Affinage

ANP32A

Acidic leucine-rich nuclear phosphoprotein 32 family member A · UniProt P39687

Length
249 aa
Mass
28.6 kDa
Annotated
2026-06-13
100 papers in source corpus 46 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANP32A is a small, leucine-rich-repeat nuclear phosphoprotein that integrates phosphatase regulation, chromatin acetylation control, apoptotic signaling, and host support of viral RNA replication (PMID:8679524, PMID:11830591, PMID:18439902). As a phosphatase regulator it is a potent and selective heat-stable inhibitor of PP2A, binding specifically the PP2A catalytic subunit through its N-terminal isotype-specific region (PMID:8679524, PMID:18245083), while in the presence of Mn2+ it associates with the PP1 catalytic subunit and redirects its substrate specificity (PMID:10734057); relief of PP2A inhibition by tyrosine phosphorylation or by direct binding of sphingoid bases links ANP32A to downstream MEK/ERK and p38 signaling (PMID:15247276, PMID:20558741), and its PP2A inhibition modulates Tau phosphorylation (PMID:18245083). In the nucleus ANP32A is a core subunit of the INHAT complex that binds unacetylated/hypoacetylated histones and masks them from acetyltransferases such as p300/CBP and PCAF, thereby repressing transcription (PMID:11830591, PMID:15136563); this histone-masking activity is regulated by casein kinase II phosphorylation at Ser158/Ser204 (PMID:15287743), operates on newly synthesized histone H4 to block HAT1-mediated acetylation (PMID:28977641), and shapes acetylation-dependent programs governing neurofilament expression, interferon-stimulated genes, and lipid-metabolism loci (PMID:19136565, PMID:21325029, PMID:29467488). Through its C-terminal region ANP32A is pro-apoptotic and tumor-suppressive, promoting apoptosome assembly together with CAS and Hsp70 by accelerating Apaf-1 nucleotide exchange to enhance caspase-9 activation (PMID:18439902), with the caspase-activating motif being required for both apoptotic and tumor-suppressor function (PMID:10400610, PMID:19121999). ANP32A also controls mRNA fate, promoting cytoplasmic translocation and caspase cleavage of HuR during lethal stress and modulating HuR–mRNA association (PMID:18180367, PMID:21152064). Finally, ANP32A (redundantly with ANP32B) is an essential host cofactor for influenza A virus polymerase: it interacts directly with the PB2 subunit, an interaction enhanced by viral RNA, and bridges two FluPol molecules into an asymmetric replication platform via its N-terminal LRR domain while its C-terminal disordered LCAR inserts between the juxtaposed PB2 627 domains (PMID:33208942, PMID:30184493, PMID:34935435). Species-specific support of avian polymerase is dictated by an avian-unique 33-amino-acid insertion in the disordered domain that restores multivalent binding lost with PB2-E627, explaining mammalian adaptation (PMID:26738596, PMID:32694517, PMID:37707433). Anp32a-deficient mice develop osteoarthritis, osteopenia and cerebellar ataxia linked to defective oxidative defense (reduced ATM) and Wnt de-repression, establishing physiological roles in tissue protection (PMID:30209244, PMID:35227892).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Established ANP32A as a dedicated enzyme regulator by showing it is a selective, high-affinity inhibitor of PP2A, defining its first molecular activity.

    Evidence In vitro phosphatase assays with purified recombinant protein against PP2A, PP1, PP2B, PP2C

    PMID:8679524

    Open questions at the time
    • Did not define the structural basis of PP2A selectivity
    • Cellular consequences of PP2A inhibition not addressed
  2. 2000 High

    Extended the phosphatase-regulatory repertoire by showing ANP32A modifies PP1 substrate specificity in a Mn2+-dependent manner, indicating it is not solely a PP2A inhibitor.

    Evidence In vitro phosphatase assays and gel filtration co-elution with recombinant proteins and multiple substrates

    PMID:10734057

    Open questions at the time
    • Physiological relevance of Mn2+-dependence unclear
    • No in vivo PP1 substrate identified
  3. 2002 High

    Defined a chromatin function by identifying ANP32A as an INHAT subunit that masks histones to inhibit HATs, establishing transcriptional repression as a core role.

    Evidence In vitro HAT inhibition assays, transfection/colocalization, domain deletion mapping

    PMID:11830591

    Open questions at the time
    • Genome-wide targets not defined at this stage
    • Regulation of INHAT activity unaddressed
  4. 2004 High

    Connected ANP32A histone masking to gene-specific repression and showed selectivity for hypoacetylated histones plus HDAC association, integrating it into the acetylation cycle.

    Evidence Histone binding assays, Co-IP with HDACs, ChIP at an estrogen-regulated gene; separate H3-binding/caspase study

    PMID:15136563 PMID:16341127

    Open questions at the time
    • Mechanism linking histone state to recruitment unresolved
    • Direct vs indirect HDAC association not separated
  5. 2004 High

    Identified post-translational control of ANP32A by CKII phosphorylation at Ser158/Ser204, providing a regulatory switch over its functions.

    Evidence In vitro kinase assay, biochemical purification, site-directed mutagenesis, phospho-specific antibodies

    PMID:15287743

    Open questions at the time
    • Which functions each phosphosite controls not fully mapped
    • Upstream signals activating CKII on ANP32A unknown
  6. 2008 High

    Established the pro-apoptotic mechanism by showing ANP32A accelerates Apaf-1 nucleotide exchange with CAS and Hsp70 to promote apoptosome assembly, and links ANP32A to HuR cytoplasmic translocation/cleavage.

