Affinage

AHNAK

Neuroblast differentiation-associated protein AHNAK · UniProt Q09666

Length
5890 aa
Mass
629.1 kDa
Annotated
2026-06-09
100 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AHNAK is a giant (~700 kDa) scaffolding phosphoprotein built from highly conserved central repeated units whose subcellular distribution between nucleus, cytoplasm, and plasma membrane is dynamically controlled by phosphorylation: PKB/Akt phosphorylation of Ser5535 drives nuclear export through an adjacent NES (PMID:11535620), while PKC activation and Ca2+-dependent signals translocate it toward the cell membrane via determinants in its C-terminal domain (PMID:7698224, PMID:10771490). At the cytosolic face of the plasma membrane AHNAK assembles a cortical actin-organizing platform: its C-terminal domain binds G- and F-actin and the annexin A2/S100A10 (A2t) heterotetramer through a defined 20-residue motif (resolved at 2.5 Å), and these interactions are required for cortical actin reorganization and cell architecture (PMID:12153988, PMID:14699089, PMID:16984913, PMID:23275167). Through its central repeated units AHNAK functions as a signaling scaffold, binding and activating PLC-γ1 in an arachidonic-acid-dependent manner and recruiting PKC-α—disrupting the inhibitory PKC-α/PP2A complex—to amplify Ca2+ mobilization and Raf/MEK/Erk and Rac signaling (PMID:10318799, PMID:15033986, PMID:18174170, PMID:23042471). A second major role is regulation of L-type voltage-gated Ca2+ channels: AHNAK binds the Cavβ2 subunit (Kd ~55–60 nM via a C-terminal PxxP motif) to act as a brake on Cav1.2 current that is relieved by PKA phosphorylation of either partner, and is required for surface expression and Ca2+ influx of L-type channels in T cells, neurons, and other cell types (PMID:10593863, PMID:12153988, PMID:14722071, PMID:16319140, PMID:22497893, PMID:20607281, PMID:30760886, PMID:18191595, PMID:19497879). AHNAK is a structural component of muscle membrane complexes including the dysferlin complex and the costamere/β-dystroglycan network, linking these to the actin cytoskeleton and influencing membrane mechanics and Schwann cell morphology (PMID:17185750, PMID:20833135, PMID:24796807). In the nucleus AHNAK shapes growth and stress responses: it potentiates TGFβ/Smad3 signaling by promoting Smad3 nuclear accumulation and drives BMP2/Smad1-dependent adipogenesis at the PPARγ promoter (PMID:24662814, PMID:26466345, PMID:30258109), and it restrains 53BP1 oligomerization and phase separation to tune the p53 DNA-damage response and senescence (PMID:33961796). Its protein levels are controlled by the UBE3C and RNF38 E3 ubiquitin ligases, providing post-translational control over its context-dependent tumor-suppressive and pro-metastatic activities (PMID:30503554, PMID:30836988).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1992 Medium

    Establishing that AHNAK is an exceptionally large protein dominated by conserved 128-aa repeats framed the central question of how a repeat-based giant functions, suggesting a modular scaffold rather than an enzyme.

    Evidence cDNA cloning, sequence analysis, and subcellular fractionation

    PMID:1608957

    Open questions at the time
    • No molecular function assigned to the repeats at this stage
    • Localization assignment was preliminary
  2. 1993 Medium

    Defining AHNAK as a serine/threonine phosphoprotein whose abundance and phosphorylation track cell-cycle exit, and its identity with the desmosomal-plaque protein desmoyokin, connected it to phosphorylation control and cell-type-specific membrane localization.

    Evidence Immunofluorescence, fractionation, [32P] labeling, and cDNA immunoscreening across cell types

    PMID:8381120 PMID:8408266

    Open questions at the time
    • Responsible kinases unidentified
    • Functional consequence of localization shift unknown
  3. 1995 Medium

    Demonstrating that PKC activation and Ca2+ are required for AHNAK translocation to the plasma membrane, where it localizes to non-desmosomal membrane, recast it as a signal-responsive membrane-associated protein.

    Evidence PKC inhibitor/TPA/calcium-switch experiments and immunoelectron microscopy in keratinocytes

    PMID:7698224 PMID:7769263

    Open questions at the time
    • Direct PKC phosphosites not mapped
    • Membrane tethering partner unknown
  4. 1999 High

    Identifying that AHNAK binds and activates PLC-γ1 in an arachidonic-acid-dependent manner and co-precipitates with the cardiac L-type Ca2+ channel β2 subunit revealed two distinct effector engagements—lipid-signaling enzyme activation and ion-channel regulation.

    Evidence GST pulldown with in vitro PLC-γ1 activity assay; co-IP and PKA back-phosphorylation in cardiomyocytes

    PMID:10318799 PMID:10593863

    Open questions at the time
    • Cellular significance of PLC-γ1 activation not yet shown
    • Functional effect on channel current not yet measured
  5. 2001 High

    Mapping PKB/Akt phosphorylation of Ser5535 to an NES-dependent nuclear export, and identifying AHNAK as the major Ca2+/Zn2+-dependent S100B target via its repeats, defined the molecular switch governing AHNAK's nucleocytoplasmic distribution and its S100-family specificity.

    Evidence In vitro kinase assay with Ser5535 mutagenesis and NES mapping; S100B pulldown/IP with truncation mapping

    PMID:11312263 PMID:11535620

    Open questions at the time
    • Upstream signals controlling Akt-dependent export not defined
    • Functional role of S100B binding unresolved
  6. 2002 High

    Quantifying the C-terminal AHNAK–Cavβ2a interaction (Kd ~55 nM) and showing the same region binds actin established AHNAK as a physical bridge between the L-type Ca2+ channel and the cortical cytoskeleton.

    Evidence GST pulldown, analytical ultracentrifugation Kd determination, and F-actin co-sedimentation

    PMID:12153988

    Open questions at the time
    • Functional consequence for channel current not measured here
    • Stoichiometry within the membrane complex unknown
  7. 2004 High

    Reconstituting four central repeated units as a dual PKC-α/PLC-γ1 scaffold, defining C-terminal actin-bundling and force-stabilizing activity, and showing C-terminal peptides directly modulate cardiac I(CaL) via the β2 subunit, established AHNAK repeats and C-terminus as functional signaling and cytoskeletal modules.

    Evidence GST pulldowns, siRNA-validated Ca2+/IP3 assays, in vitro actin bundling with EM and skinned-fiber mechanics, and whole-cell patch clamp with peptide perfusion

    PMID:14722071 PMID:15001564 PMID:15033986

    Open questions at the time
    • In vivo contribution of repeat scaffolding not yet tested by knockout
    • Link between actin bundling and channel modulation incompletely separated
  8. 2004 Medium

    Showing AHNAK binds the DNA ligase IV–XRCC4 complex and stimulates its ligation activity introduced a candidate role in non-homologous end joining, expanding AHNAK beyond membrane/cytoskeletal functions.

