Affinage

KANK1

KN motif and ankyrin repeat domain-containing protein 1 · UniProt Q14678

Length
1352 aa
Mass
147.3 kDa
Annotated
2026-06-10
57 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KANK1 is a scaffold adaptor that couples integrin-based focal adhesions to the microtubule cytoskeleton, organizing the adhesion periphery and tuning Rho-family GTPase signaling, cell migration, and growth control (PMID:27410476, PMID:18458160). It binds directly to the talin rod domain R7 through its conserved KN motif—an interaction stabilized by a β-hairpin in the KN region—and through this anchor recruits cortical microtubule-stabilizing complexes containing CLASPs, KIF21A, LL5β, and liprins to the adhesion edge (PMID:27410476, PMID:37874676, PMID:37339751). KANK1 captures KIF21A directly via a supramodule formed by a five-helix-bundle-capping domain and its ankyrin repeats, engaging the KIF21A peptide through two distinct interfaces, and disease-associated missense mutations map to this interface and abolish KIF21A recruitment (PMID:29158259, PMID:29217769). The talin–KANK1 bond is mechanically regulated: it withstands physiological shear forces, and actomyosin tension on talin excludes KANK1 from the adhesion center, retaining it at the periphery, where KANK1 liquid-liquid phase separation is required for its edge localization and cytoskeletal connectivity (PMID:31389241, PMID:37339751, PMID:37874676). KANK1 suppresses RhoA activity—by sequestering the RhoA activator Daam1 and by blocking the IRSp53–Rac1 interaction to limit lamellipodia formation—and thereby restrains stress fiber assembly, membrane ruffling, and cell migration (PMID:19171758, PMID:28284839, PMID:18458160). It functions downstream of PI3K/Akt, which phosphorylates KANK1 to promote 14-3-3 binding and modulate RhoA-dependent migration (PMID:18458160). Beyond adhesions, KANK1 acts as a growth suppressor: it limits proliferation and promotes apoptosis, restrains YAP/TAZ-dependent transcription, and at cell-cell junctions competes with Scribble for NOS1AP binding to control Hippo signaling (PMID:12133830, PMID:35805114, PMID:39613731). KANK1 is itself controlled by TRAIP-mediated polyubiquitination and proteasomal degradation, linking it to IGFBP3/AKT signaling (PMID:34349117).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2002 Medium

    Established KANK1 as a growth suppressor whose silencing in cancer follows a two-hit epigenetic/deletion mechanism, motivating study of its cellular function.

    Evidence Re-expression in expression-negative HEK293 cells with cell cycle analysis and methylation profiling

    PMID:12133830

    Open questions at the time
    • No molecular mechanism for growth arrest defined
    • Link between growth suppression and later-defined adhesion/cytoskeletal roles not drawn
  2. 2006 Medium

    Showed KANK1 shuttles between nucleus and cytoplasm and influences β-catenin transcription, raising the possibility of a signaling/transcriptional role.

    Evidence NLS/NES mutagenesis, leptomycin B, TOPFLASH reporter, and Co-IP

    PMID:16968744

    Open questions at the time
    • Direct vs indirect β-catenin regulation unresolved
    • Functional consequence in cells not established
  3. 2008 High

    Defined KANK1 as an Akt substrate whose phosphorylation creates a 14-3-3 binding site, linking PI3K/Akt signaling to RhoA suppression and migration control.

    Evidence In vitro kinase assay, reciprocal Co-IP, RhoA GTP-pulldown, and migration assays in NIH3T3 cells

    PMID:18458160

    Open questions at the time
    • Phosphosite-level mapping and stoichiometry not fully resolved
    • How 14-3-3 binding mechanistically alters RhoA suppression unclear
  4. 2009 High

    Identified the molecular basis of RhoA/Rac1 suppression: KANK1 binds IRSp53 to block its interaction with active Rac1, placing KANK1 upstream of lamellipodia formation.

    Evidence Co-IP/pulldown, RNAi epistasis (double knockdown), and lamellipodia/filopodia morphology assays

    PMID:19171758

    Open questions at the time
    • Whether IRSp53 inhibition occurs at adhesions not addressed
    • Relationship to talin-anchored pool of KANK1 undefined
  5. 2009 Medium

    Mapped the KANK1 ankyrin domain–KIF21A coiled-coil interaction and showed a CFEOM1 KIF21A mutation enhances binding and KANK1 membrane translocation, connecting KANK1 to motor regulation.