    Evidence Apoptosome reconstitution, siRNA knockdown, HuR cleavage assays with non-cleavable mutant

    PMID:18180367 PMID:18439902

    Open questions at the time
    • How nuclear ANP32A reaches the cytoplasmic apoptosome not fully defined
    • Trigger coupling apoptosis to HuR translocation incomplete
  7. 2008 High

    Mapped the PP2A interaction to the N-terminal isotype-specific region and tied PP2A inhibition to a cellular readout (Tau phosphorylation), sharpening mechanism and function.

    Evidence GST pulldown, Co-IP, deletion mutagenesis, in vitro phosphatase assay, immunofluorescence

    PMID:18245083

    Open questions at the time
    • Structural detail of the PP2Ac contact not resolved
    • In vivo Tau relevance limited to overexpression model
  8. 2015 High

    Defined ANP32A (with ANP32B) as host IREF-2 activity that engages free influenza RdRp and promotes vRNA synthesis, opening the viral-cofactor branch.

    Evidence Biochemical complementation with nuclear extracts, MS identification, siRNA knockdown

    PMID:26512887

    Open questions at the time
    • Direct polymerase contact not mapped here
    • Step-specificity of replication not fully resolved
  9. 2016 High

    Explained the avian-to-mammalian host barrier by showing an avian-unique 33-aa insertion governs which polymerases ANP32A can support, establishing it as an essential, species-restricting host factor.

    Evidence Rescue, deletion/insertion mutagenesis, polymerase activity assays in mammalian cells

    PMID:26738596

    Open questions at the time
    • Atomic mechanism of the insertion's effect not yet defined
    • Whether PB2-627 directly contacts ANP32A unresolved at this stage
  10. 2019 Medium

    Demonstrated functional redundancy of ANP32A/ANP32B for human influenza replication and extended ANP32 to HIV-1 unspliced mRNA nuclear export via Rev/CRM1.

    Evidence Single/double knockouts, polymerase reporter assays, RNA fractionation, Co-IP with Rev and CRM1, reconstitution

    PMID:30996088 PMID:31444273

    Open questions at the time
    • Direct vs scaffolding role in export not separated
    • Tissue-level relevance of redundancy untested
  11. 2020 High

    Provided structural mechanism: cryo-EM and NMR showed ANP32A bridges two FluPol via its LRR while the LCAR inserts between PB2 627 domains, explaining PB2-E627K mammalian adaptation through multivalent disordered-domain binding.

    Evidence Cryo-EM of FluPolC–ANP32A complexes; NMR of PB2 627-NLS/ANP32A complexes

    PMID:32694517 PMID:33208942

    Open questions at the time
    • Dynamics of the asymmetric dimer in cells not directly observed
    • Generality across influenza A subtypes inferred from FluPolC
  12. 2020 Medium

    Refined the host-range determinants, showing swine ANP32A residues (106V/156S) uniquely permit avian polymerase support and that SUMO/SIM-like features modulate polymerase interaction strength.

    Evidence Polymerase reporter assays, mutagenesis, Co-IP, ANP32A knockout in pig cells; split-luciferase interaction assays

    PMID:28903035 PMID:32084248 PMID:32269123

    Open questions at the time
    • Quantitative contribution of each feature to replication not partitioned
    • In vivo cross-species transmission impact not tested
  13. 2021 Medium

    Revised the replication-step model by showing ANP32A is required for both vRNA and cRNA synthesis and specifically for the actively replicating, not encapsidating, polymerase.

    Evidence Minigenome assays with knockout/rescue, infection studies, promoter mutations

    PMID:34935435

    Open questions at the time
    • Molecular distinction between replicating and encapsidating polymerase engagement unresolved
    • Step-specific structural state not captured
  14. 2018 Medium

    Established physiological roles via knockout mice, linking ANP32A to oxidative defense (ATM) and acetylation-dependent gene programs in cartilage and leukemia.

    Evidence Anp32a KO mice, OA models, ChIP-seq for H3 acetylation, rescue experiments

    PMID:29467488 PMID:30209244

    Open questions at the time
    • Direct vs indirect control of ATM/lipid genes not fully separated
    • Tissue specificity of acetylation targets incomplete
  15. 2023 High

    Resolved the multivalent ternary-complex logic, showing avian ANP32A simultaneously binds FluPol and NP through distinct linear motifs and that PB2-E627K rescues this on human ANP32A.

    Evidence NMR of FluPol/NP/ANP32A ternary complexes with interaction mapping

    PMID:37707433

    Open questions at the time
    • Functional output of NP co-recruitment in replication not quantified in cells
    • Order of assembly events unresolved
  16. 2024 Medium

    Added a SUMO regulatory layer, showing PIAS2α-mediated SUMOylation at K68/K153 recruits influenza NS2 via SIM-SUMO contacts to facilitate avian polymerase support.

    Evidence SUMOylation assays, site mutagenesis, Co-IP, vRNP assembly assays, PIAS2α/SENP1 manipulation

    PMID:39737943

    Open questions at the time
    • Whether SUMOylation also regulates non-viral ANP32A functions untested
    • Dynamics of SUMO cycling during infection unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ANP32A's multiple activities (phosphatase inhibition, histone masking, apoptosome promotion, viral polymerase support) are coordinated and switched within a single cell remains unresolved.
  • No unified model linking post-translational modifications to selection among competing functions
  • Structural basis of PP2A and PP1 contacts unsolved
  • Mechanism controlling nuclear-cytoplasmic redistribution across contexts undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0042393 histone binding 4 GO:0140110 transcription regulator activity 4 GO:0003723 RNA binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3
Pathway
R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-4839726 Chromatin organization 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953854 Metabolism of RNA 3
Partners
ANP32BAPAF-1CRM1CSNK2 (CASEIN KINASE II)HURPB2 (INFLUENZA POLYMERASE)PP1PP2A CATALYTIC SUBUNIT
Complex memberships
INHAT complexapoptosome (Apaf-1)influenza FluPol replication platformnewly synthesized histone H4 complex

