Affinage

APLP2

Amyloid beta precursor like protein 2 · UniProt Q06481

Round 2 corrected
Length
763 aa
Mass
87.0 kDa
Annotated
2026-04-28
116 papers in source corpus 47 papers cited in narrative 47 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

APLP2 is a type I transmembrane glycoprotein of the APP family that functions as a multifunctional regulator of cell adhesion, synaptic transmission, intracellular signaling, and metabolic homeostasis. APLP2 undergoes regulated ectodomain shedding by ADAM10/TACE and sequential intramembranous cleavage by β-secretase (BACE1) and γ-secretase to release a transcriptionally active intracellular domain (ALID2/AICD2) that activates gene expression through complexes with Fe65, Mint3, and co-activators Taz/Yap, as well as through NF-κB p65 (PMID:12228233, PMID:21178287, PMID:37844466). APLP2 homo- and heterodimerizes with APP and APLP1 to mediate trans-cellular adhesion, and its intracellular domain interacts with presynaptic release machinery, NMDA receptor subunit GluN1, Mint2/Munc18, and the trafficking adaptor PAT1a to regulate neurotransmitter release, synaptic plasticity, and Ca²⁺ homeostasis via SERCA and Stim1/Stim2 (PMID:16193067, PMID:21522131, PMID:25683482, PMID:34172567). Genetic studies in mice reveal essential, functionally redundant roles with APP in postnatal survival, neuromuscular junction integrity, cortical neurogenesis, glucose/insulin homeostasis, copper homeostasis, refractive eye development, and anticoagulation via its Kunitz protease inhibitor domain (PMID:9461064, PMID:23345401, PMID:18393365, PMID:10526140, PMID:26313004, PMID:19403832).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1993 Medium

    Molecular cloning established APLP2 as the closest APP homologue, defining its shared domain architecture (signal peptide, KPI domain, transmembrane segment, cytoplasmic NPXY motif) and raising the question of whether the two proteins have overlapping functions.

    Evidence cDNA cloning and sequence/domain analysis from two independent groups

    PMID:8220435 PMID:8485127

    Open questions at the time
    • No functional data; domain homology does not prove functional equivalence
    • Predicted G(o)-coupling lacked biochemical validation
  2. 1994 High

    Identification of Ser-614 as the sole chondroitin sulfate GAG modification site, and the subsequent demonstration that alternative splicing controls GAG addition, revealed an isoform-specific post-translational modification with potential implications for axonal targeting.

    Evidence Site-directed mutagenesis in CHO/COS-1 cells with chondroitinase digestion; isoform-specific expression analysis

    PMID:7622456 PMID:8071334

    Open questions at the time
    • Functional consequence of CS-GAG modification on APLP2 biology remained undefined
    • Mechanism by which the 12-aa insertion blocks GAG addition was not determined structurally
  3. 1997 High

    The demonstration that APP/APLP2 double knockout mice die postnatally while single knockouts are viable established functional redundancy between the two genes and motivated all subsequent compound genetic analyses.

    Evidence Gene targeting and double-KO mouse generation with postnatal lethality phenotype

    PMID:9461064

    Open questions at the time
    • Molecular basis of postnatal lethality was undefined
    • Whether APLP1 could also compensate remained to be tested
  4. 1999 High

    Loss-of-function studies in knockout mice revealed APLP2's role in copper homeostasis and its neurotrophic properties, broadening the functional repertoire beyond structural homology with APP.

    Evidence Atomic absorption spectrophotometry in APLP2-KO mouse tissues; recombinant sAPLP2 neurite outgrowth assay in chick sympathetic neurons

    PMID:10526140 PMID:9923612

    Open questions at the time
    • Copper-binding site on APLP2 not mapped
    • Receptor mediating sAPLP2 neurotrophic activity unknown
  5. 2002 High

    Discovery that BACE1 and γ-secretase sequentially cleave APLP2 to release a transcriptionally active intracellular domain (ALID2) that activates Fe65-dependent gene expression established APLP2 as a signaling molecule processed analogously to Notch.

    Evidence BACE1 overexpression cleavage assays combined with transcriptional reporter assays; Presenilin 1-dependent γ-secretase cleavage demonstration

    PMID:12228233 PMID:14699153

    Open questions at the time
    • Endogenous target genes of ALID2/Fe65 were not identified
    • Physiological relevance of ALID2 signaling in vivo not established
  6. 2005 High

    Identification of ADAM10 and TACE as the α-secretases mediating APLP2 ectodomain shedding, combined with the discovery that APP/APLP2 homo- and heterodimerize to mediate trans-cellular adhesion, integrated APLP2 into both regulated proteolysis and cell adhesion pathways.

    Evidence ADAM10/TACE overexpression and inhibitor studies in cells plus ADAM10-transgenic mice; Co-IP from mouse brain and KO MEF adhesion assays with rescue

    PMID:16193067 PMID:16279945

    Open questions at the time
    • Structural basis of homo/heterodimerization interface not resolved
    • Relative contributions of cis vs. trans dimerization to adhesion in vivo unclear
  7. 2006 High

    The KPI domain of APLP2 was shown to inhibit coagulation proteases with anticoagulant effects in vivo, and the trafficking adaptor PAT1a was identified as a regulator of APLP2 surface levels and processing, establishing two distinct functional axes—hemostasis and intracellular trafficking.

    Evidence Recombinant KPI domain clotting assays and APLP2-KO thrombosis models; PAT1a Co-IP, RNAi, and surface biotinylation in primary neurons

    PMID:17050537 PMID:19403832

    Open questions at the time
    • In vivo bleeding/clotting phenotype in humans not assessed
    • PAT1a binding stoichiometry and competition with Fe65 not determined
  8. 2008 High

    APP/APLP2 double knockouts revealed essential roles in glucose/insulin homeostasis and glutamatergic neurotransmission (via VGLUT2 regulation by the intracellular domain), connecting APLP2 to metabolic and synaptic functions.

    Evidence Double-KO metabolic phenotyping; ESC-derived neurons from double-KO with γ-secretase inhibition and APP-ICD rescue, VGLUT2 quantification, electrophysiology

    PMID:18393365 PMID:18535156

    Open questions at the time
    • Whether APLP2 alone is sufficient for glucose homeostasis not separated from APP contribution
    • Mechanism linking intracellular domain to VGLUT2 transcription not fully defined
  9. 2011 High

    Electrophysiological studies in compound mutant mice established that APP and APLP2 are synergistically required for neuromuscular transmission and hippocampal LTP, with the underlying mechanism involving an APP/Mint2/Munc18 presynaptic complex and Mint3-Taz/Yap transcriptional complexes.