    Evidence Immunoaffinity purification, co-IP, and in vitro DNA ligation/DNA-binding assays

    PMID:15177040

    Open questions at the time
    • No cellular NHEJ phenotype demonstrated
    • Weak DNA binding leaves recruitment mechanism unclear
  9. 2006 High

    Defining the minimal C-terminal A2t-binding motif and identifying AHNAK as a dysferlin-complex component established the precise interfaces by which AHNAK is tethered at the plasma membrane and the sarcolemma.

    Evidence Yeast triple-hybrid, in vitro binding, EGFP co-IP/imaging; co-IP/MS and GST pulldown in muscle with disease-tissue corroboration

    PMID:16984913 PMID:17185750

    Open questions at the time
    • Functional output of dysferlin–AHNAK binding in repair vs. structure unresolved
    • Regulation of A2t motif engagement in vivo unclear
  10. 2008 High

    Genetic AHNAK1 ablation in T cells and analysis of Ahnak-null MEFs demonstrated that AHNAK is required for L-type channel surface expression and Ca2+ entry/NFAT signaling and potentiates PKC-α/Erk by disrupting the PKC–PP2A complex, moving AHNAK from biochemical scaffold to physiologically required signaling regulator.

    Evidence AHNAK1 knockout mice with Cav1.1 surface/Ca2+ flux/NFAT readouts; co-IP, PKC activity, and knockout MEF rescue

    PMID:18174170 PMID:18191595

    Open questions at the time
    • Mechanism of channel trafficking by AHNAK not resolved at molecular level
    • Tissue-specific redundancy with AHNAK2 untested
  11. 2009 Medium

    Extending the AHNAK1 requirement to CD8+ CTL effector function, the NPR-C membrane tether, and osteoblast Cav1.2 Ca2+ influx generalized AHNAK as a Ca2+-entry organizer across multiple cell types.

    Evidence AHNAK1 knockout CTL assays; co-IP/MS plus domain mapping for NPR-C; FRET/co-IP/siRNA Ca2+ assays in osteoblasts

    PMID:19261907 PMID:19497879 PMID:19710363

    Open questions at the time
    • Whether AHNAK acts on trafficking versus gating differs across studies
    • NPR-C tethering generality untested
  12. 2010 Medium

    Costameric localization and increased transverse stiffness of AHNAK1-deficient fibers, without a membrane-repair defect, refined AHNAK's muscle role toward mechanical/structural support rather than wound resealing.

    Evidence Immunolocalization, atomic force microscopy, and laser wounding in AHNAK1-deficient fibers

    PMID:20833135

    Open questions at the time
    • Molecular basis of altered stiffness not defined
    • AHNAK1 vs AHNAK2 functional division unresolved
  13. 2011 Medium

    Showing calpain-3 cleavage abolishes the dysferlin–AHNAK interaction and that AHNAK is released in shed vesicles linked AHNAK mislocalization to muscular dystrophy pathology and a vesicle-shedding mechanism, while a 17 kDa isoform was found to autoregulate AHNAK splicing.

    Evidence Disease-biopsy immunofluorescence, vesicle purification/EM; isoform co-IP and splicing reporters during myogenesis

    PMID:21940993 PMID:22057634

    Open questions at the time
    • Causal role of AHNAK loss in dystrophy phenotype not established
    • Splicing feedback mechanism not mapped to specific factors
  14. 2012 High

    Atomic-level structure of the AHNAK peptide on annexin A2/S100A10 and SPR-based mapping of the Cavβ2 SH3-HOOK-GK interface with PKA-Ser296 modulation explained both the specificity of membrane tethering and the phosphorylation-tunable channel regulation, while AHNAK's PAK/PIX/Erk scaffolding drove Rac-dependent smooth-muscle migration in vivo.

    Evidence 2.5 Å crystallography; truncation binding, MS phosphosite ID, SPR; co-IP, Rac assays, and Ahnak-/- carotid injury model

    PMID:22497893 PMID:23042471 PMID:23275167

    Open questions at the time
    • Structural basis for Cavβ2 modulation lacks a complex structure
    • How distinct scaffolds are spatially segregated within one molecule unclear
  15. 2014 High

    Defining AHNAK1 as required for cardiac I(CaL) modulation via a C-terminal PxxP–Cavβ2 interaction, its β-dystroglycan/F-actin link in Schwann cells, and its Smad3-MH2 interaction promoting TGFβ-driven growth arrest and a mammary tumor-suppressive phenotype, established parallel channel, structural, and nuclear-signaling roles validated genetically.

    Evidence Patch clamp in WT/ahnak1-/- cardiomyocytes with mutagenesis; co-IP/EM/AFM/in vivo siRNA in Schwann cells; co-IP, reporter, and MMTV/Ahnak-/- mouse model

    PMID:20607281 PMID:24662814 PMID:24796807

    Open questions at the time
    • How nuclear Smad3 role integrates with membrane functions unresolved
    • Context-dependence of tumor-suppressive vs pro-tumor outputs unexplained
  16. 2015 High

    Showing AHNAK binds SMAD1 and recruits it to the PPARγ promoter to drive BMP2-dependent adipogenesis extended AHNAK's nuclear scaffolding role to a second Smad pathway and a developmental/differentiation program.

    Evidence Co-IP, ChIP on PPARγ promoter, siRNA, and Ahnak-/- adipose-derived stem cells

    PMID:26466345

    Open questions at the time
    • How AHNAK partitions between Smad1 and Smad3 signaling unclear
    • Direct DNA versus Smad-mediated promoter engagement not separated
  17. 2018 Medium

    Identifying UBE3C-mediated ubiquitination/degradation of AHNAK (relieving p53-dependent repression of stemness genes) and AHNAK-driven TGFβ/Smad3 EMT and metastasis revealed post-translational control of AHNAK's opposing roles in cancer.

    Evidence Co-IP/ubiquitination assays, ChIP, xenografts; shRNA knockdown with EMT markers and lung-metastasis model

    PMID:30258109 PMID:30503554

    Open questions at the time
    • Reconciling tumor-suppressive p53/Smad3 roles with pro-metastatic activity by context
    • Direct ubiquitination sites not mapped
  18. 2019 High

    Showing RNF38 degrades AHNAK to relieve its inhibition of TGFβ signaling, that AHNAK scaffolds the p11/Anxa2 complex with L-type VGCC in neurons to control mood-relevant Ca2+ signaling, and biophysical lipid-binding of its C-terminal peptide further unified its ubiquitin-controlled scaffolding across cancer, neuronal, and membrane contexts.

    Evidence SILAC/co-IP/ubiquitination/rescue in HCC; co-IP domain mapping, electrophysiology, and Ahnak KO mice with behavioral testing; Langmuir/ellipsometry/31P-NMR lipid assays

    PMID:30760886 PMID:30836988 PMID:31825630

    Open questions at the time
    • Lipid binding lacks cellular validation
    • Whether neuronal and cardiac channel mechanisms are identical untested
  19. 2021 High

    Demonstrating that AHNAK binds the 53BP1 oligomerization domain to restrain its multimerization, phase separation, and p53/senescence output, and that AHNAK promotes metastatic colonization through endothelial PCSK9, connected AHNAK directly to DNA-damage-response condensate control and to the tumor microenvironment.