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 ANP32A (PHAP-I/I1PP2A) was identified as a potent heat-stable inhibitor of protein phosphatase 2A (PP2A), with half-maximal inhibition at ~4 nM, and did not affect PP1, PP2B, or PP2C activities. In vitro phosphatase activity assay using purified recombinant human PHAP-I against PP2A, PP1, PP2B, PP2C Biochemistry High 8679524
2002 ANP32A (pp32) is a subunit of the INHAT (inhibitor of acetyltransferases) complex and inhibits histone acetyltransferase (HAT) activity of p300/CBP and PCAF by masking histones; its INHAT domains mediate histone binding, HAT inhibition, and transcriptional repression in vivo. In vitro HAT inhibition assays, colocalization and transfection studies, deletion/domain analysis The Journal of biological chemistry High 11830591
2004 ANP32A (pp32/Set-TAF-Ibeta) specifically binds to unacetylated and hypoacetylated histones but not hyperacetylated histones, associates with histone deacetylases in vitro and in vivo, and associates with an endogenous estrogen receptor-regulated gene (EB1) in the hypoacetylated transcriptionally inactive state but not in the active state. Histone binding assays, co-immunoprecipitation with HDACs, chromatin immunoprecipitation at endogenous gene The Journal of biological chemistry High 15136563
2008 ANP32A (PHAPI) promotes apoptosome formation by working together with CAS and Hsp70 to accelerate nucleotide exchange on Apaf-1 and prevent inactive Apaf-1/cytochrome c aggregation, thereby enhancing caspase-9 activation. Biochemical reconstitution of apoptosome activity, identification of CAS and Hsp70 as co-mediators, siRNA knockdown in cells measuring Apaf-1 aggregation and apoptosis Molecular cell High 18439902
2008 ANP32A (pp32/PHAP-I) promotes cytoplasmic translocation of HuR upon lethal stress; in the cytoplasm, ANP32A facilitates caspase-mediated cleavage of HuR at Asp226, amplifying the apoptotic response. siRNA depletion of ANP32A reduces both HuR cytoplasmic accumulation and caspase activation efficiency. siRNA knockdown, co-immunoprecipitation, HuR cleavage assays, non-cleavable mutant (D226A) overexpression The Journal of cell biology High 18180367
2008 ANP32A (I1PP2A) interacts specifically with the catalytic subunit of PP2A (PP2Ac) but not with regulatory A or B subunits; the N-terminal isotype-specific region of ANP32A is required for PP2Ac association and PP2A inhibition. Overexpression of ANP32A in PC12/Tau441 cells increases Tau phosphorylation and impairs microtubule network and neurite outgrowth. GST pulldown, co-immunoprecipitation from transfected cells, deletion mutagenesis, in vitro phosphatase assay, immunofluorescence The Journal of biological chemistry High 18245083
2004 ANP32A (pp32) directly binds to casein kinase II (CKII), which phosphorylates pp32 at serines 158 and 204 in vivo. Mutagenesis of these sites affects pp32 function. In vitro kinase assay, biochemical purification, deletion and site-directed mutagenesis, phospho-specific antibody validation Biochemistry High 15287743
2016 Species-specific differences in ANP32A account for the suboptimal activity of avian influenza polymerase in mammalian cells. Avian ANP32A has an additional 33 amino acids between the LRR and LCAR domains; deletion of this insertion abrogates support of avian polymerase, and its insertion into human ANP32A rescues avian virus polymerase function. ANP32A is an essential host partner co-opted to support influenza virus replication. Rescue experiments with avian ANP32A in mammalian cells, deletion and insertion mutagenesis, influenza polymerase activity assays Nature High 26738596
2020 Cryo-EM structures of influenza C virus polymerase in complex with human and chicken ANP32A reveal that two FluPol molecules form an asymmetric dimer bridged by the N-terminal LRR domain of ANP32A, while the C-terminal LCAR of ANP32A inserts between the two juxtaposed PB2 627 domains, providing a structural mechanism for how PB2(E627K) enables mammalian adaptation. Cryo-electron microscopy structure determination of FluPolC–ANP32A complexes Nature High 33208942
2015 ANP32A (pp32) and ANP32B (APRIL) constitute host-derived IREF-2 activity that interacts with free viral RNA-dependent RNA polymerase and preferentially upregulates vRNA synthesis from cRNA templates. Knockdown of these proteins reduces viral replication in vivo. Biochemical complementation assay with nuclear extracts, protein identification by mass spectrometry, siRNA knockdown eLife High 26512887
2020 NMR analysis of PB2 627-NLS domains in complex with avian and human ANP32A shows that human ANP32A IDD transiently binds the 627 domain via multivalent interactions; PB2-E627 disrupts polyvalency of this interaction, an effect compensated by the avian-unique 33-aa motif in avian ANP32A IDD. NMR spectroscopy, conformational ensemble determination of PB2 627-NLS/ANP32A complexes Nature communications High 32694517
2004 Tyrosine phosphorylation of ANP32A (PHAPI/pp32) by jacalin stimulation releases PP2A from ANP32A inhibition, thereby activating PP2A and leading to dephosphorylation of MEK1/2 and ERK1/2. PHAPI knockdown by RNAi abolished both PP2A activation and MEK inhibition by jacalin. Immunoprecipitation kinase assays, PP2A activity assay, siRNA knockdown, Western blot of MEK/ERK phosphorylation The Journal of biological chemistry High 15247276
2000 ANP32A (I1PP2A) associates with the catalytic subunit of PP1 in the presence of Mn2+ and modifies its substrate specificity, stimulating PP1 activity toward myelin basic protein and histone H1 (but not phosphorylase) by 15–20 fold, an activity not seen with Co2+, Mg2+, Ca2+, or Zn2+. In vitro phosphatase activity assay, gel filtration co-elution with Mn2+, recombinant proteins The Journal of biological chemistry High 10734057
2007 Crystal structure of the N-terminal LRR domain of pp32 (ANP32A) was determined, revealing a capped leucine-rich repeat fold that mediates protein-protein interactions characteristic of the ANP32 family. X-ray crystallography Protein science High 17567741
2005 ANP32A (pp32/LANP) interacts with adenovirus E4orf6, which exports pp32 from the nucleus to the cytoplasm along with HuR; this complex stabilizes ARE-containing mRNAs (c-fos, c-myc, COX-2) in the cytoplasm via a CRM1-independent mechanism. Co-immunoprecipitation, subcellular fractionation, mRNA stability assays, CRM1 inhibitor (leptomycin B) experiments The Journal of cell biology Medium 15983058
