Affinage

APBA1

Amyloid-beta A4 precursor protein-binding family A member 1 · UniProt Q02410

Length
837 aa
Mass
92.9 kDa
Annotated
2026-06-09
57 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

APBA1 (X11α/Mint1) is a multidomain neuronal adaptor protein that couples membrane cargo to intracellular trafficking and synaptic exocytosis machinery, and is a central regulator of amyloid precursor protein (APP) processing (PMID:8887653, PMID:17167098). Its phosphotyrosine-binding (PTB) domain engages the YENPTY internalization motif of APP in a phosphorylation-independent manner, a mode of binding defined at atomic resolution (PMID:8887653, PMID:9321393). Through this interaction Mint1 stabilizes APP, retains it intracellularly, and suppresses both sAPPα and Aβ secretion, acting upstream of γ-secretase rather than inhibiting the enzyme directly (PMID:9712855, PMID:18575606); in the absence of X11 proteins APP partitions into detergent-resistant membranes where BACE is active, increasing β-cleavage and Aβ accumulation (PMID:18845544). The APP-binding activity is held in check by an autoinhibitory C-terminal linker helix that folds onto the PTB domain, and by C-Src-mediated tyrosine phosphorylation of the N-terminus that drives APP retention in the trans-Golgi network; disrupting autoinhibition (e.g. Tyr633 mutation) enhances APP binding, endocytosis, and Aβ production (PMID:22355143, PMID:26865271, PMID:37499733). A tandem PDZ region carries its own autoinhibitory tail that occludes the first PDZ groove and mediates binding to presenilin-1, coordinating APP with the γ-secretase complex (PMID:11083918, PMID:16007100). At the presynaptic active zone, Mint1 localizes with synaptic vesicles and, via a short EPIWVMRQ motif, binds the CASK CaM-kinase domain with nanomolar affinity to assemble a CASK-Mint1-Munc18-1 ternary complex that governs Munc18-1 membrane localization, vesicle docking/fusion, neurotransmitter release, and glucose-stimulated insulin secretion (PMID:9952408, PMID:21763699, PMID:32348748, PMID:33318489). Mint1 additionally serves as a kinesin (KIF17) adaptor for microtubule-based cargo transport, with cargo released upon CaMKII phosphorylation of KIF17, and promotes exocytosis of extrasynaptic NMDA receptors (PMID:18066053, PMID:30411795).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1996 High

    Established that APBA1 is a direct APP-binding adaptor, defining the molecular link between Mint1 and amyloid precursor protein.

    Evidence GST pulldown and site-directed mutagenesis of the PTB/PI domain and the APP YENPTY motif in vitro

    PMID:8887653

    Open questions at the time
    • Did not establish the functional consequence of binding for APP processing
    • Cellular and in vivo relevance not yet shown
  2. 1997 High

    Resolved how a PTB domain binds an unphosphorylated NPxY motif at atomic resolution, explaining the phosphotyrosine independence of the APBA1-APP interaction.

    Evidence X-ray crystallography of the X11 PTB domain bound to APP peptide with KD measurement (0.32 µM)

    PMID:9321393

    Open questions at the time
    • Structure of full-length protein and regulatory context not addressed
    • Did not connect binding to trafficking outcomes
  3. 1998 High

    Showed that APBA1-APP binding functionally controls APP metabolism, recasting Mint1 as a regulator of amyloidogenic processing.

    Evidence Cotransfection of APP and X11 in multiple cell lines with Aβ/sAPPα ELISA and Western blot, plus YENPTY mutants

    PMID:9712855

    Open questions at the time
    • Subcellular site of suppression not defined
    • Domain requirements within Mint1 not yet mapped
  4. 2000 Medium

    Mapped the modular logic of Mint1, assigning APP stabilization to the PDZ domains, Aβ suppression to the PTB domain, and sAPP stimulation to the N-terminus, and linked Mint1 to presenilin-1.

    Evidence Domain-deletion cotransfection assays in HEK293 and Co-IP/GST pulldown for the PS1 interaction

    PMID:11010978 PMID:11083918

    Open questions at the time
    • PS1 interaction validated in a single lab
    • Whether Mint1 coordinates APP and PS1 in vivo not established
  5. 1999 Medium

    Defined the CASK-binding region of Mint1 and identified it as a presynaptic adaptor associated with synaptic vesicles.

    Evidence In vitro interaction assays with deletion mapping plus immunoelectron microscopy localization at the active zone

    PMID:10971649 PMID:9952408

    Open questions at the time
    • Functional consequence for exocytosis not yet demonstrated
    • Stoichiometry of the CASK-Mint1-Munc18 assembly unresolved
  6. 2002 Medium

    Linked Mint1 to in vivo neurotransmission and showed Munc18-1 cooperates with Mint1 in APP retention, tying together its synaptic and APP-regulatory functions.