    Evidence APPsα-KI × APLP2-KO mice with NMJ and hippocampal electrophysiology, Co-IP of APP/Mint2/Munc18; Co-IP and reporter assays for Mint3-Taz/Yap complexes

    PMID:21178287 PMID:21522131

    Open questions at the time
    • Direct target genes of Mint3-Taz/Yap complexes downstream of APLP2 not identified
    • Whether APLP2 directly recruits Mint2/Munc18 or acts indirectly through APP not resolved
  10. 2013 High

    APLP2 was shown to have unique functions not shared with APP: it mediates PCSK9-dependent LDLR lysosomal degradation and is specifically required for cortical progenitor cell cycle exit during neurogenesis, although the PCSK9 requirement was later challenged.

    Evidence APLP2 KD/KO with LDLR readout and pH-dependent binding assays; in vivo shRNA in APP/APLP1-DKO background with mitotic index quantification; PCSK9 infusion in multiple KO lines contradicting APLP2 requirement

    PMID:23345401 PMID:23430252 PMID:28495363

    Open questions at the time
    • PCSK9/APLP2 interaction is contested—in vivo infusion studies found APLP2 dispensable for PCSK9 function
    • Neurogenesis mechanism downstream of APLP2 (transcriptional targets, signaling pathway) not identified
  11. 2015 High

    Multiple studies converged on synaptic and sensory functions: APLP2's intracellular domain interacts with presynaptic release machinery to regulate glutamate release; APLP2 associates with NMDA receptors via GluN1 to enhance their surface expression; and Aplp2 knockout mice develop hyperopia with altered retinal amacrine cell function.

    Evidence Domain mapping and JCasp peptide interference with hippocampal slice electrophysiology; Co-IP of APLP2/GluN1 from brain; Aplp2-KO refraction, ERG, and retinal immunostaining

    PMID:25683482 PMID:26313004 PMID:26551565

    Open questions at the time
    • Structural basis of APLP2-GluN1 interaction not resolved
    • Molecular pathway linking APLP2 to amacrine cell physiology and emmetropization unknown
  12. 2021 High

    The mechanism by which APP/APLP2 control synaptic plasticity was traced to Ca²⁺ homeostasis: double knockout disrupts ER Ca²⁺ store refilling via altered SERCA function and Stim1/Stim2 expression, and this is rescued by secreted APPsα, linking ectodomain shedding to ER calcium signaling.

    Evidence Conditional double-KO hippocampal neurons with Ca²⁺ imaging, SERCA assays, Stim1/2 quantification, AAV-APPsα rescue, and LTP electrophysiology

    PMID:34172567

    Open questions at the time
    • Whether APLP2-derived soluble ectodomain alone can rescue Ca²⁺ defects not tested
    • Identity of the receptor mediating APPsα's effect on SERCA/Stim expression unknown
  13. 2023 Medium

    The transcriptional output of the APLP2 intracellular domain was extended to NF-κB signaling: nuclear AICD2 interacts with NF-κB p65 to upregulate IL-1β and iNOS in macrophages, and this antimicrobial pathway is exploited during mycobacterial defense; simultaneously, APLP2 was shown to inhibit TGF-β signaling by disrupting TGFBR2-Hsp90 stabilization.

    Evidence Co-IP of nuclear AICD2/p65, NF-κB reporter, KO mouse infection model; Co-IP of APLP2/TGFBR2/Hsp90 with ubiquitination and signaling readouts

    PMID:37479189 PMID:37844466

    Open questions at the time
    • NF-κB target gene repertoire regulated by AICD2 not comprehensively defined
    • TGF-β pathway modulation studied only in overexpression systems
    • Neither finding independently replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of APLP2 dimerization interfaces, the full transcriptional target repertoire of ALID2/AICD2 in vivo, whether the contested PCSK9-APLP2 axis is physiologically relevant, and the receptor(s) mediating sAPLP2 neurotrophic and Ca²⁺-regulatory signaling.
  • No crystal structure of full-length APLP2 or its dimerization interface
  • ChIP-seq or equivalent genome-wide identification of AICD2 targets not performed
  • Receptor for soluble APLP2 ectodomain signaling remains unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0098631 cell adhesion mediator activity 3 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 3 GO:0005634 nucleus 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-112316 Neuronal System 6 R-HSA-392499 Metabolism of proteins 6 R-HSA-162582 Signal Transduction 5 R-HSA-1500931 Cell-Cell communication 3 R-HSA-1266738 Developmental Biology 2 R-HSA-109582 Hemostasis 1
Partners
ADAM10APLP1APPBACE1FE65GLUN1MINT3PCSK9
Complex memberships
ALID2/Fe65 transcriptional complexAPP family homo/heterodimer complexAPP/Mint2/Munc18 presynaptic complexMint3-Taz/Yap transcriptional complex