    Evidence Co-IP, subcellular fractionation, and siRNA in cells with disease mutants

    PMID:19559006

    Open questions at the time
    • Structural basis not yet resolved at this stage
    • Functional output of membrane translocation undefined
  6. 2011 Medium

    Linked KANK1 to cell polarity and directed migration via interaction with the GEF BIG1 controlling Golgi/MTOC orientation.

    Evidence Reciprocal Co-IP, siRNA depletion, wound-healing and MTOC orientation imaging

    PMID:22084092

    Open questions at the time
    • Direct vs complex-mediated interaction not distinguished
    • Mechanism connecting BIG1 to MTOC orientation unclear
  7. 2011 Medium

    Demonstrated that the KANK1 coiled-coil oligomerization domains drive constitutive kinase activation in the leukemogenic KANK1-PDGFRβ fusion, defining the contribution of KANK1's N-terminal architecture.

    Evidence Retroviral transduction, domain mutagenesis, oligomerization analysis, JAK inhibitor treatment in hematopoietic cells

    PMID:21685469

    Open questions at the time
    • Relevance to wild-type KANK1 oligomerization at adhesions unclear
    • Single fusion-protein context
  8. 2015 High

    Placed KANK family proteins upstream of RHO GTPase signaling in podocytes across multiple model organisms, linking them to glomerular function.

    Evidence Tissue immunofluorescence, Co-IP, GTP-RhoA pulldown, siRNA, Drosophila and zebrafish knockdown

    PMID:25961457

    Open questions at the time
    • KANK1-specific (vs KANK2) ARHGDIA interaction not fully separated
    • Direct adhesion role in podocytes not tested here
  9. 2016 High

    Defined the founding molecular mechanism: KANK1 KN domain binds talin R7 to recruit cortical microtubule-stabilizing complexes to focal adhesions, establishing KANK1 as the actin–microtubule coordinator at adhesions.

    Evidence Crystal structure of KN–talin R7, Co-IP, pulldown, single point mutagenesis, and live-cell imaging

    PMID:27410476

    Open questions at the time
    • Force-dependence of the bond not yet measured
    • How recruitment is spatially restricted to the periphery unaddressed
  10. 2017 High

    Resolved the structural basis of KIF21A capture, showing a capping-domain/ankyrin supramodule binds KIF21A through two interfaces and that disease mutations destabilize this complex and block KIF21A recruitment.

    Evidence Multiple independent crystal structures (2.1 Å), mutagenesis, Co-IP, and immunofluorescence

    PMID:29158259 PMID:29183992 PMID:29217769

    Open questions at the time
    • KANK1 vs KANK2 specificity for KIF21A in vivo not resolved
    • How motor binding feeds back on microtubule dynamics not quantified
  11. 2017 Medium

    Connected KANK1 to mitotic integrity, showing its loss hyperactivates RhoA via Daam1 and causes centrosome amplification and cytokinesis failure.

    Evidence siRNA, KANK1–Daam1 Co-IP, RhoA and Aurora-A activity assays, centrosome counting

    PMID:28284839

    Open questions at the time
    • Whether centrosome phenotype derives from the adhesion pool of KANK1 unclear
    • Direct vs indirect Aurora-A regulation not established
  12. 2017 Medium

    Identified CXXC5 as a downstream effector of KANK1-induced apoptosis in malignant peripheral nerve sheath tumor cells, advancing its tumor-suppressive mechanism.

    Evidence Stable re-expression, xenograft, RNA-seq, and CXXC5 knockdown rescue

    PMID:28067315

    Open questions at the time
    • How KANK1 controls CXXC5 expression unknown
    • Link to adhesion/cytoskeletal function not drawn
  13. 2019 High

    Demonstrated the talin–KANK1 bond is a mechanically robust, force-regulated interaction, explaining tension-dependent peripheral localization.

    Evidence Single-molecule magnetic tweezer force spectroscopy with cell immunofluorescence

    PMID:31389241

    Open questions at the time
    • Force thresholds for in vivo exclusion from FA center not directly measured here
    • Coupling between force sensing and complex recruitment unresolved
  14. 2019 Medium

    Established YAP as a downstream effector of KANK1 growth suppression in oral cancer cells.

    Evidence Overexpression/knockdown, apoptosis and mitochondrial assays, xenograft, YAP rescue

    PMID:31338836

    Open questions at the time
    • Mechanism linking KANK1 to YAP regulation not defined here
    • Single tumor context
  15. 2021 Medium

    Identified TRAIP-mediated ubiquitination as a route controlling KANK1 abundance, coupling its degradation to IGFBP3/AKT signaling.

