Existing Annotations Review

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

Core Functions

ACIN1 provides RNA-binding/splicing-regulatory activity in the RNPS1-SAP18-ACIN1 ASAP complex and EJC-associated mRNP context.

Molecular Function:

RNA binding

Directly Involved In:

RNA splicing negative regulation of mRNA splicing, via spliceosome

Cellular Locations:

nuclear speck nucleoplasm nucleus

In Complex:

ASAP complex

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
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
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

Caspase-activated ACIN1/Acinus promotes apoptotic chromatin condensation and contributes to apoptosis-associated nuclear remodeling.

Molecular Function:

RNA binding

Directly Involved In:

apoptotic chromosome condensation positive regulation of apoptotic process

Cellular Locations:

nucleus nucleoplasm

Supporting Evidence:

PMID:10490026
induces apoptotic chromatin condensation after cleavage by caspase-3
PMID:10490026
essential for apoptotic chromatin condensation in vitro
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

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

PMID:10490026

Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation.

Identifies Acinus as a caspase-3-activated nuclear factor required for apoptotic chromatin condensation.

PMID:11208865

Caspase activation is required for terminal erythroid differentiation.

PMID:12393560

Specific involvement of caspases in the differentiation of monocytes into macrophages.

PMID:12665594

ASAP, a novel protein complex involved in RNA processing and apoptosis.

Defines ACIN1-containing ASAP complexes as SAP18/RNPS1/Acinus complexes that inhibit RNA processing in vitro and promote apoptosis after microinjection.

PMID:17332742

Composition and three-dimensional EM structure of double affinity-purified, human prespliceosomal A complexes.

PMID:18951082

Death by splicing: tumor suppressor RBM5 freezes splice-site pairing.

PMID:20195357

A comprehensive resource of interacting protein regions for refining human transcription factor networks.

PMID:20966198

Human SAP18 mediates assembly of a splicing regulatory multiprotein complex via its ubiquitin-like fold.

Shows RNPS1, Acinus, and SAP18 form a nuclear speckle-localized ASAP splicing regulatory complex.

PMID:22365833

Dynamic protein-protein interaction wiring of the human spliceosome.

PMID:22658674

Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.

PMID:22681889

The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.

PMID:23602568

The protein interaction landscape of the human CMGC kinase group.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:30021884

Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

Reactome:R-HSA-201630

Caspase-mediated cleavage of Acinus

Reactome:R-HSA-9770131

Formation of the Spliceosomal B* complex

Reactome:R-HSA-9770141

Formation of the Spliceosomal C* complex

Reactome:R-HSA-9770142

Formation of the Spliceosomal B complex

Reactome:R-HSA-9770145

Formation of the Spliceosomal Bact complex

Reactome:R-HSA-9770236

Formation of the Spliceosomal P complex and exon ligation

Reactome:R-HSA-9770847

Spliceosomal P complex dissociates yielding the intron-containing complex (ILS) and the spliced mRNP (new)

Reactome:R-HSA-9794542

Formation of the Spliceosomal C complex containing intron lariat

file:human/ACIN1/ACIN1-uniprot.txt

UniProtKB record for human ACIN1

UniProt summarizes ACIN1 as an EJC/ASAP-associated RNA-binding splicing factor that can induce apoptotic chromatin condensation after CASP3 activation.

file:human/ACIN1/ACIN1-notes.md

ACIN1 review notes

Manual PN-context curation notes; Drosophila Acinus autophagy evidence was kept as orthology/context rather than human ACIN1 evidence.

PMID:16314458

Biochemical analysis of the EJC reveals two new factors and a stable tetrameric protein core.

Identifies Acinus and SAP18 as EJC components and shows Acinus binds RNPS1 in the ASAP complex.

PMID:22388736

The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex.

Structural evidence for the Acinus-RNPS1-SAP18 ternary complex and its RNA/protein-binding properties.

PMID:27365209

The RNA-binding profile of Acinus, a peripheral component of the exon junction complex, reveals its role in splicing regulation.

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.
Acinus regulates splicing of the DFFA/ICAD transcript, linking its splicing-regulatory activity to the apoptotic DNA fragmentation pathway.

PMID:28539829

Multifaceted Regulation of Gene Expression by the Apoptosis- and Splicing-Associated Protein Complex and Its Components.

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.

PMID:38275765

Apoptosis Inhibitor 5: A Multifaceted Regulator of Cell Fate.

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.

Suggested Experiments

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

Deep Research

Falcon

(ACIN1-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 24 citations 2 artifacts 2026-06-07T04:13:22.291403

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## Context ID: pqac-00000028 The document provides several figures relevant to Acinus: - **Figure 1A** shows a schematic of the Acinus protein isoforms (L, S, a (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: Human ACIN1 (Acinus) functional annotation (UniProt Q9UKV3)

0) Gene/protein identity verification (mandatory)

The UniProt accession Q9UKV3 corresponds to human ACIN1, encoding Acinus ("Apoptotic chromatin condensation inducer in the nucleus"), an RNA-binding protein originally described in apoptosis and later linked to pre-mRNA processing. Peer-reviewed sources consistently use ACIN1/Acinus and describe it as a nuclear RNA-binding factor with three major isoforms (Acinus-L, Acinus-S′, Acinus-S) that share an RNA recognition motif (RRM) and a C-terminal RS-like domain; Acinus-L additionally contains an N-terminal SAP domain (rodor2016thernabindingprofile pages 1-2, rodor2016thernabindingprofile pages 2-3, deka2017multifacetedregulationof pages 2-3). A figure schematic of the isoforms and domain organization is shown in Rodor et al. (2016) (rodor2016thernabindingprofile media 9db37663).

1) Key concepts and definitions (current understanding)

1.1 ACIN1 is a non-enzymatic RNA-binding scaffold/regulator

ACIN1 is not described as an enzyme or transporter; the core functional concept is that Acinus is an RNA-binding protein (RBP) that helps organize post-transcriptional gene regulation, particularly pre-mRNA splicing and exon-junction complex (EJC)-associated processes (rodor2016thernabindingprofile pages 1-2, rodor2016thernabindingprofile pages 9-10).

1.2 ACIN1 in ASAP/PSAP and its relationship to the EJC

A central definition in the ACIN1 literature is that Acinus is a core component of the ASAP (apoptosis- and splicing-associated protein) complex together with RNPS1 and SAP18 (deka2017multifacetedregulationof pages 2-3, deka2017multifacetedregulationof pages 1-2). ASAP has been proposed to interface with the EJC, a multiprotein complex deposited ~20–24 nt upstream of exon–exon junctions after splicing; EJC core factors include eIF4A3, Y14, MAGOH, and MLN51/CASC3 (rodor2016thernabindingprofile pages 1-2, deka2017multifacetedregulationof pages 1-2). In genome-wide RNA-binding data, Acinus shows binding patterns that can align with canonical EJC positions, and it can associate with eIF4A3 at canonical sites (deka2017multifacetedregulationof pages 2-3, rodor2016thernabindingprofile pages 9-10, rodor2016thernabindingprofile media b990c3b2).

