Affinage

Showing ACBD3 — PAP7 is a alias.

ACBD3

Golgi resident protein GCP60 · UniProt Q9H3P7

Length
528 aa
Mass
60.6 kDa
Annotated
2026-06-09
49 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACBD3 (GCP60/PAP7) is a peripheral Golgi-membrane scaffolding protein that organizes lipid-modifying and signaling machinery on Golgi/TGN membranes and at ER–Golgi contact sites (PMID:11590181, PMID:27009356). Its central scaffolding output is the direct recruitment of the lipid kinase PI4KB to membranes through its GOLD domain, an interaction defined structurally by NMR that both anchors PI4KB to the Golgi and stimulates its enzymatic activity to maintain Golgi PI4P homeostasis (PMID:27009356, PMID:27989622). ACBD3 is itself targeted to the Golgi by a two-step mechanism: the Sec1/Munc-18 protein SCFD1 with the SNARE SEC22B acts upstream of an MWT374-376 motif that binds the golgins giantin and golgin-45 (PMID:38134218, PMID:11590181, PMID:28777890). Beyond PI4KB, ACBD3 acts as an A-kinase anchoring protein, binding PKA regulatory subunits (RIα and RII via the GOLD domain) to position PKA at the Golgi and at mitochondria, where it couples cholesterol transport to hormone-stimulated steroidogenesis and where it controls cargo-triggered PKA activation governing KDEL-receptor retrograde trafficking (PMID:11731621, PMID:12943713, PMID:37044218, PMID:34493279). ACBD3 is required for Golgi stack integrity and for FAPP2-mediated glucosylceramide transport and ER-to-Golgi ceramide/sphingolipid flux, with knockout producing enlarged, unstacked Golgi and altered sphingolipid pools (PMID:29750412, PMID:34298889). The same membrane-coupling activity is extensively exploited by pathogens: picornavirus 3A proteins clamp ACBD3 onto replication-organelle membranes to recruit and activate PI4KB for viral PI4P synthesis, and the OSBP–VAP cholesterol-transport machinery is co-opted through ACBD3 as well (PMID:22124328, PMID:22258260, PMID:27989622, PMID:28065508, PMID:31381608, PMID:29367253). ACBD3 also concentrates ligand-activated STING at ER–Golgi contact sites to drive ER export and type-I interferon responses (PMID:36543137), partners with Numb during mitotic Golgi fragmentation to influence asymmetric neural cell-fate specification (PMID:17418793), and modulates apoptotic signaling through a redox-sensitive Cys-463 interaction with a caspase-generated golgin-160 fragment (PMID:17711851). Salmonella effectors SseF/SseG bind ACBD3 to position Salmonella-containing vacuoles at the Golgi (PMID:27406559), underscoring ACBD3 as a recurrently hijacked membrane-organizing hub.

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 Medium

    Established ACBD3 as a Golgi-associated protein whose integrity is functionally required for Golgi architecture and ER-to-Golgi transport, defining its core cellular compartment.

    Evidence Yeast two-hybrid against giantin C-terminus with immuno-EM and overexpression-induced Golgi disassembly

    PMID:11590181

    Open questions at the time
    • Mechanism of how giantin binding stabilizes Golgi structure unresolved
    • Did not identify downstream effectors recruited by ACBD3
    • Endogenous loss-of-function not tested
  2. 2001 Medium

    Revealed a second functional pool of ACBD3 as a PKA/PBR-associated factor at mitochondria controlling steroidogenesis, framing it as an AKAP coupling cAMP signaling to cholesterol transport.

    Evidence Yeast two-hybrid and GST pulldown with RIα/PBR plus antisense knockdown and steroid assays in MA-10 Leydig cells

    PMID:11731621 PMID:12943713

    Open questions at the time
    • Direct demonstration of PKA targeting to mitochondria not structurally defined
    • Relationship between Golgi and mitochondrial pools unclear
    • Later work found no mitochondrial structural/functional defect in KO cells
  3. 2007 High

    Connected ACBD3 to apoptotic signaling via a redox-gated interaction, showing a single cysteine acts as an oxidation sensor controlling sequestration of a pro-apoptotic golgin-160 fragment.

    Evidence Site-directed mutagenesis of Cys-463 with in vitro binding, cellular localization, and H2O2/NO oxidation experiments

    PMID:16870622 PMID:17711851

    Open questions at the time
    • Physiological signals that oxidize Cys-463 in vivo not defined
    • Quantitative contribution to apoptosis regulation unknown
    • Structural basis of redox switch not solved
  4. 2007 High

    Demonstrated that cell-cycle-dependent relocalization of ACBD3 (Golgi to cytosol upon mitotic Golgi fragmentation) couples organelle dynamics to a developmental cell-fate decision via Numb.