    Evidence Co-IP, ubiquitination assay, proteasome inhibition in osteosarcoma cells

    PMID:34349117

    Open questions at the time
    • Ubiquitination site(s) not mapped
    • Whether degradation alters adhesion-localized KANK1 untested
  16. 2022 Medium

    Placed KANK1 upstream of an F-actin–YAP1 mechanotransduction axis controlling myoblast proliferation versus differentiation.

    Evidence siRNA, F-actin staining, YAP1 phosphorylation/localization, differentiation assays in C2C12

    PMID:35805114

    Open questions at the time
    • Direct molecular link from KANK1 to F-actin/YAP1 unresolved
    • Whether talin/RhoA axis mediates the effect untested
  17. 2023 High

    Showed KANK1 undergoes LLPS required for FA-edge localization and revealed the β-hairpin that confers high-affinity talin R7 binding, and that actomyosin tension excludes KANK1 from the FA center.

    Evidence Multiple crystal structures, LLPS biochemistry, and structure-guided mutant imaging with myosin inhibitors and constitutively active vinculin

    PMID:37339751 PMID:37874676

    Open questions at the time
    • Composition and stoichiometry of the phase-separated FA-edge condensate undefined
    • How LLPS integrates with force sensing unclear
  18. 2024 High

    Revealed a contact-loss-dependent KANK1 role at cell-cell junctions, where it competes with Scribble for NOS1AP to curb Hippo activity and stabilize TAZ.

    Evidence PyMT in vivo tumor model, reciprocal Co-IP, Hippo reporter, KANK1 knockout/knockdown

    PMID:39613731

    Open questions at the time
    • How adhesion loss redirects KANK1 to junctions mechanistically unclear
    • Relationship to YAP findings in other tissues not reconciled
  19. 2024 Medium

    Provided genetic evidence for KANK1 essentiality and a dose-dependent role suppressing centrosome amplification, with EGR1 as an upstream regulator of KANK1 levels.

    Evidence CRISPR/Cas9 editing (only haploinsufficiency achievable), plasmid rescue, EGR1 knockdown, RNA-seq

    PMID:38830559

    Open questions at the time
    • Mechanism by which EGR1 controls KANK1 not defined
    • Direct vs indirect centrosome regulation unresolved
  20. 2024 Medium

    Demonstrated in neurons that the KIF21A–KANK1 (and KANK1–talin1) interactions are required for dendritic spine morphogenesis, synaptic plasticity, and spatial cognition.

    Evidence Knockdown with structure-guided binding-deficient mutant rescue, spine imaging, LTP electrophysiology, and behavior in rat hippocampus

    PMID:38767486

    Open questions at the time
    • Subcellular site of KANK1 action in spines undefined
    • Whether microtubule-stabilizing complex recruitment is the relevant output untested
  21. 2025 Medium

    Showed KANK1 organizes a talin–liprin-β1–liprin-α1 complex at the β-cell capillary interface required for proper insulin granule fusion and glucose-stimulated secretion.

    Evidence siRNA, immunofluorescence, glucose-stimulated insulin secretion assay, Co-IP

    PMID:41380968

    Open questions at the time
    • Direct KANK1–liprin contacts vs bridging through talin not fully separated
    • Mechanism linking liprin organization to granule fusion unresolved
  22. 2025 Medium

    Proposed a structural mechanism by which KANK1's disordered L2 linker, via cooperative multivalent LC8 binding, forms a rigid rod long enough to bridge the membrane–microtubule gap at adhesions.

    Evidence EM structural analysis, biochemical cooperativity assays, AlphaFold prediction, in-cell assays (preprint)

