| 2016 |
KANK1 directly binds to 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 disrupting KANK1 binding abolishes this recruitment without affecting talin's adhesion function. |
Structural studies (crystal structure), Co-IP, single point mutagenesis, fluorescence microscopy |
eLife |
High |
27410476
|
| 2008 |
KANK1 is an Akt substrate downstream of PI3K; Akt-mediated phosphorylation of KANK1 promotes its binding to 14-3-3 proteins, which inhibits KANK1's suppression of RhoA activity, actin stress fiber formation, and insulin-induced cell migration. |
Kinase assay, co-immunoprecipitation, overexpression/co-expression in NIH3T3 cells, RhoA activity assay (GST-rhotekin pulldown), migration assay |
The Journal of cell biology |
High |
18458160
|
| 2009 |
KANK1 binds IRSp53 and specifically inhibits the IRSp53–Rac1 interaction, suppressing lamellipodia formation without affecting filopodia (Cdc42-dependent), thereby negatively regulating actin remodeling and cell spreading. |
Co-immunoprecipitation, GST pulldown, RNAi knockdown, overexpression, microscopy |
The Journal of cell biology |
High |
19171758
|
| 2017 |
Crystal structure of the KANK1 ankyrin repeat domain (ANKRD) in complex with a KIF21A peptide revealed that target recognition involves combinatorial use of two interfaces; mutations at either interface disrupt the KANK1–KIF21A interaction and prevent KIF21A recruitment to focal adhesions. |
X-ray crystallography (high-resolution crystal structure), mutagenesis, biochemical binding assays, immunofluorescence localization |
The Journal of biological chemistry |
High |
29217769
|
| 2017 |
Crystal structure of the KANK1·KIF21A complex at 2.1 Å showed that a five-helix-bundle-capping domain immediately preceding the ANK repeats forms a supramodule with the ANK repeats to bind a conserved KIF21A peptide; cancer-associated missense mutations at this interface destabilize the complex. |
X-ray crystallography, biochemical assays, mutagenesis |
The Journal of biological chemistry |
High |
29158259
|
| 2017 |
The KANK2 ankyrin domain binds the same ~22 amino acid KIF21A peptide as KANK1; both complex structures show KIF21A adopting helical conformations upon binding to two distinct pockets of the ankyrin domain. |
X-ray crystallography, site-directed mutagenesis, biochemical binding assays |
The Journal of biological chemistry |
High |
29183992
|
| 2019 |
The talin R7–KANK1 KN domain complex can withstand physiological forces (up to 10 pN) for seconds to minutes under shear-force geometry; mechanical stretching promotes KANK1 localization to the periphery of focal adhesions rather than the center. |
Magnetic tweezers single-molecule force spectroscopy, cell biology (live cell imaging, TIRF) |
Nano letters |
High |
31389241
|
| 2009 |
KANK1 interacts with the third and fourth coiled-coil domains of KIF21A via its ankyrin-repeat domain; KIF21A controls the subcellular distribution of KANK1, with KIF21A knockdown causing KANK1 to remain cytosolic, and the CFEOM1-associated KIF21A R954W mutation significantly enhancing KANK1 translocation to the membrane fraction. |
Co-immunoprecipitation, subcellular fractionation, siRNA knockdown, Western blotting |
Biochemical and biophysical research communications |
Medium |
19559006
|
| 2011 |
KANK1 physically and functionally associates with BIG1 (a guanine nucleotide-exchange factor for ARFs); depletion of either BIG1 or KANK1 similarly disrupts directed cell migration and Golgi/MTOC orientation toward the wound edge, indicating both function in maintaining cell polarity during migration. |
Reciprocal co-immunoprecipitation, siRNA depletion, wound-healing migration assay, Golgi/MTOC orientation imaging |
PNAS |
Medium |
22084092
|
| 2006 |
KANK1 contains functional nuclear localization signals (NLS1, NLS2) and nuclear export signals (NES1–NES3); nuclear export is CRM1-dependent (blocked by leptomycin B); KANK1 binds β-catenin and its nuclear import correlates with activation of β-catenin-dependent transcription (TOPFLASH reporter). |
NLS/NES mutagenesis, leptomycin B treatment, TOPFLASH reporter assay, co-immunoprecipitation, immunofluorescence |
Journal of cell science |
Medium |
16968744
|
| 2017 |
KANK1 knockdown causes centrosomal amplification and cytokinesis failure via hyperactivation of RhoA; KANK1 interacts with Daam1 (a RhoA activator), and excess Daam1 upon KANK1 loss hyperactivates RhoA, elevating Aurora-A activity and leading to abnormal centrosome numbers and multinucleate cells. |
RNAi knockdown, co-immunoprecipitation (KANK1–Daam1), RhoA activity assay, centrosome counting, Aurora-A activity measurement |
Experimental cell research |
Medium |
28284839
|
| 2015 |
In rat glomeruli and cultured human podocytes, KANK2 interacts with ARHGDIA (a RHO GTPase regulator); KANK2 knockdown increases active GTP-bound RHOA and decreases podocyte migration; RNAi of the Drosophila KANK homolog disrupts slit diaphragm and lacuna channel structures in nephrocytes. |
Co-immunoprecipitation, RhoA activity assay (GTP-pulldown), RNAi in Drosophila nephrocytes, zebrafish kank2 morpholino knockdown, immunofluorescence co-localization |