    Evidence Mint1 knockout mice with in vivo microdialysis/behavior, and Munc18a co-expression with Aβ40/β-secretase assays using N-terminal deletion mutants

    PMID:12016213 PMID:12103443

    Open questions at the time
    • Mechanistic link between dopamine release phenotype and molecular adaptors not resolved
    • Single-lab functional studies
  7. 2003 Medium

    Expanded the APP-regulatory complex to include accessory partners (Alcadein/calsyntenin, XB51) that tune Mint-mediated suppression of Aβ generation.

    Evidence Co-IP from brain and cells, yeast two-hybrid, GST pulldown with Aβ ELISA

    PMID:12780348 PMID:12972431

    Open questions at the time
    • Several studies concern X11L rather than APBA1 specifically
    • Physiological relevance of competing tripartite complexes unclear
  8. 2004 Medium

    Placed Mint1 within a CASK-Veli-SAP97 scaffold trafficking Kir2 channels, broadening its adaptor role beyond APP.

    Evidence Affinity pulldown, reciprocal Co-IP, immunocytochemistry, and dominant-negative CASK expression

    PMID:14960569

    Open questions at the time
    • Direct vs. CASK-bridged contact of Mint1 with channels not separated
    • In vivo channel trafficking role not tested
  9. 2005 High

    Discovered intramolecular autoinhibition of the Mint1 PDZ tandem by its own C-terminal tail, introducing autoregulation as a control layer.

    Evidence X-ray crystallography with in vitro binding competition assays

    PMID:16007100

    Open questions at the time
    • Trigger that relieves PDZ autoinhibition in cells unknown
    • Functional impact on target binding in vivo not measured
  10. 2006 High

    Demonstrated that Mint proteins are essential for presynaptic function and act through the Mint-Munc18-1 axis, establishing physiological necessity.

    Evidence Constitutive/conditional Mint1/Mint2 knockout mice with slice electrophysiology and Munc18-1 epistasis

    PMID:17167098

    Open questions at the time
    • Redundancy between Mint1 and Mint2 obscures APBA1-specific role
    • Molecular step at which Mint regulates release not pinpointed
  11. 2007 High

    Identified Mint1 as a regulated kinesin (KIF17) cargo adaptor and extended its APP/endocytosis role to ApoER2-coupled co-endocytosis, connecting trafficking to Aβ output.

    Evidence FRET, in vitro/in vivo KIF17 phosphorylation assays, and Co-IP/endocytosis/Aβ ELISA in neuroblastoma cells

    PMID:17428983 PMID:18066053

    Open questions at the time
    • Cargo identity transported by Mint1-KIF17 in neurons not fully defined
    • ApoER2 endocytosis pathway validated in a single lab
  12. 2008 High

    Defined the mechanism of Aβ suppression as exclusion of APP from BACE-active detergent-resistant membranes, and placed Mint action upstream of γ-secretase.

    Evidence X11/X11L double knockout mouse brain with subcellular DRM fractionation, plus Drosophila genetic reporter epistasis

    PMID:18575606 PMID:18845544

    Open questions at the time
    • How Mint partitions APP between membrane microdomains mechanistically unresolved
    • Conservation between fly and mammalian processing incomplete
  13. 2011 Medium

    Refined the CASK-Mint1 interface to a single linear EPIWVMRQ motif and revealed mutually exclusive scaffold assemblies, while adding a PDZ-dependent control of immature APP in the secretory pathway.

    Evidence In vitro binding/peptide competition assays and X11L domain-deletion with pulse-chase APP maturation assays

    PMID:21763699 PMID:21818298

    Open questions at the time
    • Competition between Mint1 and Caskin1 not validated in vivo
    • Immature-APP function shown for X11L, not directly APBA1
  14. 2012 High

    Established PTB-domain autoinhibition by a C-terminal helix and showed it directly gates Aβ output, identifying a druggable control point.

    Evidence Crystal structure of extended PTB fragment, Y633 mutagenesis, and cellular Aβ assays

    PMID:22355143

    Open questions at the time
    • Physiological signal relieving PTB autoinhibition not identified
    • Interplay with PDZ autoinhibition unresolved
  15. 2013 Medium

    Connected Mint1 to vesicular trafficking machinery (Rab6) and to polarized axonal APP targeting, embedding its APP role within neuronal transport.