    Evidence Reciprocal co-IP, live/fixed imaging, and loss/gain-of-function mouse models

    PMID:17418793

    Open questions at the time
    • Molecular mechanism linking cytosolic ACBD3 to Numb-dependent fate output unclear
    • Whether scaffolding of PKA/PI4KB participates not addressed
  5. 2011 High

    Identified ACBD3 as the direct bridge recruiting PI4KB to picornavirus replication sites, establishing the ACBD3–PI4KB axis as the molecular basis for viral PI4P-dependent replication-organelle biogenesis.

    Evidence Co-IP of ACBD3 with Aichi virus non-structural proteins and PI4KB plus siRNA knockdown and viral replication assays

    PMID:22124328 PMID:22258260

    Open questions at the time
    • Whether ACBD3–PI4KB binding alters kinase activity not yet shown at this stage
    • Cellular (non-viral) PI4KB recruitment role inferred but untested here
  6. 2013 Medium

    Refined the PI4KB-recruitment model as competitive and context-dependent, showing TBC1D22 GAPs occupy the same ACBD3 site as PI4KB and that ACBD3 can negatively modulate some enteroviruses.

    Evidence AP-MS, mammalian two-hybrid, domain-competition mapping, and siRNA knockdown with viral growth assays

    PMID:23572552 PMID:23926333 PMID:24012756

    Open questions at the time
    • Regulatory logic switching ACBD3 between PI4KB and TBC1D22 binding unknown
    • Mechanism of negative modulation of poliovirus replication unresolved
    • Rhes/mHtt complex role in neurodegeneration mechanistically thin
  7. 2014 High

    Showed the viral 3A/ACBD3/PI4KB ternary complex directly stimulates PI4KB catalytic activity, moving ACBD3 from a passive tether to an allosteric activator of lipid kinase output.

    Evidence In vitro kinase assay with reconstituted complexes plus siRNA and PI4P quantification

    PMID:24672044

    Open questions at the time
    • Quantitative contribution of ACBD3 versus 3A to activation not fully separated
    • Membrane requirement not yet incorporated
  8. 2016 High

    Provided the structural basis for ACBD3 function: NMR and crystal structures defined the PI4KB and 3A interfaces on the GOLD domain and proved membrane recruitment of PI4KB by ACBD3 raises its activity and sets Golgi PI4P levels.

    Evidence NMR and crystal structure determination, HDX-MS interface mapping, in vitro membrane recruitment and kinase reconstitution with interface mutagenesis

    PMID:27009356 PMID:27989622

    Open questions at the time
    • Full-length ACBD3 architecture not resolved
    • How upstream golgin/SCFD1 anchoring positions the GOLD domain unknown
  9. 2017 High

    Defined ACBD3 as a recurrently hijacked membrane hub across diverse pathogens, with viral 3A proteins acting as molecular harnesses stabilizing ACBD3 at membranes and bacterial SseF/SseG positioning Salmonella vacuoles via ACBD3.

    Evidence Crystal structures with MD simulation, plus yeast two-hybrid, co-IP, GST pulldown, and bacterial/viral replication assays with interface mutagenesis

    PMID:27406559 PMID:28065508 PMID:28303920 PMID:28701404

    Open questions at the time
    • Endogenous host signals that mimic 3A harnessing not identified
    • Whether bacterial recruitment involves PI4KB/PKA scaffolds unclear
  10. 2017 Medium

    Extended the scaffolding model to Golgi structural proteins, showing ACBD3 GOLD-domain interactions organize golgin-45, GRASP55, and TBC1D22 into a stacking-related complex.

    Evidence Proteomics, co-IP, domain mapping, and confocal microscopy

    PMID:28777890

    Open questions at the time
    • Direct role of this complex in stack formation not functionally proven here
    • Competition with PI4KB for the same site not reconciled in vivo
  11. 2019 High

    Established ACBD3 as broadly essential for enterovirus/rhinovirus replication through domain-specific PI4KB recruitment, and clarified its native lipid-transport role in glucosylceramide and ceramide trafficking and Golgi stacking.

    Evidence CRISPR knockout with domain-specific rescue, lipidomics, FAPP2 localization, and SAXS conformational analysis of the ACBD3:PI4KB complex

    PMID:29367253 PMID:29750412 PMID:30679637 PMID:30755512 PMID:31381608

    Open questions at the time
    • Mechanism coupling ACBD3 to FAPP2/ceramide transport molecularly undefined
    • How conformational flexibility of ACBD3:PI4KB is regulated on membranes unclear
    • CVB3 uses an ACBD3-independent route, leaving virus-specificity determinants open
  12. 2021 Medium

    Resolved a native AKAP function at the Golgi, showing ACBD3 tethers PKA to the KDEL receptor and acts as a negative regulator of PKA-driven retrograde trafficking and Arf1-dependent tubular carriers.