1.3 Apoptotic chromatin condensation and caspase cleavage

The apoptosis-linked definition of Acinus is tied to its caspase-3 cleavage, which yields a truncated p17 fragment that retains the RRM and is associated with induction of chromatin condensation (and reported links to DNA fragmentation pathways) (rodor2016thernabindingprofile pages 1-2, abbas2024apoptosisinhibitor5 pages 4-6). Reviews also describe Acinus as a nuclear caspase-3-activated factor that participates in apoptotic chromatin changes (deka2017multifacetedregulationof pages 1-2).

2) Molecular functions and biological processes (mechanistic detail)

2.1 Direct RNA binding and splicing regulation (primary mechanistic function)

The best-supported mechanistic function for ACIN1 is regulation of pre-mRNA splicing through direct RNA binding.

RNA-binding specificity and binding distribution: In HeLa cells, iCLIP mapping shows Acinus binds both pre-mRNAs and spliced mRNAs, with binding enriched in exons and also present in introns with enrichment near splice sites and a preference for certain “suboptimal” introns (rodor2016thernabindingprofile pages 1-2, rodor2016thernabindingprofile pages 9-10, rodor2016thernabindingprofile media 84ab139e).
Functional outcomes of ACIN1 depletion: RNA-seq after siRNA-mediated depletion of Acinus shows it is required for inclusion of specific alternative cassette exons and for faithful splicing of subsets of introns (rodor2016thernabindingprofile pages 1-2).
A mechanistically informative target—DFFA/ICAD: Rodor et al. report that Acinus regulates splicing of the DFFA/ICAD transcript, a key regulator of apoptotic DNA fragmentation (rodor2016thernabindingprofile pages 1-2). A review synthesizes the mechanistic link: Acinus depletion can drive intron retention in ICAD leading to a shorter nonfunctional ICAD isoform, thereby impairing CAD-mediated DNA fragmentation upon apoptotic stimuli (deka2017multifacetedregulationof pages 12-13).

Interpretation: Collectively, these data support a model where ACIN1 contributes to splice-site choice and exon/intron definition in a targeted, transcript-specific way, rather than acting as a general core spliceosome component.

2.2 ACIN1 as a structural node in ASAP/PSAP assemblies

Biochemical and structural work summarized in a review describes ASAP as a heterotrimer of RNPS1 (~50 kDa), Acinus-L (~220 kDa), and SAP18 (~18 kDa), identified by mass spectrometry and characterized structurally (deka2017multifacetedregulationof pages 2-3). The key interaction platform is formed by the RNPS1 RRM, SAP18 UBL fold, and the Acinus RSB motif, whose helices contact SAP18 and RNPS1 (deka2017multifacetedregulationof pages 2-3). The same review notes that RNPS1 and SAP18 can also interact with Pinin (PNN), forming an alternative PSAP complex (deka2017multifacetedregulationof pages 2-3).

Interpretation: This architecture is consistent with ACIN1 being a scaffold that couples RNA binding (via RRM and complex-mediated RNA association) to larger mRNP assemblies.

Acinus’s apoptosis role is strongly linked to caspase processing and nuclear chromatin changes. Acinus is a caspase-3 target, and caspase-3 cleavage generates an active p17 fragment that can induce chromatin condensation (rodor2016thernabindingprofile pages 1-2, abbas2024apoptosisinhibitor5 pages 4-6). A review also describes that cleavage of the SAP motif in Acinus-L can compromise chromatin scaffold binding and potentially disrupt chromatin organization during apoptosis (deka2017multifacetedregulationof pages 10-12).

3) Subcellular localization and where ACIN1 acts

Across mechanistic studies and reviews, ACIN1 is treated as a predominantly nuclear protein, acting in nuclear mRNP/splicing contexts and described as “in the nucleus” in its nomenclature and functional characterization (rodor2016thernabindingprofile pages 1-2, deka2017multifacetedregulationof pages 1-2). In translational network analyses of HCC, ACIN1-associated genes are enriched in nuclear speck/nucleoplasm/spliceosomal complex/EJC terms, reinforcing a nucleus-centered role (tang2024analysisofthe pages 4-7).

A key localization concept is that the SAP motif in Acinus-L supports chromatin targeting via AT-rich scaffold/matrix attachment regions (SARS/MARS) and links the complex to chromatin-regulatory machinery via SAP18’s connection to Sin3/HDAC systems (deka2017multifacetedregulationof pages 2-3, deka2017multifacetedregulationof pages 1-2).

4) Recent developments and latest research (prioritizing 2023–2024)

4.1 2024: Anti-apoptotic regulation of ACIN1 cleavage by API5

A 2024 review of API5 highlights an experimentally supported interaction in which API5 binds Acinus, protects it from caspase-3 cleavage, and thereby prevents Acinus-mediated apoptotic DNA fragmentation/p17 generation (abbas2024apoptosisinhibitor5 pages 4-6). This is a concrete mechanistic node connecting ACIN1 to apoptosis regulation and cancer cell survival signaling.

4.2 2024: HCC expression upregulation and regulatory network inference

Tang et al. (April 2024) report significant upregulation of Acin1 in hepatocellular carcinoma in a mouse HCC model by whole-transcriptome sequencing and RT-qPCR validation (P < 0.001), with DE thresholds |log2(FPKM ratio)| > 1 and Q < 0.05 (tang2024analysisofthe pages 4-7, tang2024analysisofthe pages 2-4). They identify a PPI neighborhood (37 proteins; top-10 list includes Eif4a3, Rnps1, Sap18b, Srrm2, Hnrnpu, Akt1 among others) and functional enrichment for spliceosome/EJC and mRNA surveillance pathways (tang2024analysisofthe pages 4-7). They also propose a ceRNA/miRNA regulatory layer: a ceRNA network (2 lncRNAs, 50 miRNAs, 49 mRNAs) and miRNAs negatively correlated with Acin1 (miR-6395, miR-674-5p, miR-7067-5p), with miR-674-5p predicted to target Acin1 by multiple databases (tang2024analysisofthe pages 4-7).

Interpretation: This work is association- and network-heavy; it strengthens the view that ACIN1 sits in nuclear RNA-processing neighborhoods in cancer, but it does not by itself demonstrate causal mechanism in HCC (tang2024analysisofthe pages 4-7).

4.3 2024: Proteomics-driven apoptosis context in lung adenocarcinoma cells

A 2024 study in A549 cells (lung adenocarcinoma) using quantitative proteomics reports that activation of TRAIL-DR5 signaling and caspase cascades is associated with increased ACIN1, positioning ACIN1 as part of a caspase-linked apoptotic program in this context (treatment: strophanthidin) (tian2024; from paper metadata and abstract snippet) (tang2024analysisofthe pages 4-7).

