ACIN1 encodes Acinus, a nuclear RNA-processing and apoptosis-associated protein. Its best-supported core functions are as an RNA-binding component of the ASAP complex and peripheral EJC-associated splicing machinery, where it participates in RNA splicing and regulation of mRNA processing, and as a caspase-activated factor that promotes apoptotic chromatin condensation. ACIN1 is localized mainly to the nucleus, nucleoplasm, and nuclear speckles. Drosophila Acinus literature links the ortholog to basal autophagy/autophagosome maturation, but current direct human evidence supports RNA processing and apoptosis more strongly than a direct human ACIN1 autophagy function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0008380 RNA splicing | IBA GO_REF:0000033 | ACCEPT | Summary: RNA splicing is a core ACIN1 process. Reason: ACIN1 is an ASAP/EJC-associated splicing factor and participates in spliceosome-linked RNA processing. Direct human iCLIP and depletion RNA-seq evidence (PMID:27365209) shows Acinus binds pre-mRNAs and spliced mRNAs and is required for inclusion of specific alternative cassette exons and faithful splicing of a subset of introns, supporting a direct role in exon/intron definition. Supporting Evidence: PMID:16314458 identified two novel EJC components, Acinus and SAP18 PMID:16314458 Acinus binds directly to another EJC component, RNPS1 file:human/ACIN1/ACIN1-uniprot.txt Auxiliary component of the splicing-dependent multiprotein exon junction complex PMID:22388736 transcriptional regulation, pre-mRNA splicing and mRNA quality control |
| GO:0061574 ASAP complex | IBA GO_REF:0000033 | ACCEPT | Summary: ASAP complex membership is a core ACIN1 cellular-component annotation. Reason: ACIN1 is a defining Acinus subunit of the RNPS1-SAP18-ACIN1 ASAP complex; this captures the specific complex context better than generic protein binding. Supporting Evidence: PMID:12665594 ASAP complexes are composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein PMID:20966198 RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex PMID:16314458 identified two novel EJC components, Acinus and SAP18 PMID:16314458 Acinus binds directly to another EJC component, RNPS1 |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MODIFY | Summary: Nucleic acid binding is too broad for the reviewed ACIN1 evidence. Reason: The specific supported molecular function is RNA binding in the ASAP/EJC splicing context, not generic nucleic acid binding. Proposed replacements: RNA binding Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt Component of the ASAP complexes which bind RNA PMID:22388736 both RNA- and protein-binding properties file:human/ACIN1/ACIN1-uniprot.txt Auxiliary component of the splicing-dependent multiprotein exon junction complex PMID:22388736 transcriptional regulation, pre-mRNA splicing and mRNA quality control |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: nucleus is a supported ACIN1 nuclear localization. Reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0005654 nucleoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: nucleoplasm is a supported ACIN1 nuclear localization. Reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0016607 nuclear speck | IEA GO_REF:0000044 | ACCEPT | Summary: nuclear speck is a supported ACIN1 nuclear localization. Reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0031981 nuclear lumen | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Nuclear lumen is a broad nuclear-location inference. Reason: The direction is correct for ACIN1, but more informative reviewed locations are nucleus, nucleoplasm, and nuclear speckle. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0005515 protein binding | IPI PMID:17332742 Composition and three-dimensional EM structure of double aff... | MARK AS OVER ANNOTATED | Summary: protein binding is too generic to represent ACIN1 function. Reason: The specific interaction biology is better represented by ASAP complex membership, EJC/RNPS1/SAP18 context, SRPK2/API5 regulatory context where relevant, and RNA binding/splicing terms. Generic binding terms add little functional information. |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | MARK AS OVER ANNOTATED | Summary: protein binding is too generic to represent ACIN1 function. Reason: The specific interaction biology is better represented by ASAP complex membership, EJC/RNPS1/SAP18 context, SRPK2/API5 regulatory context where relevant, and RNA binding/splicing terms. Generic binding terms add little functional information. |