    Evidence Co-IP, chromatin fractionation, live-cell condensate imaging, AHNAK KO; metastasis models with transcriptomics and conditional PCSK9 KO mice

    PMID:33961796 PMID:34352405

    Open questions at the time
    • How AHNAK partitions between cytoplasmic scaffold and nuclear 53BP1 regulator unresolved
    • Mechanism linking AHNAK to PCSK9 transcription unknown
  20. 2022 High

    Showing annexin A2 recruits AHNAK to spindle-pole-facing cortex where, in complex with dynein-dynactin, it is required for NuMA/dynein cortical localization and proper spindle orientation extended AHNAK's cortical actin-organizing role to mitotic spindle positioning.

    Evidence siRNA depletion, live-cell imaging, AHNAK-dynein-dynactin co-IP, and NuMA/dynein cortical immunofluorescence in HeLa cells

    PMID:35362526

    Open questions at the time
    • Whether AHNAK contacts dynein-dynactin directly is unresolved
    • Link to cell-cycle-dependent AHNAK phosphorylation not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single giant scaffold integrates and switches between its membrane-cytoskeletal, ion-channel, nuclear Smad/53BP1, and ubiquitin-controlled functions to produce its context-dependent tumor-suppressive versus pro-metastatic outcomes.
  • No full-length structure to relate distinct domains spatially
  • Quantitative phosphorylation map coupling localization to specific functions is missing
  • Determinants of opposing cancer phenotypes across tissues undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 7 GO:0060090 molecular adaptor activity 5 GO:0008092 cytoskeletal protein binding 2 GO:0008289 lipid binding 1 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 5 GO:0005886 plasma membrane 5 GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 2 R-HSA-168256 Immune System 2 R-HSA-73894 DNA Repair 2 R-HSA-1640170 Cell Cycle 1
Partners
ANXA2CACNB2DYSFPLCG1PRKCAS100A10SMAD3TP53BP1
Complex memberships
L-type Ca2+ channel (Cav1.2/Cavβ2) complexannexin A2/S100A10 (A2t) heterotetramer complexcostamere / β-dystroglycan networkdysferlin complex