    PMID:bio_10.1101_2025.07.16.665182

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Functional necessity of the LC8-rigidified rod in cells not fully established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How KANK1's distinct activities—talin-anchored microtubule coupling, RhoA/Rac1 suppression, LLPS-driven FA-edge organization, and Hippo/YAP–TAZ growth control—are integrated and switched between contexts (adhered vs junctional, mitotic vs interphase) remains unresolved.
  • No unified model coordinating the adhesion, GTPase, and Hippo functions
  • Tissue-specific partner usage not systematically mapped
  • Composition of the FA-edge phase-separated condensate undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-1640170 Cell Cycle 2
Partners
14-3-3BIG1DAAM1IRSP53KIF21ALC8NOS1APTLN1
Complex memberships
cortical microtubule-stabilizing complex (CLASP/KIF21A/LL5β/liprin)talin–KANK1–liprin-β1–liprin-α1 complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 KANK1 directly interacts with the talin rod domain R7 via its conserved KN domain, recruiting cortical microtubule stabilizing complexes (containing CLASPs, KIF21A, LL5β, and liprins) to focal adhesions. A single point mutation in talin that disrupts KANK1 binding (without affecting talin's adhesion function) abrogates association of microtubule-stabilizing complexes with focal adhesions. Structural studies (crystal structure of KN domain–talin R7), Co-IP, pulldown, single point mutagenesis, live-cell fluorescence microscopy eLife High 27410476
2019 The talin R7–KANK1 KN domain complex can withstand physiological shear forces (seconds to minutes, up to ~10 pN). Mechanical force measurements combined with cell biology experiments show that shear-force stretching promotes KANK1 localization to the periphery of focal adhesions, indicating the complex is mechanically regulated. Single-molecule magnetic tweezer force spectroscopy, immunofluorescence localization in cells Nano letters High 31389241
2023 Crystal structures of KANK1 in complex with talin and with liprin-β were determined. The KN region of KANK1 contains a novel β-hairpin motif that stabilizes an α-helical region, explaining high-affinity specific binding to talin R7. KANK1 also undergoes liquid-liquid phase separation (LLPS), which is required for its localization at the FA edge and for cytoskeleton connections at focal adhesions. X-ray crystallography, biochemical assays, LLPS assays, cell biological imaging with structure-guided mutants Cell reports High 37874676
2023 Structural determination of the talin–KANK1 complex using a non-covalent crystallographic chaperone revealed that a β-hairpin in the KANK1 KN region stabilizes the helix that binds talin R7. In cells expressing constitutively active vinculin (which maintains FA structure under myosin inhibition), KANK1 localizes throughout the entire FA, indicating that actomyosin tension on talin excludes KANK1 from the FA center, retaining it at the adhesion periphery. X-ray crystallography, site-directed mutagenesis, live fluorescence microscopy with myosin inhibitors and constitutively active vinculin Open biology High 37339751
2017 Crystal structure of the KANK1 ankyrin repeat domain (ANKRD) in complex with a KIF21A peptide at 2.1 Å resolution revealed that a five-helix-bundle-capping domain immediately preceding the ANK repeats forms a supramodule with the ANK repeats to bind an evolutionarily conserved KIF21A peptide via two distinct interfaces. Mutations at either interface disrupted the interaction and blocked KIF21A recruitment to focal adhesions by KANK1. X-ray crystallography (2.1 Å), site-directed mutagenesis, co-immunoprecipitation, cellular immunofluorescence localization The Journal of biological chemistry High 29158259
2017 Crystal structure of the KANK1 ankyrin domain in complex with a ~22 amino acid KIF21A peptide showed that KIF21A is recognized by two distinct pockets of the ankyrin domain and adopts helical conformations upon binding. The same ankyrin domain in KANK2 binds the identical KIF21A peptide in an analogous manner. X-ray crystallography, site-directed mutagenesis, biochemical binding assays The Journal of biological chemistry High 29183992
2017 Crystal structure of the KANK1 ankyrin repeat domain with KIF21A showed combinatorial use of two interfaces for target binding. Disease-associated missense mutations in KANK1 map to the KANK1–KIF21A interface and destabilize complex formation. Binding-deficient KANK1 mutations block KIF21A recruitment to focal adhesions in cells. X-ray crystallography, site-directed mutagenesis, immunofluorescence in cells The Journal of biological chemistry High 29217769
2008 KANK1 is an Akt substrate; Akt-mediated phosphorylation of KANK1 enables its interaction with 14-3-3. This phosphorylation-dependent interaction is stimulated by insulin and EGF (PI3K/Akt signaling). KANK1 expression reduces actin stress fibers and inhibits RhoA activation; co-expression of 14-3-3 disrupts this effect. KANK1 also inhibits insulin-induced cell migration through 14-3-3 binding. In vitro Akt kinase assay, co-immunoprecipitation, overexpression/knockdown in NIH3T3 cells, RhoA activity (GTP-pull-down) assay, cell migration assay The Journal of cell biology High 18458160
