Affinage

GAK

Cyclin-G-associated kinase · UniProt O14976

Length
1311 aa
Mass
143.2 kDa
Annotated
2026-06-10
53 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GAK (cyclin G-associated kinase) is a constitutively active Ser/Thr kinase that operates as an essential cofactor in clathrin-mediated membrane trafficking, organizing the assembly, remodeling, and disassembly of clathrin lattices through its modular architecture comprising an N-terminal kinase domain and a C-terminal clathrin-binding/J-domain and PTEN-like domain (PMID:9013862, PMID:24438162). At clathrin-coated pits, GAK is transiently recruited after dynamin via phospholipid binding through its PTEN-like domain, and its J-domain recruits and activates Hsc70 to drive early curvature-enabling remodeling of nascent flat lattices as well as late uncoating; J-domain mutations that abolish Hsc70 recruitment trap GAK at pits and block CCP stabilization and invagination, generating abortive pits (PMID:16895969, PMID:40424130). GAK loss reduces receptor-mediated endocytosis and depletes AP2/epsin and TGN adaptors, placing GAK upstream of Hsc70 in adaptor recruitment, and GAK directly phosphorylates the AP2 mu2 subunit AP2M1 within coated vesicles (PMID:12010461, PMID:16155256). The C-terminal clathrin-binding and J-domains alone suffice to rescue clathrin-dependent trafficking and organismal viability, establishing the PTEN-like domain as dispensable for Hsc70-dependent uncoating (PMID:26345367). Beyond endocytosis, GAK directly phosphorylates the Na+/K+-ATPase alpha-subunit Atp1a3 to control pump trafficking in neurons (PMID:30623173), cooperates with clathrin during mitosis to maintain centrosome integrity, chromosome congression, and astral-microtubule-dependent spindle positioning (PMID:19654208, PMID:31253758), and supports autophagic and mitophagic pathways: its kinase activity drives PRKN-independent mitophagy and lysosomal remodeling (PMID:34671015), it interacts with ULK1/Atg1 via its uncoating domain to govern Atg9 trafficking (PMID:37428930), and its intrinsically disordered region binds the RhoA-GEF ARHGEF2 to antagonize ROCK-dependent actomyosin dynamics independently of catalysis (PMID:41995027). GAK kinase activity is essential in vivo, as kinase-dead knock-in mice die at birth from pulmonary surfactant defects (PMID:22022498), and GAK protein abundance is controlled by FBXO22-mediated ubiquitin-dependent proteasomal degradation (PMID:37442264).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 High

    Established GAK as a kinase physically partnered with cell-cycle machinery, framing it as a potential cell-cycle regulator and defining its domain architecture.

    Evidence Co-IP and BIAcore showing direct GAK–cyclin G binding; domain mapping of N-terminal kinase and C-terminal tensin/auxilin-like domains

    PMID:9013862 PMID:9299234

    Open questions at the time
    • Functional consequence of the cyclin G/CDK5 association not established
    • Substrates of the kinase activity not identified at this stage
  2. 2002 High

    Identified GAK as a clathrin-coated-vesicle-associated kinase with a defined substrate, connecting its catalytic activity to adaptor function.

    Evidence In vitro kinase assays on purified brain CCVs and recombinant AP2M1 (mu2)

    PMID:12010461

    Open questions at the time
    • Phenotypic consequence of mu2 phosphorylation in cells not yet shown
    • Did not address GAK recruitment to pits
  3. 2005 High

    Demonstrated GAK is required for clathrin-mediated endocytosis and adaptor recruitment, positioning it upstream of Hsc70.

    Evidence shRNA knockdown in HeLa with transferrin/EGF uptake, adaptor localization, and dominant-negative Hsp70 epistasis

    PMID:16155256

    Open questions at the time
    • Did not resolve the temporal step of GAK action at pits
    • Direct vs indirect effects on adaptor recruitment not separated
  4. 2006 High

    Resolved the timing of GAK at coated pits and the role of its lipid-binding domain, distinguishing recruitment from uncoating.