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 AHNAK encodes an unusually large (~700 kDa) protein with a large internal domain composed of highly conserved 128-amino-acid repeated elements displaying a redundant proline-at-every-seventh-residue motif; preliminary fractionation indicated predominantly nuclear residence. cDNA cloning, sequence analysis, subcellular fractionation Proceedings of the National Academy of Sciences of the United States of America Medium 1608957
1993 AHNAK protein is located principally in the nucleus and is phosphorylated on both serine and threonine; protein abundance increases when cells withdraw from the division cycle (serum withdrawal or differentiation), while the degree of phosphorylation diminishes in those settings. Immunofluorescence, subcellular fractionation, [32P]-orthophosphate metabolic labeling The Journal of cell biology Medium 8381120
1993 Desmoyokin, a 680 kDa desmosomal plaque protein, is identical to AHNAK; its distribution in keratinocytes (closely associated with the plasma membrane) differs from non-keratinocyte cells where it is diffusely cytoplasmic, suggesting cell-type-specific localization and function. cDNA immunoscreening, sequence homology, immunofluorescence, Southern blot Journal of cell science Medium 8408266
1995 PKC activation (by TPA or high calcium) is required for translocation of desmoyokin/AHNAK from the cytoplasm/nucleus to the plasma membrane in keratinocytes; selective PKC inhibitors completely block this translocation, and calcium-induced phosphorylation of AHNAK was confirmed by [32P] labeling. PKC inhibitor treatment, TPA stimulation, calcium switch, immunofluorescence, [32P]-orthophosphate immunoprecipitation Experimental cell research Medium 7698224
1995 In human epidermis, desmoyokin/AHNAK localizes to the non-desmosomal and non-hemidesmosomal plasma membrane of keratinocytes, not to desmosomes themselves, established by post-embedding immunoelectron microscopy with double-labeling against desmosomal markers. Post-embedding immunoelectron microscopy, double immunolabeling with desmosomal markers The Journal of investigative dermatology Medium 7769263
1999 AHNAK binds and activates phospholipase C-gamma1 (PLC-γ1) in the presence of arachidonic acid; arachidonic acid promotes a physical interaction between AHNAK and PLC-γ1, and activation is attributable to reduction of the enzyme's apparent Km toward PIP2. Recombinant AHNAK fragments containing one or four repeated motifs activated PLC-γ1 at nanomolar concentrations, establishing multiple activation sites per molecule. GST fusion protein pulldown, in vitro PLC-γ1 activity assay, recombinant protein purification The Journal of biological chemistry High 10318799
1999 AHNAK (pp700) interacts specifically with the beta2 subunit of cardiac L-type Ca2+ channels as revealed by co-precipitation with anti-channel subunit antibodies; membrane-associated AHNAK undergoes substantial in vivo PKA phosphorylation upon beta-adrenergic stimulation (isoproterenol), specifically in the fraction that co-precipitates with the Ca2+ channel beta subunit. Co-immunoprecipitation, back-phosphorylation assay, immunofluorescence on cardiomyocytes, RT-PCR FASEB journal Medium 10593863
2000 The C-terminal domain of desmoyokin/AHNAK is responsible for its nuclear localization in low-calcium conditions and for its calcium/PKC-induced translocation from nucleus toward the cytoplasm and cell membrane; N-terminal and central domains alone showed no calcium-dependent redistribution. Transient transfection of N-terminal, central, and C-terminal domain expression constructs in COS-7, HeLa, and keratinocytes; immunofluorescence in low vs. normal calcium conditions The Journal of investigative dermatology Medium 10771490
2001 AHNAK is the major and most specific Ca2+-dependent target of S100B in fibroblast and astrocytoma cells; interaction requires both Ca2+ and Zn2+ (2 Zn2+ per S100B enhance Ca2+-dependent binding), and the binding domains on AHNAK map to its repeated motifs. AHNAK does not bind calmodulin, S100A6, or S100A11 under these conditions. S100B-Sepharose pulldown, anti-S100B immunoprecipitation, truncated AHNAK fragment binding assays The Journal of biological chemistry Medium 11312263
2001 PKB/Akt phosphorylates AHNAK in vitro and in vivo on serine 5535; this phosphorylation mediates nuclear export of AHNAK via a nuclear export signal (NES) and is a major determinant of AHNAK's extranuclear localization in epithelial cells. In vitro kinase assay, phospho-specific mutagenesis (Ser5535), NES identification, subcellular fractionation, immunofluorescence The Journal of cell biology High 11535620
2002 The C-terminal region of AHNAK (aa 5262–5643) interacts with the beta2a subunit of the cardiac L-type Ca2+ channel with Kd ~55 nM (for the beta2a C-terminal truncate), and the same region binds G-actin and co-sediments with F-actin, providing a structural link between the L-type Ca2+ channel and the actin-based cytoskeleton. GST pulldown, equilibrium sedimentation/analytical ultracentrifugation (Kd determination), F-actin co-sedimentation, confocal immunofluorescence FASEB journal High 12153988
2003 AHNAK forms a multimeric complex with actin and the annexin 2/S100A10 heterotetramer at the cytosolic face of the plasma membrane; the S100A10 subunit mediates the annexin 2–AHNAK interaction at the AHNAK C-terminal domain. siRNA-mediated knockdown of annexin 2/S100A10 prevents AHNAK plasma membrane association, and AHNAK siRNA prevents cortical actin cytoskeleton reorganization required for cell height in MDCK cells. Co-immunoprecipitation, siRNA knockdown, immunofluorescence in MDCK cells, confocal microscopy The Journal of cell biology High 14699089
2004 Four central repeated units (4 CRUs) of AHNAK act as a scaffolding motif that binds both PKC-α and PLC-γ1; AHNAK-bound PKC-α stimulates arachidonic acid release near PLC-γ1, and the concerted action of 4 CRUs with arachidonic acid activates PLC-γ1, leading to IP3 generation and intracellular Ca2+ mobilization in a PLC-γ1-dependent manner. GST pulldown, siRNA depletion of PLC-γ1, inositol phosphate (IP) measurement, Ca2+ mobilization assay in NIH3T3 cells expressing 4 CRUs The Journal of biological chemistry High 15033986
2004 The C-terminal ahnak fragment (ahnak-C2) induces actin filament bundling into paracrystalline-like structures in vitro and stabilizes isometric force development in demembranated skeletal muscle fibers. An endogenous 72 kDa C-terminal ahnak fragment co-purifies with myofibrillar proteins and localizes to intercalated discs and near the Z-line in cardiomyocytes. Recombinant protein/actin bundling assay (electron microscopy), demembranated fiber force measurement, immunocytochemistry/confocal microscopy FASEB journal High 15001564
2004 The carboxyl-terminal ahnak fragments P3 (aa 5456–5556) and P4 (aa 5556–5643) modulate the L-type Ca2+ current in rat ventricular cardiomyocytes: P4 increases current amplitude by ~23% while both P3 and P4 slow current inactivation. These effects are mediated via the ahnak–beta2 subunit interaction rather than the ahnak–F-actin interaction, as actin-stabilizing agents did not alter their effect. Whole-cell patch clamp on rat cardiomyocytes, intracellular perfusion of recombinant ahnak peptides, pharmacological controls (phalloidin, jasplakinolide) The Journal of biological chemistry High 14722071
2004 AHNAK interacts specifically with the DNA ligase IV–XRCC4 complex (but not with other DNA ligases or other NHEJ components), stimulates the double-stranded ligation activity of DNA ligase IV–XRCC4, has weak DNA-binding activity, and forms a stable complex with DNA ligase IV–XRCC4 on DNA. Immunoaffinity purification, co-immunoprecipitation, in vitro DNA ligation assay, DNA-binding assay DNA repair Medium 15177040
