id: Q9UKV3 gene_symbol: ACIN1 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- 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. alternative_products: - name: 1 (L) id: Q9UKV3-1 - name: 2 (S') id: Q9UKV3-2 sequence_note: VSP_004025, VSP_004028 - name: 3 (S) id: Q9UKV3-3 sequence_note: VSP_004026, VSP_004029 - name: '4' id: Q9UKV3-5 sequence_note: VSP_042204, VSP_042205 existing_annotations: - term: id: GO:0008380 label: RNA splicing evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: RNA splicing is a core ACIN1 process. action: ACCEPT 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. supported_by: - reference_id: PMID:16314458 supporting_text: identified two novel EJC components, Acinus and SAP18 - reference_id: PMID:16314458 supporting_text: Acinus binds directly to another EJC component, RNPS1 - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: Auxiliary component of the splicing-dependent multiprotein exon junction complex - reference_id: PMID:22388736 supporting_text: transcriptional regulation, pre-mRNA splicing and mRNA quality control - term: id: GO:0061574 label: ASAP complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: ASAP complex membership is a core ACIN1 cellular-component annotation. action: ACCEPT 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. supported_by: - reference_id: PMID:12665594 supporting_text: ASAP complexes are composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein - reference_id: PMID:20966198 supporting_text: RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex - reference_id: PMID:16314458 supporting_text: identified two novel EJC components, Acinus and SAP18 - reference_id: PMID:16314458 supporting_text: Acinus binds directly to another EJC component, RNPS1 - term: id: GO:0003676 label: nucleic acid binding evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables review: summary: Nucleic acid binding is too broad for the reviewed ACIN1 evidence. action: MODIFY reason: The specific supported molecular function is RNA binding in the ASAP/EJC splicing context, not generic nucleic acid binding. proposed_replacement_terms: - id: GO:0003723 label: RNA binding supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: Component of the ASAP complexes which bind RNA - reference_id: PMID:22388736 supporting_text: both RNA- and protein-binding properties - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: Auxiliary component of the splicing-dependent multiprotein exon junction complex - reference_id: PMID:22388736 supporting_text: transcriptional regulation, pre-mRNA splicing and mRNA quality control - term: id: GO:0005634 label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: nucleus is a supported ACIN1 nuclear localization. action: ACCEPT reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0005654 label: nucleoplasm evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: nucleoplasm is a supported ACIN1 nuclear localization. action: ACCEPT reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0016607 label: nuclear speck evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: nuclear speck is a supported ACIN1 nuclear localization. action: ACCEPT reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0031981 label: nuclear lumen evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: Nuclear lumen is a broad nuclear-location inference. action: KEEP_AS_NON_CORE reason: The direction is correct for ACIN1, but more informative reviewed locations are nucleus, nucleoplasm, and nuclear speckle. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17332742 qualifier: enables review: summary: protein binding is too generic to represent ACIN1 function. action: MARK_AS_OVER_ANNOTATED 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20195357 qualifier: enables review: summary: protein binding is too generic to represent ACIN1 function. action: MARK_AS_OVER_ANNOTATED 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22365833 qualifier: enables review: summary: protein binding is too generic to represent ACIN1 function. action: MARK_AS_OVER_ANNOTATED 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23602568 qualifier: enables review: summary: protein binding is too generic to represent ACIN1 function. action: MARK_AS_OVER_ANNOTATED 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28514442 qualifier: enables review: summary: protein binding is too generic to represent ACIN1 function. action: MARK_AS_OVER_ANNOTATED 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:30021884 qualifier: enables review: summary: protein binding is too generic to represent ACIN1 function. action: MARK_AS_OVER_ANNOTATED 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables review: summary: protein binding is too generic to represent ACIN1 function. action: MARK_AS_OVER_ANNOTATED 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35271311 qualifier: enables review: summary: protein binding is too generic to represent ACIN1 function. action: MARK_AS_OVER_ANNOTATED 