    Evidence TIRF live imaging, PTEN-like domain phospholipid-binding assays, actin depolymerization perturbation

    PMID:16895969

    Open questions at the time
    • Mechanistic link between GAK flashing and curvature generation not yet defined
    • Role of J-domain in early remodeling not addressed
  5. 2009 High

    Extended GAK's repertoire beyond endocytosis to mitosis, showing it cooperates with clathrin to maintain spindle and centrosome integrity, and identified nuclear complexes.

    Evidence siRNA knockdown with spindle/centrosome phenotyping and mitotic Co-IP; GST pulldown of nuclear cyclin G1/p53/CHC/PP2A complexes

    PMID:19371378 PMID:19654208

    Open questions at the time
    • Molecular basis of GAK–clathrin cooperation in spindle formation not defined
    • Functional role of nuclear GAK complexes not established
  6. 2011 High

    Established that GAK kinase activity is essential for organismal viability and tissue-specific function.

    Evidence Kinase-dead knock-in mice with immunohistochemistry of pulmonary surfactant and adhesion/signaling markers

    PMID:22022498

    Open questions at the time
    • Direct substrate underlying the lung phenotype not identified
    • Cell-type-specific contributions not dissected
  7. 2014 High

    Defined the structural basis of GAK as a constitutively active kinase with a plastic catalytic domain and inhibitor-binding mode.

    Evidence X-ray crystallography of apo, nanobody-bound, and inhibitor-bound forms with enzyme kinetics

    PMID:24438162 PMID:25822739

    Open questions at the time
    • Structures cover the catalytic domain, not full-length GAK or its C-terminal domains
    • Physiological relevance of the inactive dimeric state unresolved
  8. 2015 High

    Showed the clathrin-binding/J-domain fragment is sufficient for clathrin chaperoning and viability, ranking domain contributions to function.

    Evidence Conditional knockout mice with 62-kDa GAK fragment rescue and fibroblast trafficking assays

    PMID:26345367

    Open questions at the time
    • Functions requiring the PTEN-like or kinase domains in other contexts not covered
    • Did not address non-endocytic roles
  9. 2018 High

    Identified a second direct GAK substrate and a physiological trafficking role in neurons, broadening its kinase function beyond adaptors.

    Evidence Analog-sensitive kinase chemical genetics, conditional KO neuron electrophysiology, trafficking assays

    PMID:30623173

    Open questions at the time
    • Whether Atp1a3 phosphorylation acts via clathrin pathway not fully resolved
    • Phosphosite on Atp1a3 not mapped
  10. 2021 High

    Connected GAK kinase activity to selective mitophagy and lysosomal/autophagic dynamics, revealing a degradative-pathway role.

    Evidence siRNA/kinase-dead rescue, CRISPR KO, mitophagy reporters, C. elegans and zebrafish loss-of-function, ROCK epistasis

    PMID:34468012 PMID:34671015

    Open questions at the time
    • Direct substrate driving mitophagy/lysosomal remodeling not identified
    • Relationship between mitophagy role and clathrin function unclear
  11. 2023 High

    Mapped GAK to the autophagy initiation machinery via a direct ULK1/Atg1 interaction controlling Atg9 trafficking, and identified its regulated turnover.

    Evidence Co-IP with domain mapping (uncoating domain–ULK1), Drosophila/microglia loss-of-function; separately proteomics, ubiquitination and proteasome assays for FBXO22

    PMID:37428930 PMID:37442264

    Open questions at the time
    • Whether GAK phosphorylates ULK1/Atg9 directly not established here
    • FBXO22-driven degradation not linked to a specific GAK function
  12. 2025 High

    Defined an early, J-domain/Hsc70-dependent remodeling step required for coated-pit curvature, distinguishing it from late uncoating.

    Evidence GAK knockdown and J-domain point mutations with quantitative live TIRF CCP lifetime analysis

    PMID:40424130

    Open questions at the time
    • Direct demonstration of pentagon incorporation by GAK–Hsc70 not provided
    • Kinase contribution to this step not dissected
  13. 2026 High

    Revealed a kinase-independent function of GAK's disordered region in regulating actomyosin contractility through a RhoA-GEF.