    Evidence Yeast two-hybrid/Co-IP/MS for an isoform-specific Rab6 interaction and Drosophila loss-of-function imaging/epistasis with endocytosis mutants

    PMID:23658195 PMID:23737971

    Open questions at the time
    • Rab6 interaction restricted to a specific isoform
    • Mammalian relevance of axonal targeting role not established
  16. 2016 High

    Showed C-Src sequentially phosphorylates the Mint1 N-terminus to control APP retention at the trans-Golgi, adding kinase-driven regulation of APP trafficking.

    Evidence Phosphoproteomic MS, Y202F mutagenesis, Src inhibition, and imaging in transfected cells and primary neurons

    PMID:26865271

    Open questions at the time
    • Upstream signals activating Src toward Mint1 unknown
    • Effect on Aβ production not directly quantified here
  17. 2018 Medium

    Extended Mint adaptor function to extrasynaptic NMDA receptor surface levels via promotion of exocytosis, broadening its receptor-trafficking role.

    Evidence Membrane fractionation of knockout brain and Co-IP with deletion mutants

    PMID:30411795

    Open questions at the time
    • Direct vs. indirect Mint-NMDAR contact not resolved
    • Role assayed in combined X11/X11L loss, not APBA1 alone
  18. 2020 High

    Provided the structural and functional definition of the CASK-Mint1-Munc18-1 ternary complex and showed it controls glucose-stimulated insulin secretion, generalizing the synaptic exocytosis module to β cells.

    Evidence Crystal structure of CASK-CaMK/Mint1 with ITC (KD ~7.5 nM), plus Co-IP, CASK knockdown/overexpression, and insulin secretion/vesicle docking assays

    PMID:32348748 PMID:33159991 PMID:33318489

    Open questions at the time
    • How the ternary complex is dynamically regulated by glucose signaling not fully resolved
    • Contribution of Mint1 autoinhibition to complex assembly unaddressed
  19. 2023 High

    Established the APP-Mint1 interaction itself, and its autoinhibitory control, as a critical determinant of Aβ production in neurons.

    Evidence Y633A and Y549A/F610A mutagenesis, Co-IP, APP endocytosis assay in primary neurons, Aβ ELISA, and siRNA knockdown

    PMID:37499733

    Open questions at the time
    • Whether modulating this interface alters pathology in vivo not tested
    • Endogenous trigger of Y633 autoinhibition release unknown
  20. 2024 Medium

    Showed the Mint-CaV2 calcium channel PDZ interaction and PDZ autoinhibition are deeply conserved across animals, indicating an ancient adaptor role at the presynapse.

    Evidence Yeast and bacterial two-hybrid assays plus in situ hybridization in cnidarian/placozoan systems

    PMID:39284887

    Open questions at the time
    • Functional consequence of CaV2 binding for channel activity not measured
    • Demonstrated in non-mammalian systems only