2005 A naturally occurring missense variant Ile5236Thr in AHNAK critically reduces beta2 subunit binding affinity (~50% decrease after PKA phosphorylation or with the mutant peptide) and, when applied intracellularly, mimics PKA effects on L-type Ca2+ current (increases amplitude ~60%, slows inactivation, leftward voltage shift) and prevents further up-regulation by isoprenaline. GST pulldown binding with wild-type vs. mutant ahnak fragments, whole-cell patch clamp on native cardiomyocytes with intracellular peptide application FASEB journal High 16319140
2006 AHNAK is a component of the dysferlin protein complex in skeletal muscle; the C2A domain of dysferlin binds the C-terminal domain of AHNAK (defined by GST pulldown); reduction or absence of dysferlin causes secondary muscle-specific loss of AHNAK from the sarcolemma; during regeneration, both proteins redistribute to the cytoplasm in concert. Co-immunoprecipitation coupled with mass spectrometry, GST pulldown domain mapping, immunofluorescence on human and rat muscle biopsies FASEB journal High 17185750
2006 A specific 20-amino-acid peptide in the AHNAK C-terminal domain (A2tBP1) constitutes the minimal binding motif for the annexin 2/S100A10 tetramer (A2t); binding requires both the annexin 2 N-terminal tail and S100A10 together (neither alone is sufficient); a second, lower-affinity A2t-binding motif (A2tBP2) exists in the N-terminal AHNAK domain. Overexpressed A2tBP1-EGFP co-fractionates with and co-immunoprecipitates S100A10/annexin 2 in a calcium-dependent manner, and relocalizes to the plasma membrane under oxidative/mechanical stress. Yeast triple-hybrid assay, in vitro binding assay, EGFP fusion overexpression/co-IP, live-cell imaging The Journal of biological chemistry High 16984913
2008 AHNAK1 is required for plasma membrane expression of L-type calcium channel alpha1S (Cav1.1) subunit in CD4+ T cells, likely through interaction with the beta regulatory subunit; AHNAK1-deficient mice exhibit reduced Ca2+ influx upon TCR crosslinking and poor NFAT activation. AHNAK1 knockout mouse model, flow cytometry for Cav1.1 surface expression, Ca2+ flux measurement, NFAT reporter assay Immunity High 18191595
2008 AHNAK central repeated units (CRUs) bind and activate PKC-α in a phosphatidylserine/DAG-independent manner and disrupt the PKC-α–protein phosphatase 2A (PP2A) inhibitory complex, thereby potentiating PKC-α activation and downstream Raf/MEK/Erk phosphorylation; Ahnak-null MEFs show enhanced PKC–PP2A complex formation and reduced membrane translocation of PKC-α in response to stimuli. Co-immunoprecipitation, GST pulldown, PKC activity assay, Ahnak knockout MEFs, immunofluorescence for PKC translocation The Journal of biological chemistry High 18174170
2009 AHNAK1 is required for Ca2+ entry into mature cytolytic CD8+ T cells (CTLs); AHNAK1-deficient CTLs show markedly reduced Cav1.1 alpha1S subunit expression, reduced granzyme-B production, cytolytic activity, and IFN-γ secretion after TCR stimulation. AHNAK1 knockout mouse model, Ca2+ flux assay, flow cytometry (granzyme-B, IFN-γ), cytolysis assay Proceedings of the National Academy of Sciences of the United States of America High 19497879
2009 The C-type natriuretic peptide receptor (NPR-C) tethers AHNAK1 at the plasma membrane via the AHNAK1 C1 domain; siRNA knockdown of NPR-C results in AHNAK1 nuclear accumulation, and knockdown of either NPR-C or AHNAK1 attenuates arachidonic acid/phorbol ester-induced intracellular Ca2+ mobilization. Co-immunoprecipitation/MS, GST pulldown domain mapping, sucrose density gradient fractionation, siRNA knockdown, Ca2+ mobilization assay American journal of physiology. Cell physiology Medium 19710363
2009 In osteoblastic MC3T3-E1 cells, AHNAK associates with the Cav1.2/beta2-subunit complex at the plasma membrane via the beta2 subunit; siRNA knockdown of AHNAK significantly impairs Ca2+ influx without disrupting the actin cytoskeleton or disassembling the Cav1.2/beta2 complex. Co-immunoprecipitation, FRET (fluorescence resonance energy transfer), siRNA knockdown, Ca2+ influx measurement, immunohistochemistry American journal of physiology. Cell physiology Medium 19261907
2009 AHNAK is constitutively expressed by myelinating Schwann cells; siRNA silencing of AHNAK affects Schwann cell morphology and laminin-substrate attachment, and alters expression and distribution of dystroglycan, suggesting AHNAK targets the dystroglycan-associated receptor complex at the plasma membrane. siRNA knockdown in primary Schwann cells, immunofluorescence, western blot for dystroglycan, morphology assay Glia Medium 18837049
2010 AHNAK1 and AHNAK2 are both components of the costameric network in skeletal muscle (co-localize with vinculin); AHNAK1 is absent from the T-tubule system; AHNAK1-deficient fibers show significantly higher transverse stiffness by atomic force microscopy, but AHNAK1 is not required for membrane repair in a laser wounding assay. Specific antibody immunofluorescence/co-localization, atomic force microscopy, laser wounding assay in AHNAK1-deficient fibers Biochemical and biophysical research communications Medium 20833135
2011 AHNAK interaction with dysferlin is lost upon cleavage by calpain 3 protease; in muscular dystrophies (LGMD2B from dysferlin mutations and LGMD2A from calpain 3 mutations), ahnak1 loses sarcolemmal localization and appears in muscle connective tissue. Ca2+-stimulated vesicle shedding from primary human myotubes releases ahnak1-containing vesicles (~150 nm diameter), establishing a vesicle-release mechanism for abnormal ahnak1 localization. Immunofluorescence on human muscle biopsies, vesicle purification, electron microscopy, western blot Journal of muscle research and cell motility Medium 22057634
2011 A small 17 kDa AHNAK isoform (generated by alternative splicing) interacts with the large 700 kDa AHNAK in the cytoplasm; the small isoform is also present in the nucleus and establishes a positive feedback loop to regulate mRNA splicing at its own locus during muscle differentiation. RT-PCR, western blot, co-immunoprecipitation of isoforms, transfection experiments during muscle differentiation FASEB journal Medium 21940993
2012 Crystal structure of a 20-aa AHNAK C-terminal peptide (residues 5654–5673) bound to the annexin A2/S100A10 heterotetramer at 2.5 Å resolution shows that binding is governed by hydrophobic interactions between AHNAK side chains and pockets on S100A10, while hydrogen bonds predominantly involve backbone AHNAK atoms, explaining the binding's specificity for S100A10 over other S100 proteins. X-ray crystallography (2.5 Å resolution) Acta crystallographica. Section D, Biological crystallography High 23275167
2012 Ahnak1 interacts with the SH3-HOOK-GK core region of Cavβ2 (C- and N-terminal Cavβ2 regions are dispensable); PKA phosphorylation of Ser-296 in the GK domain of Cavβ2 increases ahnak1 binding affinity ~2.4-fold but reduces binding capacity ~60%, constituting a mechanism by which PKA phosphorylation modulates ahnak1's effect on Cav1.2 channel activity. In vitro binding assay with Cavβ2 truncation mutants, mass spectrometry (phosphosite identification), surface plasmon resonance (SPR/Kd), immunocytochemistry Biochemical and biophysical research communications High 22497893