    Evidence CRISPR KO with IDR-vs-kinase-dead rescue, ARHGEF2 Co-IP, ROCK inhibitor and ARHGEF2 knockdown epistasis, migration assays

    PMID:41995027

    Open questions at the time
    • Structural basis of GAK IDR–ARHGEF2 binding not defined
    • How actomyosin regulation integrates with endocytic/autophagic roles unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GAK's distinct domains and its catalytic versus scaffolding activities are coordinated across endocytosis, mitosis, autophagy, and cytoskeletal regulation remains unresolved.
  • Full-length GAK structure and inter-domain regulation unknown
  • Complete in vivo substrate set beyond AP2M1 and Atp1a3 not defined
  • Mechanistic switch governing context-specific functions not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0044183 protein folding chaperone 2 GO:0060090 molecular adaptor activity 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0008289 lipid binding 1
Localization
GO:0005634 nucleus 2 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2 GO:0005764 lysosome 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9612973 Autophagy 3 R-HSA-1640170 Cell Cycle 2 R-HSA-9609507 Protein localization 2 R-HSA-382551 Transport of small molecules 1
Partners
AP2M1ARHGEF2CCNG1CLTCFBXO22HSPA8MCM3ULK1
Complex memberships
AP2 adaptor complexclathrin-coated vesicle