2005 Adenovirus protein VII associates with ANP32A (pp32) and SET in vitro, with distinct protein VII domains responsible for binding each; protein VII, ANP32A, and SET co-associate with viral DNA during early infection. In vitro binding assays, chromatin immunoprecipitation, immunofluorescence Journal of virology Medium 15681448
2007 ANP32A (LANP) forms a complex with transcriptional repressor E4F and modulates its repressive activity; ataxin-1 competes with E4F for LANP binding, relieving LANP-E4F-mediated transcriptional repression. This links ANP32A to SCA1 pathology. Co-immunoprecipitation, transcriptional reporter assays, competition binding experiments EMBO reports Medium 17557114
2005 ANP32A (pp32) tumor suppression requires amino acids 150–174; deletion or truncation of this region abolishes inhibition of oncogene-mediated (RAS+MYC) transformation in rat embryo fibroblasts. The oncogenic pp32r1 and pp32r2 differ from pp32 precisely in this region. Deletion and truncation mutagenesis, rat embryo fibroblast transformation assays (focus formation, soft agar) The Journal of biological chemistry Medium 10400610
2005 Hyperphosphorylated Rb interacts with ANP32A (pp32) but not with closely related pp32r1 or pp32r2; this Rb-pp32 interaction inhibits the apoptotic activity of pp32 and stimulates cell proliferation. Co-immunoprecipitation, apoptosis functional assays, proliferation assays The Journal of biological chemistry Medium 15716273
2009 ANP32A (PHAPI) apoptotic activity—stimulation of caspase activation via the apoptosome—is required for its tumor suppressive function. The PHAPI close homolog pp32R1 (an oncoprotein) cannot stimulate caspase activation; the critical difference maps to amino acids in the caspase activation motif. ANP32A translocates from nucleus to cytoplasm during apoptosis; disruption of its NLS modestly decreases tumor suppression. Truncation mutagenesis, in vitro caspase activation assay, subcellular fractionation, tumor suppression assays The Journal of biological chemistry Medium 19121999
2010 Sphingosine (and DMS, phytosphingosine) directly binds ANP32A identified by affinity chromatography/proteomics; sphingoid base binding relieves ANP32A-mediated PP2A inhibition in vitro and activates PP2A in endothelial cells, leading to p38 SAPK activation and COX-2 induction. ANP32A siRNA knockdown enhanced basal and DMS-activated PP2A activity. Affinity chromatography with sphingosine, proteomics, in vitro PP2A activity assay, siRNA knockdown The Journal of biological chemistry Medium 20558741
2009 ANP32A (LANP) depletion promotes neurite outgrowth in neuronal cell lines and primary neurons from LANP null mice; LANP directly binds the neurofilament light chain (NF-L) gene promoter and suppresses histone acetylation at this locus, repressing NF-L expression. siRNA knockdown in neuronal cell lines, primary neuron culture from LANP KO mice, ChIP at NF-L promoter, histone acetylation analysis The Journal of biological chemistry Medium 19136565
2011 ANP32A (pp32) interacts with STAT1 and STAT2 in an IFN-dependent manner and is required for maximal transcriptional induction of IFN-stimulated genes (ISGs) by promoting assembly of transcription initiation complexes at ISG promoters; siRNA knockdown of pp32 reduces histone acetylation on ISG promoters. Co-immunoprecipitation (IFN-dependent), ChIP at ISG promoters, siRNA knockdown with IFN-stimulated gene expression readout Journal of cell science Medium 21325029
2017 ANP32A (PP32) and SET/TAF-Iβ are components of the newly synthesized histone H4 complex identified by proteomics; they function to prevent HAT1-mediated acetylation of H4K5 and H4K12 in vitro. Depletion of PP32 and SET/TAF-Iβ causes hyperacetylation of H4 lysine residues, destabilizes H4-Hsp90 interaction, and results in S-phase arrest. Proteomic analysis of newly synthesized H4 complex, in vitro HAT inhibition assay, siRNA knockdown with histone acetylation and cell cycle analysis Nucleic acids research Medium 28977641
2010 ANP32A (pp32) overexpression in pancreatic cancer cells reduces HuR association with mRNAs encoding dCK, VEGF, and HuR itself; silencing pp32 enhances HuR binding to these mRNA targets, affecting gemcitabine sensitivity through altered dCK protein levels. RNA immunoprecipitation (RIP), overexpression and siRNA knockdown, mRNA binding assays, gemcitabine sensitivity assays PloS one Medium 21152064
2018 ANP32A deficiency in AML cells reduces genome-wide histone H3 acetylation, with significant H3 acetylation changes at lipid metabolism genes (APOC1, PCSK9, P2RX1, LPPR3); overexpression of APOC1 partially rescues the proliferation defect of ANP32A-deficient AML cells. Genome-wide ChIP-seq for H3 acetylation, gene expression analysis, APOC1 overexpression rescue experiment Leukemia Medium 29467488
2018 ANP32A protects cartilage against oxidative stress and OA by promoting expression of ATM (a key cellular oxidative defense regulator); Anp32a-deficient mice show reduced ATM expression and develop OA, osteopenia, and cerebellar ataxia, all rescued by antioxidant treatment. Microarray profiling in Anp32a KO mice, in vivo OA model, antioxidant treatment, immunohistochemistry Science translational medicine Medium 30209244
2019 ANP32A and ANP32B mediate nuclear export of unspliced/partially spliced HIV-1 mRNA via interactions with Rev and CRM1; double (but not single) knockout of ANP32A and ANP32B accumulates unspliced viral mRNA in the nucleus and reduces Gag protein expression; reconstitution of either restores viral production. Double knockout, RNA nuclear/cytoplasmic fractionation, co-immunoprecipitation with Rev and CRM1, Gag expression assay The Journal of biological chemistry Medium 31444273
2019 Human ANP32A or ANP32B alone is indispensable for human influenza A virus RNA replication; two amino acids at positions 129–130 of chicken ANP32B are responsible for its inability to support viral replication and its weak interaction with the viral polymerase complex. siRNA/KO of ANP32A and ANP32B, polymerase activity reporter assays, co-immunoprecipitation, site-directed mutagenesis Journal of virology Medium 30996088
2020 Swine ANP32A uniquely (among mammalian ANP32 proteins) supports avian influenza polymerase activity; this is mapped to amino acids 106V and 156S in swANP32A. Mutation of these residues weakens interaction with chicken viral polymerase and reduces polymerase activity. ANP32A knockout in pig (PK15) cells dramatically reduces avian influenza polymerase activity. Polymerase activity reporter assays, site-directed mutagenesis, co-immunoprecipitation, ANP32A knockout in pig cells PLoS pathogens / Journal of virology Medium 32084248 32269123