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 APLP2 was isolated as a close homologue of APP, sharing domain architecture including a cytoplasmic domain predicted to couple with the GTP-binding protein G(o), suggesting APLP2 may function as a cell surface activator of this G protein. Molecular cloning, sequence analysis, expression analysis Nature genetics Low 8220435
1993 APLP2 (also called APPH) encodes a type I transmembrane protein with a signal peptide, large extracellular domain including a Kunitz protease inhibitor domain, transmembrane region, and short cytoplasmic domain, establishing it as the closest known relative of APP in an emerging multigene family. Molecular cloning, cDNA sequencing, domain analysis Biochemistry Medium 8485127
1994 APLP2 is modified by chondroitin sulfate glycosaminoglycan (CS GAG) addition at a single site (Ser-614); a serine-to-alanine substitution at position 614 abolishes CS GAG modification, establishing this as the sole modification site. Stable transfection in CHO and COS-1 cells, chondroitinase AC digestion, site-directed mutagenesis The Journal of biological chemistry High 8071334
1995 CS GAG modification of APLP2 is regulated by alternative splicing: the APLP2-763 isoform containing a 12-amino acid insertion immediately N-terminal to Ser-614 is not modified by CS GAG, whereas the APLP2-751 isoform is. Similarly, APP isoforms lacking exon 15 (L-APP) are CS GAG modified while exon 15-containing isoforms are not. Transfection of isoform constructs, biochemical analysis of GAG modification The Journal of biological chemistry High 7622456
1995 APLP2 is enriched in postsynaptic compartments in cortex and hippocampus, but is abundant in presynaptic olfactory sensory axons and axon terminals in olfactory glomeruli; CS GAG-modified APLP2 mRNA is specifically enriched in the olfactory epithelium and CS-modified APLP2 accumulates in the olfactory bulb, consistent with a role in axonal pathfinding and/or synaptogenesis. Immunocytochemistry with APLP2-specific antibodies, confocal microscopy, biochemical fractionation, in situ hybridization The Journal of neuroscience Medium 7472397
1997 APLP2 and APP are functionally redundant in vivo: APLP2 single knockout mice are viable and fertile, but APP/APLP2 double knockout mice show ~80% postnatal lethality within the first week, demonstrating that APLP2 and APP can substitute for each other functionally during early postnatal development. Gene targeting/knockout, genetic epistasis in double KO mice Neurobiology of aging High 9461064
1998 APLP2 is required for correct genomic segregation in dividing cells: homozygous APLP2 deletion arrests embryos before the blastocyst stage, and antisense suppression of APLP2 in embryonic fibroblasts produces daughter cells with abnormal DNA contents (>4C and <2C), indicating a role in mitotic genome segregation. Germline deletion, antisense RNA expression with GFP co-transfection, DNA content analysis by flow cytometry The EMBO journal Medium 9707424
1999 APP and APLP2 modulate copper homeostasis in vivo: APP(-/-) and APLP2(-/-) knockout mice show significantly elevated copper levels specifically in cerebral cortex (40% and 16% respectively) and liver (80% and 36% respectively), while zinc and iron levels are unaffected, indicating that APP and APLP2 expression specifically modulates copper homeostasis. Atomic absorption spectrophotometry in APP and APLP2 knockout mouse tissues Brain research High 10526140
1999 The recombinant APLP2 ectodomain (sAPLP2) promotes neurite outgrowth in chick sympathetic neurons with activity similar to sAPP695 and sAPP751, supporting a neurotrophic function for APLP2 analogous to APP. Recombinant protein expression in Pichia pastoris, neurite outgrowth assay on chick sympathetic neurons FEBS letters Medium 9923612
2001 APLP2 ectodomain shedding in corneal epithelial cells is regulated by PKC-epsilon and MAP kinase (MAPK) signaling: PKC activation by PMA and EGF increased APLP2 shedding, which was blocked by the MEK inhibitor U-0126, establishing that basal and stimulated APLP2 shedding requires MAPK activity. Western blotting, flow cytometry, pharmacological inhibitors (staurosporine, PKC-epsilon peptide inhibitor, U-0126) in corneal epithelial cells American journal of physiology. Cell physiology Medium 11443060
2002 APLP2 (like APP and APLP1) is cleaved by BACE1 and the resulting intracellular domain (ALID2) enhances Fe65-dependent gene activation in a transcriptional transactivation assay, indicating that BACE1/γ-secretase processing of APLP2 generates a transcriptionally active intracellular fragment. Overexpression of BACE1 with APLP2 in cells, co-transfection transcriptional reporter assays, biochemical analysis The Journal of biological chemistry High 12228233 14699153
2002 APLP2 intracellular domain (ALID2), produced by γ-secretase cleavage in a Presenilin 1-dependent manner, enhances Fe65-dependent gene activation, establishing that γ-secretase processing of APLP2 regulates transcription. Presenilin 1-dependent γ-secretase cleavage assays, transcriptional reporter assays with Fe65 co-transfection The Journal of biological chemistry High 12228233
2004 APLP2 is processed by α-secretase-like, β-secretase-like (BACE), γ-secretase-like, and ε-site cleavages in neuroblastoma cells; p3-like and Aβ-like fragments of APLP2 are detectable in cell media, and APLP2 processing is the most elaborate among APP family members with alternative cleavage sites. Stably transfected SH-SY5Y cells with C-terminally tagged constructs, pharmacological protease inhibitors, Western blotting, mass spectrometry The Journal of biological chemistry High 14970212
2004 BACE1 modulates APLP2 processing in vivo: APLP2 proteolytic products are decreased in BACE knockout mice and increased in BACE transgenic mice; overexpression of BACE in cultured cells increases APLP2 processing. BACE knockout and transgenic mice, immunoblotting of brain extracts, BACE overexpression in cultured cells Molecular and cellular neurosciences High 15080893
2004 F-spondin binds the conserved central extracellular domain of APP and inhibits beta-secretase cleavage; APLP2 shares this domain and is subject to similar extracellular ligand-mediated regulation of processing. Binding assays, proteolytic cleavage assays Proceedings of the National Academy of Sciences of the United States of America Low 14983046
2005 APLP2 shedding is mediated by the disintegrin-metalloproteinases ADAM10 and TACE (ADAM17): overexpression of either enzyme in HEK293 cells increases soluble APLP2 release; ADAM10-preferring inhibitors most strongly block APLP2 shedding in neuroblastoma cells; ADAM10-transgenic mice show increased soluble APLP2 and C-terminal fragments. Overexpression of ADAM10/TACE in HEK293 cells, pharmacological inhibitors, ADAM10-transgenic mice, Western blotting The FEBS journal High 16279945
2005 APP and APLP2 homo- and heterodimerize and promote trans-cellular adhesion: all three APP family members form homo- and heterocomplexes; endogenous APLP2 is required for cell-cell adhesion in mouse embryonic fibroblasts; APP/APLP2 interact in synaptically enriched membrane compartments in mouse brain. Co-immunoprecipitation from mouse brain, cell aggregation assays with MEFs from APLP2 KO mice, subcellular fractionation The EMBO journal High 16193067