2009 KANK1 binds directly to IRSp53 and specifically inhibits the interaction between IRSp53 and active Rac1 (Rac1-G12V) but not active Cdc42, thereby suppressing IRSp53-dependent lamellipodia formation without affecting filopodia. Knockdown of both KANK1 and IRSp53 phenocopies IRSp53 knockdown, placing KANK1 upstream of IRSp53-Rac1 in the lamellipodia pathway. KANK1 also suppresses insulin-induced membrane ruffling and integrin-dependent cell spreading. Co-immunoprecipitation/pulldown, RNAi knockdown epistasis, overexpression, lamellipodia/filopodia morphology assays, cell spreading assay The Journal of cell biology High 19171758
2009 KANK1 interacts with the third and fourth coiled-coil domains of KIF21A through its ankyrin repeat domain. The CFEOM1-associated KIF21A mutation R954W (and M947T) enhances interaction with KANK1 and significantly increases translocation of KANK1 to the membrane fraction. Knockdown of KIF21A causes KANK1 to accumulate predominantly in the cytosolic fraction. Co-immunoprecipitation, subcellular fractionation, siRNA knockdown, Western blotting Biochemical and biophysical research communications Medium 19559006
2011 KANK1 physically interacts with BIG1 (brefeldin A-inhibited guanine nucleotide-exchange protein 1) by reciprocal immunoprecipitation. Both BIG1 and KANK1 depletion produce strikingly similar defects in directed cell migration and Golgi/MTOC orientation toward the leading edge during wound healing, placing both proteins in overlapping complexes that regulate cell polarity. Reciprocal co-immunoprecipitation, siRNA depletion, wound-healing migration assay, Golgi/MTOC orientation imaging Proceedings of the National Academy of Sciences of the United States of America Medium 22084092
2006 KANK1 shuttles between nucleus and cytoplasm via CRM1-dependent export; active nuclear localization signals (NLS1, NLS2) and nuclear export signals (NES1–NES3) were mapped by mutagenesis. Nuclear KANK1 positively correlates with β-catenin-dependent transcription (TOPFLASH reporter), and KANK1 binds β-catenin and regulates its subcellular distribution. NLS/NES mutagenesis, leptomycin B treatment, TOPFLASH reporter assay, co-immunoprecipitation, fluorescence microscopy Journal of cell science Medium 16968744
2015 KANK1 (and KANK2, KANK4) localize to podocytes in rat glomeruli, and KANK1 partially colocalizes with synaptopodin. KANK2 interacts with ARHGDIA (a RHO GTPase regulator) in rat glomeruli and cultured human podocytes; knockdown of KANK2 increases active GTP-bound RHOA and decreases podocyte migration, placing KANK proteins upstream of RHO GTPase signaling in podocyte function. Immunofluorescence localization in rat/human tissue, co-immunoprecipitation, GTP-RhoA pulldown assay, siRNA knockdown, cell migration assay, Drosophila nephrocyte RNAi screen, zebrafish knockdown The Journal of clinical investigation High 25961457
2017 KANK1 depletion induces centrosomal amplification and cytokinesis failure (multinucleate/micronuclei cells). KANK1 interacts with Daam1 (a RhoA activator in actin assembly); KANK1 knockdown or Daam1 overexpression each hyperactivate RhoA, leading to dysregulation of Aurora-A activity and centrosomal amplification. KANK1 is also associated with contractile ring formation. siRNA knockdown, co-immunoprecipitation (KANK1–Daam1), RhoA activity assay, centrosome counting, Aurora-A activity measurement, overexpression Experimental cell research Medium 28284839
2021 TRAIP (an E3 ubiquitin ligase) promotes KANK1 polyubiquitination and subsequent proteasomal degradation in osteosarcoma cells, leading to downregulation of IGFBP3 and activation of the AKT pathway. Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor treatment, Western blotting, overexpression/knockdown in osteosarcoma cells Cell death & disease Medium 34349117
2017 Restoration of KANK1 in human MPNST cells inhibits cell growth by increasing apoptosis. RNA-seq identified CXXC5 as a KANK1-regulated downstream gene; knockdown of CXXC5 diminished KANK1-induced apoptosis, placing CXXC5 downstream of KANK1 in the apoptosis pathway. Stable KANK1 re-expression, xenograft assay, RNA-seq, siRNA knockdown of CXXC5, apoptosis assay Scientific reports Medium 28067315
2014 Drosophila Kank (ortholog of human KANK1) binds EB1 directly; this interaction is essential for Kank localization to microtubule plus ends in cultured cells. In late embryos, Drosophila Kank accumulates at muscle–tendon attachment sites. Direct binding assay (pulldown), site-directed mutagenesis of EB1-binding motif, live fluorescence imaging in cultured cells and embryos, genetic deletion mutant PloS one Medium 25203404