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:40205054 qualifier: enables review: summary: protein binding is too generic to represent ACIN1 function. action: MARK_AS_OVER_ANNOTATED 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. - term: id: GO:0005654 label: nucleoplasm evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: nucleoplasm is a supported ACIN1 nuclear localization. action: ACCEPT reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:12665594 qualifier: located_in review: summary: nucleus is a supported ACIN1 nuclear localization. action: ACCEPT reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0043065 label: positive regulation of apoptotic process evidence_type: IDA original_reference_id: PMID:12665594 qualifier: involved_in review: summary: Positive regulation of apoptotic process is supported for ACIN1/ASAP. action: ACCEPT 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). supported_by: - reference_id: PMID:12665594 supporting_text: microinjection of ASAP complexes into mammalian cells resulted in acceleration of cell death - reference_id: PMID:12665594 supporting_text: after induction of apoptosis the ASAP complex disassembles - reference_id: PMID:10490026 supporting_text: induces apoptotic chromatin condensation after cleavage by caspase-3 - reference_id: PMID:10490026 supporting_text: essential for apoptotic chromatin condensation in vitro - term: id: GO:0050684 label: regulation of mRNA processing evidence_type: IDA original_reference_id: PMID:12665594 qualifier: involved_in review: summary: Regulation of mRNA processing is sound but can be made more specific. action: MODIFY reason: ASAP complexes inhibit RNA processing in vitro splicing reactions; UniProt already represents this as negative regulation of mRNA splicing via spliceosome. proposed_replacement_terms: - id: GO:0048025 label: negative regulation of mRNA splicing, via spliceosome supported_by: - reference_id: PMID:12665594 supporting_text: Addition of ASAP isoforms to in vitro splicing reactions inhibits RNA processing - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: The ASAP complex can inhibit RNA processing during in vitro splicing reactions - reference_id: PMID:12665594 supporting_text: ASAP complexes are composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein - reference_id: PMID:20966198 supporting_text: RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex - term: id: GO:0061574 label: ASAP complex evidence_type: IPI original_reference_id: PMID:12665594 qualifier: part_of review: summary: ASAP complex membership is a core ACIN1 cellular-component annotation. action: ACCEPT 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. supported_by: - reference_id: PMID:12665594 supporting_text: ASAP complexes are composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein - reference_id: PMID:20966198 supporting_text: RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex - reference_id: PMID:16314458 supporting_text: identified two novel EJC components, Acinus and SAP18 - reference_id: PMID:16314458 supporting_text: Acinus binds directly to another EJC component, RNPS1 - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-9770131 qualifier: located_in review: summary: nucleoplasm is a supported ACIN1 nuclear localization. action: ACCEPT reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-9770141 qualifier: located_in review: summary: nucleoplasm is a supported ACIN1 nuclear localization. action: ACCEPT reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-9770142 qualifier: located_in review: summary: nucleoplasm is a supported ACIN1 nuclear localization. action: ACCEPT reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-9770145 qualifier: located_in review: summary: nucleoplasm is a supported ACIN1 nuclear localization. action: ACCEPT reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-9770236 qualifier: located_in review: summary: nucleoplasm is a supported ACIN1 nuclear localization. action: ACCEPT reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-9770847 qualifier: located_in review: summary: nucleoplasm is a supported ACIN1 nuclear localization. action: ACCEPT reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-9794542 qualifier: located_in review: summary: nucleoplasm is a supported ACIN1 nuclear localization. action: ACCEPT reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0003723 label: RNA binding evidence_type: HDA original_reference_id: PMID:22658674 qualifier: enables review: summary: RNA binding is consistent with ACIN1/ASAP complex function. action: ACCEPT 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. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: Component of the ASAP complexes which bind RNA - reference_id: PMID:22388736 supporting_text: both RNA- and protein-binding properties - reference_id: PMID:12665594 supporting_text: ASAP complexes are composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein - reference_id: PMID:20966198 supporting_text: RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex - term: id: GO:0003723 label: RNA binding evidence_type: HDA original_reference_id: PMID:22681889 qualifier: enables review: summary: RNA binding is consistent with ACIN1/ASAP complex function. action: ACCEPT 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. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: Component of the ASAP complexes which bind RNA - reference_id: PMID:22388736 supporting_text: both RNA- and protein-binding properties - reference_id: PMID:12665594 supporting_text: ASAP complexes are composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein - reference_id: PMID:20966198 supporting_text: RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex - term: id: GO:0061574 label: ASAP complex evidence_type: IDA original_reference_id: PMID:12665594 qualifier: part_of review: summary: ASAP complex membership is a core ACIN1 cellular-component annotation. action: ACCEPT 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. supported_by: - reference_id: PMID:12665594 supporting_text: ASAP complexes are composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein - reference_id: PMID:20966198 supporting_text: RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex - reference_id: PMID:16314458 supporting_text: identified two novel EJC components, Acinus and SAP18 - reference_id: PMID:16314458 supporting_text: Acinus binds directly to another EJC component, RNPS1 - term: id: GO:0016607 label: nuclear speck evidence_type: IDA original_reference_id: PMID:20966198 qualifier: located_in review: summary: nuclear speck is a supported ACIN1 nuclear localization. action: ACCEPT reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-201630 qualifier: located_in review: summary: Cytosol is not the supported core ACIN1 location. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18951082 qualifier: enables review: summary: protein binding is too generic to represent ACIN1 function. action: MARK_AS_OVER_ANNOTATED 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. - term: id: GO:0003676 label: nucleic acid binding evidence_type: NAS original_reference_id: PMID:10490026 qualifier: enables review: summary: Nucleic acid binding is too broad for the reviewed ACIN1 evidence. action: MODIFY reason: The specific supported molecular function is RNA binding in the ASAP/EJC splicing context, not generic nucleic acid binding. proposed_replacement_terms: - id: GO:0003723 label: RNA binding supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: Component of the ASAP complexes which bind RNA - reference_id: PMID:22388736 supporting_text: both RNA- and protein-binding properties - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: Auxiliary component of the splicing-dependent multiprotein exon junction complex - reference_id: PMID:22388736 supporting_text: transcriptional regulation, pre-mRNA splicing and mRNA quality control - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:10490026 qualifier: located_in review: summary: nucleus is a supported ACIN1 nuclear localization. action: ACCEPT reason: ACIN1 localizes to nucleus, nucleoplasm, and nuclear speckles, matching its ASAP/EJC splicing regulatory role. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Nucleus, nucleoplasm.' - reference_id: PMID:20966198 supporting_text: nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus - term: id: GO:0016887 label: ATP hydrolysis activity evidence_type: NAS original_reference_id: PMID:10490026 qualifier: enables review: summary: ATP hydrolysis activity is not supported for ACIN1. action: REMOVE 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. supported_by: - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: InterPro; IPR034257; Acinus_RRM - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: InterPro; IPR003034; SAP_dom - term: id: GO:0019899 label: enzyme binding evidence_type: NAS original_reference_id: PMID:10490026 qualifier: enables review: summary: enzyme binding is too generic to represent ACIN1 function. action: MARK_AS_OVER_ANNOTATED 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. - term: id: GO:0030218 label: erythrocyte differentiation evidence_type: IEP original_reference_id: PMID:11208865 qualifier: involved_in review: summary: Erythrocyte differentiation is a non-core caspase-substrate context for ACIN1. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:11208865 supporting_text: cleave proteins involved in nucleus integrity (lamin B) and chromatin condensation (acinus)without inducing cell death - reference_id: PMID:11208865 supporting_text: normal erythroid differentiation requires the transient activation of several caspases - term: id: GO:0030263 label: apoptotic chromosome condensation evidence_type: IDA original_reference_id: PMID:10490026 qualifier: involved_in review: summary: Apoptotic chromosome condensation is a core ACIN1 apoptosis function. action: ACCEPT reason: The original Acinus study directly identified ACIN1 as a caspase-3-activated nuclear factor required for apoptotic chromatin condensation. supported_by: - reference_id: PMID:10490026 supporting_text: induces apoptotic chromatin condensation after cleavage by caspase-3 - reference_id: PMID:10490026 supporting_text: essential for apoptotic chromatin condensation in vitro - term: id: GO:0045657 label: positive regulation of monocyte differentiation evidence_type: IEP original_reference_id: PMID:12393560 qualifier: involved_in review: summary: Positive regulation of monocyte differentiation is a non-core caspase-substrate context for ACIN1. action: KEEP_AS_NON_CORE reason: The evidence shows Acinus cleavage during caspase-dependent monocyte-to-macrophage differentiation, but this is secondary to the core ACIN1 functions reviewed here. supported_by: - reference_id: PMID:12393560 supporting_text: leads to the cleavage of the protein acinus - reference_id: PMID:12393560 supporting_text: caspase activation specifically contributes to the differentiation of monocytes into macrophages references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000052 title: Gene Ontology annotation based on curation of immunofluorescence data findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: PMID:10490026 title: Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation. findings: - statement: Identifies Acinus as a caspase-3-activated nuclear factor required for apoptotic chromatin condensation. - id: PMID:11208865 title: Caspase activation is required for terminal erythroid differentiation. findings: [] - id: PMID:12393560 title: Specific involvement of caspases in the differentiation of monocytes into macrophages. findings: [] - id: PMID:12665594 title: ASAP, a novel protein complex involved in RNA processing and apoptosis. findings: - statement: Defines ACIN1-containing ASAP complexes as SAP18/RNPS1/Acinus complexes that inhibit RNA processing in vitro and promote apoptosis after microinjection. - id: PMID:17332742 title: Composition and three-dimensional EM structure of double affinity-purified, human prespliceosomal A complexes. findings: [] - id: PMID:18951082 title: 'Death by splicing: tumor suppressor RBM5 freezes splice-site pairing.' findings: [] - id: PMID:20195357 title: A comprehensive resource of interacting protein regions for refining human transcription factor networks. findings: [] - id: PMID:20966198 title: Human SAP18 mediates assembly of a splicing regulatory multiprotein complex via its ubiquitin-like fold. findings: - statement: Shows RNPS1, Acinus, and SAP18 form a nuclear speckle-localized ASAP splicing regulatory complex. - id: PMID:22365833 title: Dynamic protein-protein interaction wiring of the human spliceosome. findings: [] - id: PMID:22658674 title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. findings: [] - id: PMID:22681889 title: The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. findings: [] - id: PMID:23602568 title: The protein interaction landscape of the human CMGC kinase group. findings: [] - id: PMID:28514442 title: Architecture of the human interactome defines protein communities and disease networks. findings: [] - id: PMID:30021884 title: Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. findings: [] - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] - id: PMID:35271311 title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.' findings: [] - id: PMID:40205054 title: Multimodal cell maps as a foundation for structural and functional genomics. findings: [] - id: Reactome:R-HSA-201630 title: Caspase-mediated cleavage of Acinus findings: [] - id: Reactome:R-HSA-9770131 title: Formation of the Spliceosomal B* complex findings: [] - id: Reactome:R-HSA-9770141 title: Formation of the Spliceosomal C* complex findings: [] - id: Reactome:R-HSA-9770142 title: Formation of the Spliceosomal B complex findings: [] - id: Reactome:R-HSA-9770145 title: Formation of the Spliceosomal Bact complex findings: [] - id: Reactome:R-HSA-9770236 title: Formation of the Spliceosomal P complex and exon ligation findings: [] - id: Reactome:R-HSA-9770847 title: Spliceosomal P complex dissociates yielding the intron-containing complex (ILS) and the spliced mRNP (new) findings: [] - id: Reactome:R-HSA-9794542 title: Formation of the Spliceosomal C complex containing intron lariat findings: [] - id: file:human/ACIN1/ACIN1-uniprot.txt title: UniProtKB record for human ACIN1 findings: - statement: UniProt summarizes ACIN1 as an EJC/ASAP-associated RNA-binding splicing factor that can induce apoptotic chromatin condensation after CASP3 activation. - id: file:human/ACIN1/ACIN1-notes.md title: ACIN1 review notes findings: - statement: Manual PN-context curation notes; Drosophila Acinus autophagy evidence was kept as orthology/context rather than human ACIN1 evidence. - id: PMID:16314458 title: Biochemical analysis of the EJC reveals two new factors and a stable tetrameric protein core. findings: - statement: Identifies Acinus and SAP18 as EJC components and shows Acinus binds RNPS1 in the ASAP complex. - id: PMID:22388736 title: The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex. findings: - statement: Structural evidence for the Acinus-RNPS1-SAP18 ternary complex and its RNA/protein-binding properties. - id: PMID:27365209 title: The RNA-binding profile of Acinus, a peripheral component of the exon junction complex, reveals its role in splicing regulation. full_text_unavailable: true findings: - statement: iCLIP shows human Acinus binds pre-mRNAs (a subset of suboptimal introns) and spliced mRNAs as a peripheral EJC factor, and Acinus depletion alters inclusion of specific alternative cassette exons and faithful splicing of subsets of introns, indicating a direct role in exon and intron definition. - statement: Acinus regulates splicing of the DFFA/ICAD transcript, linking its splicing-regulatory activity to the apoptotic DNA fragmentation pathway. - id: PMID:28539829 title: Multifaceted Regulation of Gene Expression by the Apoptosis- and Splicing-Associated Protein Complex and Its Components. full_text_unavailable: true findings: - statement: Reviews the RNPS1-Acinus-SAP18 ASAP complex (and an alternative Pinin-containing PSAP complex), its nuclear-speckle localization, EJC association, and roles spanning transcription, splicing, translation and nonsense-mediated decay. - id: PMID:38275765 title: 'Apoptosis Inhibitor 5: A Multifaceted Regulator of Cell Fate.' full_text_unavailable: true findings: - statement: Reviews API5/AAC-11 as a binding partner that protects Acinus from caspase-3 cleavage, thereby restraining Acinus-mediated apoptotic chromatin condensation and DNA fragmentation. core_functions: - molecular_function: id: GO:0003723 label: RNA binding description: ACIN1 provides RNA-binding/splicing-regulatory activity in the RNPS1-SAP18-ACIN1 ASAP complex and EJC-associated mRNP context. directly_involved_in: - id: GO:0008380 label: RNA splicing - id: GO:0048025 label: negative regulation of mRNA splicing, via spliceosome locations: - id: GO:0016607 label: nuclear speck - id: GO:0005654 label: nucleoplasm - id: GO:0005634 label: nucleus in_complex: id: GO:0061574 label: ASAP complex supported_by: - reference_id: PMID:12665594 supporting_text: ASAP complexes are composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein - reference_id: PMID:20966198 supporting_text: RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex - reference_id: PMID:16314458 supporting_text: identified two novel EJC components, Acinus and SAP18 - reference_id: PMID:16314458 supporting_text: Acinus binds directly to another EJC component, RNPS1 - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: Component of the ASAP complexes which bind RNA - reference_id: PMID:22388736 supporting_text: both RNA- and protein-binding properties - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: Auxiliary component of the splicing-dependent multiprotein exon junction complex - reference_id: PMID:22388736 supporting_text: transcriptional regulation, pre-mRNA splicing and mRNA quality control - reference_id: PMID:12665594 supporting_text: Addition of ASAP isoforms to in vitro splicing reactions inhibits RNA processing - reference_id: file:human/ACIN1/ACIN1-uniprot.txt supporting_text: The ASAP complex can inhibit RNA processing during in vitro splicing reactions - molecular_function: id: GO:0003723 label: RNA binding description: Caspase-activated ACIN1/Acinus promotes apoptotic chromatin condensation and contributes to apoptosis-associated nuclear remodeling. directly_involved_in: - id: GO:0030263 label: apoptotic chromosome condensation - id: GO:0043065 label: positive regulation of apoptotic process locations: - id: GO:0005634 label: nucleus - id: GO:0005654 label: nucleoplasm supported_by: - reference_id: PMID:10490026 supporting_text: induces apoptotic chromatin condensation after cleavage by caspase-3 - reference_id: PMID:10490026 supporting_text: essential for apoptotic chromatin condensation in vitro - reference_id: PMID:12665594 supporting_text: microinjection of ASAP complexes into mammalian cells resulted in acceleration of cell death - reference_id: PMID:12665594 supporting_text: after induction of apoptosis the ASAP complex disassembles proposed_new_terms: [] suggested_questions: - question: 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? experts: - GO autophagy editors - Drosophila autophagy experts - human RNA-processing curators - question: Should broad ACIN1 protein-binding interaction rows be replaced by more specific complex membership and RNA-binding/splicing annotations? experts: - GO molecular-function editors - ComplexPortal curators - question: 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)? experts: - GO apoptosis editors - human RNA-processing curators suggested_experiments: - description: 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. experiment_type: cell biology/autophagy flux assay - description: 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. experiment_type: RNA-seq/splicing reporter - description: 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. experiment_type: splicing reporter/apoptosis DNA-fragmentation assay