2005 APP and APLP2 modulate Cu/Zn-nitric oxide-catalyzed degradation of glypican-1 heparan sulfate: in cell-free experiments, the Cu(I) form of APLP2 (and Cu(II) form) inhibits glypican-1 autodegradation; in primary cortical neurons and fibroblasts from APLP2 knockout mice, nitric oxide-catalyzed heparan sulfate degradation is increased, indicating APLP2 normally inhibits this process particularly in fibroblasts. Cell-free biochemical assays, confocal immunofluorescence, flow cytometry, primary neurons and fibroblasts from APP/APLP2 KO mice The Journal of biological chemistry High 15677459
2006 PAT1a binds directly to the basolateral sorting signal of APLP2 (and APP/APLP1) cytoplasmic domains, co-localizes in trans-Golgi network vesicles/endosomes in primary neurons, and regulates APP/APLP2 cell surface levels and processing: PAT1a overexpression or knockdown modulates surface levels and promotes APP/APLP2 processing with increased Aβ secretion. Co-immunoprecipitation, co-localization in primary neurons, RNAi knockdown, overexpression, cell surface biotinylation, Aβ ELISA The Journal of biological chemistry High 17050537
2006 APLP2 KPI domain functions as a Kunitz serine proteinase inhibitor that inhibits plasma clotting in vitro; APLP2(-/-) mice show shorter times to carotid artery occlusion (prothrombotic phenotype) and smaller intracerebral hematomas, demonstrating that APLP2 exerts anticoagulant function via its KPI domain in vivo. Recombinant KPI domain expression, plasma clotting assays, carotid artery thrombosis model, intracerebral hemorrhage model in APLP2(-/-) mice The Journal of neuroscience High 19403832
2006 Keratinocytes from APP/APLP2 double-knockout mice show reduced proliferation (~40% reduction in vivo and in vitro), reduced migration velocity, and compromised cell-substrate adhesion; these defects can be rescued by exogenous recombinant sAPPα, indicating that APP/APLP2-derived soluble ectodomains are required for keratinocyte proliferation, adhesion, and migration. Primary keratinocytes from APP/APLP2 KO mice, proliferation assays, migration assays, adhesion assays, rescue with recombinant sAPPα Experimental cell research High 16584729
2008 APP and APLP2 are essential modulators of glucose and insulin homeostasis: APP/APLP2 double knockout mice show 66% lower plasma glucose and hyperinsulinemia at birth; single knockouts also show hyperinsulinemia and ~31% lower plasma glucose, and reduced plasma calcium, magnesium, phosphate, and growth restriction. APP/APLP2 double and single KO mice, plasma glucose, insulin, calcium, magnesium, phosphate measurements at embryonic day E17 and postnatally The Journal of pathology High 18393365
2008 Loss of APP and APLP2 in embryonic stem cell-derived glutamatergic neurons leads to decreased VGLUT2 expression (mRNA and protein) and reduced glutamate uptake/release; blocking γ-secretase cleavage of APP in WT neurons similarly reduces VGLUT2; and VGLUT2 levels can be restored by a construct encoding the APP C-terminal intracellular domain, establishing that APP/APLP2 intracellular domain signaling regulates glutamatergic neurotransmission. ESC differentiation to neurons from APP/APLP2 double KO, γ-secretase inhibition, APP intracellular domain rescue construct, VGLUT2 mRNA/protein quantification, glutamate uptake assay, hippocampal organotypic slice electrophysiology Stem cells High 18535156
2009 APP, APLP1, and APLP2 form homo- and heterotypic cis interactions via two conserved regions; APLP2 and APP primarily localize to intracellular compartments (unlike APLP1 which is mostly at the cell surface); APLP1 uniquely forms trans interactions; and co-expression of APP with APLP1 or APLP2 diminishes Aβ42 generation due to heteromeric complex formation. Live cell imaging, FRET, co-immunoprecipitation, deletion mutants in multiple cell lines Journal of cell science High 19126676
2011 APLP2 and APP are synergistically required for neuromuscular transmission: APPsα-DM (APP secreted ectodomain knock-in on APLP2-null background) mice show reduced quantal content, depleted readily releasable pool, fragmented postsynaptic specializations, and muscular weakness; these deficits are associated with loss of an APP/Mint2/Munc18 complex; additionally, APPsα-DM mice show impaired hippocampal LTP and spatial learning. Genetic double mutant (APPsα-KI × APLP2-KO), electrophysiological recordings at NMJ, co-immunoprecipitation of APP/Mint2/Munc18 complex, behavioral assays, GABA-A rescue experiment The EMBO journal High 21522131
2011 APLP2 mediates signaling via Mint3-Taz and Mint3-Yap transcriptional complexes: APLP2 forms transcriptionally active triple complexes with Mint3 and each of the co-activators Taz and Yap; complex formation and nuclear translocation are regulated by γ-secretase cleavage of APLP2; presence of Mint1 instead of Mint3 prevents nuclear translocation. Co-immunoprecipitation, transcriptional reporter assays, γ-secretase inhibitor treatment, subcellular fractionation Journal of Alzheimer's disease Medium 21178287
2012 Bat3 interacts with APLP2, enhances its stability by reducing ubiquitination and proteasomal degradation; the proline-rich domain of Bat3 is required for this binding; nuclear export of Bat3 under apoptotic stimulation elevates APLP2 levels, promoting cell survival. Co-immunoprecipitation, domain deletion constructs, ubiquitination assays, proteasome inhibitor treatment, apoptosis assays Journal of cell science Medium 22641691
2013 APLP2 is required for cell cycle exit of cortical progenitors during neurogenesis: APLP2 silencing in vivo in an APP/APLP1 double knockout background causes cortical progenitors to remain undifferentiated with higher mitotic cell numbers, establishing a specific role for APLP2 in priming cortical progenitors for neuronal differentiation. In vivo shRNA silencing in APP/APLP1 double KO mouse background, BrdU/EdU labeling, immunostaining, mitotic index quantification Journal of cell science High 23345401
2013 PCSK9 interacts directly and in a pH-dependent manner with APLP2 (but not APP) via its C-terminal domain; APLP2 (but not APP) mediates postendocytic delivery of PCSK9 to lysosomes and is required for PCSK9 function in targeting LDLR for degradation. Co-immunoprecipitation, pH-dependent binding assays, APLP2 knockdown/KO functional assays measuring LDLR levels and lysosomal delivery The Journal of biological chemistry High 23430252
2014 APP/APLP2 expression is required to initiate endosome-to-nucleus transport of glypican-1-derived anhydromannose-containing heparan sulfate (HS): nuclear translocation of HS is absent in APP(-/-) and APLP2(-/-) MEFs, restored by APP transfection, and blocked by β- or γ-secretase inhibitors in WT cells, suggesting that APP/APLP2 degradation products mediate HS nuclear import. Deconvolution immunofluorescence microscopy with anMan-specific antibody, 35S labeling, secretase inhibitors, APP KO rescue transfection, confocal microscopy The Journal of biological chemistry High 24898256
2015 APP and APLP2 interact with the synaptic release machinery (presynaptic proteins) via the NH2-terminal region of their intracellular domain; a naturally produced peptide JCasp (from γ-secretase/caspase double cleavage of APP) interferes with this interaction and reduces glutamate release in hippocampal slices from WT but not APP-deficient mice; deletion of APP and APLP2 produces synaptic deficits consistent with facilitated transmitter release. Domain mapping, cell-penetrating peptide (JCasp), glutamate release assays in acute hippocampal slices, APP/APLP2 double KO electrophysiology eLife High 26551565