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple autoinhibitory layers (PTB helix, PDZ tail) and post-translational signals (Src, CaMKII) are integrated in vivo to switch Mint1 between APP-trafficking, synaptic exocytosis, and receptor-targeting roles remains unresolved.
  • No integrated model linking autoinhibition relief to specific physiological cues
  • APBA1-specific (vs. redundant Mint2) contributions to each function incompletely separated
  • In vivo therapeutic modulation of the APP-Mint1 interface untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 2 GO:0005794 Golgi apparatus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-9609507 Protein localization 3 R-HSA-112316 Neuronal System 2
Partners
APPCACNA1 (CAV2)CASKKIF17PSEN1RAB6SRCSTXBP1
Complex memberships
APP-Mint1-presenilin-1 complexCASK-Mint1-Munc18-1 ternary complexSAP97-CASK-Veli-Mint1 complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 The PTB/PI domain of X11 (APBA1) binds to the YENPTY motif in the cytoplasmic domain of APP (amyloid precursor protein) in a phosphotyrosine-independent manner. Site-directed mutagenesis identified a crucial residue within the PI domain involved in binding, and mutations within the YENPTY motif differentially affect X11 versus FE65 binding, indicating distinct binding sites on APP. GST pulldown, site-directed mutagenesis, in vitro binding assays Molecular and cellular biology High 8887653
1997 Crystal structure of the X11 PTB domain in complex with unphosphorylated APP peptides (NPxY motif) was determined; eight peptide residues make specific contacts achieving high affinity (KD = 0.32 µM). The mode of binding resembles phosphopeptide binding to Shc/IRS-1 PTB domains but does not require tyrosine phosphorylation. X-ray crystallography, in vitro binding affinity measurement The EMBO journal High 9321393
1998 X11 binding to the YENPTY motif of APP stabilizes cellular APP, retains it intracellularly, and reduces both soluble APPα secretion and Aβ secretion. Mutations in the YENPTY motif that impair X11 interaction increase sAPPα secretion, establishing X11 as a regulator of APP processing and internalization. Cotransfection of APP and X11 in multiple cell lines, Western blot, ELISA for Aβ and sAPPα The Journal of biological chemistry High 9712855
1999 X11α (APBA1) directly interacts with the CASK (mLin-2) CaM kinase II domain via a 63 amino acid peptide in X11α located between the Munc-18-1 binding site and the PTB domain. A secondary interaction involves the CASK guanylate kinase domain with lower affinity. Ca2+/calmodulin binding to CASK does not modify the X11α-CASK interaction. In vitro protein-protein interaction assays, deletion mapping, immunostaining The Journal of neuroscience High 9952408
2000 X11α and X11β interact with presenilin-1 via their PDZ domains, binding sequences within the carboxy-terminus of presenilin-1. X11α and X11β mediate formation of complexes between APP and presenilin-1, suggesting that X11 modulates APP processing partly through coordinating APP with the γ-secretase component presenilin-1. Co-immunoprecipitation, GST pulldown, deletion mutant analysis Molecular and cellular neurosciences Medium 11083918
2000 Deletion analysis of X11α domains in APP metabolism showed that the PTB domain is necessary for inhibition of Aβ40/42 secretion, the C-terminal PDZ domains are required for APP stabilization, and the N-terminal domain is required to stimulate sAPP secretion. X11α lacking the PDZ domains (ΔC) fails to stabilize APP. Deletion mutant cotransfection in HEK293 cells, ELISA for Aβ40/42 and sAPPα, Western blot The Journal of biological chemistry Medium 11010978
2000 Mint1 (APBA1) is localized at the presynaptic active zone and associated with synaptic vesicles in mouse hippocampus, largely overlapping with Munc18-1 distribution, consistent with a presynaptic role in vesicle exocytosis. Immunoelectron microscopy, immunostaining The European journal of neuroscience Medium 10971649
2000 NF-κB/p65 binds to the PDZ domain of X11-like (X11L/X11β/APBA2, closely related to APBA1) and this interaction suppresses NF-κB/p65-induced Aβ42 production. The amino acids 161-163 in the Rel homology domain of p65 are critical for X11L interaction. NF-κB/p50 and p50/p65 heterodimers do not bind X11L. Co-immunoprecipitation, reporter assays, mutagenesis, cell transfection The Journal of biological chemistry Low 10777610
2002 Munc18a interacts with the N-terminal Munc18a-interacting domain (MID) of X11α and potentiates X11α-mediated APP retention and suppression of Aβ40 secretion. Munc18a combined with X11α nearly abolishes constitutive Aβ40 release and enhances suppression of γ-secretase processing of APP. Cotransfection, ELISA for Aβ40, beta-secretase activity assay, N-terminal deletion mutants of X11α/β The Journal of biological chemistry Medium 12016213
2002 Deletion of Mint-1 (APBA1) in mice leads to significantly attenuated methamphetamine-induced striatal dopamine release (measured by microdialysis) and reduced METH-induced stereotypy, implicating Mint-1 in transporter-mediated dopamine release. Mint-1 knockout mice, in vivo microdialysis, behavioral testing Neuroscience research Medium 12103443