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 GAK (cyclin G-associated kinase) directly associates with cyclin G and CDK5 in vivo. Co-immunoprecipitation and BIAcore analysis demonstrated the direct GAK–cyclin G interaction. GAK harbors an N-terminal Ser/Thr protein kinase domain and a C-terminal tensin/auxilin-like domain with a leucine zipper region. Co-immunoprecipitation, Western blotting, BIAcore surface plasmon resonance, West-Western blotting FEBS letters High 9013862
1997 GAK kinase activity (from anti-cyclin G immunoprecipitates) fluctuates during the cell cycle with a peak at G1 phase, even though cyclin G expression remains nearly constant, indicating cell-cycle-regulated kinase activity. Synchronized HeLa cell-cycle analysis, histone H1 kinase assay on immunoprecipitates Genomics Medium 9299234
2002 GAK/auxilin2 phosphorylates the mu2 (AP2M1) medium subunit of the AP2 adaptor complex both within intact clathrin-coated vesicles (CCVs) and in solution, establishing GAK as a CCV-associated kinase with AP2M1 as a direct substrate. In vitro kinase assay using purified CCVs and recombinant substrates; kinase activity fractionation from porcine brain CCVs Traffic (Copenhagen, Denmark) High 12010461
2005 GAK knockdown by shRNA in HeLa cells markedly reduces internalization of transferrin and EGF (receptor-mediated endocytosis), decreases perinuclear clathrin at the trans-Golgi network, reduces the number and dynamics of plasma membrane clathrin-coated pits, and dramatically reduces AP2 and epsin on the plasma membrane and AP1/GGA at the TGN. Expression of dominant-negative Hsp70 phenocopies this, placing GAK upstream of Hsc70 in clathrin/adaptor recruitment. Vector-based shRNA knockdown, fluorescence microscopy, transferrin/EGF internalization assays, dominant-negative Hsp70 expression Journal of cell science High 16155256
2006 GAK is transiently recruited to clathrin-coated pits after dynamin recruitment and before pit invagination, as directly visualized by TIRF microscopy. GAK recruitment depends on its PTEN-like domain, which binds phospholipids. Synchronous recruitment of GAK (and subsequent Hsc70 recruitment) is required for irreversible clathrin uncoating; actin depolymerization prevents scission and irreversible uncoating despite repeated GAK flashing. Total internal reflectance fluorescence (TIRF) microscopy, phospholipid-binding assays, actin depolymerization experiments Journal of cell science High 16895969
2009 GAK localizes to both the cytoplasm and nucleus. In the nucleus, GAK forms complexes with cyclin G1, p53, clathrin heavy chain (CHC), and PP2A B'alpha1. CHC associates with GAK via a different domain depending on whether it is cytoplasmic or nuclear. Immunostaining, GFP-GAK ectopic expression, GST pulldown assays with dissected GAK fragments, co-immunoprecipitation Genes to cells Medium 19371378
2009 GAK is required for proper centrosome maturation and mitotic chromosome congression. GAK knockdown by siRNA causes metaphase arrest via spindle-assembly checkpoint activation, multi-aster formation from abnormal pericentriolar material fragmentation (not centriole fragmentation), and chromosome misalignment. GAK and clathrin heavy chain interact during mitosis and cooperate in the same pathway to regulate functional spindle formation. siRNA knockdown, cell-cycle analysis, immunofluorescence, co-immunoprecipitation during mitosis Journal of cell science High 19654208
2010 In zebrafish, GAK (but not auxilin alone) knockdown by morpholino increases neuronal cell specification and decreases expression of the Notch target gene Her4, indicating that GAK function is required for Notch-dependent neuronal patterning. GAK knockdown also causes elevated apoptosis in neural tissues. Morpholino-mediated knockdown in zebrafish, in situ hybridization for Notch target genes, functional complementation with Drosophila auxilin BMC developmental biology Medium 20082716