Limitations of 2023–2024 coverage: In the retrieved corpus, 2024 sources were available and informative, but 2023 ACIN1-specific mechanistic papers were not retrieved by the search calls used here.

5) Pathways and networks involving ACIN1 (integrated view)

5.1 Splicing/EJC-centered post-transcriptional regulation

ACIN1 connects to the EJC via peripheral association and colocalization with canonical EJC sites and eIF4A3 in iCLIP studies (rodor2016thernabindingprofile pages 9-10, rodor2016thernabindingprofile media b990c3b2). The ASAP complex provides a mechanistic bridge between classical splicing regulators (e.g., RNPS1) and chromatin-associated modules (via SAP18 and the Acinus SAP motif), potentially enabling coordinated regulation across transcription/splicing/mRNP maturation (deka2017multifacetedregulationof pages 2-3, deka2017multifacetedregulationof pages 1-2).

5.2 Apoptosis execution and chromatin remodeling

ACIN1 can be proteolytically switched by caspase-3 to a p17 fragment that promotes chromatin condensation, and this switch is modulated by interacting proteins such as API5 (abbas2024apoptosisinhibitor5 pages 4-6). Splicing regulation of ICAD/DFFA by ACIN1 provides a second, indirect route to influence DNA fragmentation downstream of apoptotic stimuli by controlling availability of functional ICAD/CAD machinery (deka2017multifacetedregulationof pages 12-13).

6) Current applications and real-world implementations

6.1 ACIN1 as a candidate biomarker/association signal in cancer

Recent work supports ACIN1 as a biomarker candidate (expression association) rather than a validated drug target.

Hepatocellular carcinoma (2024): ACIN1 overexpression in tumor vs control tissues (P < 0.001) and network position among RNA-processing factors provide a rationale for follow-up validation as a biomarker or mechanistic node (tang2024analysisofthe pages 4-7, tang2024analysisofthe pages 2-4).
Cervical cancer (2022): ACIN1 is positioned downstream of METTL3/IGF2BP3, with evidence that METTL3 affects ACIN1 m6A enrichment and mRNA stability and that ACIN1 overexpression rescues phenotypes caused by METTL3 depletion (su2022methyltransferaselike3induces pages 4-8). (METTL3 itself shows strong diagnostic performance in that study with AUC 0.9681, P < 0.0001; ACIN1 is part of the proposed axis.) (su2022methyltransferaselike3induces pages 4-8)

6.2 Clinical trials and therapeutic targeting status

A registry search using ACIN1/Acinus terms returned studies that were not ACIN1-targeted interventional trials (nonspecific keyword matches); thus, there is no evidence here of ACIN1 being directly targeted clinically as of the retrieved trial records (clinical_trials_search results; no citeable ACIN1-specific trial evidence in retrieved chunks).

7) Expert opinion and authoritative synthesis

Two sources in the retrieved set provide higher-level synthesis:

A dedicated review of the ASAP complex positions ACIN1 as a multi-functional regulator linking RNA processing and apoptosis, emphasizing ASAP’s interactions with EJC-related pathways and chromatin regulatory linkages via SAP18/HDAC, while noting unresolved aspects of how directly ASAP associates with EJC in all contexts (deka2017multifacetedregulationof pages 1-2, deka2017multifacetedregulationof pages 10-12).
A 2024 review focused on API5 highlights ACIN1 as a mechanistically tractable effector whose caspase-3 processing can be blocked by API5 binding, underscoring ACIN1’s relevance in cell-fate control and cancer-associated apoptosis resistance paradigms (abbas2024apoptosisinhibitor5 pages 4-6).

8) Relevant statistics and recent data points (selected)

HCC (Apr 2024): ACIN1 significantly upregulated in tumor vs controls (P < 0.001); DE criteria |log2(FPKM ratio)| > 1 and Q < 0.05; ceRNA network size 2 lncRNAs, 50 miRNAs, 49 mRNAs; negatively correlated miRNAs include miR-6395, miR-674-5p, miR-7067-5p (tang2024analysisofthe pages 4-7, tang2024analysisofthe pages 2-4).
Cervical cancer (Mar 2022): METTL3 diagnostic statistic AUC = 0.9681 (P < 0.0001) in a study proposing METTL3→IGF2BP3→ACIN1 mRNA stability regulation (su2022methyltransferaselike3induces pages 4-8).
Open Targets (platform evidence): ACIN1 shows disease associations (e.g., hepatocellular carcinoma, neurodegenerative disease) with modest scores in the retrieved snapshot (OpenTargets Search: -ACIN1).

9) Evidence map (summary table)

The following table consolidates identity, domains, complexes, functions, localization, regulation, recent (2024) developments, and translational statistics with URLs and citations.