2011 KANK1-PDGFRβ fusion protein (from t(5;9) translocation) constitutively activates STAT5 and ERK in hematopoietic cells independently of JAK2. The three N-terminal coiled-coil domains of KANK1 are required for KANK1-PDGFRβ-induced cell growth and signaling; the fusion protein forms homotrimeric and higher-order oligomeric complexes via multiple oligomerization domains. Retroviral transduction of Ba/F3 and CD34+ cells, JAK inhibitor treatment, mutagenesis of coiled-coil domains, size-exclusion chromatography/co-immunoprecipitation, phosphorylation assays Haematologica Medium 21685469
2022 Depletion of KANK1 in C2C12 myoblasts increases filamentous actin (F-actin) accumulation and promotes nuclear localization of YAP1 by reducing YAP1 phosphorylation, activating YAP1 target genes, accelerating proliferation, and blocking myogenic differentiation. This places KANK1 upstream of F-actin–YAP1 in the mechanotransduction pathway controlling myoblast fate. siRNA knockdown (siKank1), F-actin staining (phalloidin), YAP1 phosphorylation/localization analysis by Western blot and immunofluorescence, qRT-PCR, myotube formation assay Cells Medium 35805114
2019 KANK1 overexpression in OSCC cells inhibits proliferation and increases apoptosis. YAP overexpression reverses these effects, placing YAP downstream of KANK1 in OSCC growth suppression. Overexpression, siRNA knockdown, apoptosis assay, mitochondrial membrane potential measurement, in vivo xenograft, rescue by YAP overexpression Journal of cellular physiology Medium 31338836
2023 In neurons, the KIF21A–KANK1 interaction is critical for dendritic spine morphogenesis and synaptic plasticity. Knockdown of either KIF21A or KANK1 inhibits dendritic spine morphogenesis and dendritic branching; these deficits are rescued by full-length protein but not by binding-deficient mutants (disrupting KIF21A–KANK1 or KANK1–talin1 interaction). In vivo hippocampal KIF21A knockdown impairs LTP amplitude and spatial cognition. siRNA knockdown with full-length and binding-deficient mutant rescue, confocal imaging of spine morphology, electrophysiology (LTP), rat hippocampal in vivo stereotaxic injection, behavior testing Neural regeneration research Medium 38767486
2025 KANK1 is locally enriched at the β-cell capillary interface and its knockdown disrupts subcellular localization of liprin-α1, reduces glucose-induced insulin secretion, and causes mistargeting of insulin granule fusion. KANK1 acts as a component of a complex linking focal adhesion protein talin to liprin-β1, which in turn anchors liprin-α1 through its C-terminus. siRNA knockdown, immunofluorescence imaging, glucose-stimulated insulin secretion assay, co-immunoprecipitation The Journal of biological chemistry Medium 41380968
2024 In mammary tumor cells, when cells lose basement membrane contact and disassemble integrin adhesions, KANK1 is found at cell-cell junctions where it competes with the polarity protein Scribble for NOS1AP binding, thereby curbing Scribble's ability to promote Hippo pathway activity, leading to TAZ stabilization and nuclear accumulation. In vivo PyMT mouse tumor model, co-immunoprecipitation, immunofluorescence imaging, Hippo pathway reporter, KANK1 knockout/knockdown Nature communications High 39613731
2024 KANK1 haploinsufficiency (achieved via CRISPR/Cas9 genome editing) increases centrosome amplification in a dose-dependent manner; complete KANK1 knockout was not achievable, suggesting essentiality. Rescue with KANK1-expressing plasmid restores normal centrosome numbers. EGR1 knockdown also increases centrosome amplification and reduces KANK1 protein, suggesting a functional link. CRISPR/Cas9 genome editing, rescue by plasmid expression, centrosome counting, siRNA (EGR1), RNA-seq Biochimica et biophysica acta. General subjects Medium 38830559
2025 The intrinsically disordered linker L2 of KANK1 contains multiple weak LC8-binding motifs; cooperative multivalent binding to the hub protein LC8 converts the disordered L2 into an elongated, rigid, rod-like assembly (~35–50 nm) sufficient to bridge the membrane–microtubule gap at focal adhesions. Isolated single motif peptides do not bind LC8 at physiological concentrations, demonstrating cooperativity is required. In-cell assays, biochemical binding assays, biophysical assays, AlphaFold-based motif prediction, electron microscopy structural analysis bioRxiv (preprint)preprint Medium bio_10.1101_2025.07.16.665182
2020 KANK1 localizes to the basal side of epithelial cells in all mouse tissues tested, as determined by subcellular fractionation and immunofluorescence on tissue sections. KANK1 protein localization is distinct from other KANK family members (KANK2 in mesenchymal cells, KANK3 in endothelial cells, KANK4 in smooth muscle/pericytes). Immunofluorescence on mouse tissue sections, subcellular fractionation, Western blotting Experimental cell research Medium 33253712
2002 Expression of KANK1 in expression-negative HEK293 cells induced growth retardation at G0/G1 and morphological changes, establishing its function as a growth suppressor. Loss of expression was found due to CpG methylation, with a two-hit mechanism (methylation then deletion). Stable transfection/re-expression, cell cycle analysis (flow cytometry), RT-PCR, Western blotting, methylation analysis The Journal of biological chemistry Medium 12133830