2015 APLP2 regulates refractive eye development: Aplp2 knockout mice develop high hyperopia (+11.5 D) and exhibit dose-dependent reduction in susceptibility to environmentally induced myopia; this phenotype is associated with reduced contrast sensitivity and changes in electrophysiological properties of retinal amacrine cells, which express Aplp2. Aplp2 KO mice, refraction measurement, visual evoked potentials, electroretinography, retinal cell type immunostaining PLoS genetics High 26313004
2015 APLP1 and APLP2 associate with assembled NMDA receptors (GluN1/GluN2A and GluN1/GluN2B) via interaction with the obligatory GluN1 subunit in both transfected cells and adult mammalian brain extracts; like APP, APLP2 enhances GluN1/GluN2A and GluN1/GluN2B surface expression. Co-immunoprecipitation from transfected mammalian cells and adult brain detergent extracts, cell surface expression assays Journal of neurochemistry Medium 25683482
2015 APLP2 affects the actin cytoskeleton in pancreatic cancer cells: APLP2 knockdown decreases cortical actin and increases intracellular actin filaments; stable APLP2 knockdown reduces pancreatic cancer cell migration, invasion, and orthotopic tumor metastasis in vivo. Inducible shRNA knockdown, phalloidin staining/actin imaging, migration/invasion assays, orthotopic tumor mouse model Oncotarget Medium 25576918
2016 Zinc induces multimerization of APLP2 (and APP/APLP1) and enriches them at cellular adhesion sites; however, unlike APLP1, zinc does not facilitate de novo APLP2-containing adhesion complex formation; zinc binding prevents cleavage of APLP2 by extracellular secretases. Live-cell microscopy, microcontact printing adhesion assay, ELISA for shed ectodomains, zinc treatment in cell culture and rat neurons Journal of neurochemistry Medium 26801522
2017 APP, APLP2, and LRP1 all interact with PCSK9; however, infusion of PCSK9 into App(-/-), Aplp2(-/-), Aplp2-depleted App(-/-), or liver-specific Lrp1(-/-) mice reduces hepatic LDLR levels similarly to WT, demonstrating that APP, APLP2, and LRP1 are not required for PCSK9-mediated LDLR degradation in vivo. Co-immunoprecipitation, PCSK9 infusion into multiple KO mouse lines, hepatic LDLR quantification Biochimica et biophysica acta. Molecular and cell biology of lipids High 28495363
2020 APP and APLP2 are required in GABAergic forebrain neurons for synaptic plasticity and cognition: conditional double KO in GABAergic neurons (DlxCre) causes cognitive deficits, impaired LTP, altered basal synaptic transmission at Schaffer collateral/CA1, reduced action potential firing of CA1 pyramidal cells, and disrupted excitation/inhibition balance. Conditional double KO (DlxCre), hippocampal slice electrophysiology, behavioral tests (spatial learning, nesting, burrowing), neuronal morphology analysis Cerebral cortex High 32219307
2021 APP and APLP2 control neuronal Ca2+ homeostasis: loss of both APP and APLP2 (but not APLP2 alone) impairs Ca2+ handling, endoplasmic reticulum Ca2+ store refill, and synaptic plasticity via altered SERCA-ATPase function and expression of store-operated Ca2+ channel proteins Stim1 and Stim2; long-term AAV-mediated APPsα expression restores Ca2+ homeostasis and LTP in APP/APLP2 cDKO cultures. Conditional double KO hippocampal neurons, Ca2+ imaging, ER Ca2+ store measurements, SERCA ATPase functional assays, Stim1/2 protein expression, AAV-APPsα rescue, LTP electrophysiology Proceedings of the National Academy of Sciences of the United States of America High 34172567
2022 APLP2 in spinal GABAergic inhibitory interneurons interacts trans-cellularly with microglia-specific integrin CD11b; peripheral nerve injury reduces spinal APLP2 specifically in GABAergic interneurons, and targeted APLP2 knockdown in GAD2-positive neurons disrupts this APLP2-CD11b interaction, causing microglia-dependent pain sensitization. Conditional knockdown in GAD2-Cre mice, co-immunoprecipitation of APLP2/CD11b, immunostaining, behavioral pain assays, microglial activation markers Neuropharmacology Medium 36442651
2023 The APLP2 intracellular domain (AICD2), generated by γ-secretase cleavage, translocates to the nucleus and interacts with NF-κB p65, enhancing NF-κB transcriptional activity to upregulate IL-1β and iNOS expression; this pathway is exploited for antimycobacterial defense, and M. tuberculosis suppresses APLP2 expression to evade this host response. APLP2 knockdown/mutant macrophages, APLP2 mutant mice, nuclear AICD2 co-immunoprecipitation with p65, NF-κB reporter assay, iNOS/IL-1β expression, M. bovis BCG infection model International immunopharmacology Medium 37844466
2023 YWK-II/APLP2 inhibits TGF-β signaling by interacting with TGFBR2 in a TGF-β-dependent manner and binding Hsp90, thereby interfering with the TGFBR2-Hsp90 stabilization interaction, leading to enhanced ubiquitination and degradation of TGFBR2. Co-immunoprecipitation (APLP2/TGFBR2 and APLP2/Hsp90), ubiquitination assays, TGFBR2 stability assays upon APLP2 knockdown/overexpression, TGF-β signaling reporter assays Biochimica et biophysica acta. Molecular cell research Medium 37479189
2023 In human cerebrospinal fluid, APLP2 ectodomain shedding occurs predominantly via β-secretase-like activity (not α-secretase as in HEK293 cells); APLP2 undergoes intramembranous cleavage at three sites by γ-secretase, establishing the in vivo processing pattern of APLP2 in the human CNS. Novel anti-APLP2 juxtamembrane antibody (OA603), HEK293 overexpression, human CSF analysis, MALDI mass spectrometry for cleavage site identification Psychogeriatrics Medium 36691315
2018 APLP2 expression promotes JNK-dependent cell migration in Drosophila: ectopic APLP2 expression induces cell migration that is suppressed by JNK loss-of-function and enhanced by JNK gain-of-function; APLP2 activates JNK signaling by promoting JNK phosphorylation, which triggers MMP1 expression required for basement membrane degradation. Drosophila ectopic expression, JNK pathway genetic epistasis (loss- and gain-of-function), JNK phosphorylation assay, MMP1 expression analysis BioMed research international Medium 30155482
2025 APLP2 binds K-Ras indirectly via C-Raf, as identified by TurboID-based proximity proteomics and validated by BRET and co-immunoprecipitation assays. TurboID proximity proteomics, BRET assay, co-immunoprecipitation bioRxiv (preprint)preprint Low bio_10.1101_2025.06.13.659437
1996 FE65L (hFE65L), a human homologue of rat FE65, interacts with the cytoplasmic domain of APLP2 (but not APLP1) via a single phosphotyrosine interaction (PI) domain binding the NPXY motif; endogenous APP and APLP2 co-immunoprecipitate with HA-tagged hFE65L from mammalian cells. Yeast two-hybrid screening, co-immunoprecipitation from mammalian cells overexpressing HA-hFE65L Proceedings of the National Academy of Sciences of the United States of America Medium 8855266
1999 Disabled-1 (Dab1) interacts with APLP2 (and APP and APLP1) via its PI domain binding the conserved cytoplasmic NPxY motif; co-transfection of APP family members increases serine phosphorylation of Dab1. Yeast two-hybrid, biochemical co-immunoprecipitation, co-transfection phosphorylation assays The Journal of neuroscience Medium 10460257
2013 APLP2 co-immunoprecipitates with and downregulates MHC class I surface expression on Ewing's sarcoma cells; irradiation induces redistribution of APLP2 to cell surface, correlated with reduced MHC class I surface expression; siRNA knockdown of APLP2 increases MHC class I surface expression. Co-immunoprecipitation of APLP2/MHC class I, siRNA knockdown, flow cytometry surface staining, irradiation treatment Oncoimmunology Medium 24353913