2003 Alcadein (Alc/calsyntenin) interacts with X11L and simultaneously with APP to form a tripartite complex in brain. This complex stabilizes intracellular APP metabolism and enhances X11L-mediated suppression of Aβ secretion. X11L and Alc also form a complex with C99 (CTFβ) that inhibits C99 interaction with presenilin, suppressing γ-secretase cleavage. Co-immunoprecipitation from brain and transfected cells, GST pulldown, Aβ ELISA The Journal of biological chemistry Medium 12972431
2003 XB51α binds to the N-terminal domain of X11L and forms a tripartite complex with X11L and APP, blocking X11L's suppression of Aβ generation. XB51β associates with X11L and inhibits its interaction with APP, suppressing Aβ generation in an X11L-independent manner. Yeast two-hybrid, co-immunoprecipitation, Aβ ELISA in transfected cells The Biochemical journal Medium 12780348
2004 Mint1 (APBA1) is part of a multiprotein complex (SAP97-CASK-Veli-Mint1) that associates with inward rectifier Kir2 potassium channels via C-terminal PDZ-binding motifs. Specific Veli isoforms participate in distinct complex compositions: Veli-2 associates with CASK and Mint1; Veli-3 with CASK, SAP97, and Mint1. A dominant-negative form of CASK causes Kir2.2 mislocalization, indicating CASK is central to this trafficking complex. Affinity pulldown, co-immunoprecipitation from brain and transfected cells, immunocytochemistry, dominant-negative expression The Journal of biological chemistry Medium 14960569
2005 The highly conserved C-terminal tail of X11α (APBA1) folds back and inserts into the target-binding groove of its first PDZ domain, creating an autoinhibited conformation that occludes binding of other target peptides. This autoinhibition requires the two PDZ domains and the C-terminal tail to be covalently connected. X-ray crystallography, in vitro binding competition assays Nature structural & molecular biology High 16007100
2006 Mice lacking both neuron-specific Mint isoforms (Mint1/APBA1 and Mint2) exhibit ~80% lethality at birth, decreased spontaneous neurotransmitter release, lowered synaptic strength, and enhanced paired-pulse facilitation. Acute deletion of Mints in cultured neurons also reduced spontaneous release. Selective increase in Munc18-1 after Mint deletion, and overexpression of Munc18-1 alone also decreased spontaneous release, suggesting the Mint-Munc18-1 interaction contributes to presynaptic function. Constitutive and conditional knockout mice, hippocampal slice electrophysiology, synaptic protein quantitation, cultured neuron acute deletion The Journal of neuroscience High 17167098
2007 CaMKII-dependent phosphorylation of KIF17 on Ser1029 disrupts the KIF17-Mint1 (APBA1) association, resulting in cargo release from microtubule-based transport. The interaction was directly visualized by FRET and confirmed by in vitro and in vivo phosphorylation assays. FRET-based protein-protein interaction visualization, in vitro phosphorylation assay, in vivo phosphorylation assay, mutagenesis Nature cell biology High 18066053
2007 X11α/β (including APBA1) PTB domains bind to the YENPTY motif of APP and a newly recognized motif in the cytosolic domain of ApoER2. ApoE binding to ApoER2 triggers co-endocytosis of APP, β-secretase, and ApoER2 in a process mediated by X11α/β, leading to Aβ production. ApoE4 triggers more Aβ production than ApoE2/3 via this mechanism. Co-immunoprecipitation, endocytosis assay, Aβ ELISA in neuroblastoma cells The Journal of neuroscience Medium 17428983
2008 In X11/X11L double knockout mouse brain, APP and its β-C-terminal fragment are shifted to the detergent-resistant membrane (DRM) fraction where BACE is active, leading to enhanced β-site cleavage and increased Aβ accumulation. X11 proteins primarily associate with APP outside DRM, and their absence allows APP entry into DRM and increased BACE cleavage. Double knockout mice, subcellular fractionation (DRM), Aβ ELISA, Western blot, co-localization analysis The Journal of biological chemistry High 18845544
2008 In Drosophila, X11/Mint PTB domain is required for regulating APP at the level of the AICD, but overexpression of X11L or human X11 does not alter γ-secretase cleavage of APP or Notch. This indicates X11 acts upstream of γ-secretase rather than directly inhibiting it. Drosophila genetic reporter system (GAMAREP, AICDREP), transgenic overexpression, PTB domain mutants PloS one Medium 18575606
2011 X11L (X11β/Mint2) accumulates immature APP (imAPP) in the early secretory pathway via its C-terminal PDZ domains independently of direct PTB-APP binding. This novel function suppresses overall APP metabolism and Aβ generation. The PTB domain separately suppresses mature APP amyloidogenic cleavage. Both functions together provide multi-step suppression of Aβ generation. Domain-deletion mutants of X11L, cell fractionation, pulse-chase metabolic labeling, APP maturation assays PloS one Medium 21818298
2011 The molecular basis of the Mint1 (APBA1)–CASK interaction was defined: a short linear EPIWVMRQ peptide motif from Mint1 is sufficient for CASK CaM kinase domain binding. This motif competes with Caskin1 for the same CASK binding site, explaining the formation of mutually exclusive CASK/Mint1/Velis and CASK/Caskin1/Velis complexes. In vitro binding assays, peptide competition assays Journal of molecular biology Medium 21763699