    Evidence Proximity-based tagging, co-IP, siRNA knockdown, and live-cell trafficking assays; CRISPR-KO Golgi morphology and lipidomics

    PMID:34298889 PMID:34493279

    Open questions at the time
    • Signal triggering PKA release at the Golgi not defined here
    • Reconciliation of negative regulation with mitochondrial steroidogenic role incomplete
  13. 2022 High

    Identified ACBD3 as an innate-immune trafficking factor that concentrates ligand-bound STING at non-canonical ER–Golgi contact sites to drive ER export and type-I interferon responses.

    Evidence Unbiased proteomics, super-resolution and live-cell imaging, siRNA knockdown, STING trafficking and IFN reporter assays

    PMID:36543137

    Open questions at the time
    • Whether STING concentration uses PI4KB/PKA scaffolds or a distinct mode unknown
    • Structural basis of STING recognition not defined
  14. 2023 High

    Defined the upstream logic of ACBD3 membrane targeting and confirmed a GOLD-domain PKA-RII interaction coupling forward cargo flux to Golgi PKA activation.

    Evidence CRISPR knockout of SCFD1, MWT-motif mutagenesis, unbiased proteomics, co-IP, PKA activity and KDEL trafficking assays

    PMID:37044218 PMID:38134218

    Open questions at the time
    • How SCFD1/SEC22B SNARE machinery hands ACBD3 to golgins mechanistically unresolved
    • Cargo sensor linking secretion to PKA activation unidentified
  15. 2025 Medium

    Broadened ACBD3's roles to ferroptosis control, PI4KB-independent flavivirus support, and context-dependent oncogenic versus metastasis-suppressive functions in lung cancer.

    Evidence siRNA/CRISPR knockdown with iron/lipid-peroxidation measurements, proximity proteomics and viral assays for TBEV, and xenograft/migration assays with NOTCH readouts