Source papers

Stage 0 corpus · 116 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1993 Isolation and characterization of APLP2 encoding a homologue of the Alzheimer's associated amyloid beta protein precursor. Nature genetics 336 8220435
1997 Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice. Neurobiology of aging 275 9461064
2005 Homo- and heterodimerization of APP family members promotes intercellular adhesion. The EMBO journal 247 16193067
2004 Functional proteomics mapping of a human signaling pathway. Genome research 247 15231748
2009 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). Journal of proteome research 237 19199708
2001 Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2. Traffic (Copenhagen, Denmark) 223 11247302
1999 Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. Brain research 222 10526140
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2003 Cleavage of amyloid-beta precursor protein and amyloid-beta precursor-like protein by BACE 1. The Journal of biological chemistry 194 14699153
2004 The proteolytic processing of the amyloid precursor protein gene family members APLP-1 and APLP-2 involves alpha-, beta-, gamma-, and epsilon-like cleavages: modulation of APLP-1 processing by n-glycosylation. The Journal of biological chemistry 181 14970212
2004 Binding of F-spondin to amyloid-beta precursor protein: a candidate amyloid-beta precursor protein ligand that modulates amyloid-beta precursor protein cleavage. Proceedings of the National Academy of Sciences of the United States of America 177 14983046
1999 Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2. Oncogene 172 10490823
1993 Molecular cloning of the cDNA for a human amyloid precursor protein homolog: evidence for a multigene family. Biochemistry 170 8485127
2010 A human MAP kinase interactome. Nature methods 165 20936779
1999 Disabled-1 binds to the cytoplasmic domain of amyloid precursor-like protein 1. The Journal of neuroscience : the official journal of the Society for Neuroscience 156 10460257
1996 Association of a novel human FE65-like protein with the cytoplasmic domain of the beta-amyloid precursor protein. Proceedings of the National Academy of Sciences of the United States of America 154 8855266
2005 Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer. Molecular & cellular proteomics : MCP 153 15778465
2011 APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP. The EMBO journal 152 21522131
2009 Ubiquitin-mediated proteolysis of HuR by heat shock. The EMBO journal 142 19322201
2017 RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination. BMC biology 135 29117863
2002 Processing of beta-amyloid precursor-like protein-1 and -2 by gamma-secretase regulates transcription. The Journal of biological chemistry 134 12228233
2004 Time-controlled transcardiac perfusion cross-linking for the study of protein interactions in complex tissues. Nature biotechnology 133 15146195
2019 The Functional Proximal Proteome of Oncogenic Ras Includes mTORC2. Molecular cell 124 30639242
2004 BACE (beta-secretase) modulates the processing of APLP2 in vivo. Molecular and cellular neurosciences 96 15080893
2015 APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans. PLoS genetics 79 26313004
2009 Subcellular localization and dimerization of APLP1 are strikingly different from APP and APLP2. Journal of cell science 79 19126676
2006 APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential signaling complex. Molecular and cellular endocrinology 78 17030088
1995 Distribution of an APP homolog, APLP2, in the mouse olfactory system: a potential role for APLP2 in axogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 77 7472397
2005 Shedding of the amyloid precursor protein-like protein APLP2 by disintegrin-metalloproteinases. The FEBS journal 73 16279945
2015 APP and APLP2 interact with the synaptic release machinery and facilitate transmitter release at hippocampal synapses. eLife 70 26551565
1994 Amyloid precursor-like protein 2 (APLP2) is modified by the addition of chondroitin sulfate glycosaminoglycan at a single site. The Journal of biological chemistry 66 8071334
2005 Increased processing of APLP2 and APP with concomitant formation of APP intracellular domains in BDNF and retinoic acid-differentiated human neuroblastoma cells. Journal of neurochemistry 59 16150056
2009 Endosomal adaptor proteins APPL1 and APPL2 are novel activators of beta-catenin/TCF-mediated transcription. The Journal of biological chemistry 54 19433865
2013 Characterization of proprotein convertase subtilisin/kexin type 9 (PCSK9) trafficking reveals a novel lysosomal targeting mechanism via amyloid precursor-like protein 2 (APLP2). The Journal of biological chemistry 53 23430252
1999 Recombinant human amyloid precursor-like protein 2 (APLP2) expressed in the yeast Pichia pastoris can stimulate neurite outgrowth. FEBS letters 52 9923612
2008 Identification of the Alzheimer's disease amyloid precursor protein (APP) and its homologue APLP2 as essential modulators of glucose and insulin homeostasis and growth. The Journal of pathology 49 18393365
2007 Membrane targeting by APPL1 and APPL2: dynamic scaffolds that oligomerize and bind phosphoinositides. Traffic (Copenhagen, Denmark) 45 18034774
2005 The amyloid precursor protein (APP) of Alzheimer disease and its paralog, APLP2, modulate the Cu/Zn-Nitric Oxide-catalyzed degradation of glypican-1 heparan sulfate in vivo. The Journal of biological chemistry 45 15677459