Category	Key points	Key evidence/citations	Publication (first author year)	URL
Identity/isoforms/domains	Verified target is human ACIN1 or Acinus (UniProt Q9UKV3), a nuclear RNA-binding protein. Three main isoforms are described: Acinus-L, Acinus-S′, and Acinus-S. All share an RRM and C-terminal RS-like domain; Acinus-L additionally contains an N-terminal SAP domain. ASAP structural work identifies an RSB motif in Acinus that binds RNPS1 and SAP18.	Isoforms and domain architecture are explicitly described in peer-reviewed sources; figure evidence shows SAP, RRM, and RS-like organization (deka2017multifacetedregulationof pages 2-3, rodor2016thernabindingprofile pages 1-2, rodor2016thernabindingprofile pages 2-3, rodor2016thernabindingprofile media 9db37663)	Deka 2017; Rodor 2016	https://doi.org/10.7150/ijbs.18649 ; https://doi.org/10.1261/rna.057158.116
Complexes/partners	ACIN1 is a core component of the ASAP complex with RNPS1 and SAP18; related work indicates an alternative PSAP complex with PNN. ACIN1 is a peripheral or auxiliary EJC component associated with core EJC proteins including eIF4A3, Y14, MAGOH, and MLN51 or CASC3. An additional experimentally supported partner is API5, which binds ACIN1 and modulates apoptotic cleavage.	Mass spectrometry, structural, iCLIP, and yeast-two-hybrid evidence support ASAP, PSAP, and EJC associations and API5 binding (rodor2016thernabindingprofile pages 1-2, deka2017multifacetedregulationof pages 10-12, deka2017multifacetedregulationof pages 2-3, abbas2024apoptosisinhibitor5 pages 4-6, deka2017multifacetedregulationof pages 1-2, rodor2016thernabindingprofile pages 9-10)	Rodor 2016; Deka 2017; Abbas 2024	https://doi.org/10.1261/rna.057158.116 ; https://doi.org/10.7150/ijbs.18649 ; https://doi.org/10.3390/biom14010136
Molecular functions	ACIN1 is not an enzyme or transporter; its primary function is as a nuclear RNA-binding scaffold or regulator that helps coordinate pre-mRNA splicing, exon and intron definition, and EJC-linked post-transcriptional regulation. It binds pre-mRNAs and spliced mRNAs, especially suboptimal introns, promotes inclusion of selected cassette exons, and supports faithful splicing of certain introns, including DFFA or ICAD. In apoptosis, caspase-processed ACIN1 promotes chromatin condensation and contributes to DNA fragmentation pathways.	iCLIP, RNA-seq, siRNA depletion, and apoptosis studies support splicing and apoptotic functions (rodor2016thernabindingprofile pages 1-2, deka2017multifacetedregulationof pages 12-13, rodor2016thernabindingprofile pages 9-10)	Rodor 2016; Deka 2017	https://doi.org/10.1261/rna.057158.116 ; https://doi.org/10.7150/ijbs.18649
Cellular localization	ACIN1 acts mainly in the nucleus, including nuclear speck, nucleoplasm, and chromatin-associated contexts. The SAP motif contributes to chromatin targeting via binding to AT-rich SARs or MARs and influences isoform-specific subcellular localization. ACIN1 also shows EJC-related RNA association and has been discussed in mRNP or export contexts, but its principal annotated site of action is nuclear.	Nuclear localization and chromatin targeting are described across ASAP and EJC studies and reviews; HCC enrichment also places ACIN1-associated genes in nuclear speck and spliceosomal compartments (deka2017multifacetedregulationof pages 2-3, rodor2016thernabindingprofile pages 1-2, deka2017multifacetedregulationof pages 1-2, tang2024analysisofthe pages 4-7)	Deka 2017; Rodor 2016; Tang 2024	https://doi.org/10.7150/ijbs.18649 ; https://doi.org/10.1261/rna.057158.116 ; https://doi.org/10.5152/tjg.2024.23454
Regulation/PTMs	A key regulatory event is caspase-3 cleavage of ACIN1, generating the active p17 fragment that promotes apoptotic chromatin condensation. API5 binding protects ACIN1 from caspase-3 cleavage and blocks ACIN1-mediated DNA fragmentation. Prior work summarized in reviews also notes Akt phosphorylation can inhibit ACIN1 proteolysis and chromatin condensation, and SRPK2 phosphorylation links ACIN1 to growth-related splicing regulation.	Cleavage and protection by API5 are summarized in a 2024 review; phosphorylation and PTM links are summarized in review literature (abbas2024apoptosisinhibitor5 pages 4-6, teixeira2025acinusaputative pages 11-12, deka2017multifacetedregulationof pages 12-13)	Abbas 2024; Deka 2017	https://doi.org/10.3390/biom14010136 ; https://doi.org/10.7150/ijbs.18649
Recent 2024 developments	2024 literature adds translational and systems-level context. In HCC, ACIN1 is reported as upregulated and embedded in a network enriched for EJC, spliceosome, and nuclear speck biology, with predicted regulation by miR-674-5p and related ceRNA components. A 2024 review highlights API5 and ACIN1 as a direct anti-apoptotic mechanism. A 2024 proteomics and apoptosis study in A549 lung adenocarcinoma identifies increased ACIN1 in the context of TRAIL-DR5 and caspase activation.	Recent developments come from 2024 primary and review papers (tang2024analysisofthe pages 7-9, tang2024analysisofthe pages 4-7, abbas2024apoptosisinhibitor5 pages 4-6)	Tang 2024; Abbas 2024; Tian 2024	https://doi.org/10.5152/tjg.2024.23454 ; https://doi.org/10.3390/biom14010136 ; https://doi.org/10.3390/molecules29040877
Disease/translational evidence	ACIN1 has emerging biomarker or association value rather than established direct therapeutic targeting. Evidence links ACIN1 to hepatocellular carcinoma overexpression and ceRNA or miRNA regulation, cervical cancer through METTL3 and IGF2BP3-mediated mRNA stabilization, and prior reports of elevated platelet ACIN1 mRNA in lung cancer. Open Targets shows disease associations including HCC, acute lymphoblastic leukemia, and neurodegenerative disease, but evidence strength is currently modest for most indications. No direct ACIN1-targeted clinical trials were identified in the registry search.	Translational associations are from HCC, cervical cancer, and Open Targets evidence synthesis (tang2024analysisofthe pages 4-7, tang2024analysisofthe pages 1-2, OpenTargets Search: -ACIN1, su2022methyltransferaselike3induces pages 4-8)	Tang 2024; Su 2022; Open Targets 2025 platform query	https://doi.org/10.5152/tjg.2024.23454 ; https://doi.org/10.1080/21655979.2022.2044261
Quantitative stats	HCC data show ACIN1 significantly upregulated in tumor versus paracancerous and healthy tissue with P less than .001; differential-expression thresholds were absolute log2 FPKM ratio greater than 1 and Q less than .05. PPI analysis identified 37 closely related proteins; the top 10 were Slc3a2, Wiz, Srrm2, Akt1, Hnrnpu, Sap18b, Pabpn1, Ddx39b, Eif4a3, and Rnps1. The ceRNA network size was 2 lncRNAs, 50 miRNAs, and 49 mRNAs; negatively correlated miRNAs included miR-6395, miR-674-5p, and miR-7067-5p. In cervical cancer, METTL3 showed AUC 0.9681 and P less than 0.0001 in the study that positioned ACIN1 downstream of METTL3 and IGF2BP3. Open Targets disease-target scores in the retrieved query were about 0.062 for HCC and 0.549 for neurodegenerative disease.	Quantitative values extracted directly from gathered evidence (tang2024analysisofthe pages 4-7, tang2024analysisofthe pages 2-4, OpenTargets Search: -ACIN1, su2022methyltransferaselike3induces pages 4-8)	Tang 2024; Su 2022; Open Targets 2025 platform query	https://doi.org/10.5152/tjg.2024.23454 ; https://doi.org/10.1080/21655979.2022.2044261

Table: This table summarizes verified identity, domains, complexes, molecular functions, localization, regulation, recent 2024 developments, and translational evidence for human ACIN1 or Acinus (UniProt Q9UKV3). It provides a compact evidence map linking functional annotation to specific cited sources and quantitative findings.