2012 The Mint1 PTB domain is autoinhibited by an adjacent C-terminal linker region that forms a short α-helix folding back onto the PTB domain and sterically hindering APP binding. Crystal structure of the C-terminally extended PTB fragment revealed this mechanism. Mutation of Tyr633 within the autoinhibitory helix disrupts intramolecular inhibition, enhances APP binding, and increases β-amyloid production. X-ray crystallography, in vitro binding assay, site-directed mutagenesis (Y633 mutant), cellular Aβ production assay Proceedings of the National Academy of Sciences of the United States of America High 22355143
2013 Drosophila X11/Mint proteins are required for targeting APP (and APPL) to axonal membranes and excluding them from dendrites in mushroom body neurons. Loss of X11/Mint dramatically increases cell-surface levels of APPL especially on dendrites. X11/Mint-dependent endocytosis in dendrites promotes axonal localization, as mutations in endocytosis genes show similar dendritic mislocalization and enhance X11/Mint mutant defects. Drosophila genetics, loss-of-function mutants, fluorescence imaging, genetic epistasis with endocytosis mutants The Journal of neuroscience Medium 23658195
2013 A novel Mint1 isoform (Mint1 826) lacking 11 amino acids in the conserved C-terminal region interacts with Rab6 GTPase via the PTB domain in a nucleotide-dependent, Rab6-specific manner. This interaction influences subcellular localization of Mint1 826 and is proposed to bridge APP to Rab6-positive vesicles. The conventional Mint1 does not interact with Rab6. Yeast two-hybrid, co-immunoprecipitation, mass spectrometry, subcellular localization imaging PloS one Medium 23737971
2016 Mint1 (APBA1) is phosphorylated on multiple N-terminal tyrosines by C-Src kinase. A canonical SH2-binding motif (202YEEI) is phosphorylated first and recruits active Src for sequential phosphorylation of Y191 and Y187. Phosphorylation of Mint1 causes APP accumulation in the trans-Golgi network; unphosphorylatable Mint1(Y202F) or Src inhibition permits APP trafficking to distal neurites in hippocampal neurons. Mass spectrometry phosphoproteomics, site-directed mutagenesis (Y202F), pharmacological Src inhibition, subcellular localization imaging in transfected cells and primary neurons Journal of neurochemistry High 26865271
2018 X11 and X11L (APBA1 and APBA2) regulate the level of NMDA receptors in the extrasynaptic (non-PSD) membrane fraction. Loss of X11 and X11L decreases glutamate receptor levels in non-PSD fractions. Co-immunoprecipitation studies with deletion mutants indicate multiple interactions between NMDA receptor subunits and X11/X11L regulated by protein phosphorylation. The mechanism involves impaired exocytosis (not endocytosis) of NMDA receptors. Membrane fractionation of knockout mouse brain, co-immunoprecipitation with deletion mutants, CREB phosphorylation analysis Journal of neurochemistry Medium 30411795
2020 The high-resolution crystal structure of the CASK CaM kinase domain in complex with a Mint1 (APBA1) N-terminal fragment revealed that Mint1 uses a unique 'whip'-like extended structure: the C-lobe of CASK-CaMK binds a short sequence common to known CaMK targets, while the N-lobe engages an α-helix unique to Mint1, yielding a KD of ~7.5 nM. The CASK-Mint1 interaction is not regulated by Ca2+/CaM. Several CASK disease mutations map to the Mint1 binding interface. X-ray crystallography, isothermal titration calorimetry (ITC), mutagenesis Structure High 32348748
2020 CASK, Mint1 (APBA1), and Munc18-1 form a ternary complex in β cells regulated by glucose stimulation. CASK-Mint1 binding is critical for ternary complex formation, controlling Munc18-1 membrane localization and insulin secretion. CASK depletion reduces vesicle docking/fusion and insulin secretion; Cask overexpression rescues lipotoxicity-induced insulin release defects. Co-immunoprecipitation, crystal structure (CASK/Mint1), CASK knockdown and overexpression in islets/β cells, insulin secretion assay, vesicle docking analysis Cell discovery High 33318489
2020 CASK, APBA1 (Mint1), and STXBP1 (Munc18-1) form a tripartite complex during insulin secretion. CASK enhances APBA1-STXBP1 interaction and mediates their trafficking from cytoplasm to plasma membrane during insulin release. Cask overexpression enhances this complex function and rescues lipotoxicity-induced insulin-release defects. Co-immunoprecipitation, liquid chromatography-mass spectrometry, bioinformatic analysis, overexpression experiments Molecular and cellular endocrinology Medium 33159991
2023 The APP-Mint1 (APBA1) interaction tightly controls Aβ production. Mint1(Y633A) mutation disrupts autoinhibition and enhances binding specifically to APP and presenilin1, increasing APP endocytosis and Aβ production in primary neurons. Mint1(Y549A/F610A) reduces APP affinity and Aβ secretion more effectively than triple Mint knockdown, establishing the APP-Mint1 interaction itself as a critical determinant of Aβ production. Site-directed mutagenesis (Y633A; Y549A/F610A), co-immunoprecipitation, APP endocytosis assay in primary neurons, Aβ ELISA, siRNA knockdown Brain research High 37499733
2024 The Mint1 (APBA1) PDZ domains interact with CaV2 calcium channel C-termini in a manner that predates bilaterian animals. Yeast and bacterial two-hybrid experiments showed Mint and CaV2 from cnidarians and placozoans interact, and the C-terminal auto-inhibitory element binds and inhibits PDZ-1. The interaction is evolutionarily conserved and co-expression with CaV2 was confirmed in cnidarian neurons. Yeast two-hybrid, bacterial two-hybrid, in situ hybridization, in silico domain conservation analysis Scientific reports Medium 39284887