Source papers

Stage 0 corpus · 57 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 KANK deficiency leads to podocyte dysfunction and nephrotic syndrome. The Journal of clinical investigation 155 25961457
2016 Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions. eLife 153 27410476
2005 Deletion of the ANKRD15 gene at 9p24.3 causes parent-of-origin-dependent inheritance of familial cerebral palsy. Human molecular genetics 107 16301218
2008 Kank regulates RhoA-dependent formation of actin stress fibers and cell migration via 14-3-3 in PI3K-Akt signaling. The Journal of cell biology 100 18458160
2002 A novel ankyrin repeat-containing gene (Kank) located at 9p24 is a growth suppressor of renal cell carcinoma. The Journal of biological chemistry 87 12133830
2009 Kank proteins: structure, functions and diseases. Cellular and molecular life sciences : CMLS 85 19554261
2020 CircDDX17 reduces 5-fluorouracil resistance and hinders tumorigenesis in colorectal cancer by regulating miR-31-5p/KANK1 axis. European review for medical and pharmacological sciences 49 32141542
2009 Kank attenuates actin remodeling by preventing interaction between IRSp53 and Rac1. The Journal of cell biology 44 19171758
2007 Kank proteins: a new family of ankyrin-repeat domain-containing proteins. Biochimica et biophysica acta 43 17996375
2011 Effects of brefeldin A-inhibited guanine nucleotide-exchange (BIG) 1 and KANK1 proteins on cell polarity and directed migration during wound healing. Proceedings of the National Academy of Sciences of the United States of America 34 22084092
2021 TRAIP modulates the IGFBP3/AKT pathway to enhance the invasion and proliferation of osteosarcoma by promoting KANK1 degradation. Cell death & disease 32 34349117
2017 KANK1 inhibits cell growth by inducing apoptosis through regulating CXXC5 in human malignant peripheral nerve sheath tumors. Scientific reports 30 28067315
2009 A major mutation of KIF21A associated with congenital fibrosis of the extraocular muscles type 1 (CFEOM1) enhances translocation of Kank1 to the membrane. Biochemical and biophysical research communications 30 19559006
2019 Force-Dependent Regulation of Talin-KANK1 Complex at Focal Adhesions. Nano letters 29 31389241
2006 Nucleo-cytoplasmic shuttling of human Kank protein accompanies intracellular translocation of beta-catenin. Journal of cell science 29 16968744
2018 The Kank family proteins in adhesion dynamics. Current opinion in cell biology 28 29909279
2017 Structural insights into ankyrin repeat-mediated recognition of the kinesin motor protein KIF21A by KANK1, a scaffold protein in focal adhesion. The Journal of biological chemistry 25 29217769
2012 The last step of kanamycin biosynthesis: unique deamination reaction catalyzed by the α-ketoglutarate-dependent nonheme iron dioxygenase KanJ and the NADPH-dependent reductase KanK. Angewandte Chemie (International ed. in English) 25 22374809
2020 KANK1 regulates paclitaxel resistance in lung adenocarcinoma A549 cells. Artificial cells, nanomedicine, and biotechnology 21 32064933
2011 Multiple oligomerization domains of KANK1-PDGFRβ are required for JAK2-independent hematopoietic cell proliferation and signaling via STAT5 and ERK. Haematologica 21 21685469
2016 Evolutionary and developmental analysis reveals KANK genes were co-opted for vertebrate vascular development. Scientific reports 20 27292017
2013 Familial KANK1 deletion that does not follow expected imprinting pattern. European journal of medical genetics 20 23454270
2019 Aberrant Kank1 expression regulates YAP to promote apoptosis and inhibit proliferation in OSCC. Journal of cellular physiology 19 31338836
2017 In vivo and in vitro inhibition of human gastric cancer progress by upregulating Kank1 gene. Oncology reports 19 28731169
2005 Pathological characterization of Kank in renal cell carcinoma. Experimental and molecular pathology 19 15596059
2020 KANK family proteins in cancer. The international journal of biochemistry & cell biology 18 33309958
2022 Kank1 Is Essential for Myogenic Differentiation by Regulating Actin Remodeling and Cell Proliferation in C2C12 Progenitor Cells. Cells 16 35805114
2014 Upregulation of the Kank1 gene-induced brain glioma apoptosis and blockade of the cell cycle in G0/G1 phase. International journal of oncology 16 24399197
2018 Clinical significance of copy number variants involving KANK1 in patients with neurodevelopmental disorders. European journal of medical genetics 15 29729439