2011 Mice expressing kinase-dead GAK (GAK-kd) die within 30 minutes after birth due to respiratory dysfunction. Immunohistochemical analysis shows surfactant protein A (SP-A) is absent from alveolar spaces, and E-cadherin/phospho-EGFR signals are abnormal in GAK-kd pups, indicating that GAK kinase activity is required for proper pulmonary alveolar function. Kinase-dead knock-in mouse model, immunohistochemistry, histological analysis PloS one High 22022498
2014 Crystal structures of the GAK catalytic domain alone and in complex with nanobodies revealed: (i) GAK is constitutively active; (ii) the apo structure adopts a dimeric inactive state mediated by an unusual activation segment interaction; (iii) nanobody NbGAK_1 captures the monomeric active conformation with well-ordered activation segment; (iv) GAK has unusually high catalytic domain plasticity; (v) ATP-competitive inhibitors bind in a type I mode. X-ray crystallography, enzyme kinetics, size-exclusion chromatography The Biochemical journal High 24438162
2015 The clathrin-binding and J-domains of GAK (a C-terminal 62-kDa fragment) are sufficient to rescue clathrin-dependent trafficking in GAK-knockout fibroblasts and to rescue lethality/histological defects caused by liver- or brain-specific GAK knockout in mice. When both GAK and auxilin are knocked out in the brain, the 62-kDa GAK fragment maintains viability. This establishes that the PTEN-like domain is dispensable for Hsc70-dependent clathrin chaperoning/uncoating. Conditional knockout mice, transgenic rescue with 62-kDa GAK fragment, histology, trafficking assays in fibroblasts Journal of cell science High 26345367
2015 Isothiazolo[5,4-b]pyridine-based compounds are selective GAK inhibitors acting as ATP-competitive (type I) kinase inhibitors, as determined by co-crystallization. These inhibitors also inhibit two temporally distinct steps in the HCV lifecycle (viral entry and assembly), linking GAK kinase activity to HCV intracellular trafficking. Co-crystallization/X-ray structure, in vitro kinase binding assays, antiviral assays Journal of medicinal chemistry High 25822739
2017 GAK is phosphorylated by c-Src at Y412 and Y1149. GAK-pY412/pY1149 undergoes dynamic subcellular redistribution during mitosis: nucleus during interphase → chromosomes at prophase/prometaphase → centrosomes at metaphase → chromosomes at end of telophase. Mass spectrometry and co-immunoprecipitation identified MCM3 (a DNA licensing factor) as a GAK-interacting partner, suggesting a GAK–c-Src–MCM3 axis in DNA replication licensing. In vivo phosphorylation with anti-phospho-specific antibody, immunofluorescence, mass spectrometry, co-immunoprecipitation Cell cycle (Georgetown, Tex.) Medium 28135906
2018 Using a chemical genetics approach (analog-sensitive kinase), GAK was shown to directly phosphorylate the Na+/K+-ATPase alpha-subunit Atp1a3. GAK regulates trafficking of Na+/K+-ATPase to the plasma membrane, and conditional GAK knockout in CA1 pyramidal neurons results in greater resting membrane potential change upon Na+/K+-ATPase blockade with ouabain, indicating compromised pump function. Chemical genetics (analog-sensitive kinase method), whole-cell patch clamp electrophysiology, conditional knockout mice, trafficking assays Life science alliance High 30623173
2019 GAK depletion leads to impaired astral microtubules and spindle positioning defects, phenocopying depletion of the GAK interactor clathrin, placing GAK and clathrin in the same pathway for spindle positioning in human cells. Live imaging siRNA screen on fibronectin micropatterns, siRNA knockdown, immunofluorescence Nature communications Medium 31253758
2021 GAK kinase activity is required for efficient PRKN-independent mitophagy (but is dispensable for PRKN-dependent mitophagy and starvation-induced autophagy). GAK knockdown/knockout in C. elegans (gakh-1) inhibits basal mitophagy in vivo, demonstrating evolutionary conservation. GAK modifies the mitochondrial network and lysosomal morphology to enable efficient transport of mitochondria for degradation. siRNA screen, kinase-dead mutant rescue, in vivo C. elegans knockdown (gakh-1), zebrafish PRKCD knockout, fluorescence-based mitophagy reporters Nature communications High 34671015