2017 Downregulating ANP32A in hippocampal CA3 of tau transgenic mice rescues memory loss and synaptic deficits by reducing INHAT complex formation and unmasking histones for acetylation; ANP32A levels are upregulated by tau accumulation, β-amyloid, and H2O2 via C/EBPβ activation. Lentiviral shRNA stereotaxic injection, Morris water maze, electrophysiology, Golgi staining, ChIP, Western blot Molecular neurodegeneration Medium 28472990
2022 ANP32A represses Wnt signaling in articular cartilage via histone acetylation masking; ANP32A co-immunoprecipitates with components at Wnt target gene loci, and its loss triggers Wnt hyper-activation and cardiac hypertrophy. Combined antioxidant and Wnt inhibitor treatment ameliorates OA in Anp32a-deficient mice. Co-immunoprecipitation, ChIP-qPCR, luciferase assays, Anp32a KO mouse DMM OA model, Wnt inhibitor/antioxidant treatment Osteoarthritis and cartilage Medium 35227892
2004 ANP32A (pp32) specifically binds to histone H3 and blocks both its acetylation and phosphorylation; pp32 overexpression inhibits cell growth in Jurkat T cells and directly initiates caspase activity and promotes granzyme A-mediated caspase-independent cell death. Histone binding assays, histone acetylation/phosphorylation analysis, caspase activity assay, cell growth assays Cell death and differentiation Medium 16341127
2006 ANP32A (LANP/I1PP2A) is pulled down by the cytoplasmic domain of integrin α3A and co-localizes with integrin α3β1; GST-ANP32A pulls down both integrin α3β1 and PP1 from cell lysates, and PP1 can dephosphorylate integrin α3β1 at T1046 in vitro, suggesting ANP32A bridges PP1 and integrin α3β1. Affinity chromatography, GST pulldown, co-localization by immunofluorescence, in vitro phosphatase assay Journal of neuroscience research Low 17016859
2008 The NMR solution structure of the ANP32A LRR domain was determined; the LRR domain interacts with the AXH domain of ataxin-1 with millimolar (very weak) affinity, suggesting additional partners or post-translational modification is needed for stable binding. Two-hybrid screening identified Clip-170/Restin as a new LRR domain partner. NMR spectroscopy, yeast two-hybrid screening, in vitro binding assay The FEBS journal Medium 18410380
2017 Direct species-independent interactions exist between all ANP32A splice variants and the PB2 polymerase subunit; this interaction is enhanced in the presence of viral genomic RNA. However, only avian ANP32A (containing the 33-aa or 29-aa insertion) restored RNP complex assembly and enhanced RNA synthesis for a restricted polymerase. Split luciferase complementation assays, co-immunoprecipitation, influenza minigenome assays Cell reports Medium 30184493
2020 Human ANP32A interacts weakly with influenza polymerase; the 33-aa insertion of avian ANP32A and a hydrophobic SIM-like sequence unique to avian ANP32A both promote stronger polymerase interaction. SUMOylation of the host cell contributes to vPol activity including avian ANP32A function. Split luciferase complementation, co-immunoprecipitation, in situ split Venus interaction, mutagenesis, SUMO pathway manipulation Cell reports Medium 28903035
2021 ANP32A is required for both vRNA and cRNA synthesis by the influenza A virus polymerase (not just vRNA from cRNA as previously proposed); ANP32A is needed for the actively replicating polymerase but not the encapsidating polymerase. Minigenome assays with ANP32A knockout/rescue, virus infection studies, viral promoter mutations Journal of virology Medium 34935435
2013 ANP32A (LANP/pp32) interacts with LIM-homeodomain transcription factor LHX3 via the LHX3 carboxyl terminus; LANP is associated with LHX3 target genes in pituitary cells (by ChIP), and experimental alteration of LANP levels affects LHX3-mediated pituitary gene regulation. Mass spectrometry, biochemical domain mapping, co-immunoprecipitation, ChIP, gain/loss-of-function transcription assays PloS one Medium 23861948
2024 Human ANP32A is SUMOylated at K68 and K153 by the E3 SUMO ligase PIAS2α and deSUMOylated by SENP1; SUMOylated ANP32A recruits influenza NS2 via a SIM-SUMO interaction, facilitating ANP32A-supported avian polymerase activity and vRNP-ANP32A interactions. SUMOylation assays, mutagenesis of SUMOylation sites, co-immunoprecipitation, vRNP assembly assays, PIAS2α/SENP1 manipulation Nature communications Medium 39737943
2023 NMR characterization of ternary complexes shows avian ANP32A simultaneously binds influenza FluPol and NP via distinct linear motifs in its longer disordered domain; the 33-aa deletion in human ANP32A blocks this simultaneous colocalization. PB2-E627K mutation enables FluPol and NP to bind the same extended linear motif on human ANP32A in a highly dynamic multivalent ternary complex. NMR spectroscopy of ternary FluPol/NP/ANP32A complexes, interaction mapping Journal of the American Chemical Society High 37707433
2022 AIMP1 interacts with ANP32A (identified by protein chip assay) and this interaction regulates histone H3 acetylation in multiple myeloma cells; disruption of AIMP1 expression reduces H3 acetylation enrichment at GAREM2 locus and decreases ERK1/2 phosphorylation. Protein chip assay, co-immunoprecipitation, ChIP-seq, siRNA knockdown Cancer communications Low 36042007
2004 ANP32A (pp32) overexpression suppresses Raf-1 activation, downregulating ERK activation; the C-terminal half of pp32 is required for Raf-1 suppression. siRNA knockdown of pp32 enhances ERK and MEK activation. Overexpression and siRNA knockdown, Western blot of Raf-1/MEK/ERK phosphorylation, deletion mutagenesis Cancer letters Low 16039954
2015 Cranial high-resolution X-ray crystal structure of the ANP32A LRR domain was determined at 1.56 Å, showing displacement in the turn connecting α1 to β1 compared to prior 2.4/2.69 Å structures. X-ray crystallography at 1.56 Å resolution Acta crystallographica Section F Medium 26057796
2021 ANP32A binds HMGA1 mRNA via RNA immunoprecipitation and maintains HMGA1 mRNA stability, thereby promoting HMGA1 protein expression and subsequent STAT3 activation in hepatocellular carcinoma cells. RNA immunoprecipitation (RIP), siRNA knockdown and overexpression, Western blot, xenograft model Carcinogenesis Low 33332531