2017 Structural analyses of key features in the KANK1·KIF21A complex yield mechanistic insights into the cross-talk between microtubules and the cell cortex. The Journal of biological chemistry 15 29158259
2017 Structural basis for the recognition of kinesin family member 21A (KIF21A) by the ankyrin domains of KANK1 and KANK2 proteins. The Journal of biological chemistry 15 29183992
2020 Long non-coding RNA CASC2 enhances cisplatin sensitivity in oral squamous cell cancer cells by the miR-31-5p/KANK1 axis. Neoplasma 14 32787433
2018 Upregulation of the Kank1 gene inhibits human lung cancer progression in vitro and in vivo. Oncology reports 14 29956815
2023 KANK1 shapes focal adhesions by orchestrating protein binding, mechanical force sensing, and phase separation. Cell reports 13 37874676
2021 LncRNA-ENST00000421645 Upregulates Kank1 to Inhibit IFN-γ Expression and Promote T Cell Apoptosis in Neurosyphilis. Frontiers in microbiology 12 34917045
2023 The structural basis of the talin-KANK1 interaction that coordinates the actin and microtubule cytoskeletons at focal adhesions. Open biology 11 37339751
2015 Interstitial 9p24.3 deletion involving only DOCK8 and KANK1 genes in two patients with non-overlapping phenotypic traits. European journal of medical genetics 11 26656975
2005 Alternative splicing of the human Kank gene produces two types of Kank protein. Biochemical and biophysical research communications 11 15823577
2014 Kank Is an EB1 interacting protein that localises to muscle-tendon attachment sites in Drosophila. PloS one 10 25203404
2023 The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons. Neural regeneration research 9 38767486
2017 Depletion of tumor suppressor Kank1 induces centrosomal amplification via hyperactivation of RhoA. Experimental cell research 9 28284839
2016 Enrichment of small pathogenic deletions at chromosome 9p24.3 and 9q34.3 involving DOCK8, KANK1, EHMT1 genes identified by using high-resolution oligonucleotide-single nucleotide polymorphism array analysis. Molecular cytogenetics 9 27891178
2024 A germline chimeric KANK1-DMRT1 transcript derived from a complex structural variant is associated with a congenital heart defect segregating across five generations. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 8 38504027
2015 Kank1 reexpression induced by 5-Aza-2'-deoxycytidine suppresses nasopharyngeal carcinoma cell proliferation and promotes apoptosis. International journal of clinical and experimental pathology 8 25973051
2020 KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas. BMC medical genetics 7 33046021
2020 Tissue distribution and subcellular localization of the family of Kidney Ankyrin Repeat Domain (KANK) proteins. Experimental cell research 7 33253712
2024 KANK1 promotes breast cancer development by compromising Scribble-mediated Hippo activation. Nature communications 4 39613731
2024 Potential involvement of KANK1 haploinsufficiency in centrosome aberrations. Biochimica et biophysica acta. General subjects 3 38830559
2024 Response of a Novel KANK1::ALK Fusion to Alectinib in an Advanced Lung Adenocarcinoma: A Case Report. Journal of the National Comprehensive Cancer Network : JNCCN 2 38364363
2024 cNPAS2 induced β cell dysfunction by regulating KANK1 expression in type 2 diabetes. World journal of diabetes 2 39280178
2023 Loss of the KN Motif and AnKyrin Repeat Domain 1 (KANK1) Leads to Lymphoid Compartment Dysregulation in Murine Model. Genes 2 37895296
2021 Case Report: A Pancreatic Ductal Adenocarcinoma Patient With Concurrent Targetable Somatic Novel KANK1-ALK, UPP2-NTRK3 Fusion, and Pathogenetic Germline BRCA Mutation. Frontiers in oncology 2 34671564
2019 Small interstitial 9p24.3 deletions principally involving KANK1 are likely benign copy number variants. European journal of medical genetics 2 30684669
2025 Identification of KANK1 as a tumor suppressor gene in pancreatic ductal adenocarcinoma. Biochemical and biophysical research communications 1 40288262
2025 KANK1 regulates the positioning of liprin-α1 and the spatial organization of insulin granule fusion in pancreatic β cells. The Journal of biological chemistry 0 41380968
2023 A germline chimeric KANK1-DMRT1 transcript derived from a complex structural variant is associated with a congenital heart defect segregating across five generations. Research square 0 38168413
2022 Long non-coding RNA H19X promotes tumorigenesis and metastasis of colorectal cancer through regulating the miR-503-5p/KANK1 axis. Genes & genomics 0 35567714

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