10) Key takeaways (functional annotation)

Primary molecular role: ACIN1 (Acinus) functions primarily as a nuclear RNA-binding splicing regulator/scaffold, acting through direct RNA binding and through assembly into ASAP/PSAP complexes that interface with EJC-associated mRNP biology (rodor2016thernabindingprofile pages 1-2, deka2017multifacetedregulationof pages 2-3, rodor2016thernabindingprofile pages 9-10).
Pathway placement: ACIN1 links pre-mRNA splicing to apoptosis, both by regulating splicing of apoptosis-related transcripts (e.g., DFFA/ICAD) and by being a caspase-3 substrate that yields a chromatin-condensation-promoting fragment (deka2017multifacetedregulationof pages 12-13, abbas2024apoptosisinhibitor5 pages 4-6).
Where it acts: Predominantly nuclear (nuclear speck/nucleoplasm/chromatin-associated contexts), consistent with its roles in splicing and chromatin condensation (deka2017multifacetedregulationof pages 1-2, tang2024analysisofthe pages 4-7).
Recent 2024 direction: Emphasis has shifted toward (i) cancer-relevant regulation (expression upregulation and miRNA/ceRNA hypotheses in HCC) and (ii) protein-interaction checkpoints controlling apoptotic cleavage (API5–Acinus) (tang2024analysisofthe pages 4-7, abbas2024apoptosisinhibitor5 pages 4-6).

URLs and publication dates for key sources used

Rodor et al. 2016-06. RNA. “The RNA-binding profile of Acinus…” https://doi.org/10.1261/rna.057158.116 (rodor2016thernabindingprofile pages 1-2)
Deka & Singh 2017-04. Int J Biol Sci. “Multifaceted Regulation…” https://doi.org/10.7150/ijbs.18649 (deka2017multifacetedregulationof pages 1-2)
Abbas et al. 2024-01. Biomolecules. “Apoptosis Inhibitor 5…” https://doi.org/10.3390/biom14010136 (abbas2024apoptosisinhibitor5 pages 4-6)
Tang et al. 2024-04. Turk J Gastroenterol. “Analysis of the Upregulated Expression Mechanism…” https://doi.org/10.5152/tjg.2024.23454 (tang2024analysisofthe pages 4-7)
Su et al. 2022-03. Bioengineered. “METTL3 induces cervical cancer…” https://doi.org/10.1080/21655979.2022.2044261 (su2022methyltransferaselike3induces pages 4-8)

References

(rodor2016thernabindingprofile pages 1-2): Julie Rodor, Qun Pan, Benjamin J. Blencowe, Eduardo Eyras, and Javier F. Cáceres. The rna-binding profile of acinus, a peripheral component of the exon junction complex, reveals its role in splicing regulation. RNA, 22:1411-1426, Jun 2016. URL: https://doi.org/10.1261/rna.057158.116, doi:10.1261/rna.057158.116. This article has 52 citations and is from a domain leading peer-reviewed journal.
(rodor2016thernabindingprofile pages 2-3): Julie Rodor, Qun Pan, Benjamin J. Blencowe, Eduardo Eyras, and Javier F. Cáceres. The rna-binding profile of acinus, a peripheral component of the exon junction complex, reveals its role in splicing regulation. RNA, 22:1411-1426, Jun 2016. URL: https://doi.org/10.1261/rna.057158.116, doi:10.1261/rna.057158.116. This article has 52 citations and is from a domain leading peer-reviewed journal.
(deka2017multifacetedregulationof pages 2-3): Bhagyashree Deka and Kusum Kumari Singh. Multifaceted regulation of gene expression by the apoptosis- and splicing-associated protein complex and its components. International Journal of Biological Sciences, 13:545-560, Apr 2017. URL: https://doi.org/10.7150/ijbs.18649, doi:10.7150/ijbs.18649. This article has 31 citations and is from a peer-reviewed journal.
(rodor2016thernabindingprofile media 9db37663): Julie Rodor, Qun Pan, Benjamin J. Blencowe, Eduardo Eyras, and Javier F. Cáceres. The rna-binding profile of acinus, a peripheral component of the exon junction complex, reveals its role in splicing regulation. RNA, 22:1411-1426, Jun 2016. URL: https://doi.org/10.1261/rna.057158.116, doi:10.1261/rna.057158.116. This article has 52 citations and is from a domain leading peer-reviewed journal.
(rodor2016thernabindingprofile pages 9-10): Julie Rodor, Qun Pan, Benjamin J. Blencowe, Eduardo Eyras, and Javier F. Cáceres. The rna-binding profile of acinus, a peripheral component of the exon junction complex, reveals its role in splicing regulation. RNA, 22:1411-1426, Jun 2016. URL: https://doi.org/10.1261/rna.057158.116, doi:10.1261/rna.057158.116. This article has 52 citations and is from a domain leading peer-reviewed journal.
(deka2017multifacetedregulationof pages 1-2): Bhagyashree Deka and Kusum Kumari Singh. Multifaceted regulation of gene expression by the apoptosis- and splicing-associated protein complex and its components. International Journal of Biological Sciences, 13:545-560, Apr 2017. URL: https://doi.org/10.7150/ijbs.18649, doi:10.7150/ijbs.18649. This article has 31 citations and is from a peer-reviewed journal.
(rodor2016thernabindingprofile media b990c3b2): Julie Rodor, Qun Pan, Benjamin J. Blencowe, Eduardo Eyras, and Javier F. Cáceres. The rna-binding profile of acinus, a peripheral component of the exon junction complex, reveals its role in splicing regulation. RNA, 22:1411-1426, Jun 2016. URL: https://doi.org/10.1261/rna.057158.116, doi:10.1261/rna.057158.116. This article has 52 citations and is from a domain leading peer-reviewed journal.
(abbas2024apoptosisinhibitor5 pages 4-6): Hafsia Abbas, Dalia Kheira Derkaoui, Louise Jeammet, Emilie Adicéam, Jérôme Tiollier, Hélène Sicard, Thorsten Braun, and Jean-Luc Poyet. Apoptosis inhibitor 5: a multifaceted regulator of cell fate. Biomolecules, 14:136, Jan 2024. URL: https://doi.org/10.3390/biom14010136, doi:10.3390/biom14010136. This article has 15 citations.
(rodor2016thernabindingprofile media 84ab139e): Julie Rodor, Qun Pan, Benjamin J. Blencowe, Eduardo Eyras, and Javier F. Cáceres. The rna-binding profile of acinus, a peripheral component of the exon junction complex, reveals its role in splicing regulation. RNA, 22:1411-1426, Jun 2016. URL: https://doi.org/10.1261/rna.057158.116, doi:10.1261/rna.057158.116. This article has 52 citations and is from a domain leading peer-reviewed journal.
(deka2017multifacetedregulationof pages 12-13): Bhagyashree Deka and Kusum Kumari Singh. Multifaceted regulation of gene expression by the apoptosis- and splicing-associated protein complex and its components. International Journal of Biological Sciences, 13:545-560, Apr 2017. URL: https://doi.org/10.7150/ijbs.18649, doi:10.7150/ijbs.18649. This article has 31 citations and is from a peer-reviewed journal.
(deka2017multifacetedregulationof pages 10-12): Bhagyashree Deka and Kusum Kumari Singh. Multifaceted regulation of gene expression by the apoptosis- and splicing-associated protein complex and its components. International Journal of Biological Sciences, 13:545-560, Apr 2017. URL: https://doi.org/10.7150/ijbs.18649, doi:10.7150/ijbs.18649. This article has 31 citations and is from a peer-reviewed journal.
(tang2024analysisofthe pages 4-7): Yuliang Tang, Anni Ni, Lishuang Sun, Shu Li, and Genliang Li. Analysis of the upregulated expression mechanism of apoptotic chromatin condensation inducer 1 in hepatocellular carcinoma based on bioinformatics. The Turkish Journal of Gastroenterology, 35:307-315, Apr 2024. URL: https://doi.org/10.5152/tjg.2024.23454, doi:10.5152/tjg.2024.23454. This article has 3 citations.
(tang2024analysisofthe pages 2-4): Yuliang Tang, Anni Ni, Lishuang Sun, Shu Li, and Genliang Li. Analysis of the upregulated expression mechanism of apoptotic chromatin condensation inducer 1 in hepatocellular carcinoma based on bioinformatics. The Turkish Journal of Gastroenterology, 35:307-315, Apr 2024. URL: https://doi.org/10.5152/tjg.2024.23454, doi:10.5152/tjg.2024.23454. This article has 3 citations.
(su2022methyltransferaselike3induces pages 4-8): Cui-hong Su, Yan Zhang, Ping Chen, Wei-Kang Yang, Jiaqi Du, and Danfeng Zhang. Methyltransferase-like 3 induces the development of cervical cancer by enhancing insulin-like growth factor 2 mrna-binding proteins 3-mediated apoptotic chromatin condensation inducer 1 mrna stability. Bioengineered, 13:7034-7048, Mar 2022. URL: https://doi.org/10.1080/21655979.2022.2044261, doi:10.1080/21655979.2022.2044261. This article has 18 citations.
(OpenTargets Search: -ACIN1): Open Targets Query (-ACIN1, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(teixeira2025acinusaputative pages 11-12): Felipe Castro Teixeira, Victor Breno Faustino Bezerra, Jochuan Israel Bezerra do Nascimento, João Victor Dourado Alves Brito, Gabriela Oliveira Matos, Lorenna Maria Neves Freitas, and Murilo Siqueira Alves. Acinus: a putative integrant of programmed cell death in plants. Discover Plants, Nov 2025. URL: https://doi.org/10.1007/s44372-025-00406-x, doi:10.1007/s44372-025-00406-x. This article has 0 citations.
(tang2024analysisofthe pages 7-9): Yuliang Tang, Anni Ni, Lishuang Sun, Shu Li, and Genliang Li. Analysis of the upregulated expression mechanism of apoptotic chromatin condensation inducer 1 in hepatocellular carcinoma based on bioinformatics. The Turkish Journal of Gastroenterology, 35:307-315, Apr 2024. URL: https://doi.org/10.5152/tjg.2024.23454, doi:10.5152/tjg.2024.23454. This article has 3 citations.
(tang2024analysisofthe pages 1-2): Yuliang Tang, Anni Ni, Lishuang Sun, Shu Li, and Genliang Li. Analysis of the upregulated expression mechanism of apoptotic chromatin condensation inducer 1 in hepatocellular carcinoma based on bioinformatics. The Turkish Journal of Gastroenterology, 35:307-315, Apr 2024. URL: https://doi.org/10.5152/tjg.2024.23454, doi:10.5152/tjg.2024.23454. This article has 3 citations.