    PMID:38953242 PMID:40189704 PMID:40207930

    Open questions at the time
    • Mechanism linking ACBD3 loss to NCOA4-dependent ferritinophagy unclear
    • PI4KB-independent ER–Golgi coupling activity for TBEV undefined
    • Determinants of pro- versus anti-tumor switch by 1q copy number unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single Golgi scaffold partitions its competing GOLD-domain interactions (PI4KB, PKA-RII, golgin-45, TBC1D22, viral 3A, STING) into distinct spatial and temporal outputs, and what signals govern this switching, remains unresolved.
  • No integrated regulatory model coordinating mutually exclusive partners
  • Full-length structure on native membranes lacking
  • In vivo physiological hierarchy among ACBD3's roles undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2
Localization
GO:0005794 Golgi apparatus 5 GO:0005783 endoplasmic reticulum 3 GO:0005739 mitochondrion 2 GO:0005829 cytosol 1
Pathway
R-HSA-1643685 Disease 6 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-168256 Immune System 1
Partners
GIANTINGOLGA1/GOLGIN-45KDELRPI4KBPRKAR1ASCFD1SEC22BTBC1D22A
Complex memberships
ACBD3:PI4KB complexACBD3:PI4KB:Rab11 membrane complexACBD3:PKA holoenzyme (AKAP) complexgolgin-45:GRASP55:TBC1D22 stacking complex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 GCP60 (ACBD3) was identified as a peripheral Golgi membrane protein that interacts with the C-terminal cytoplasmic domain of the integral membrane protein giantin; overexpression of the GCP60 C-terminal domain caused Golgi disassembly and blocked ER-to-Golgi protein transport. Yeast two-hybrid screening, immunofluorescence, immunoelectron microscopy, overexpression assay The Journal of biological chemistry Medium 11590181
2001 PAP7 (ACBD3) interacts with both the mitochondrial peripheral-type benzodiazepine receptor (PBR) and the cytosolic PKA regulatory subunit RIα; overexpression of full-length PAP7 increased hCG-induced steroid production, while a dominant-negative partial PAP7 and antisense oligonucleotides inhibited hormone-stimulated cholesterol transport and steroidogenesis in MA-10 Leydig cells. Yeast two-hybrid, GST pulldown, antisense oligonucleotide knockdown, steroid production assay Molecular endocrinology (Baltimore, Md.) Medium 11731621
2003 PAP7 (ACBD3) functions as an A-kinase anchoring protein (AKAP) that localizes to the trans-Golgi apparatus and mitochondria in Leydig cells; inhibition of PAP7 expression reduced hormone-induced cholesterol transport into mitochondria and decreased steroid formation, suggesting it targets PKA to PBR-rich organelles. Immunofluorescence confocal microscopy, antisense inhibition, steroid formation assay The Journal of steroid biochemistry and molecular biology Medium 12943713
2006 GCP60 (ACBD3) preferentially interacts with a caspase-generated golgin-160 fragment (residues 140–311) and prevents its nuclear translocation; cells overexpressing GCP60 showed increased sensitivity to staurosporine-induced apoptosis. Yeast two-hybrid, co-immunoprecipitation, overexpression/localization assay, apoptosis assay The Journal of biological chemistry Medium 16870622
2007 A single redox-sensitive cysteine (Cys-463) in GCP60 (ACBD3) is critical for its interaction with the golgin-160 caspase fragment (residues 140–311); mutation of Cys-463 abolished interaction in vitro and disrupted Golgi retention of the fragment; oxidation by H2O2 or a nitric oxide donor restored the interaction. Site-directed mutagenesis, in vitro binding assay, cellular localization assay, oxidation experiments The Journal of biological chemistry High 17711851
2007 ACBD3 associates with the Golgi in neurons and interphase progenitor cells but becomes cytosolic upon Golgi fragmentation during mitosis; ACBD3 interacts with Numb through an essential Numb domain, and cytosolic ACBD3 acts synergistically with Numb to specify neural cell fates; loss- and gain-of-function mouse mutants share phenotypic similarities linking ACBD3 to asymmetric cell division. Co-immunoprecipitation, live/fixed-cell imaging, loss-of-function/gain-of-function mouse models Cell High 17418793
2011 ACBD3 interacts with multiple Aichi virus non-structural proteins (2B, 2BC, 2C, 3A, 3AB) and directly with PI4KB; this ACBD3–PI4KB interaction recruits PI4KB to viral RNA replication sites, enabling PI4P synthesis essential for Aichi virus RNA replication; knockdown of ACBD3 or PI4KB suppressed replication. Co-immunoprecipitation, siRNA knockdown, immunofluorescence microscopy, viral replication assay The EMBO journal High 22124328
2012 Multiple picornavirus 3A proteins (Aichi virus, bovine kobuvirus, poliovirus, coxsackievirus B2/B3/B5, HRV14) co-purify with ACBD3; ACBD3 itself binds PI4KIIIβ in the absence of 3A; alanine-scanning mutagenesis of Aichi virus 3A identified residues that selectively abolish PI4KIIIβ co-purification without affecting ACBD3 binding; N-terminal glycines of some 3A proteins are myristoylated. Affinity purification with Strep-tag, mass spectrometry, Western blotting, alanine-scanning mutagenesis, siRNA knockdown, viral replication assay Journal of virology High 22258260
2012 ACBD3 recruits the protein phosphatase PPM1L to ER–Golgi membrane contact sites via its GOLD domain, implicating ACBD3 in ceramide trafficking regulation at the ER–Golgi interface. Co-immunoprecipitation, domain mapping, subcellular fractionation/localization FEBS letters Medium 22796112