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Species difference in ANP32A underlies influenza A virus polymerase host restriction. Nature 257 26738596
1996 Molecular identification of I1PP2A, a novel potent heat-stable inhibitor protein of protein phosphatase 2A. Biochemistry 161 8679524
2020 Host ANP32A mediates the assembly of the influenza virus replicase. Nature 136 33208942
2002 Regulation of histone acetylation and transcription by nuclear protein pp32, a subunit of the INHAT complex. The Journal of biological chemistry 123 11830591
2011 MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4. Oncogene 121 21317927
1991 A functional complex is formed in human T lymphocytes between the protein tyrosine phosphatase CD45, the protein tyrosine kinase p56lck and pp32, a possible common substrate. European journal of immunology 120 1655467
2008 Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis. The Journal of cell biology 111 18180367
1994 Purification and characterization of two putative HLA class II associated proteins: PHAPI and PHAPII. Biological chemistry Hoppe-Seyler 91 8192856
2004 A signaling role of histone-binding proteins and INHAT subunits pp32 and Set/TAF-Ibeta in integrating chromatin hypoacetylation and transcriptional repression. The Journal of biological chemistry 83 15136563
2008 PHAPI, CAS, and Hsp70 promote apoptosome formation by preventing Apaf-1 aggregation and enhancing nucleotide exchange on Apaf-1. Molecular cell 80 18439902
2015 pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA. eLife 74 26512887
2008 I1PP2A affects tau phosphorylation via association with the catalytic subunit of protein phosphatase 2A. The Journal of biological chemistry 72 18245083
1996 Structure of pp32, an acidic nuclear protein which inhibits oncogene-induced formation of transformed foci. Molecular biology of the cell 71 8970164
2019 Fundamental Contribution and Host Range Determination of ANP32A and ANP32B in Influenza A Virus Polymerase Activity. Journal of virology 70 30996088
2001 Tumor suppression and potentiation by manipulation of pp32 expression. Oncogene 62 11360199
2004 Protein phosphatase 2A, a negative regulator of the ERK signaling pathway, is activated by tyrosine phosphorylation of putative HLA class II-associated protein I (PHAPI)/pp32 in response to the antiproliferative lectin, jacalin. The Journal of biological chemistry 60 15247276
2018 Differential Splicing of ANP32A in Birds Alters Its Ability to Stimulate RNA Synthesis by Restricted Influenza Polymerase. Cell reports 58 30184493
1992 Four CD45/P56lck-associated phosphorproteins (pp29-pp32) undergo alterations in human T cell activation. European journal of immunology 57 1352500
1988 Properties of avian sarcoma-leukosis virus pp32-related pol-endonucleases produced in Escherichia coli. Journal of virology 57 2836618
1984 Requirement of the avian retrovirus pp32 DNA binding protein domain for replication. Virology 56 6091334
2017 Functional Insights into ANP32A-Dependent Influenza A Virus Polymerase Host Restriction. Cell reports 55 28903035
2005 Adenovirus protein VII functions throughout early phase and interacts with cellular proteins SET and pp32. Journal of virology 55 15681448
1982 Avian retrovirus pp32 DNA-binding protein. I. Recognition of specific sequences on retrovirus DNA terminal repeats. Journal of virology 52 6292495
2020 Molecular basis of host-adaptation interactions between influenza virus polymerase PB2 subunit and ANP32A. Nature communications 46 32694517
1999 Identification of sequences required for inhibition of oncogene-mediated transformation by pp32. The Journal of biological chemistry 46 10400610
1998 Novel nuclear phosphoprotein pp32 is highly expressed in intermediate- and high-grade prostate cancer. The Prostate 46 9492852
2005 Adenovirus E4orf6 targets pp32/LANP to control the fate of ARE-containing mRNAs by perturbing the CRM1-dependent mechanism. The Journal of cell biology 43 15983058
2010 pp32 (ANP32A) expression inhibits pancreatic cancer cell growth and induces gemcitabine resistance by disrupting HuR binding to mRNAs. PloS one 42 21152064
2000 Protein phosphatase 2A inhibitors, I(1)(PP2A) and I(2)(PP2A), associate with and modify the substrate specificity of protein phosphatase 1. The Journal of biological chemistry 42 10734057
2007 The crystal structure of the tumor suppressor protein pp32 (Anp32a): structural insights into Anp32 family of proteins. Protein science : a publication of the Protein Society 41 17567741
2020 A unique feature of swine ANP32A provides susceptibility to avian influenza virus infection in pigs. PLoS pathogens 40 32084248
2010 Sphingosine interaction with acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) regulates PP2A activity and cyclooxygenase (COX)-2 expression in human endothelial cells. The Journal of biological chemistry 40 20558741
2023 Mammalian ANP32A and ANP32B Proteins Drive Differential Polymerase Adaptations in Avian Influenza Virus. Journal of virology 39 37074204