2021 GAK knockout in A549 cells impairs autophagosome–lysosome fusion and autophagic lysosome reformation, causing accumulation of enlarged autophagosomes and autolysosomes during starvation. GAK controls lysosomal dynamics via actomyosin regulation; ROCK1 knockdown or ROCK inhibitor treatment rescues the GAK KO phenotype, placing GAK upstream of ROCK1 in lysosomal dynamics regulation. CRISPR knockout, GAK inhibitor, autophagic flux analysis, morphological analysis of lysosomes/autophagosomes, ROCK inhibitor rescue, ROCK1 siRNA knockdown International journal of molecular medicine Medium 34468012
2023 GAK/dAux (Drosophila homolog) interacts with the autophagy initiation kinase ULK1/Atg1 via its uncoating domain and regulates the trafficking of Atg1 and Atg9 to autophagosomes in glia. Loss of GAK/dAux increases autophagosome number and size, upregulates PI3K class III complex components, and impairs autophagic flux. dAux also contributes to dopaminergic neurodegeneration and locomotor function in fly models. Co-immunoprecipitation (GAK–ULK1/Atg1 interaction), genetic loss-of-function in Drosophila and mouse microglia, fluorescence imaging of autophagosome markers, behavioral assays Proceedings of the National Academy of Sciences of the United States of America High 37428930
2023 FBXO22 mediates ubiquitin-dependent proteasomal degradation of GAK. Proteomics identified GAK as an FBXO22 target; altered abundance (depletion or overexpression) of FBXO22 inversely changes GAK protein levels; proteasome inhibition blocks FBXO22-mediated GAK reduction; cellular ubiquitination assays confirmed GAK ubiquitination downstream of FBXO22. Proteomics, FBXO22 overexpression/depletion, proteasome inhibitor treatment, protein stability (decay rate) assay, cellular ubiquitination assay Experimental cell research Medium 37442264
2025 GAK knockdown inhibits clathrin-coated pit (CCP) stabilization and invagination, resulting in a striking increase in highly transient abortive CCPs. Mutations in the J-domain of GAK that abolish Hsc70 recruitment and activation at CCPs lead to GAK accumulation at CCPs and hinder CCP stabilization and invagination. This establishes that early GAK–Hsc70-mediated remodeling of nascent flat clathrin lattices (pentagon incorporation) is required for CCP curvature development. GAK knockdown, J-domain point mutations, live TIRF microscopy, CCP lifetime analysis Proceedings of the National Academy of Sciences of the United States of America High 40424130
2026 GAK intrinsically disordered region (IDR) interacts with ARHGEF2 (a RhoA GEF) and antagonizes ROCK-dependent actomyosin signaling. GAK-knockout cells show enhanced stress fiber formation, increased myosin light chain (MLC) phosphorylation, and increased cell migration. These effects are suppressed by ROCK inhibitor or ARHGEF2 knockdown. The IDR, rather than GAK kinase activity, is the primary mediator of this regulation. GAK IDR also contributes to regulation of MLC expression. CRISPR knockout, co-immunoprecipitation (GAK IDR–ARHGEF2), immunofluorescence (stress fibers/MLC phosphorylation), ROCK inhibitor rescue, ARHGEF2 siRNA knockdown, cell migration assays Journal of cell science High 41995027
2024 In the Drosophila GAK homolog (dAux) context, lack of glial dAux enhances phosphorylation of the autophagy protein Atg9 at T62 and T69. This phosphorylation is regulated through Atg1 (ULK1 homolog), which is required for Atg9–dAux interaction. Enhanced Atg9 phosphorylation promotes autophagosome formation and Atg9 trafficking to autophagosomes. Non-phosphorylatable Atg9 suppresses the dAux-loss phenotype and phosphomimetic Atg9 rescues Atg1-loss phenotype, defining a dAux–Atg1–Atg9 phosphorylation axis. Genetic epistasis in Drosophila, phospho-specific analysis, non-phosphorylatable/phosphomimetic Atg9 mutants, co-immunoprecipitation, fluorescence imaging bioRxivpreprint Medium bio_10.1101_2024.07.03.601894