2012 Ahnak functions as a scaffolding protein in aortic smooth muscle cells (ASMCs) connecting a complex of Erk, PAK (p21-activated kinase), and PIXβ (PAK-interacting exchange factor β); Ahnak knockout ASMCs show reduced Rac activation, impaired lamellipodial protrusion, and decreased PDGF-dependent migration; neointimal formation and SMC migration after carotid ligation injury are significantly retarded in Ahnak knockout mice. Co-immunoprecipitation with anti-PAK antibody, Rac activation assay, transwell/wound-healing migration assay, carotid ligation model in Ahnak-/- mice Cardiovascular research High 23042471
2014 Ahnak directly interacts with Smad3 through its MH2 domain and stimulates Smad3 nuclear localization, potentiating TGFβ-induced transcriptional activity; Ahnak overexpression causes c-Myc and cyclin D1/D2 downregulation and cell cycle arrest; Ahnak-null mice in the MMTV-middle T background show significantly accelerated mammary hyperplasia. Co-immunoprecipitation, nuclear fractionation/immunofluorescence, reporter assay, western blot (c-Myc, cyclin D1/D2), MMTV-Tg/Ahnak-/- mouse model Oncogene High 24662814
2014 Crystal structures of the PDZ-like domain of AHNAK2 reveal intertwined, domain-swapped homodimers; the AHNAK2 PDZ domain contains a bound class III ligand peptide in the preformed binding pocket with two salt bridges and weak C-terminus recognition, providing a structural basis for homodimerization and scaffolding function. X-ray crystallography of PDZ-like domains from PRX and AHNAK2 The Journal of biological chemistry Medium 24675079
2015 AHNAK directly interacts with SMAD1 and facilitates Smad1 binding to the PPARγ2 promoter, thereby stimulating BMP2-mediated adipocyte differentiation; loss of AHNAK impairs Smad1 phosphorylation and nuclear localization, downregulates PPARγ expression, and severely impairs adipocyte differentiation. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP) on PPARγ promoter, siRNA knockdown, Ahnak-/- adipose-derived stem cells, Oil Red O staining PloS one High 26466345
2016 AHNAK is the most abundant protein component of extracellular vesicles produced by mammary carcinoma cells and is necessary for their formation; AHNAK-depleted carcinoma cells produce fewer vesicles that are less capable of promoting recipient fibroblast migration. Proteomic analysis (non-biased MS) of vesicle contents, AHNAK knockdown, fibroblast migration assay Oncotarget Medium 27374178
2018 UBE3C ubiquitin E3 ligase ubiquitinates AHNAK and promotes its proteasomal degradation; AHNAK functions as a cofactor assisting p53 binding to stemness-related gene promoters to inhibit transcription; UBE3C-mediated AHNAK degradation removes this p53-mediated inhibition, enhancing cancer stem cell properties. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, ChIP for AHNAK-p53 on promoters, in vivo xenograft Cancer letters Medium 30503554
2018 Ahnak induces EMT in response to TGFβ by activating Smad3 phosphorylation and enhancing Smad3 transcriptional activity; stable knockdown of Ahnak in B16F10 cells reduces N-cadherin expression and Smad3 phosphorylation, and abrogates TGFβ-induced migration, invasion, and lung metastasis in C57BL/6 mice. siRNA/shRNA knockdown, western blot (Smad3-phos, N-cadherin, EMT markers), migration/invasion assay, tail-vein lung metastasis model Scientific reports Medium 30258109
2019 RNF38 RING-finger E3 ubiquitin ligase ubiquitinates and degrades AHNAK, thereby relieving AHNAK-mediated inhibition of TGFβ signaling and promoting HCC cell migration and invasion; re-introduction of AHNAK interference restores invasion capacity diminished by RNF38 downregulation. SILAC proteomics, Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, in vitro/in vivo invasion assays Journal of experimental & clinical cancer research Medium 30836988
2019 Ahnak scaffolds the p11 (S100A10)/Anxa2 complex and L-type VGCC: through its N-terminal region it interacts with the pore-forming α1 subunit, and through its C-terminal region it interacts with the β subunit and the p11/Anxa2 complex. Ahnak knockout neurons show reduced α1 surface expression and L-type Ca2+ current, and constitutive or forebrain-specific Ahnak KO mice display depression-like behavior similar to p11 KO mice. Co-immunoprecipitation, domain mapping, electrophysiology (L-type Ca2+ current), confocal microscopy, Ahnak conditional/constitutive knockout mice, behavioral testing Molecular psychiatry High 30760886
2019 AHNAK C-terminal peptide (residues 5654–5673) preferentially and strongly binds negatively charged phospholipids with unsaturated acyl chains, established by Langmuir monolayer tensiometry, ellipsometry, and 31P solid-state NMR on lipid bilayers. Langmuir monolayer surface tensiometry, ellipsometry, 31P solid-state NMR Langmuir Medium 31825630
2021 AHNAK binds to the 53BP1 oligomerization domain and controls 53BP1 multimerization and phase separation; loss of AHNAK results in hyper-accumulation of 53BP1 on chromatin, enhanced phase separation, and elevated p53 response, leading to senescence in non-transformed cells and sensitizing cancer cells. Co-immunoprecipitation (G1 phase enrichment), chromatin fractionation, live-cell imaging of 53BP1 condensates, AHNAK knockout/knockdown, phase separation assay Molecular cell High 33961796
2021 Ahnak regulates tumor metastasis colonization through PCSK9 expression: Ahnak-/- mice show higher resistance to pulmonary B16F10 metastasis; transcriptomic analysis of Ahnak-/- pulmonary endothelial cells reveals PCSK9 downregulation, and lung epithelium-specific PCSK9 conditional KO mice also show suppressed B16F10 pulmonary metastasis. Tail-vein metastasis model in Ahnak-/- mice, transcriptomic analysis of primary endothelial cells, tissue-specific conditional PCSK9 KO mouse model Neoplasia Medium 34352405
2022 In mitotic HeLa cells, annexin A2 (Anx2) recruits AHNAK to the cell cortex facing spindle poles; depletion of either protein or impaired cortical AHNAK localization causes delayed anaphase onset and unstable spindle anchoring, resulting in altered spindle orientation; AHNAK is found in a complex with dynein-dynactin, and both AHNAK and Anx2 are required for correct NuMA and dynein cortical localization and dynamics. siRNA depletion, live-cell imaging, co-immunoprecipitation (AHNAK-dynein-dynactin), immunofluorescence (NuMA, dynein cortical localization) Journal of cell science High 35362526
2014 AHNAK1 modulates L-type Ca2+ channel inactivation in cardiomyocytes; in vitro binding studies show that the most C-terminal 188 aa of ahnak1 containing a PxxP motif (188-PSTP) binds Cavβ2 with Kd ~60 nM, while proline-to-alanine substitutions reduce affinity ~20-fold; both 188-PSTP and 188-ASTA affect I(CaL) only in ahnak1-expressing cardiomyocytes and not in ahnak1-deficient cardiomyocytes, demonstrating that endogenous ahnak1 is required. In vitro binding assay, whole-cell patch clamp (rat, WT mouse, ahnak1-/- mouse cardiomyocytes), intracellular peptide perfusion, proline-to-alanine mutagenesis Pflugers Archiv : European journal of physiology High 20607281
2014 AHNAK1 co-localizes with β-dystroglycan in Cajal bands of myelinated Schwann cells; β-dystroglycan co-immunoprecipitates with AHNAK1, shows reduced expression in ahnak1-/- Schwann cells, and is undetectable in Cajal bands of ahnak1-/- sciatic nerve. AHNAK1-deficient Schwann cells show reduced migration velocity on laminin, greater mechanical rigidity of processes, and decreased internodal lengths, suggesting AHNAK1 links dystroglycan to F-actin to regulate Schwann cell morphology and myelination. Co-immunoprecipitation, immunofluorescence/electron microscopy, scratch wound migration assay, atomic force microscopy, siRNA knockdown in developing sciatic nerve Glia High 24796807

