containing activatin... | ACCEPT | Summary: Nuclear localization is well supported for the ASCC DNA alkylation repair role. Reason: ASCC3 was originally purified from HeLa nuclei as an ASC-1 complex subunit and later shown to form alkylation-induced nuclear foci with ALKBH3/ASCC repair machinery. This is a core location for the DNA repair arm of ASCC3 biology. Supporting Evidence: PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent PMID:12077347 ASC-1 exists as a steady-state complex associated with three polypeptides, P200, P100, and P50, in HeLa nuclei |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-112123 | ACCEPT | Summary: Nucleoplasm annotations from Reactome ALKBH3 repair events are consistent with ASCC3 nuclear DNA repair function. Reason: Reactome ALKBH3 dealkylation events correctly place the ASCC1:ASCC2:ASCC3 repair complex in the nucleoplasm during alkylated DNA repair. This is compatible with direct nuclear foci evidence. Supporting Evidence: Reactome:R-HSA-112123 The reversal of alkylating damage of dsDNA by ALKBH3 requires the presence of DNA helicase ASCC3 PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-112124 | ACCEPT | Summary: Nucleoplasm annotations from Reactome ALKBH3 repair events are consistent with ASCC3 nuclear DNA repair function. Reason: Reactome ALKBH3 dealkylation events correctly place the ASCC1:ASCC2:ASCC3 repair complex in the nucleoplasm during alkylated DNA repair. This is compatible with direct nuclear foci evidence. Supporting Evidence: Reactome:R-HSA-112123 The reversal of alkylating damage of dsDNA by ALKBH3 requires the presence of DNA helicase ASCC3 PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-112125 | ACCEPT | Summary: Nucleoplasm annotations from Reactome ALKBH3 repair events are consistent with ASCC3 nuclear DNA repair function. Reason: Reactome ALKBH3 dealkylation events correctly place the ASCC1:ASCC2:ASCC3 repair complex in the nucleoplasm during alkylated DNA repair. This is compatible with direct nuclear foci evidence. Supporting Evidence: Reactome:R-HSA-112123 The reversal of alkylating damage of dsDNA by ALKBH3 requires the presence of DNA helicase ASCC3 PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5657617 | ACCEPT | Summary: Nucleoplasm annotations from Reactome ALKBH3 repair events are consistent with ASCC3 nuclear DNA repair function. Reason: Reactome ALKBH3 dealkylation events correctly place the ASCC1:ASCC2:ASCC3 repair complex in the nucleoplasm during alkylated DNA repair. This is compatible with direct nuclear foci evidence. Supporting Evidence: Reactome:R-HSA-112123 The reversal of alkylating damage of dsDNA by ALKBH3 requires the presence of DNA helicase ASCC3 PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5657637 | ACCEPT | Summary: Nucleoplasm annotations from Reactome ALKBH3 repair events are consistent with ASCC3 nuclear DNA repair function. Reason: Reactome ALKBH3 dealkylation events correctly place the ASCC1:ASCC2:ASCC3 repair complex in the nucleoplasm during alkylated DNA repair. This is compatible with direct nuclear foci evidence. Supporting Evidence: Reactome:R-HSA-112123 The reversal of alkylating damage of dsDNA by ALKBH3 requires the presence of DNA helicase ASCC3 PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5657642 | ACCEPT | Summary: Nucleoplasm annotations from Reactome ALKBH3 repair events are consistent with ASCC3 nuclear DNA repair function. Reason: Reactome ALKBH3 dealkylation events correctly place the ASCC1:ASCC2:ASCC3 repair complex in the nucleoplasm during alkylated DNA repair. This is compatible with direct nuclear foci evidence. Supporting Evidence: Reactome:R-HSA-112123 The reversal of alkylating damage of dsDNA by ALKBH3 requires the presence of DNA helicase ASCC3 PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | REMOVE | Summary: The high-throughput membrane localization is not consistent with the curated ASCC3 functional picture. Reason: ASCC3 is a soluble nuclear/cytosolic helicase in ASCC and hRQT complexes and lacks a compelling membrane-associated core role. The membrane-proteome HDA row is likely a peripheral or proteomics-carryover signal and should not be retained. Supporting Evidence: file:human/ASCC3/ASCC3-notes.md Remove the high-throughput `membrane` localization: ASCC3 is a soluble nuclear/cytosolic protein with no transmembrane-domain basis |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | KEEP AS NON CORE | Summary: RNA binding is plausible for ASCC3 but is less specific than its characterized helicase/RQT roles. Reason: ASCC3 contacts nucleic acids in both the DNA repair and ribosome-rescue settings, and purified ASCC3 can bind ssRNA in vitro, but RNA binding alone does not capture the core ATP-dependent activities. Keep the annotation as contextual rather than using it as the main MF. Supporting Evidence: PMID:29144457 Purified ASCC3 bound to ssRNA in vitro |