Artifacts

Edison artifact artifact-00

Citations

deka2017multifacetedregulationof pages 1-2
rodor2016thernabindingprofile pages 1-2
deka2017multifacetedregulationof pages 12-13
deka2017multifacetedregulationof pages 2-3
deka2017multifacetedregulationof pages 10-12
tang2024analysisofthe pages 4-7
rodor2016thernabindingprofile pages 2-3
rodor2016thernabindingprofile pages 9-10
tang2024analysisofthe pages 2-4
teixeira2025acinusaputative pages 11-12
tang2024analysisofthe pages 7-9
tang2024analysisofthe pages 1-2
https://doi.org/10.7150/ijbs.18649
https://doi.org/10.1261/rna.057158.116
https://doi.org/10.3390/biom14010136
https://doi.org/10.5152/tjg.2024.23454
https://doi.org/10.3390/molecules29040877
https://doi.org/10.1080/21655979.2022.2044261
https://doi.org/10.1261/rna.057158.116,
https://doi.org/10.7150/ijbs.18649,
https://doi.org/10.3390/biom14010136,
https://doi.org/10.5152/tjg.2024.23454,
https://doi.org/10.1080/21655979.2022.2044261,
https://doi.org/10.1007/s44372-025-00406-x,

📚 Additional Documentation

Notes

(ACIN1-notes.md)

ACIN1 notes

ACIN1 is reviewed in the PN "specific function in autophagosome maturation and lysosome fusion unknown" bucket. That PN row is no-mapping/context-only and its autophagy citations are Drosophila Acinus studies, so it was used as search context rather than as direct human ACIN1 evidence.

The strongest human ACIN1 function is nuclear RNA processing/splicing through EJC/ASAP-associated complexes. UniProt describes ACIN1 as an "Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC)" and as a "Component of the ASAP complexes which bind RNA" [file:human/ACIN1/ACIN1-uniprot.txt, "Auxiliary component of the splicing-dependent multiprotein exon junction complex"; file:human/ACIN1/ACIN1-uniprot.txt, "Component of the ASAP complexes which bind RNA"]. The EJC biochemical paper identified "two novel EJC components, Acinus and SAP18" and showed that "Acinus binds directly to another EJC component, RNPS1" [PMID:16314458, "identified two novel EJC components, Acinus and SAP18"; PMID:16314458, "Acinus binds directly to another EJC component, RNPS1"]. The ASAP structural paper states that ASAP subunits Acinus, RNPS1, and SAP18 are implicated in "transcriptional regulation, pre-mRNA splicing and mRNA quality control" and that the Acinus-RNPS1-SAP18 ternary complex has "both RNA- and protein-binding properties" [PMID:22388736, "transcriptional regulation, pre-mRNA splicing and mRNA quality control"; PMID:22388736, "both RNA- and protein-binding properties"].

ASAP complex and nuclear-speckle localization are well supported. Schwerk et al. isolated ASAP complexes from HeLa extract and found they were "composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein" [PMID:12665594, "composed of the polypeptides SAP18 and RNPS1 and different isoforms of the Acinus protein"]. Singh et al. later summarized that "RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex" and demonstrated that SAP18 assembles a "nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus" [PMID:20966198, "RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex"; PMID:20966198, "nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus"].