2007 The role of LANP and ataxin 1 in E4F-mediated transcriptional repression. EMBO reports 38 17557114
2017 Downregulating ANP32A rescues synapse and memory loss via chromatin remodeling in Alzheimer model. Molecular neurodegeneration 37 28472990
2007 pp32/PHAPI determines the apoptosis response of non-small-cell lung cancer. Cell death and differentiation 37 17962813
1985 Site-specific nicking at the avian retrovirus LTR circle junction by the viral pp32 DNA endonuclease. Nucleic acids research 36 2995920
2018 ANP32A regulates histone H3 acetylation and promotes leukemogenesis. Leukemia 35 29467488
2005 Phosphorylated retinoblastoma protein complexes with pp32 and inhibits pp32-mediated apoptosis. The Journal of biological chemistry 35 15716273
2004 Generation and characterization of LANP/pp32 null mice. Molecular and cellular biology 35 15060138
2020 Swine ANP32A Supports Avian Influenza Virus Polymerase. Journal of virology 33 32269123
1986 Nuclease mechanism of the avian retrovirus pp32 endonuclease. Journal of virology 33 3009900
2018 ANP32A regulates ATM expression and prevents oxidative stress in cartilage, brain, and bone. Science translational medicine 32 30209244
2005 Novel cytosolic binding partners of the neural cell adhesion molecule: mapping the binding domains of PLC gamma, LANP, TOAD-64, syndapin, PP1, and PP2A. Biochemistry 32 15865439
1984 Avian retrovirus pp32 DNA binding protein. Preferential binding to the promoter region of long terminal repeat DNA. Biochemistry 32 6320867
2009 Neuronal differentiation is regulated by leucine-rich acidic nuclear protein (LANP), a member of the inhibitor of histone acetyltransferase complex. The Journal of biological chemistry 30 19136565
2009 PHAPI/pp32 suppresses tumorigenesis by stimulating apoptosis. The Journal of biological chemistry 29 19121999
2021 The Host Factor ANP32A Is Required for Influenza A Virus vRNA and cRNA Synthesis. Journal of virology 28 34935435
2020 Elucidating the Interactions between Influenza Virus Polymerase and Host Factor ANP32A. Journal of virology 28 31694956
2001 Expression of pp32 gene family members in breast cancer. Breast cancer research and treatment 28 11678310
2011 pp32, an INHAT component, is a transcription machinery recruiter for maximal induction of IFN-stimulated genes. Journal of cell science 27 21325029
2017 PP32 and SET/TAF-Iβ proteins regulate the acetylation of newly synthesized histone H4. Nucleic acids research 26 28977641
2017 ANP32A modulates cell growth by regulating p38 and Akt activity in colorectal cancer. Oncology reports 23 28731192
2004 pp32 reduction induces differentiation of TSU-Pr1 cells. The American journal of pathology 23 14695340
2015 Inhibition of Protein Phosphatase-2A (PP2A) by I1PP2A Leads to Hyperphosphorylation of Tau, Neurodegeneration, and Cognitive Impairment in Rats. Journal of Alzheimer's disease : JAD 20 25589718
2014 Capping motifs stabilize the leucine-rich repeat protein PP32 and rigidify adjacent repeats. Protein science : a publication of the Protein Society 20 24659532
2012 LANP mediates neuritic pathology in Spinocerebellar ataxia type 1. Neurobiology of disease 20 22884877
1983 Antibodies against a synthetic peptide of the avian retrovirus pp32 protein and the beta DNA polymerase subunit. Virology 20 6314648
2009 Variation at the ANP32A gene is associated with risk of hip osteoarthritis in women. Arthritis and rheumatism 19 19565487
2004 pp32/ I-1(PP2A) negatively regulates the Raf-1/MEK/ERK pathway. Cancer letters 19 16039954
1980 Partial phosphorylation in vivo of the avian retrovirus pp32 DNA endonuclease. Journal of virology 19 6257933
2015 Highly polarized C-terminal transition state of the leucine-rich repeat domain of PP32 is governed by local stability. Proceedings of the National Academy of Sciences of the United States of America 18 25902505
2007 Reduction of pp32 expression in poorly differentiated pancreatic ductal adenocarcinomas and intraductal papillary mucinous neoplasms with moderate dysplasia. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 18 17906614
2022 AIMP1 promotes multiple myeloma malignancy through interacting with ANP32A to mediate histone H3 acetylation. Cancer communications (London, England) 16 36042007
2019 ANP32A and ANP32B are key factors in the Rev-dependent CRM1 pathway for nuclear export of HIV-1 unspliced mRNA. The Journal of biological chemistry 16 31444273
2019 Bergapten alleviates osteoarthritis by regulating the ANP32A/ATM signaling pathway. FEBS open bio 15 31037830
2019 Insights into species-specific regulation of ANP32A on the mammalian-restricted influenza virus polymerase activity. Emerging microbes & infections 15 31608791
2005 Tumor suppressor pp32 represses cell growth through inhibition of transcription by blocking acetylation and phosphorylation of histone H3 and initiating its proapoptotic activity. Cell death and differentiation 15 16341127