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 AHNAK interaction with the annexin 2/S100A10 complex regulates cell membrane cytoarchitecture. The Journal of cell biology 172 14699089
2006 AHNAK, a novel component of the dysferlin protein complex, redistributes to the cytoplasm with dysferlin during skeletal muscle regeneration. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 131 17185750
1992 A human gene (AHNAK) encoding an unusually large protein with a 1.2-microns polyionic rod structure. Proceedings of the National Academy of Sciences of the United States of America 119 1608957
2002 The carboxyl-terminal region of ahnak provides a link between cardiac L-type Ca2+ channels and the actin-based cytoskeleton. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 115 12153988
2014 Ahnak functions as a tumor suppressor via modulation of TGFβ/Smad signaling pathway. Oncogene 103 24662814
2014 AHNAK: the giant jack of all trades. Cellular signalling 100 25172424
2008 A scaffold protein, AHNAK1, is required for calcium signaling during T cell activation. Immunity 95 18191595
2001 The giant protein AHNAK is a specific target for the calcium- and zinc-binding S100B protein: potential implications for Ca2+ homeostasis regulation by S100B. The Journal of biological chemistry 92 11312263
2001 Protein kinase B phosphorylates AHNAK and regulates its subcellular localization. The Journal of cell biology 74 11535620
1993 The human gene AHNAK encodes a large phosphoprotein located primarily in the nucleus. The Journal of cell biology 71 8381120
2021 AHNAK controls 53BP1-mediated p53 response by restraining 53BP1 oligomerization and phase separation. Molecular cell 69 33961796
2018 Quantitative Proteomic Analysis Identifies AHNAK (Neuroblast Differentiation-associated Protein AHNAK) as a Novel Candidate Biomarker for Bladder Urothelial Carcinoma Diagnosis by Liquid-based Cytology. Molecular & cellular proteomics : MCP 68 29950347
2005 Ahnak is critical for cardiac Ca(V)1.2 calcium channel function and its beta-adrenergic regulation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 67 16319140
1999 AHNAK, a protein that binds and activates phospholipase C-gamma1 in the presence of arachidonic acid. The Journal of biological chemistry 67 10318799
1999 Signaling from beta-adrenoceptor to L-type calcium channel: identification of a novel cardiac protein kinase A target possessing similarities to AHNAK. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 66 10593863
1995 Regulation of translocation of the desmoyokin/AHNAK protein to the plasma membrane in keratinocytes by protein kinase C. Experimental cell research 61 7698224
2008 Ahnak protein activates protein kinase C (PKC) through dissociation of the PKC-protein phosphatase 2A complex. The Journal of biological chemistry 56 18174170
2006 Ahnak, a new player in beta-adrenergic regulation of the cardiac L-type Ca2+ channel. Cardiovascular research 56 17045254
2017 AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways in triple-negative breast cancer. Journal of experimental & clinical cancer research : CR 55 28494797
2016 AHNAK enables mammary carcinoma cells to produce extracellular vesicles that increase neighboring fibroblast cell motility. Oncotarget 54 27374178
2019 Ahnak scaffolds p11/Anxa2 complex and L-type voltage-gated calcium channel and modulates depressive behavior. Molecular psychiatry 53 30760886
2005 Specific AHNAK expression in brain endothelial cells with barrier properties. Journal of cellular physiology 53 15493012
1993 Desmoyokin, a 680 kDa keratinocyte plasma membrane-associated protein, is homologous to the protein encoded by human gene AHNAK. Journal of cell science 53 8408266
2018 Ubiquitin-protein ligase E3C maintains non-small-cell lung cancer stemness by targeting AHNAK-p53 complex. Cancer letters 52 30503554
2019 Overexpression of RNF38 facilitates TGF-β signaling by Ubiquitinating and degrading AHNAK in hepatocellular carcinoma. Journal of experimental & clinical cancer research : CR 49 30836988
2004 AHNAK-mediated activation of phospholipase C-gamma1 through protein kinase C. The Journal of biological chemistry 49 15033986
2018 Ahnak promotes tumor metastasis through transforming growth factor-β-mediated epithelial-mesenchymal transition. Scientific reports 47 30258109
2009 Requirement for AHNAK1-mediated calcium signaling during T lymphocyte cytolysis. Proceedings of the National Academy of Sciences of the United States of America 44 19497879
2003 Expression of the giant protein AHNAK (desmoyokin) in muscle and lining epithelial cells. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 42 12588962
2017 Fluorescence-Reported Allelic Exchange Mutagenesis Reveals a Role for Chlamydia trachomatis TmeA in Invasion That Is Independent of Host AHNAK. Infection and immunity 40 28970272
2009 Roles of Ca(v) channels and AHNAK1 in T cells: the beauty and the beast. Immunological reviews 40 19754902
2019 BRD4 Regulates Metastatic Potential of Castration-Resistant Prostate Cancer through AHNAK. Molecular cancer research : MCR 38 31110158
2013 AHNAK is highly expressed and plays a key role in cell migration and invasion in mesothelioma. International journal of oncology 38 24253341
2004 The carboxyl-terminal ahnak domain induces actin bundling and stabilizes muscle contraction. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38 15001564
2019 Matrine involves in the progression of gastric cancer through inhibiting miR-93-5p and upregulating the expression of target gene AHNAK. Journal of cellular biochemistry 37 31736157
2004 Calcium current in rat cardiomyocytes is modulated by the carboxyl-terminal ahnak domain. The Journal of biological chemistry 37 14722071
1995 Desmoyokin/AHNAK protein localizes to the non-desmosomal keratinocyte cell surface of human epidermis. The Journal of investigative dermatology 37 7769263
2006 Identification of an AHNAK binding motif specific for the Annexin2/S100A10 tetramer. The Journal of biological chemistry 36 16984913
2000 C-Terminus of desmoyokin/AHNAK protein is responsible for its translocation between the nucleus and cytoplasm. The Journal of investigative dermatology 36 10771490
2010 1H NMR-based metabolomic study on resistance to diet-induced obesity in AHNAK knock-out mice. Biochemical and biophysical research communications 32 21094140
2004 Ahnak/Desmoyokin is dispensable for proliferation, differentiation, and maintenance of integrity in mouse epidermis. The Journal of investigative dermatology 29 15373775
2020 Genomic Mapping Identifies Mutations in RYR2 and AHNAK as Associated with Favorable Outcome in Basal-Like Breast Tumors Expressing PD1/PD-L1. Cancers 28 32796628
2014 Periaxin and AHNAK nucleoprotein 2 form intertwined homodimers through domain swapping. The Journal of biological chemistry 28 24675079
2009 Dynamic interactions between L-type voltage-sensitive calcium channel Cav1.2 subunits and ahnak in osteoblastic cells. American journal of physiology. Cell physiology 28 19261907
2021 AHNAK: The quiet giant in calcium homeostasis. Cell calcium 27 33813182
2019 AHNAK Nucleoprotein 2 Performs a Promoting Role in the Proliferation and Migration of Uveal Melanoma Cells. Cancer biotherapy & radiopharmaceuticals 27 31621397
2011 Self-regulated alternative splicing at the AHNAK locus. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 21940993
2010 AHNAK1 and AHNAK2 are costameric proteins: AHNAK1 affects transverse skeletal muscle fiber stiffness. Biochemical and biophysical research communications 27 20833135
2009 The giant protein AHNAK involved in morphogenesis and laminin substrate adhesion of myelinating Schwann cells. Glia 27 18837049
2002 Identification of AHNAK as a novel autoantigen in systemic lupus erythematosus. Biochemical and biophysical research communications 27 11866458