| GO:0005515 protein binding | IPI PMID:22365833 Dynamic protein-protein interaction wiring of the human spli... | MARK AS OVER ANNOTATED | Summary: protein binding is too generic to represent ACIN1 function. Reason: The specific interaction biology is better represented by ASAP complex membership, EJC/RNPS1/SAP18 context, SRPK2/API5 regulatory context where relevant, and RNA binding/splicing terms. Generic binding terms add little functional information. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MARK AS OVER ANNOTATED | Summary: protein binding is too generic to represent ACIN1 function. Reason: The specific interaction biology is better represented by ASAP complex membership, EJC/RNPS1/SAP18 context, SRPK2/API5 regulatory context where relevant, and RNA binding/splicing terms. Generic binding terms add little functional information. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: protein binding is too generic to represent ACIN1 function. Reason: The specific interaction biology is better represented by ASAP complex membership, EJC/RNPS1/SAP18 context, SRPK2/API5 regulatory context where relevant, and RNA binding/splicing terms. Generic binding terms add little functional information. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | MARK AS OVER ANNOTATED | Summary: protein binding is too generic to represent ACIN1 function. Reason: The specific interaction biology is better represented by ASAP complex membership, EJC/RNPS1/SAP18 context, SRPK2/API5 regulatory context where relevant, and RNA binding/splicing terms. Generic binding terms add little functional information. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: protein binding is too generic to represent ACIN1 function. Reason: The specific interaction biology is better represented by ASAP complex membership, EJC/RNPS1/SAP18 context, SRPK2/API5 regulatory context where relevant, and RNA binding/splicing terms. Generic binding terms add little functional information. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: protein binding is too generic to represent ACIN1 function. Reason: The specific interaction biology is better represented by ASAP complex membership, EJC/RNPS1/SAP18 context, SRPK2/API5 regulatory context where relevant, and RNA binding/splicing terms. Generic binding terms add little functional information. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: protein binding is too generic to represent ACIN1 function. Reason: The specific interaction biology is better represented by ASAP complex membership, EJC/RNPS1/SAP18 context, SRPK2/API5 regulatory context where relevant, and RNA binding/splicing terms. Generic binding terms add little functional information. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: nucleoplasm is a supported ACIN1 nuclear localization. Reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0005634 nucleus | IDA PMID:12665594 ASAP, a novel protein complex involved in RNA processing and... | ACCEPT | Summary: nucleus is a supported ACIN1 nuclear localization. Reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:12665594 ASAP, a novel protein complex involved in RNA processing and... | ACCEPT | Summary: Positive regulation of apoptotic process is supported for ACIN1/ASAP. Reason: ASAP complex microinjection accelerates cell death, and ACIN1 is a caspase-activated apoptosis-associated factor. ACIN1 additionally couples its splicing activity to apoptosis by regulating splicing of the DFFA/ICAD transcript, a major regulator of apoptotic DNA fragmentation (PMID:27365209); caspase-3 cleavage of ACIN1 is restrained by the API5/AAC-11 interaction (PMID:38275765, review). Supporting Evidence: PMID:12665594 microinjection of ASAP complexes into mammalian cells resulted in acceleration of cell death PMID:12665594 after induction of apoptosis the ASAP complex disassembles PMID:10490026 induces apoptotic chromatin condensation after cleavage by caspase-3 PMID:10490026 essential for apoptotic chromatin condensation in vitro |
| GO:0050684 regulation of mRNA processing | IDA PMID:12665594 ASAP, a novel protein complex involved in RNA processing and... | MODIFY | Summary: Regulation of mRNA processing is sound but can be made more specific. Reason: ASAP complexes inhibit RNA processing in vitro splicing reactions; UniProt already represents this as negative regulation of mRNA splicing via spliceosome. Proposed replacements: negative regulation of mRNA splicing, via spliceosome Supporting Evidence: PMID:12665594 Addition of ASAP isoforms to in vitro splicing reactions inhibits RNA processing file:human/ACIN1/ACIN1-uniprot.txt The ASAP complex can inhibit RNA processing during in vitro splicing reactions PMID:12665594 ASAP complexes are composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein PMID:20966198 RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex |
| GO:0061574 ASAP complex | IPI PMID:12665594 ASAP, a novel protein complex involved in RNA processing and... | ACCEPT | Summary: ASAP complex membership is a core ACIN1 cellular-component annotation. Reason: ACIN1 is a defining Acinus subunit of the RNPS1-SAP18-ACIN1 ASAP complex; this captures the specific complex context better than generic protein binding. Supporting Evidence: PMID:12665594 ASAP complexes are composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein PMID:20966198 RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex PMID:16314458 identified two novel EJC components, Acinus and SAP18 PMID:16314458 Acinus binds directly to another EJC component, RNPS1 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770131 | ACCEPT | Summary: nucleoplasm is a supported ACIN1 nuclear localization. Reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770141 | ACCEPT | Summary: nucleoplasm is a supported ACIN1 nuclear localization. Reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770142 | ACCEPT | Summary: nucleoplasm is a supported ACIN1 nuclear localization. Reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770145 | ACCEPT | Summary: nucleoplasm is a supported ACIN1 nuclear localization. Reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770236 | ACCEPT | Summary: nucleoplasm is a supported ACIN1 nuclear localization. Reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9770847 | ACCEPT | Summary: nucleoplasm is a supported ACIN1 nuclear localization. Reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9794542 | ACCEPT | Summary: nucleoplasm is a supported ACIN1 nuclear localization. Reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | ACCEPT | Summary: RNA binding is consistent with ACIN1/ASAP complex function. Reason: ACIN1 confers RNA-binding to the ASAP complex and is supported by RNA-binding proteome datasets, so the HDA RNA-binding rows are appropriate. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt Component of the ASAP complexes which bind RNA PMID:22388736 both RNA- and protein-binding properties PMID:12665594 ASAP complexes are composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein PMID:20966198 RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | ACCEPT | Summary: RNA binding is consistent with ACIN1/ASAP complex function. Reason: ACIN1 confers RNA-binding to the ASAP complex and is supported by RNA-binding proteome datasets, so the HDA RNA-binding rows are appropriate. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt Component of the ASAP complexes which bind RNA PMID:22388736 both RNA- and protein-binding properties PMID:12665594 ASAP complexes are composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein PMID:20966198 RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex |
| GO:0061574 ASAP complex | IDA PMID:12665594 ASAP, a novel protein complex involved in RNA processing and... | ACCEPT | Summary: ASAP complex membership is a core ACIN1 cellular-component annotation. Reason: ACIN1 is a defining Acinus subunit of the RNPS1-SAP18-ACIN1 ASAP complex; this captures the specific complex context better than generic protein binding. Supporting Evidence: PMID:12665594 ASAP complexes are composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein PMID:20966198 RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex PMID:16314458 identified two novel EJC components, Acinus and SAP18 PMID:16314458 Acinus binds directly to another EJC component, RNPS1 |
| GO:0016607 nuclear speck | IDA PMID:20966198 Human SAP18 mediates assembly of a splicing regulatory multi... | ACCEPT | Summary: nuclear speck is a supported ACIN1 nuclear localization. Reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201630 | MARK AS OVER ANNOTATED | Summary: Cytosol is not the supported core ACIN1 location. Reason: ACIN1 is primarily nuclear/nucleoplasmic/nuclear-speckle localized. The Reactome cytosol row is tied to caspase-mediated cleavage context and should not override the nuclear localization evidence. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0005515 protein binding | IPI PMID:18951082 Death by splicing: tumor suppressor RBM5 freezes splice-site... | MARK AS OVER ANNOTATED | Summary: protein binding is too generic to represent ACIN1 function. Reason: The specific interaction biology is better represented by ASAP complex membership, EJC/RNPS1/SAP18 context, SRPK2/API5 regulatory context where relevant, and RNA binding/splicing terms. Generic binding terms add little functional information. |
| GO:0003676 nucleic acid binding | NAS PMID:10490026 Acinus is a caspase-3-activated protein required for apoptot... | MODIFY | Summary: Nucleic acid binding is too broad for the reviewed ACIN1 evidence. Reason: The specific supported molecular function is RNA binding in the ASAP/EJC splicing context, not generic nucleic acid binding. Proposed replacements: RNA binding Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt Component of the ASAP complexes which bind RNA PMID:22388736 both RNA- and protein-binding properties file:human/ACIN1/ACIN1-uniprot.txt Auxiliary component of the splicing-dependent multiprotein exon junction complex PMID:22388736 transcriptional regulation, pre-mRNA splicing and mRNA quality control |
| GO:0005634 nucleus | IDA PMID:10490026 Acinus is a caspase-3-activated protein required for apoptot... | ACCEPT | Summary: nucleus is a supported ACIN1 nuclear localization. Reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm. PMID:20966198 nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus |
| GO:0016887 ATP hydrolysis activity | NAS PMID:10490026 Acinus is a caspase-3-activated protein required for apoptot... | REMOVE | Summary: ATP hydrolysis activity is not supported for ACIN1. Reason: ACIN1 is an RRM/SAP-domain RNA-processing and apoptosis-associated factor. The reviewed UniProt function and cached primary papers do not support ACIN1 as an ATPase. Supporting Evidence: file:human/ACIN1/ACIN1-uniprot.txt InterPro; IPR034257; Acinus_RRM file:human/ACIN1/ACIN1-uniprot.txt InterPro; IPR003034; SAP_dom |
| GO:0019899 enzyme binding | NAS PMID:10490026 Acinus is a caspase-3-activated protein required for apoptot... | MARK AS OVER ANNOTATED | Summary: enzyme binding is too generic to represent ACIN1 function. Reason: The specific interaction biology is better represented by ASAP complex membership, EJC/RNPS1/SAP18 context, SRPK2/API5 regulatory context where relevant, and RNA binding/splicing terms. Generic binding terms add little functional information. |
| GO:0030218 erythrocyte differentiation | IEP PMID:11208865 Caspase activation is required for terminal erythroid differ... | KEEP AS NON CORE | Summary: Erythrocyte differentiation is a non-core caspase-substrate context for ACIN1. Reason: Human erythroid differentiation involves transient caspase activation and Acinus cleavage, but the annotation reflects a broader differentiation program rather than ACIN1's core RNA-processing/apoptotic-chromatin-condensation function. Supporting Evidence: PMID:11208865 cleave proteins involved in nucleus integrity (lamin B) and chromatin condensation (acinus)without inducing cell death PMID:11208865 normal erythroid differentiation requires the transient activation of several caspases |
| GO:0030263 apoptotic chromosome condensation | IDA PMID:10490026 Acinus is a caspase-3-activated protein required for apoptot... | ACCEPT | Summary: Apoptotic chromosome condensation is a core ACIN1 apoptosis function. Reason: The original Acinus study directly identified ACIN1 as a caspase-3-activated nuclear factor required for apoptotic chromatin condensation. Supporting Evidence: PMID:10490026 induces apoptotic chromatin condensation after cleavage by caspase-3 PMID:10490026 essential for apoptotic chromatin condensation in vitro |
| GO:0045657 positive regulation of monocyte differentiation | IEP PMID:12393560 Specific involvement of caspases in the differentiation of m... | KEEP AS NON CORE | Summary: Positive regulation of monocyte differentiation is a non-core caspase-substrate context for ACIN1. Reason: The evidence shows Acinus cleavage during caspase-dependent monocyte-to-macrophage differentiation, but this is secondary to the core ACIN1 functions reviewed here. Supporting Evidence: PMID:12393560 leads to the cleavage of the protein acinus PMID:12393560 caspase activation specifically contributes to the differentiation of monocytes into macrophages |
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Download this section (compressed HTML)Q: Does human ACIN1 retain the Drosophila Acinus basal-autophagy/autophagosome-maturation role suggested by the PN context, or is that function lineage- or tissue-specific?
Suggested experts: GO autophagy editors, Drosophila autophagy experts, human RNA-processing curators
Q: Should broad ACIN1 protein-binding interaction rows be replaced by more specific complex membership and RNA-binding/splicing annotations?
Suggested experts: GO molecular-function editors, ComplexPortal curators
Q: Does ACIN1-dependent splicing of DFFA/ICAD constitute a direct regulatory link between its RNA-processing and apoptosis functions that warrants a distinct annotation (e.g., regulation of an apoptosis-related splicing target)?
Suggested experts: GO apoptosis editors, human RNA-processing curators
Experiment: Test basal autophagic flux, autophagosome maturation, and lysosomal cargo clearance in human ACIN1 knockout/rescue cells using endogenous ACIN1 isoforms and Drosophila-aligned phosphorylation/caspase-site mutants.
Hypothesis: The Drosophila Acinus basal-autophagy function is conserved in human ACIN1 only under specific stress, neuronal, or proteotoxic contexts.
Type: cell biology/autophagy flux assay
Experiment: Map ACIN1-dependent RNA targets and splicing changes after ACIN1 depletion, with rescue by ASAP-complex-binding mutants, and compare them with apoptosis/autophagy pathway transcripts.
Hypothesis: ACIN1 affects proteostasis-related phenotypes indirectly through ASAP/EJC-mediated RNA processing rather than as a direct autophagy machinery component.
Type: RNA-seq/splicing reporter
Experiment: Quantify DFFA/ICAD intron retention and functional ICAD/CAD output in ACIN1-depleted cells versus cells rescued with RNA-binding-competent ACIN1, and assay downstream apoptotic DNA fragmentation, including under API5 overexpression that blocks caspase-3 cleavage of ACIN1.
Hypothesis: ACIN1 couples its splicing activity to apoptotic DNA fragmentation via DFFA/ICAD splicing, and this axis is modulated by API5-dependent protection of ACIN1 from caspase-3 cleavage.
Type: splicing reporter/apoptosis DNA-fragmentation assay
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