1995 Novel regulation of chondroitin sulfate glycosaminoglycan modification of amyloid precursor protein and its homologue, APLP2. The Journal of biological chemistry 44 7622456
2013 APLP2 regulates neuronal stem cell differentiation during cortical development. Journal of cell science 42 23345401
2018 Baicalin Modulates APPL2/Glucocorticoid Receptor Signaling Cascade, Promotes Neurogenesis, and Attenuates Emotional and Olfactory Dysfunctions in Chronic Corticosterone-Induced Depression. Molecular neurobiology 40 29675572
2009 AbetaPP/APLP2 family of Kunitz serine proteinase inhibitors regulate cerebral thrombosis. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 19403832
2008 Embryonic stem cell-derived neurons as a cellular system to study gene function: lack of amyloid precursor proteins APP and APLP2 leads to defective synaptic transmission. Stem cells (Dayton, Ohio) 40 18535156
2015 Rab31 and APPL2 enhance FcγR-mediated phagocytosis through PI3K/Akt signaling in macrophages. Molecular biology of the cell 35 25568335
2010 Neurons generated from APP/APLP1/APLP2 triple knockout embryonic stem cells behave normally in vitro and in vivo: lack of evidence for a cell autonomous role of the amyloid precursor protein in neuronal differentiation. Stem cells (Dayton, Ohio) 33 20049903
2006 PAT1a modulates intracellular transport and processing of amyloid precursor protein (APP), APLP1, and APLP2. The Journal of biological chemistry 33 17050537
2006 Keratinocytes from APP/APLP2-deficient mice are impaired in proliferation, adhesion and migration in vitro. Experimental cell research 32 16584729
1998 APLP2, a member of the Alzheimer precursor protein family, is required for correct genomic segregation in dividing mouse cells. The EMBO journal 32 9707424
1994 Complete nucleotide and deduced amino acid sequence of rat amyloid protein precursor-like protein 2 (APLP2/APPH): two amino acids length difference to human and murine homologues. Biochimica et biophysica acta 32 8086458
2020 The adaptor protein APPL2 controls glucose-stimulated insulin secretion via F-actin remodeling in pancreatic β-cells. Proceedings of the National Academy of Sciences of the United States of America 29 33122440
2012 Deletion of the amyloid precursor-like protein 2 (APLP2) does not affect hippocampal neuron morphology or function. Molecular and cellular neurosciences 29 22353605
2014 The adaptor protein APPL2 inhibits insulin-stimulated glucose uptake by interacting with TBC1D1 in skeletal muscle. Diabetes 28 24879834
2015 APLP1 and APLP2, members of the APP family of proteins, behave similarly to APP in that they associate with NMDA receptors and enhance NMDA receptor surface expression. Journal of neurochemistry 27 25683482
1996 Quantification of APP and APLP2 mRNA in APOE genotyped Alzheimer's disease brains. Brain research. Molecular brain research 27 9037522
2014 Amyloid precursor protein (APP)/APP-like protein 2 (APLP2) expression is required to initiate endosome-nucleus-autophagosome trafficking of glypican-1-derived heparan sulfate. The Journal of biological chemistry 26 24898256
2010 Generation of conditional null alleles for APP and APLP2. Genesis (New York, N.Y. : 2000) 26 20140888
2017 APP, APLP2 and LRP1 interact with PCSK9 but are not required for PCSK9-mediated degradation of the LDLR in vivo. Biochimica et biophysica acta. Molecular and cell biology of lipids 25 28495363
2015 Amyloid precursor-like protein 2 (APLP2) affects the actin cytoskeleton and increases pancreatic cancer growth and metastasis. Oncotarget 25 25576918
2011 Signaling via amyloid precursor-like proteins APLP1 and APLP2. Journal of Alzheimer's disease : JAD 25 21178287
2003 Accumulation of the amyloid precursor-like protein APLP2 and reduction of APLP1 in retinoic acid-differentiated human neuroblastoma cells upon curcumin-induced neurite retraction. Brain research. Molecular brain research 25 14597230
2001 A role for MAP kinase in regulating ectodomain shedding of APLP2 in corneal epithelial cells. American journal of physiology. Cell physiology 24 11443060
2020 Lack of APP and APLP2 in GABAergic Forebrain Neurons Impairs Synaptic Plasticity and Cognition. Cerebral cortex (New York, N.Y. : 1991) 22 32219307
2012 Regulation of apoptosis by Bat3-enhanced YWK-II/APLP2 protein stability. Journal of cell science 22 22641691
1994 The gene for the amyloid precursor-like protein APLP2 is assigned to human chromosome 11q23-q25. Genomics 21 8020984
2016 Amyloid precursor-like protein 1 (APLP1) exhibits stronger zinc-dependent neuronal adhesion than amyloid precursor protein and APLP2. Journal of neurochemistry 20 26801522
2013 APLP2 regulates the expression of MHC class I molecules on irradiated Ewing's sarcoma cells. Oncoimmunology 18 24353913
2013 Hippocampal network oscillations in APP/APLP2-deficient mice. PloS one 17 23585881
2013 Association of genetic variation in adaptor protein APPL1/APPL2 loci with non-alcoholic fatty liver disease. PloS one 17 23977033
2012 Multifunctional protein APPL2 contributes to survival of human glioma cells. Molecular oncology 17 22989406
2010 APPL proteins FRET at the BAR: direct observation of APPL1 and APPL2 BAR domain-mediated interactions on cell membranes using FRET microscopy. PloS one 17 20814572
1995 The mouse APLP2 gene. Chromosomal localization and promoter characterization. The Journal of biological chemistry 17 7592716
2012 Tol2 gene trap integrations in the zebrafish amyloid precursor protein genes appa and aplp2 reveal accumulation of secreted APP at the embryonic veins. Developmental dynamics : an official publication of the American Association of Anatomists 16 22275008