2022 Sevoflurane inhibits histone acetylation and contributes to cognitive dysfunction by enhancing the expression of ANP32A in aging mice. Behavioural brain research 14 35659510
1988 Avian retrovirus pp32 DNA endonuclease is phosphorylated on Ser in the carboxyl-terminal region. Journal of virology 14 2835511
2021 ANP32A promotes the proliferation, migration and invasion of hepatocellular carcinoma by modulating the HMGA1/STAT3 pathway. Carcinogenesis 13 33332531
2024 Avian ANP32A incorporated in avian influenza A virions promotes interspecies transmission by priming early viral replication in mammals. Science advances 12 38295177
2022 ANP32A represses Wnt signaling across tissues thereby protecting against osteoarthritis and heart disease. Osteoarthritis and cartilage 12 35227892
2015 The expression and distributions of ANP32A in the developing brain. BioMed research international 12 25866766
2005 A pp32-retinoblastoma protein complex modulates androgen receptor-mediated transcription and associates with components of the splicing machinery. Biochemical and biophysical research communications 12 16009334
2018 Inhibition of Histone Acetylation by ANP32A Induces Memory Deficits. Journal of Alzheimer's disease : JAD 11 29782322
2010 CXCL12-mediated regulation of ANP32A/Lanp, a component of the inhibitor of histone acetyl transferase (INHAT) complex, in cortical neurons. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 11 20617464
2008 Structural bases for recognition of Anp32/LANP proteins. The FEBS journal 10 18410380
2021 Asp149 and Asp152 in chicken and human ANP32A play an essential role in the interaction with influenza viral polymerase. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 33982347
2017 Knockdown of pp32 Increases Histone Acetylation and Ameliorates Cognitive Deficits. Frontiers in aging neuroscience 9 28473768
2023 Multivalent Dynamic Colocalization of Avian Influenza Polymerase and Nucleoprotein by Intrinsically Disordered ANP32A Reveals the Molecular Basis of Human Adaptation. Journal of the American Chemical Society 8 37707433
2022 Hypoxia and Wnt signaling inversely regulate expression of chondroprotective molecule ANP32A in articular cartilage. Osteoarthritis and cartilage 8 36370958
2020 SRSF10 inhibits the polymerase activity and replication of avian influenza virus by regulating the alternative splicing of chicken ANP32A. Virus research 8 32574681
2018 High-Pressure NMR and SAXS Reveals How Capping Modulates Folding Cooperativity of the pp32 Leucine-rich Repeat Protein. Journal of molecular biology 8 29545082
2013 LHX3 interacts with inhibitor of histone acetyltransferase complex subunits LANP and TAF-1β to modulate pituitary gene regulation. PloS one 8 23861948
2004 The identification of phosphorylation sites of pp32 and biochemical purification of a cellular pp32-kinase. Biochemistry 8 15287743
1996 pp32 overexpression induces nuclear pleomorphism in rat prostatic carcinoma cells. Cell proliferation 8 9146727
2019 The interaction of cellular protein ANP32A with influenza A virus polymerase component PB2 promotes vRNA synthesis. Archives of virology 7 30666459
2022 Anp32a Promotes Neuronal Regeneration after Spinal Cord Injury of Zebrafish Embryos. International journal of molecular sciences 6 36555564
2021 Small peptide targeting ANP32A as a novel strategy for acute myeloid leukemia therapy. Translational oncology 6 34678588
2006 Integrin alpha3beta1 interacts with I1PP2A/lanp and phosphatase PP1. Journal of neuroscience research 6 17016859
2024 H3K4 Trimethylation Mediate Hyperhomocysteinemia Induced Neurodegeneration via Suppressing Histone Acetylation by ANP32A. Molecular neurobiology 5 38351418
2022 KPNA6 is a Cofactor of ANP32A/B in Supporting Influenza Virus Polymerase Activity. Microbiology spectrum 5 35044222
2017 Prothymosin α interacts with SET, ANP32A and ANP32B and other cytoplasmic and mitochondrial proteins in proliferating cells. Archives of biochemistry and biophysics 5 29106904
2016 The Avian Influenza Virus Polymerase Brings ANP32A Home to Roost. Cell host & microbe 5 26867171
2024 PB2 residue 473 contributes to the mammalian virulence of H7N9 avian influenza virus by modulating viral polymerase activity via ANP32A. Journal of virology 4 38421166
2024 Human ANP32A/B are SUMOylated and utilized by avian influenza virus NS2 protein to overcome species-specific restriction. Nature communications 4 39737943
2015 High-resolution crystal structure of the leucine-rich repeat domain of the human tumour suppressor PP32A (ANP32A). Acta crystallographica. Section F, Structural biology communications 4 26057796
2006 Highly acidic C-terminal domain of pp32 is required for the interaction with histone chaperone, TAF-Ibeta. Biological & pharmaceutical bulletin 4 17142970
2021 Gga-miR-181a modulates ANP32A expression and inhibits MDCC-MSB-1 cell. In vitro cellular & developmental biology. Animal 3 33686586

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