Source papers

Stage 0 corpus · 57 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein. Molecular and cellular biology 435 8887653
2007 Disruption of KIF17-Mint1 interaction by CaMKII-dependent phosphorylation: a molecular model of kinesin-cargo release. Nature cell biology 154 18066053
1997 Sequence-specific recognition of the internalization motif of the Alzheimer's amyloid precursor protein by the X11 PTB domain. The EMBO journal 147 9321393
2004 A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels. The Journal of biological chemistry 130 14960569
1998 X11 interaction with beta-amyloid precursor protein modulates its cellular stabilization and reduces amyloid beta-protein secretion. The Journal of biological chemistry 125 9712855
2003 Novel cadherin-related membrane proteins, Alcadeins, enhance the X11-like protein-mediated stabilization of amyloid beta-protein precursor metabolism. The Journal of biological chemistry 121 12972431
2007 Apolipoprotein receptor 2 and X11 alpha/beta mediate apolipoprotein E-induced endocytosis of amyloid-beta precursor protein and beta-secretase, leading to amyloid-beta production. The Journal of neuroscience : the official journal of the Society for Neuroscience 96 17428983
2006 The X11 proteins, Abeta production and Alzheimer's disease. Trends in neurosciences 90 16545469
2000 X11 alpha and x11 beta interact with presenilin-1 via their PDZ domains. Molecular and cellular neurosciences 86 11083918
2006 Genetic analysis of Mint/X11 proteins: essential presynaptic functions of a neuronal adaptor protein family. The Journal of neuroscience : the official journal of the Society for Neuroscience 83 17167098
1999 Molecular analysis of the X11-mLin-2/CASK complex in brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 82 9952408
1999 Mint2/X11-like colocalizes with the Alzheimer's disease amyloid precursor protein and is associated with neuritic plaques in Alzheimer's disease. The European journal of neuroscience 77 10336668
1999 X11L2, a new member of the X11 protein family, interacts with Alzheimer's beta-amyloid precursor protein. Biochemical and biophysical research communications 74 10049767
2006 The X11/Mint family of adaptor proteins. Brain research reviews 69 16764936
2022 Lactobacillus paracasei X11 Ameliorates Hyperuricemia and Modulates Gut Microbiota in Mice. Frontiers in immunology 68 35874662
2005 Autoinhibition of X11/Mint scaffold proteins revealed by the closed conformation of the PDZ tandem. Nature structural & molecular biology 67 16007100
2008 X11 proteins regulate the translocation of amyloid beta-protein precursor (APP) into detergent-resistant membrane and suppress the amyloidogenic cleavage of APP by beta-site-cleaving enzyme in brain. The Journal of biological chemistry 58 18845544
2000 Modulation of amyloid precursor protein metabolism by X11alpha /Mint-1. A deletion analysis of protein-protein interaction domains. The Journal of biological chemistry 56 11010978
2004 Facilitation of stress-induced phosphorylation of beta-amyloid precursor protein family members by X11-like/Mint2 protein. The Journal of biological chemistry 43 14970211
2002 Synergistic effects of Munc18a and X11 proteins on amyloid precursor protein metabolism. The Journal of biological chemistry 43 12016213
2000 PDZ domain-dependent suppression of NF-kappaB/p65-induced Abeta42 production by a neuron-specific X11-like protein. The Journal of biological chemistry 42 10777610
2011 The molecular basis of the Caskin1 and Mint1 interaction with CASK. Journal of molecular biology 35 21763699
2002 Alteration of methamphetamine-induced striatal dopamine release in mint-1 knockout mice. Neuroscience research 32 12103443
2010 Increased amyloidogenic processing of transgenic human APP in X11-like deficient mouse brain. Molecular neurodegeneration 30 20843325
2016 Multisite tyrosine phosphorylation of the N-terminus of Mint1/X11α by Src kinase regulates the trafficking of amyloid precursor protein. Journal of neurochemistry 29 26865271
2011 Intracellular trafficking of the amyloid β-protein precursor (APP) regulated by novel function of X11-like. PloS one 29 21818298
2000 Ultrastructural localization of mint1 at synapses in mouse hippocampus. The European journal of neuroscience 27 10971649