2013 ACBD3 interacts with TBC1D22A and TBC1D22B (putative Rab33 GAPs) via the same binding site on ACBD3 used by PI4KB; TBC1D22A/B and PI4KB interactions with ACBD3 are mutually exclusive, suggesting a competitive regulatory mechanism for PI4KB recruitment. Affinity purification–mass spectrometry, mammalian two-hybrid, co-immunoprecipitation, domain mapping mBio Medium 23572552
2013 ACBD3 forms a complex with Rhes and mutant huntingtin (mHtt) in the striatum; ACBD3 levels are elevated in HD striatum; ACBD3 deletion abolishes mHtt-mediated neurotoxicity, while overexpression increases it, placing ACBD3 downstream of Rhes/mHtt as a mediator of HD cytotoxicity. Co-immunoprecipitation, ACBD3 deletion/overexpression, cell viability assay, Western blot in HD mouse brain and patient tissue Cell reports Medium 24012756
2013 ACBD3 interacts with poliovirus 3A proteins at viral RNA replication sites; siRNA-mediated downregulation of ACBD3 significantly increased poliovirus replication, indicating ACBD3 can negatively modulate enterovirus replication; the amino acid at position 12 of 3A influences sensitivity to this effect. Co-immunoprecipitation, siRNA knockdown, viral growth assay, replicon assay, immunofluorescence Journal of virology Medium 23926333
2013 ACBD3 depletion did not affect PI4KIIIβ recruitment to coxsackievirus B3 (CVB3) replication organelles and did not impair CVB3 RNA replication, demonstrating that CVB3 recruits PI4KIIIβ by an ACBD3-independent mechanism (NEGATIVE finding for CVB3). siRNA knockdown, immunofluorescence, viral replication assay Journal of virology Medium 24352456
2014 The viral protein/ACBD3/PI4KB complex stimulates PI4KB kinase activity in vitro; Aichi virus 3A and 3AB proteins stimulate PI4KB activity through forming a 3A(3AB)/ACBD3/PI4KB complex, enhancing PI4P synthesis at replication organelles and facilitating viral replication complex formation. In vitro kinase assay, siRNA knockdown, immunofluorescence, PI4P quantification Journal of virology High 24672044
2016 NMR structure of the PI4KB–ACBD3 complex was determined; ACBD3 recruits PI4KB to membranes both in vitro and in vivo, and membrane recruitment of PI4KB by ACBD3 increases its enzymatic activity; ACBD3:PI4KB complex formation is essential for proper Golgi PI4P homeostasis. NMR structure determination, in vitro membrane recruitment assay, enzymatic activity assay, cellular localization experiments Scientific reports High 27009356
2016 Salmonella effectors SseF and SseG interact directly with ACBD3; SseG binds ACBD3 alone, while SseF binding requires SseG; ACBD3 knockdown reduces Golgi association of Salmonella-containing vacuoles, and ACBD3-interaction-deficient SseF/SseG mutants display an intracellular replication defect. Yeast two-hybrid, co-immunoprecipitation, GST pulldown, siRNA knockdown, confocal microscopy, bacterial replication assay mBio High 27406559
2016 Crystal structure of the ACBD3 GOLD domain revealed a unique N terminus that mediates interaction with Aichi virus 3A; hydrogen-deuterium exchange mass spectrometry mapped the PI4KIIIβ–ACBD3 and ACBD3–3A interfaces; 3A directly activates PI4KIIIβ and this is sensitized by ACBD3; rationally designed interface mutations abrogated kinase activation by ACBD3. Crystal structure determination, HDX-MS, in vitro kinase reconstitution, site-directed mutagenesis Structure (London, England : 1993) High 27989622
2017 Crystal structures of Aichi virus and bovine kobuvirus 3A proteins in complex with the ACBD3 GOLD domain showed that viral 3A proteins act as molecular harnesses to stabilize ACBD3 at target membranes; molecular dynamics simulation revealed 3A-mediated ACBD3 stabilization at lipid bilayers. Crystal structure determination, molecular dynamics simulation Structure (London, England : 1993) High 28065508
2017 ACBD3 interacts with EV71 3A protein; this interaction is required for EV71 RNA replication and plaque formation; EV71 3A redirects ACBD3 to viral replication sites; I44A or H54Y substitutions in 3A disrupt ACBD3 binding and impair replication. cDNA library screening, co-immunoprecipitation, ACBD3 CRISPR knockout/knockdown, immunofluorescence, viral replication assay, mutagenesis Scientific reports High 28303920
2017 EV71 3A protein stimulates the ACBD3–PI4KB interaction; ACBD3 is required for PI4KB recruitment to EV71 RNA replication sites; EV71 infection induces PI4P production in an ACBD3- and PI4KB-dependent manner; I44A or H54Y in 3A abolish stimulation of ACBD3–PI4KB interaction. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, PI4P quantification, mutagenesis Journal of virology High 28701404
2017 ACBD3 interacts with Golgin45 via its GOLD domain; ACBD3 co-expression increases Golgin45 Golgi targeting; ACBD3 recruits TBC1D22 (a Rab33b GAP) to a multi-protein complex containing Golgin45 and GRASP55, suggesting a scaffolding role in organizing Golgi stacking proteins. Proteomics, co-immunoprecipitation, confocal microscopy, domain mapping FEBS letters Medium 28777890
2018 AiV non-structural proteins (2B, 2BC, 2C, 3A, 3AB) interact with ACBD3, OSBP, VAP-A/B, and SAC1; ACBD3 mediates recruitment of OSBP-VAP cholesterol transport machinery to AiV replication organelles through protein–protein interactions; silencing OSBP, VAP-A/B, or SAC1 inhibited AiV replication; cholesterol accumulates at AiV replication organelles in an OSBP-dependent manner. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, cholesterol staining, electron microscopy Journal of virology Medium 29367253