2020 MicroRNA-93-5p promotes epithelial-mesenchymal transition in gastric cancer by repressing tumor suppressor AHNAK expression. Cancer cell international 26 32190000
2018 AHNAK Loss in Mice Promotes Type II Pneumocyte Hyperplasia and Lung Tumor Development. Molecular cancer research : MCR 26 29724814
2009 The C type natriuretic peptide receptor tethers AHNAK1 at the plasma membrane to potentiate arachidonic acid-induced calcium mobilization. American journal of physiology. Cell physiology 26 19710363
2011 Ahnak1 abnormally localizes in muscular dystrophies and contributes to muscle vesicle release. Journal of muscle research and cell motility 25 22057634
2020 SORBS1 serves a metastatic role via suppression of AHNAK in colorectal cancer cell lines. International journal of oncology 24 32319594
2018 Doxorubicin resistance in breast cancer: A novel role for the human protein AHNAK. Biochemical pharmacology 24 29309757
2016 AHNAK deficiency promotes browning and lipolysis in mice via increased responsiveness to β-adrenergic signalling. Scientific reports 24 26987950
2012 Function of Ahnak protein in aortic smooth muscle cell migration through Rac activation. Cardiovascular research 24 23042471
2012 Structure of a C-terminal AHNAK peptide in a 1:2:2 complex with S100A10 and an acetylated N-terminal peptide of annexin A2. Acta crystallographica. Section D, Biological crystallography 24 23275167
2019 Long Non-coding RNA XIST May Influence Cervical Ossification of the Posterior Longitudinal Ligament Through Regulation of miR-17-5P/AHNAK/BMP2 Signaling Pathway. Calcified tissue international 23 31511959
2015 Obesity Resistance and Enhanced Insulin Sensitivity in Ahnak-/- Mice Fed a High Fat Diet Are Related to Impaired Adipogenesis and Increased Energy Expenditure. PloS one 23 26466345
2021 Proprotein convertase subtilisin/kexin Type 9 is required for Ahnak-mediated metastasis of melanoma into lung epithelial cells. Neoplasia (New York, N.Y.) 21 34352405
2021 AHNAK suppresses ovarian cancer progression through the Wnt/β-catenin signaling pathway. Aging 21 34689136
2006 Spinal cord injury-induced up-regulation of AHNAK, expressed in cells delineating cystic cavities, and associated with neoangiogenesis. The European journal of neuroscience 21 16930430
2001 Subtractive hybridization reveals tissue-specific expression of ahnak during embryonic development. Development, growth & differentiation 21 11284963
2016 Ahnak stimulates BMP2-mediated adipocyte differentiation through Smad1 activation. Obesity (Silver Spring, Md.) 20 26813528
2014 AHNAK KO mice are protected from diet-induced obesity but are glucose intolerant. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 18 25153686
2004 AHNAK interacts with the DNA ligase IV-XRCC4 complex and stimulates DNA ligase IV-mediated double-stranded ligation. DNA repair 18 15177040
2011 Ahnak1 is a tuneable modulator of cardiac Ca(v)1.2 calcium channel activity. Journal of muscle research and cell motility 17 22038483
2001 Multiple antibodies to titin immunoreact with AHNAK and localize to the mitotic spindle machinery. Cell motility and the cytoskeleton 17 11746675
2021 Ahnak deficiency attenuates high-fat diet-induced fatty liver in mice through FGF21 induction. Experimental & molecular medicine 16 33785868
1995 Localization of the human AHNAK/desmoyokin gene (AHNAK) to chromosome band 11q12 by somatic cell hybrid analysis and fluorescence in situ hybridization. Cytogenetics and cell genetics 16 7789175
2012 Ahnak1 interaction is affected by phosphorylation of Ser-296 on Cavβ₂. Biochemical and biophysical research communications 15 22497893
2022 The AHNAK induces increased IL-6 production in CD4+ T cells and serves as a potential diagnostic biomarker for recurrent pregnancy loss. Clinical and experimental immunology 14 35766885
2018 Essential role of Ahnak in adipocyte differentiation leading to the transcriptional regulation of Bmpr1α expression. Cell death & disease 14 30154465
2002 Multiple developmental roles of Ahnak are suggested by localization to sites of placentation and neural plate fusion in the mouse conceptus. Mechanisms of development 14 14516657
2022 CircRNA_0008194 functions as a ceRNA to promote invasion of hepatocellular carcinoma via inhibiting miR-190a/AHNAK signaling pathway. Journal of clinical laboratory analysis 13 35199873
2015 Increased Cell Proliferations and Neurogenesis in the Hippocampal Dentate Gyrus of Ahnak Deficient Mice. Neurochemical research 12 26007245
2014 Giant scaffolding protein AHNAK1 interacts with β-dystroglycan and controls motility and mechanical properties of Schwann cells. Glia 12 24796807
2019 Ahnak-knockout mice show susceptibility to Bartonella henselae infection because of CD4+ T cell inactivation and decreased cytokine secretion. BMB reports 11 30940323
2015 Regulation of c-Myc Expression by Ahnak Promotes Induced Pluripotent Stem Cell Generation. The Journal of biological chemistry 11 26598518
2010 Ahnak1 modulates L-type Ca(2+) channel inactivation of rodent cardiomyocytes. Pflugers Archiv : European journal of physiology 11 20607281
2021 Age-related decline in murine heart and skeletal muscle performance is attenuated by reduced Ahnak1 expression. Journal of cachexia, sarcopenia and muscle 10 34212535
2018 Distinctive pattern of AHNAK methylation level in peripheral blood mononuclear cells and the association with HBV-related liver diseases. Cancer medicine 10 30259695
2022 AHNAK Contributes to Hepatocellular Carcinoma Growth by Interacting with IGF-1R. Molecules (Basel, Switzerland) 9 36557813
2022 Annexin A2 and Ahnak control cortical NuMA-dynein localization and mitotic spindle orientation. Journal of cell science 8 35362526
2022 Ahnak depletion accelerates liver regeneration by modulating the TGF-β/Smad signaling pathway. BMB reports 8 35880432
2015 Tetrandrine Inhibits the Intracellular Calcium Ion Level and Upregulates the Expression of Brg1 and AHNAK in Hep-2 Cells. Clinical laboratory 8 26642721
2023 Silencing AHNAK promotes nasopharyngeal carcinoma progression by upregulating the ANXA2 protein. Cellular oncology (Dordrecht, Netherlands) 7 37962808
2022 Inhibition of AHNAK nucleoprotein 2 alleviates pulmonary fibrosis by downregulating the TGF-β1/Smad3 signaling pathway. The journal of gene medicine 7 35882062
2022 AHNAK-modified microbubbles for the intracranial delivery of triptolide: In-vitro and in-vivo investigations. International journal of pharmaceutics 7 36404486
2021 Gm40600 promotes CD4+ T-cell responses by interacting with Ahnak. Immunology 7 33987830
2020 Intensive morphometric analysis of enormous alterations in skeletal bone system with micro-CT for AHNAK-/- mice. Anatomical science international 7 32067190
2020 MiR-222-5p promotes the growth and migration of trophoblasts by targeting AHNAK. European review for medical and pharmacological sciences 7 33215408
2019 AHNAK C-Terminal Peptide Membrane Binding-Interactions between the Residues 5654-5673 of AHNAK and Phospholipid Monolayers and Bilayers. Langmuir : the ACS journal of surfaces and colloids 7 31825630
2002 Multiple developmental roles of Ahnak are suggested by localization to sites of placentation and neural plate fusion in the mouse conceptus. Gene expression patterns : GEP 7 12617833
2022 Downregulation of Circ_0088196 Contributes to the Development of Trophoblastic Cells through miR-133b Sponging Function to Affect the AHNAK Expression. Gynecologic and obstetric investigation 6 36198257
2021 Peptide Derived from AHNAK Inhibits Cell Migration and Proliferation in Hirschsprung's Disease by Targeting the ERK1/2 Pathway. Journal of proteome research 6 33853325
2017 Protective Function of Ahnak1 in Vascular Healing after Wire Injury. Journal of vascular research 6 28468000
2023 Ahnak is required to balance calcium ion homeostasis and smooth muscle development in the urinary system. Cell & bioscience 5 37308968

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