2002 Expression and characterization of the Drosophila X11-like/Mint protein during neural development. Journal of neurochemistry 26 12068070
2001 Neuronal expression of mint1 and mint2, novel multimodular proteins, in adult murine brain. Brain research. Molecular brain research 25 11483239
2009 X11-like protein deficiency is associated with impaired conflict resolution in mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 23 19420255
2007 High-throughput screen for small molecule inhibitors of Mint1-PDZ domains. Assay and drug development technologies 21 18078379
2003 XB51 isoforms mediate Alzheimer's beta-amyloid peptide production by X11L (X11-like protein)-dependent and -independent mechanisms. The Biochemical journal 20 12780348
2013 X11/Mint genes control polarized localization of axonal membrane proteins in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 19 23658195
2008 Role of X11 and ubiquilin as in vivo regulators of the amyloid precursor protein in Drosophila. PloS one 19 18575606
2012 Autoinhibition of Mint1 adaptor protein regulates amyloid precursor protein binding and processing. Proceedings of the National Academy of Sciences of the United States of America 18 22355143
2020 Structural Basis for the High-Affinity Interaction between CASK and Mint1. Structure (London, England : 1993) 16 32348748
2004 Mint1, a Munc-18-interacting protein, is expressed in insulin-secreting beta-cells. Biochemical and biophysical research communications 16 15240107
1999 Genomic organization of the human X11L2 gene (APBA3), a third member of the X11 protein family interacting with Alzheimer's beta-amyloid precursor protein. Neuroreport 15 10574372
2021 The edible Lactobacillus paracasei X11 with Konjac glucomannan promotes intestinal motility in zebrafish. Neurogastroenterology and motility 11 34337833
2020 CASK modulates the assembly and function of the Mint1/Munc18-1 complex to regulate insulin secretion. Cell discovery 11 33318489
2016 Expression and localization of X11 family proteins in neurons. Brain research 11 27268412
2020 CASK, APBA1, and STXBP1 collaborate during insulin secretion. Molecular and cellular endocrinology 10 33159991
2013 A new Mint1 isoform, but not the conventional Mint1, interacts with the small GTPase Rab6. PloS one 9 23737971
2000 Changes in mint1, a novel synaptic protein, after transient global ischemia in mouse hippocampus. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 8 11043906
2018 X11 and X11-like proteins regulate the level of extrasynaptic glutamate receptors. Journal of neurochemistry 5 30411795
2007 Reduction of mint-1, mint-2, and APP overexpression in okadaic acid-treated neurons. Neuroreport 5 18007179
2003 Levels of the synaptic protein X11 alpha/mint1 are increased in hippocampus of rats with epilepsy. Epilepsy research 5 14706732
2022 Recurrent hypoglycemia dampens functional regulation mediated via Neurexin-1, Neuroligin-2 and Mint-1 docking proteins: Intensified complications during diabetes. Cellular signalling 4 36587752
2023 Tight control of the APP-Mint1 interaction in regulating amyloid production. Brain research 2 37499733
2011 Genomic organization and promoter cloning of the human X11α gene APBA1. DNA and cell biology 2 22136355
2024 Mint/X11 PDZ domains from non-bilaterian animals recognize and bind CaV2 calcium channel C-termini in vitro. Scientific reports 1 39284887
2014 Early-flowering sweet orange mutant 'x11' as a model for functional genomic studies of Citrus. BMC research notes 1 25108567
2026 Genomic insights into the broad-spectrum antifungal activity of a novel Paenibacillus polymyxa strain X-11. BMC microbiology 0 41639771
2026 Protein-truncating variants in APBA1 in minors with severe, early-onset obesity: implications for genetic testing. Molecular and cellular pediatrics 0 42018264
2025 Inhibition of miR-4284 could reduce apoptosis and neuroinflammation by targeting APBA1/JAK1/STAT3 signaling in Alzheimer's disease. Cell & bioscience 0 41174814
2024 Mint/X11 PDZ domains from non-bilaterian animals recognize and bind Ca V 2 calcium channel C-termini in vitro . bioRxiv : the preprint server for biology 0 38463976
2024 Replicating the Association of Variants in BSN and APBA1 with Obesity in Diverse Populations. medRxiv : the preprint server for health sciences 0 39228706

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