2019 ACBD3 knockout impaired replication of representative viruses from four enterovirus and two rhinovirus species; PI4KB recruitment to replication organelles requires ACBD3; absence of ACBD3 causes 3A mis-localization to ER instead of Golgi; ACB and CAR domains of ACBD3 are dispensable, while other domains are required for 3A-mediated PI4KB recruitment. CRISPR knockout, rescue with ACBD3/PI4KB mutants, immunofluorescence, viral replication assay, domain deletion analysis mBio High 30755512
2019 SAXS analysis showed that the ACBD3:PI4KB complex adopts highly flexible conformations (both compact and extended), while 14-3-3:PI4KB:Rab11 has 2:1:1 stoichiometry; membrane is required for formation of the ACBD3:PI4KB:Rab11 complex at physiological concentrations. Small-angle X-ray scattering (SAXS), in vitro reconstitution Scientific reports Medium 30679637
2019 Crystal structures of ACBD3 GOLD domain complexed with 3A proteins from poliovirus, EV-A71, EV-D68, and rhinovirus B14 revealed convergent structural mechanisms for 3A–ACBD3 interaction; 3A–3A interactions drive assembly of ACBD3–3A heterotetramers; structure-guided mutations disrupting these interfaces impaired PI4KB recruitment and enterovirus replication. Crystal structure determination, molecular dynamics, co-immunoprecipitation, viral replication assay, mutagenesis PLoS pathogens High 31381608
2019 ACBD3 is required for FAPP2-mediated glucosylceramide transport; ACBD3 knockdown causes Golgi fragmentation, FAPP2 dispersal from trans-Golgi network, and abnormal sphingolipid metabolism; re-expression of full-length ACBD3 rescues these defects. Co-immunoprecipitation, siRNA knockdown, quantitative lipidomics, confocal microscopy, rescue experiment Journal of molecular cell biology Medium 29750412
2021 ACBD3 knockout cells exhibit enlarged Golgi with absence of stacks and ribbon-like formation, confirming ACBD3 role in Golgi stacking; cholesterol levels and mitochondrial structure/function are not altered in ACBD3-KO HEK293 and HeLa cells; decreased sphingomyelins with normal ceramide and sphingomyelin synthase activity reveal ACBD3 role in ceramide transport from ER to Golgi. CRISPR knockout, electron microscopy, Golgi morphology analysis, lipidomics, mitochondrial function assays International journal of molecular sciences Medium 34298889
2021 ACBD3 directly interacts with KDEL receptor and recruits PKA to the Golgi; ACBD3 depletion causes accelerated retrograde trafficking of KDEL receptor by altering its interaction with PKA and Arf1/ArfGAP1, leading to increased Arf1-GTP-dependent tubular carrier formation; ACBD3 functions as a negative regulator of PKA activity on KDEL receptor. Proximity-based in vivo tagging, co-immunoprecipitation, siRNA knockdown, live-cell imaging, trafficking assay BMC biology Medium 34493279
2022 The Golgi-resident ACBD3 recognizes and concentrates ligand-bound STING at specialized ER–Golgi contact sites (non-canonical ER exit sites); ACBD3 depletion impairs STING ER-to-Golgi trafficking and type-I interferon responses. Unbiased proteomic screen, super-resolution microscopy, live-cell imaging, ACBD3 siRNA knockdown, STING trafficking assay, IFN reporter assay Cell reports High 36543137
2023 ACBD3 is recruited to the Golgi by two redundant mechanisms: (1) an MWT374-376 motif in the ACBD3 region upstream of the GOLD domain, which interacts with golgins golgin-45 and giantin; (2) interaction with SCFD1 (a Sec1/Munc-18 protein) and SEC22B (a SNARE); CRISPR-KO of SCFD1 causes ACBD3 to become cytosolic, acting upstream of golgin interactions. CRISPR knockout, unbiased proteomics, mutagenesis (MWT motif), co-immunoprecipitation, immunofluorescence Molecular biology of the cell High 38134218
2023 ACBD3 GOLD domain directly interacts with the regulatory subunit RII of PKA, recruiting PKA holoenzyme to the Golgi; forward trafficking of proteins from the ER triggers PKA activation (release of catalytic subunit from RII) at the Golgi; ACBD3 depletion reduces Golgi-localized RII and causes constitutive PKA activation and KDEL receptor retrograde transport. Co-immunoprecipitation, domain mapping, PKA activity assay, siRNA knockdown, KDEL receptor trafficking assay The Journal of biological chemistry Medium 37044218
2024 ACBD3 knockdown increases labile iron levels by promoting ferritinophagy, leading to ferroptosis sensitivity; this is coupled with reduced GPX4 levels and elevated polyunsaturated fatty acid-containing glycerophospholipids; knockdown of NCOA4 or Bafilomycin A1 treatment blocked ferritinophagy and impeded ferroptosis in ACBD3-depleted cells. siRNA knockdown, iron measurement, lipid peroxidation assay, lipidomics, ferritinophagy inhibition Cell biology international Medium 38953242
2025 ACBD3 colocalizes with TBEV NS4B at ER–Golgi contact sites and promotes TBEV infection; ACBD3 depletion inhibits virus replication and causes abnormal ER transformation and reduced virion release; the proviral mechanism is independent of PI4KB recruitment, requiring the full-length ACBD3 to coordinate ER-Golgi coupling. siRNA knockdown, proximity proteomics, confocal/electron microscopy, viral replication assay, virion release assay Journal of virology Medium 40207930
2025 ACBD3 promotes primary lung cancer growth by recruiting PI4KB to the Golgi, enhancing oncogenic secretion in chromosome 1q-amplified cells; conversely, in chromosome 1q-diploid cells, ACBD3 suppresses metastasis by inhibiting NOTCH signaling and reducing cell motility. CRISPR knockout, co-immunoprecipitation, cell migration/invasion assay, xenograft model, NOTCH signaling assay Oncogene Medium 40189704