ACIN1's apoptosis annotation is also supported, but it is separate from the PN autophagy question. The original Acinus paper identified a nuclear factor that "induces apoptotic chromatin condensation after cleavage by caspase-3" and found Acinus "essential for apoptotic chromatin condensation in vitro" [PMID:10490026, "induces apoptotic chromatin condensation after cleavage by caspase-3"; PMID:10490026, "essential for apoptotic chromatin condensation in vitro"]. The ASAP paper also reports that microinjected ASAP complexes accelerated cell death and that the complex disassembles after apoptosis induction [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"].

Hematopoietic differentiation rows are real caspase/substrate contexts but not central ACIN1 core functions. During erythroid differentiation, acinus is cleaved as part of caspase-dependent nuclear changes [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"]. During monocyte-to-macrophage differentiation, the abstract reports that differentiation-associated caspase activation "leads to the cleavage of the protein acinus" [PMID:12393560, "leads to the cleavage of the protein acinus"].

Curation decisions:
- Accept RNA splicing, RNA binding, ASAP complex, nucleus/nucleoplasm/nuclear speck, apoptotic chromatin condensation, and positive regulation of apoptotic process.
- Modify broad nucleic acid binding to RNA binding.
- Modify regulation of mRNA processing to negative regulation of mRNA splicing via spliceosome, based on UniProt/ASAP-complex evidence that the complex can inhibit in vitro splicing reactions.
- Keep erythrocyte and monocyte differentiation as non-core hematopoietic/caspase contexts.
- Remove ATP hydrolysis activity; ACIN1 is an RRM/SAP-domain RNA-processing factor, and neither UniProt function nor cached primary evidence supports an ACIN1 ATPase activity.
- Mark generic protein binding and enzyme binding as over-annotated; specific interactions are better represented by ASAP complex membership, EJC context, or regulatory evidence.
- Keep the Drosophila Acinus basal-autophagy PN signal as a suggested question/experiment for human ACIN1 rather than a new human annotation.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

Moved out of the YAML description: the prior wording said the human GOA evidence reviewed here supports RNA processing and apoptosis rather than a direct human ACIN1 autophagy annotation. That is a curation observation, not part of the standalone gene description.

Falcon deep research findings (2026-06-07)

Synthesis of the Falcon (Edison) report, emphasizing what is NEW relative to the existing review. PMIDs verified against PubMed via DOI conversion.

NEW primary mechanistic evidence (Rodor 2016): genome-wide iCLIP shows human Acinus binds both pre-mRNAs (enriched at a subset of "suboptimal" introns, near splice sites) and spliced mRNAs, confirming it as a peripheral EJC factor; siRNA depletion + RNA-seq shows Acinus is required for inclusion of specific alternative cassette exons and faithful splicing of certain introns, supporting a direct role in exon/intron definition PMID:27365209. This strengthens the existing IBA RNA-splicing ACCEPT with direct human experimental data, which the review previously lacked.
NEW specific splicing target with apoptosis relevance: Acinus regulates splicing of the DFFA/ICAD transcript, a major regulator of apoptotic DNA fragmentation; depletion can drive ICAD intron retention/short nonfunctional isoform and impair CAD-mediated DNA fragmentation PMID:27365209. This mechanistically links ACIN1's splicing function to its apoptosis function — a connection not captured in the current review.
NEW interaction/regulatory node (review-level): API5/AAC-11 binds Acinus and protects it from caspase-3 cleavage, preventing Acinus-mediated p17 generation and apoptotic DNA fragmentation [PMID:38275765 (Abbas 2024 review) "API5...protects it from caspase-3 cleavage"]. Review-derived; not used to change annotations. Falcon also restates Akt phosphorylation inhibiting Acinus proteolysis and SRPK2 phosphorylation links (review-level, consistent with existing SRPK2/API5 mention in protein-binding reasons).
NEW complex context (review-level, Deka & Singh 2017): structural description of ASAP as an RNPS1(RRM)–SAP18(UBL)–Acinus(RSB motif) heterotrimer, and an alternative PSAP complex where RNPS1/SAP18 pair with Pinin (PNN); SAP18 links the complex to Sin3/HDAC, and the Acinus-L SAP motif targets AT-rich SAR/MAR chromatin [PMID:28539829 "RNPS1, Acinus and SAP18...ASAP complex"; the PSAP/Pinin alternative is also described]. Consistent with, and enriching, the existing ASAP-complex annotation; PSAP/PNN is a genuinely new partner relationship noted here for context.
NEW disease/association context (provisional, association-grade — NOT used to change annotations): ACIN1/Acin1 is reported upregulated in hepatocellular carcinoma with a spliceosome/EJC PPI neighborhood and predicted miR-674-5p/ceRNA regulation [PMID:39128105 (Tang 2024)], and positioned downstream of a METTL3→IGF2BP3 m6A axis stabilizing ACIN1 mRNA in cervical cancer [PMID:35255776 (Su 2022)]. These are network/expression-association studies, not causal mechanism, so they remain notes-only.
A 2025 "Acinus in plant programmed cell death" item (doi:10.1007/s44372-025-00406-x, 0 citations) and a 2024 A549/strophanthidin proteomics item (doi:10.3390/molecules29040877) appear in the Falcon corpus but are tangential/provisional for human ACIN1 function and are not incorporated.

Pn Notes

(ACIN1-pn-notes.md)

ACIN1 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q9UKV3
AIGR review status: COMPLETE
Review batch: proteostasis-pr-1217 (PR 1217)
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/ACIN1/ACIN1-ai-review.yaml
AIGR review HTML: present - genes/human/ACIN1/ACIN1-ai-review.html
Gene notes: present - genes/human/ACIN1/ACIN1-notes.md
GOA TSV: present - genes/human/ACIN1/ACIN1-goa.tsv
UniProt record: present - genes/human/ACIN1/ACIN1-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/ACIN1.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/ACIN1.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

genes/human/ACIN1/ACIN1-deep-research-falcon.md

AIGR Review Snapshot

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.
Existing/core annotation action counts: ACCEPT: 22; KEEP_AS_NON_CORE: 3; MARK_AS_OVER_ANNOTATED: 12; MODIFY: 3; REMOVE: 1