2017 Adaptor Protein APPL2 Affects Adult Antidepressant Behaviors and Hippocampal Neurogenesis via Regulating the Sensitivity of Glucocorticoid Receptor. Molecular neurobiology 15 28965332
2014 Quantitation and localization of intracellular redox active metals by X-ray fluorescence microscopy in cortical neurons derived from APP and APLP2 knockout tissue. Metallomics : integrated biometal science 15 25098278
2015 Appl1 and Appl2 are Expendable for Mouse Development But Are Essential for HGF-Induced Akt Activation and Migration in Mouse Embryonic Fibroblasts. Journal of cellular physiology 14 26445298
2016 Distinct Roles for APPL1 and APPL2 in Regulating Toll-like Receptor 4 Signaling in Macrophages. Traffic (Copenhagen, Denmark) 13 27219021
2021 APPsα rescues impaired Ca2+ homeostasis in APP- and APLP2-deficient hippocampal neurons. Proceedings of the National Academy of Sciences of the United States of America 12 34172567
2014 Absence of Appl2 sensitizes endotoxin shock through activation of PI3K/Akt pathway. Cell & bioscience 12 25328665
1996 Studies on the metabolism and biological function of APLP2. Annals of the New York Academy of Sciences 11 8624130
1996 A new quantitative solution hybridisation-RNase protection assay for APP and APLP2 mRNA. Brain research. Molecular brain research 10 9037521
2009 PAT1 induces cell death signal and SET mislocalization into the cytoplasm by increasing APP/APLP2 at the cell surface. Neurobiology of aging 9 19570594
2023 Comparative binding analysis of WGX50 and Alpha-M with APP family proteins APLP1 and APLP2 using structural-dynamics and free energy calculation approaches. Physical chemistry chemical physics : PCCP 8 37199163
2023 Comprehensive intratumoral heterogeneity landscaping of liver hepatocellular carcinoma and discerning of APLP2 in cancer progression. Environmental toxicology 8 37515494
2018 The reversal effect of physical exercise on aging-related increases in APPL2 content in skeletal muscle. Life sciences 8 30189216
2016 APLP2, RRM2, and PRC1: New Putative Markers for the Differential Diagnosis of Thyroid Follicular Lesions. Thyroid : official journal of the American Thyroid Association 8 27796194
2006 YWK-II protein/APLP2 in mouse gametes: potential role in fertilization. Molecular reproduction and development 8 16177981
2004 Identification and expression of the first nonmammalian amyloid-beta precursor-like protein APLP2 in the amphibian Xenopus laevis. European journal of biochemistry 8 15128300
1996 Genomic structure and chromosomal localization of the mouse CDEI-binding protein CDEBP (APLP2) gene and promoter sequences. Genomics 7 8661100
2017 Amyloid-precursor Like Proteins APLP1 and APLP2 Are Dispensable for Normal Development of the Neonatal Respiratory Network. Frontiers in molecular neuroscience 6 28690498
2018 Oral administration of alcalase potato protein hydrolysate-APPH attenuates high fat diet-induced cardiac complications via TGF-β/GSN axis in aging rats. Environmental toxicology 5 30240538
2023 Mycobacterium tuberculosis suppresses APLP2 expression to enhance its survival in macrophage. International immunopharmacology 4 37844466
2022 Reduced expression of APLP2 in spinal GABAergic inhibitory neurons contributed to nerve injury-induced microglial activation and pain sensitization. Neuropharmacology 4 36442651
2018 APLP2 Modulates JNK-Dependent Cell Migration in Drosophila. BioMed research international 4 30155482
2018 Overexpressed in colorectal carcinoma gene (OCC-1) upregulation and APPL2 gene downregulation in breast cancer specimens. Molecular biology reports 4 30218350
2023 YWK-II/APLP2 inhibits TGF-β signaling by interfering with the TGFBR2-Hsp90 interaction. Biochimica et biophysica acta. Molecular cell research 3 37479189
2023 APLP2 is predominantly cleaved by β-secretase and γ-secretase in the human brain. Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society 2 36691315
2020 APLP2 gene polymorphisms are associated with high TC and LDL-C levels in Chinese population in Xinjiang, China. Bioscience reports 2 32716039
2020 APPL2 Negatively Regulates Olfactory Functions by Switching Fate Commitments of Neural Stem Cells in Adult Olfactory Bulb via Interaction with Notch1 Signaling. Neuroscience bulletin 1 32468397
2006 Delineation of the functional domains of the extracellular region of YWK-II Protein/APLP2 of sperm membrane. Frontiers in bioscience : a journal and virtual library 1 16720320
2005 The amyloid-beta precursor-like protein APLP2 and its relative APP are differentially regulated during neuroendocrine cell activation. Molecular and cellular neurosciences 1 16154762
2002 Crystallization and preliminary crystallographic analysis of a partial extracellular fragment of a sperm membrane protein YWK-II/APPH related to the Alzheimer betaA4-amyloid precursor protein. Acta crystallographica. Section D, Biological crystallography 1 12499552
2024 Aspongopus chinensis ach-miR-276a-3p induces breast cancer cell cycle arrest by targeting APPL2 to regulate the CDK2-Rb-E2F1 signaling pathway. Toxicology and applied pharmacology 0 38431228
2024 Lack of T04C9.1, the Homologue of Mammalian APPL2, Leads to Premature Ageing and Shortens Lifespan in Caenorhabditis elegans. Genes 0 38927595
2003 Crystallization and preliminary crystallographic analysis of extracellular fragment X3 of YWK-II/APPH: a human sperm membrane protein related to the Alzheimer betaA4-amyloid precursor protein. Acta crystallographica. Section D, Biological crystallography 0 12595709