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 ACBD3-mediated recruitment of PI4KB to picornavirus RNA replication sites. The EMBO journal 158 22124328
2012 The 3A protein from multiple picornaviruses utilizes the golgi adaptor protein ACBD3 to recruit PI4KIIIβ. Journal of virology 151 22258260
2001 Identification, localization, and function in steroidogenesis of PAP7: a peripheral-type benzodiazepine receptor- and PKA (RIalpha)-associated protein. Molecular endocrinology (Baltimore, Md.) 125 11731621
2001 Identification and characterization of a novel Golgi protein, GCP60, that interacts with the integral membrane protein giantin. The Journal of biological chemistry 113 11590181
2010 Acyl-coenzyme A binding domain containing 3 (ACBD3; PAP7; GCP60): an emerging signaling molecule. Progress in lipid research 111 20043945
2007 The mammalian Golgi regulates numb signaling in asymmetric cell division by releasing ACBD3 during mitosis. Cell 90 17418793
2016 Structural insights and in vitro reconstitution of membrane targeting and activation of human PI4KB by the ACBD3 protein. Scientific reports 80 27009356
2003 PAP7, a PBR/PKA-RIalpha-associated protein: a new element in the relay of the hormonal induction of steroidogenesis. The Journal of steroid biochemistry and molecular biology 68 12943713
2013 Recruitment of PI4KIIIβ to coxsackievirus B3 replication organelles is independent of ACBD3, GBF1, and Arf1. Journal of virology 65 24352456
2017 Enterovirus 3A Facilitates Viral Replication by Promoting Phosphatidylinositol 4-Kinase IIIβ-ACBD3 Interaction. Journal of virology 61 28701404
2016 Salmonella Effectors SseF and SseG Interact with Mammalian Protein ACBD3 (GCP60) To Anchor Salmonella-Containing Vacuoles at the Golgi Network. mBio 58 27406559
2013 ACBD3 interaction with TBC1 domain 22 protein is differentially affected by enteroviral and kobuviral 3A protein binding. mBio 57 23572552
2013 Golgi protein ACBD3 mediates neurotoxicity associated with Huntington's disease. Cell reports 55 24012756
2019 ACBD3 Is an Essential Pan-enterovirus Host Factor That Mediates the Interaction between Viral 3A Protein and Cellular Protein PI4KB. mBio 54 30755512
2018 Model of OSBP-Mediated Cholesterol Supply to Aichi Virus RNA Replication Sites Involving Protein-Protein Interactions among Viral Proteins, ACBD3, OSBP, VAP-A/B, and SAC1. Journal of virology 51 29367253
2014 A complex comprising phosphatidylinositol 4-kinase IIIβ, ACBD3, and Aichi virus proteins enhances phosphatidylinositol 4-phosphate synthesis and is critical for formation of the viral replication complex. Journal of virology 51 24672044
2013 The Golgi protein ACBD3, an interactor for poliovirus protein 3A, modulates poliovirus replication. Journal of virology 46 23926333
2016 The Molecular Basis of Aichi Virus 3A Protein Activation of Phosphatidylinositol 4 Kinase IIIβ, PI4KB, through ACBD3. Structure (London, England : 1993) 44 27989622
2006 GCP60 preferentially interacts with a caspase-generated golgin-160 fragment. The Journal of biological chemistry 40 16870622
2017 Kobuviral Non-structural 3A Proteins Act as Molecular Harnesses to Hijack the Host ACBD3 Protein. Structure (London, England : 1993) 37 28065508
2019 Convergent evolution in the mechanisms of ACBD3 recruitment to picornavirus replication sites. PLoS pathogens 32 31381608
2017 The Golgi protein ACBD3 facilitates Enterovirus 71 replication by interacting with 3A. Scientific reports 32 28303920
2012 Acyl-CoA binding domain containing 3 (ACBD3) recruits the protein phosphatase PPM1L to ER-Golgi membrane contact sites. FEBS letters 31 22796112
2022 The Golgi-resident protein ACBD3 concentrates STING at ER-Golgi contact sites to drive export from the ER. Cell reports 29 36543137