PN Consistency Summary

Consistency (deep research ↔ review YAML ↔ PN ↔ mapping): Consistent, and the review handled the tension well. The human review's core functions are RNA binding in the RNPS1–SAP18–ACIN1 ASAP complex (GO:0061574) / EJC-associated splicing (GO:0008380) and caspase-activated apoptotic chromatin condensation (GO:0030263). The PN row instead places ACIN1 in the ALP branch on the strength of Drosophila Acinus basal-autophagy work. The review's description and a suggested_question explicitly name this divergence and conclude human evidence supports RNA processing/apoptosis over a direct autophagy role.
Does the PN taxonomy tell a story GO misses? (NEW-annotation pressure): Yes — PN asserts a candidate conserved autophagosome-maturation role that is absent from human GOA. The review correctly does not mint a NEW autophagy term (proposed_new_terms: []); instead it captures the PN story as a suggested_question (is the Drosophila basal-autophagy role conserved?) and two suggested_experiments (autophagic-flux assay; RNA-target mapping). This is the right altitude: PN flags a hypothesis, not a GO-annotatable human fact. No new annotation warranted now.
Evidence alignment (did PN and the review pick the same papers?): No — deliberately divergent. PN cites two Drosophila papers (Nagy et al., acinus endocytic/autophagic trafficking; Cdk5/Ser437 eLife). The review's supported_by cites none of these; it relies on human ASAP/EJC/apoptosis literature (PMID:12665594, 20966198, 16314458, 22388736, 27365209, 10490026). The divergence is itself the finding: PN's evidence is orthology-based and the human review intentionally does not import it as human evidence.
Verdict: Fully consistent; exemplary handling of an orthology-driven PN inclusion. No edits needed. Template/positive-control case for the phase-1 review.

Full Consistency Review

UniProt: Q9UKV3 · batch: proteostasis-pr-1217 · review status: COMPLETE
PN placement: Autophagy-Lysosome Pathway → Autophagosome closure maturation and lysosome fusion → "Specific function in autophagosome maturation and lysosome fusion unknown" (1 row, ALP branch)
PN-node mapping: leaf group = no_mapping ("unknown/residual" bucket); parent class = context_only / too_broad_to_propagate → GO:0016236 macroautophagy; branch = no_mapping. No GO propagates to ACIN1 from PN.

Consistency (deep research ↔ review YAML ↔ PN ↔ mapping): Consistent, and the review handled the tension well. The human review's core functions are RNA binding in the RNPS1–SAP18–ACIN1 ASAP complex (GO:0061574) / EJC-associated splicing (GO:0008380) and caspase-activated apoptotic chromatin condensation (GO:0030263). The PN row instead places ACIN1 in the ALP branch on the strength of Drosophila Acinus basal-autophagy work. The review's description and a suggested_question explicitly name this divergence and conclude human evidence supports RNA processing/apoptosis over a direct autophagy role.

Does the PN taxonomy tell a story GO misses? (NEW-annotation pressure): Yes — PN asserts a candidate conserved autophagosome-maturation role that is absent from human GOA. The review correctly does not mint a NEW autophagy term (proposed_new_terms: []); instead it captures the PN story as a suggested_question (is the Drosophila basal-autophagy role conserved?) and two suggested_experiments (autophagic-flux assay; RNA-target mapping). This is the right altitude: PN flags a hypothesis, not a GO-annotatable human fact. No new annotation warranted now.

Does PN inclusion change mapping strategy? No. ACIN1's own PN node is the residual "function unknown" group → correctly no_mapping; the class is correctly held at context_only/too_broad_to_propagate. The PN authors themselves signalled uncertainty (the group label literally says function "unknown"), so the conservative no-propagation call is well-aligned. ACIN1 is a good negative control for "membership ≠ GO assertion."

Evidence alignment (did PN and the review pick the same papers?): No — deliberately divergent. PN cites two Drosophila papers (Nagy et al., acinus endocytic/autophagic trafficking; Cdk5/Ser437 eLife). The review's supported_by cites none of these; it relies on human ASAP/EJC/apoptosis literature (PMID:12665594, 20966198, 16314458, 22388736, 27365209, 10490026). The divergence is itself the finding: PN's evidence is orthology-based and the human review intentionally does not import it as human evidence.

Verdict: Fully consistent; exemplary handling of an orthology-driven PN inclusion. No edits needed. Template/positive-control case for the phase-1 review.

PN Dossier Context

review_batch: proteostasis-pr-1217
review_yaml: genes/human/ACIN1/ACIN1-ai-review.yaml
PN workbook rows: 1

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Specific function in autophagosome maturation and lysosome fusion unknown

UniProt: Q9UKV3
In branches: ALP
Notes: Drosophila ACN promotes autophagosome maturation in basal autophagy.
PN references (titles):
- Drosophila acinus encodes a novel regulator of endocytic and autophagic trafficking | Development | The Company of Biologists
- Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in Drosophila melanogaster by phosphorylating acinus at serine437 | eLife (elifesciences.org)
PN-node mapping records (path + ancestors):
- [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Specific function in autophagosome maturation and lysosome fusion unknown
  status=no_mapping scope= GO=[]
  rationale: Reviewed as an unknown or residual PN category. The label does not provide a shared GO-mappable biological process, molecular function, or cellular component.
- [class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
  status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
  rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

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

ACIN1

Gene Description

Existing Annotations Review

Core Functions

ACIN1 provides RNA-binding/splicing-regulatory activity in the RNPS1-SAP18-ACIN1 ASAP complex and EJC-associated mRNP context.

Caspase-activated ACIN1/Acinus promotes apoptotic chromatin condensation and contributes to apoptosis-associated nuclear remodeling.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research report: Human ACIN1 (Acinus) functional annotation (UniProt Q9UKV3)

0) Gene/protein identity verification (mandatory)

1) Key concepts and definitions (current understanding)

1.1 ACIN1 is a non-enzymatic RNA-binding scaffold/regulator

1.2 ACIN1 in ASAP/PSAP and its relationship to the EJC

1.3 Apoptotic chromatin condensation and caspase cleavage

2) Molecular functions and biological processes (mechanistic detail)

2.1 Direct RNA binding and splicing regulation (primary mechanistic function)

2.2 ACIN1 as a structural node in ASAP/PSAP assemblies

2.3 Apoptosis-related chromatin effects

3) Subcellular localization and where ACIN1 acts

4) Recent developments and latest research (prioritizing 2023–2024)

4.1 2024: Anti-apoptotic regulation of ACIN1 cleavage by API5

4.2 2024: HCC expression upregulation and regulatory network inference

4.3 2024: Proteomics-driven apoptosis context in lung adenocarcinoma cells

5) Pathways and networks involving ACIN1 (integrated view)

5.1 Splicing/EJC-centered post-transcriptional regulation

5.2 Apoptosis execution and chromatin remodeling

6) Current applications and real-world implementations

6.1 ACIN1 as a candidate biomarker/association signal in cancer

6.2 Clinical trials and therapeutic targeting status

7) Expert opinion and authoritative synthesis

8) Relevant statistics and recent data points (selected)

9) Evidence map (summary table)

10) Key takeaways (functional annotation)

URLs and publication dates for key sources used

Artifacts

Citations

📚 Additional Documentation

Notes

ACIN1 notes

Description cleanup note

Falcon deep research findings (2026-06-07)

Pn Notes

ACIN1 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Specific function in autophagosome maturation and lysosome fusion unknown

Note

📄 View Raw YAML