| GO:0005515 protein binding | IPI PMID:22055184 DNA unwinding by ASCC3 helicase is coupled to ALKBH3-depende... | MARK AS OVER ANNOTATED | Summary: The interaction evidence is real but generic protein binding is not an informative ASCC3 molecular-function annotation. Reason: These rows reflect physical associations from targeted or large-scale interaction data. They are useful as support for ASCC/ALKBH3/hRQT complex biology when specific partners are considered, but the generic GO protein binding term should not be retained as a core MF for ASCC3. Supporting Evidence: file:human/ASCC3/ASCC3-notes.md Treat generic binding annotations conservatively. `protein binding` rows are interaction evidence but not informative molecular-function curation. |
| GO:0005634 nucleus | TAS PMID:22055184 DNA unwinding by ASCC3 helicase is coupled to ALKBH3-depende... | ACCEPT | Summary: Nuclear localization is well supported for the ASCC DNA alkylation repair role. Reason: ASCC3 was originally purified from HeLa nuclei as an ASC-1 complex subunit and later shown to form alkylation-induced nuclear foci with ALKBH3/ASCC repair machinery. This is a core location for the DNA repair arm of ASCC3 biology. Supporting Evidence: PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent PMID:12077347 ASC-1 exists as a steady-state complex associated with three polypeptides, P200, P100, and P50, in HeLa nuclei |
| GO:0006307 DNA alkylation repair | IDA PMID:22055184 DNA unwinding by ASCC3 helicase is coupled to ALKBH3-depende... | ACCEPT | Summary: DNA alkylation repair is a directly supported core ASCC3 function. Reason: ASCC3 unwinds alkylated duplex DNA and supports ALKBH3-dependent DNA dealkylation repair. Later studies show alkylation-specific nuclear recruitment of the ASCC repair complex. Supporting Evidence: PMID:22055184 ASCC3 unwinds DNA to generate the single-stranded substrate needed for ALKBH3-mediated DNA repair PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent file:human/ASCC3/ASCC3-notes.md ASCC3 is a large ATP-dependent SF2 helicase with two well-supported functional contexts. |
| GO:0043138 3'-5' DNA helicase activity | IDA PMID:22055184 DNA unwinding by ASCC3 helicase is coupled to ALKBH3-depende... | ACCEPT | Summary: ASCC3 3'-5' DNA helicase activity is directly supported and central to ALKBH3-coupled dealkylation repair. Reason: The ALKBH3-ASCC paper demonstrates that ASCC3 unwinds duplex DNA to produce the single-stranded substrate preferred by ALKBH3. This is the most specific molecular-function term for the nuclear DNA repair activity. Supporting Evidence: PMID:22055184 ASCC3 unwinds DNA to generate the single-stranded substrate needed for ALKBH3-mediated DNA repair PMID:29144457 Endogenous ASCC3 formed nuclear foci upon treatment of U2OS cells with the alkylating agent file:human/ASCC3/ASCC3-notes.md ASCC3 is a large ATP-dependent SF2 helicase with two well-supported functional contexts. |
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Download this section (compressed HTML)Q: Should PN ribosome-associated QC mappings continue to project the broad GO:0006515 term to genes like ASCC3 when more specific ribosome-rescue and RQC catabolic-process terms are already present?
Q: Which endogenous mammalian stall substrates, beyond XBP1u and poly(A)-based reporters, depend most strongly on ASCC3/hRQT for ribosome rescue?
Q: Can ASCC3 disease-associated variants be separated into nuclear DNA-repair defects, cytosolic RQC defects, or combined helicase-loss mechanisms?
Q: Does the ASCC3/ASC-1 complex role in promoting translation initiation by scanning ribosomes at 5'-UTRs (Kito et al. 2023) warrant a distinct molecular-function or biological-process annotation separate from its collided-ribosome rescue activity?
Q: Are the neurodevelopmental/neuromuscular phenotypes of biallelic ASCC3 loss-of-function variants driven primarily by impaired ribosome-associated quality control, impaired DNA alkylation repair, impaired translation initiation, or a combination?
Q: Is the reported STAT3/CAND1-stabilizing, interferon-dampening activity of ASCC3 in NSCLC a direct helicase-dependent function or an indirect consequence of altered proteostasis or translation, and should it be curated as a molecular function?
Experiment: Use acute ASCC3 depletion or degron tagging with wild-type and ATPase-dead rescue constructs, then quantify endogenous collided-ribosome clearance by disome profiling and nascent-chain ubiquitination/degradation assays.
Hypothesis: ASCC3 ATPase activity is required for clearance of endogenous mammalian collided ribosomes, not only engineered stalling reporters.
Type: cell biology and ribosome profiling
Experiment: Engineer complex-selective ASCC3 separation-of-function variants or localization-restricted rescue constructs to compare MMS-induced ALKBH3 repair foci with hRQT-mediated poly(A)/XBP1u ribosome rescue.
Hypothesis: The nuclear dealkylation repair and cytosolic hRQT roles can be genetically decoupled.
Type: separation-of-function rescue
Experiment: Test ASCC3 patient variants in parallel assays for ALKBH3-dependent alkylation damage resistance and hRQT-dependent stalled-ribosome splitting.
Hypothesis: Some ASCC3 variants impair one functional context more strongly than the other.
Type: variant functional assay
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