2019 Acyl-CoA-Binding Domain-Containing 3 (ACBD3; PAP7; GCP60): A Multi-Functional Membrane Domain Organizer. International journal of molecular sciences 29 31022988
2003 Molecular cloning, chromosomal localization of human peripheral-type benzodiazepine receptor and PKA regulatory subunit type 1A (PRKAR1A)-associated protein PAP7, and studies in PRKAR1A mutant cells and tissues. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 29 12692076
2017 Light and Plastid Signals Regulate Different Sets of Genes in the Albino Mutant Pap7-1. Plant physiology 28 28935841
2019 ACBD3 is required for FAPP2 transferring glucosylceramide through maintaining the Golgi integrity. Journal of molecular cell biology 26 29750412
2019 Phosphatidylinositol 4-kinase IIIβ (PI4KB) forms highly flexible heterocomplexes that include ACBD3, 14-3-3, and Rab11 proteins. Scientific reports 22 30679637
2017 ACBD3 functions as a scaffold to organize the Golgi stacking proteins and a Rab33b-GAP. FEBS letters 19 28777890
2007 Identification of a redox-sensitive cysteine in GCP60 that regulates its interaction with golgin-160. The Journal of biological chemistry 19 17711851
2014 Hepatitis C virus NS5A competes with PI4KB for binding to ACBD3 in a genotype-dependent manner. Antiviral research 17 24792752
2003 Molecular cloning, genomic organization, chromosomal mapping and subcellular localization of mouse PAP7: a PBR and PKA-RIalpha associated protein. Gene 15 12711385
2021 ACBD3 modulates KDEL receptor interaction with PKA for its trafficking via tubulovesicular carrier. BMC biology 13 34493279
2019 Structural insights into Acyl-coenzyme A binding domain containing 3 (ACBD3) protein hijacking by picornaviruses. Protein science : a publication of the Protein Society 9 31583778
2024 Golgi protein ACBD3 downregulation sensitizes cells to ferroptosis. Cell biology international 7 38953242
2023 An A-kinase anchoring protein (ACBD3) coordinates traffic-induced PKA activation at the Golgi. The Journal of biological chemistry 7 37044218
2019 Structural basis for hijacking of the host ACBD3 protein by bovine and porcine enteroviruses and kobuviruses. Archives of virology 7 31845156
2023 Recruitment of PI4KIIIβ to the Golgi by ACBD3 is dependent on an upstream pathway of a SNARE complex and golgins. Molecular biology of the cell 6 38134218
2021 A Crucial Role of ACBD3 Required for Coxsackievirus Infection in Animal Model Developed by AAV-Mediated CRISPR Genome Editing Technique. Viruses 3 33546322
2021 Knock-Out of ACBD3 Leads to Dispersed Golgi Structure, but Unaffected Mitochondrial Functions in HEK293 and HeLa Cells. International journal of molecular sciences 3 34298889
2021 ACBD3 is up-regulated in gastric cancer and promotes cell cycle G1-to-S transition in an AKT-dependent manner. Experimental cell research 3 34332983
2025 Dichotomous roles of ACBD3 in NSCLC growth and metastasis. Oncogene 1 40189704
2025 The ACBD3 protein coordinates ER-Golgi contacts to enable productive TBEV infection. Journal of virology 1 40207930
2024 PAP1 and PAP7 are required for association of plastid-encoded RNA polymerase with DNA. Plant molecular biology 1 39302509
2024 The Chlamydia pneumoniae inclusion membrane protein Cpn0308 interacts with host protein ACBD3. Journal of bacteriology 1 39723831
2017 Protoporphyrin IX regulates peripheral benzodiazepine receptor associated protein 7 (PAP7) and divalent metal transporter 1 (DMT1) in K562 cells. Biochemistry and biophysics reports 1 28955733
2026 Chlamydia pneumoniae facilitates its development by recruiting PI4P to inclusion bodies via the Cpn0308-ACBD3-PI4KB pathway. Infection and immunity 0 42240327
2023 KDEL Receptor Trafficking to the Plasma Membrane Is Regulated by ACBD3 and Rab4A-GTP. Cells 0 37048152

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