The Journal of clinical investigation |
Medium |
25961457
|
| 2011 |
The KANK1-PDGFRβ fusion protein (from t(5;9) translocation) constitutively activates STAT5 and ERK1/2 in a JAK2-independent manner; three N-terminal coiled-coil domains of KANK1 are required for KANK1-PDGFRβ-induced oligomerization (homotrimers and heavier oligomers), signaling, and hematopoietic cell growth. |
Retroviral transduction of Ba/F3 cells and CD34+ progenitors, JAK inhibitor treatment, phosphorylation assays, mutagenesis of coiled-coil domains, gel filtration oligomerization analysis |
Haematologica |
Medium |
21685469
|
| 2023 |
KANK1 structures in complex with talin R7 and liprin-β were determined; KANK1 undergoes liquid-liquid phase separation (LLPS) important for its localization at the focal adhesion edge; KANK1 scaffolds the FA core and associated proteins to modulate FA shape in response to mechanical force. |
X-ray crystallography, biochemical assays, LLPS assay, cell biological analysis (immunofluorescence, live-cell imaging) |
Cell reports |
High |
37874676
|
| 2023 |
The talin-KANK1 complex structure revealed a novel β-hairpin motif in the KN region of KANK1 that stabilizes its α-helical talin-binding interface with high affinity; actomyosin forces on talin exclude KANK1 from the FA center while retaining it at the adhesion periphery (adhesion belt). |
Non-covalent crystallographic chaperone approach (crystal structure), site-directed mutagenesis, myosin inhibitor treatment, constitutively active vinculin expression, immunofluorescence |
Open biology |
High |
37339751
|
| 2014 |
Drosophila Kank (ortholog of human KANK1) directly binds EB1, and this interaction is essential for Kank localization to microtubule plus ends in cultured cells; in late embryos Kank accumulates at muscle-tendon attachment sites. |
Direct binding assay, immunofluorescence, deletion mutant analysis |
PloS one |
Medium |
25203404
|
| 2021 |
TRAIP promotes polyubiquitination and proteasomal degradation of KANK1, leading to downregulation of IGFBP3 and activation of the AKT pathway, thereby enhancing osteosarcoma cell invasion and proliferation. |
Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor treatment, KANK1 overexpression/knockdown, AKT pathway readouts |
Cell death & disease |
Medium |
34349117
|
| 2022 |
In C2C12 myoblasts, KANK1 depletion increases F-actin accumulation and promotes nuclear localization of YAP1 by reducing YAP1 phosphorylation in the cytoplasm, activating YAP1 target genes and promoting proliferation while inhibiting myogenic differentiation. |
siRNA knockdown, F-actin staining (phalloidin), YAP1 phosphorylation/localization by immunofluorescence and western blot, myogenic marker expression, myotube formation assay |
Cells |
Medium |
35805114
|
| 2017 |
KANK1 restoration in MPNST cells induces apoptosis and inhibits growth via upregulation of CXXC5; knockdown of CXXC5 diminishes KANK1-induced apoptosis, placing CXXC5 downstream of KANK1 in apoptosis signaling. |
Overexpression and knockdown in cell lines, xenograft assay, RNA-seq, CXXC5 siRNA epistasis |
Scientific reports |
Medium |
28067315
|
| 2025 |
KANK1 is locally enriched at the β-cell capillary interface and forms a complex linking talin (focal adhesion) to liprin-β1 (which anchors liprin-α1); KANK1 knockdown disrupts liprin-α1 subcellular localization, reduces glucose-induced insulin secretion, and misdirects insulin granule fusion away from the capillary interface. |
siRNA knockdown, co-immunoprecipitation, immunofluorescence localization, live-cell TIRF imaging of granule fusion, insulin secretion assay |
The Journal of biological chemistry |
Medium |
41380968
|
| 2023 |
The KIF21A–KANK1 interaction is critical for dendritic spine morphogenesis and synaptic plasticity in neurons; knockdown of KIF21A or KANK1 inhibits spine morphogenesis and dendritic branching, rescued only by wild-type proteins but not by binding-deficient mutants (disrupting KIF21A–KANK1 or KANK1–talin1 interfaces). |
siRNA knockdown in neurons, rescue with binding-deficient mutants, LTP recording, cognitive behavioral assay |
Neural regeneration research |
Medium |
38767486
|
| 2024 |
KANK1 localizes to the basal side of BM-attached epithelial tumor cells; upon BM contact loss, KANK1 relocates to cell-cell junctions where it competes with Scribble for NOS1AP binding, thereby reducing Scribble's ability to activate the Hippo pathway, leading to TAZ nuclear accumulation and tumor cell survival. |
In vivo PyMT mammary tumor model, KANK1 knockout, co-immunoprecipitation (KANK1–NOS1AP, Scribble–NOS1AP competition), TAZ/YAP nuclear localization assay, Hippo pathway reporters |
Nature communications |
High |
39613731
|
| 2025 |
The hub protein LC8 binds multiple weak motifs in the intrinsically disordered linker L2 of KANK1 cooperatively, converting this ~600 aa disordered region into an elongated rod-like assembly (~35–50 nm) long enough to bridge the membrane–microtubule gap at focal adhesions. |
In-cell assays, biochemical binding assays, AlphaFold multivalent assembly prediction, electron microscopy structural analysis |
bioRxivpreprint |
Medium |
|