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 GAK: a cyclin G associated kinase contains a tensin/auxilin-like domain. FEBS letters 113 9013862
2006 Recruitment dynamics of GAK and auxilin to clathrin-coated pits during endocytosis. Journal of cell science 103 16895969
2002 CK2 and GAK/auxilin2 are major protein kinases in clathrin-coated vesicles. Traffic (Copenhagen, Denmark) 85 12010461
2005 Depletion of GAK/auxilin 2 inhibits receptor-mediated endocytosis and recruitment of both clathrin and clathrin adaptors. Journal of cell science 75 16155256
2009 GAK, a regulator of clathrin-mediated membrane traffic, also controls centrosome integrity and chromosome congression. Journal of cell science 66 19654208
2021 GAK and PRKCD are positive regulators of PRKN-independent mitophagy. Nature communications 60 34671015
2010 Replication of GWAS associations for GAK and MAPT in Parkinson's disease. Annals of human genetics 52 21058943
1997 Structure, expression, and chromosomal localization of human GAK. Genomics 52 9299234
2015 Selective Inhibitors of Cyclin G Associated Kinase (GAK) as Anti-Hepatitis C Agents. Journal of medicinal chemistry 48 25822739
2014 Structure of cyclin G-associated kinase (GAK) trapped in different conformations using nanobodies. The Biochemical journal 47 24438162
2019 SGC-GAK-1: A Chemical Probe for Cyclin G Associated Kinase (GAK). Journal of medicinal chemistry 43 30768268
2018 Optimization of Isothiazolo[4,3- b]pyridine-Based Inhibitors of Cyclin G Associated Kinase (GAK) with Broad-Spectrum Antiviral Activity. Journal of medicinal chemistry 32 29953812
2017 LncRNA OIP5-AS1/cyrano suppresses GAK expression to control mitosis. Oncotarget 32 28472763
2019 Design of a Cyclin G Associated Kinase (GAK)/Epidermal Growth Factor Receptor (EGFR) Inhibitor Set to Interrogate the Relationship of EGFR and GAK in Chordoma. Journal of medicinal chemistry 28 30973735
2009 GAK, a regulator of clathrin-mediated membrane trafficking, localizes not only in the cytoplasm but also in the nucleus. Genes to cells : devoted to molecular & cellular mechanisms 28 19371378
2015 The clathrin-binding and J-domains of GAK support the uncoating and chaperoning of clathrin by Hsc70 in the brain. Journal of cell science 23 26345367
2011 Neonatal lethality in knockout mice expressing the kinase-dead form of the gefitinib target GAK is caused by pulmonary dysfunction. PloS one 23 22022498
2016 The 4p16.3 Parkinson Disease Risk Locus Is Associated with GAK Expression and Genes Involved with the Synaptic Vesicle Membrane. PloS one 22 27508417
2013 Genetic variations of GAK in two Chinese Parkinson's disease populations: a case-control study. PloS one 20 23826309
2019 Utilizing comprehensive and mini-kinome panels to optimize the selectivity of quinoline inhibitors for cyclin G associated kinase (GAK). Bioorganic & medicinal chemistry letters 19 31129055
2022 GAK and PRKCD kinases regulate basal mitophagy. Autophagy 18 35001811
2019 Design and Analysis of the 4-Anilinoquin(az)oline Kinase Inhibition Profiles of GAK/SLK/STK10 Using Quantitative Structure-Activity Relationships. ChemMedChem 16 31675459
2018 Cyclin G-associated kinase (GAK) affinity and antiviral activity studies of a series of 3-C-substituted isothiazolo[4,3-b]pyridines. European journal of medicinal chemistry 16 30529544
2011 GWAS-linked GAK locus in Parkinson's disease in Han Chinese and meta-analysis. Human genetics 16 22198721
2016 miR-206 inhibits renal cell cancer growth by targeting GAK. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 15 27924503
2013 Reaffirmation of GAK, but not HLA-DRA, as a Parkinson's disease susceptibility gene in a Taiwanese population. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 15 24039160
2023 Cyclin-G-associated kinase GAK/dAux regulates autophagy initiation via ULK1/Atg1 in glia. Proceedings of the National Academy of Sciences of the United States of America 14 37428930
2021 Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics. International journal of molecular medicine 14 34468012
2010 Disruption of zebrafish cyclin G-associated kinase (GAK) function impairs the expression of Notch-dependent genes during neurogenesis and causes defects in neuronal development. BMC developmental biology 14 20082716
2019 Towards the Development of an In vivo Chemical Probe for Cyclin G Associated Kinase (GAK). Molecules (Basel, Switzerland) 13 31698822
2020 Targeting the Water Network in Cyclin G-Associated Kinase (GAK) with 4-Anilino-quin(az)oline Inhibitors. ChemMedChem 11 32358915
2015 Interaction between SNCA, LRRK2 and GAK increases susceptibility to Parkinson's disease in a Chinese population. eNeurologicalSci 11 29479569
2018 Chemical genetic identification of GAK substrates reveals its role in regulating Na+/K+-ATPase. Life science alliance 10 30623173
2015 Quantitative assessment of the association between GAK rs1564282 C/T polymorphism and the risk of Parkinson's disease. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 10 25975492
2015 Genome-wide haplotype association analysis identifies SERPINB9, SERPINE2, GAK, and HSP90B1 as novel risk genes for oral squamous cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 10 26318431
2024 Back-Pocket Optimization of 2-Aminopyrimidine-Based Macrocycles Leads to Potent EPHA2/GAK Kinase Inhibitors. Journal of medicinal chemistry 9 39028937
2019 SNCA but not DNM3 and GAK modifies age at onset of LRRK2-related Parkinson's disease in Chinese population. Journal of neurology 8 31041581
2015 The Potential Mutation of GAK Gene in the Typical Sporadic Parkinson's Disease from the Han Population of Chinese Mainland. Molecular neurobiology 7 26676575
2013 A kinome-wide siRNA screen identifies multiple roles for protein kinases in hypoxic stress adaptation, including roles for IRAK4 and GAK in protection against apoptosis in VHL-/- renal carcinoma cells, despite activation of the NF-κB pathway. Journal of biomolecular screening 7 23591012
2023 FBXO22 inhibits proliferation and metastasis of cervical cancer cells by mediating ubiquitination-dependent degradation of GAK. Experimental cell research 6 37442264
2025 Dynamic early recruitment of GAK-Hsc70 regulates coated pit maturation. Proceedings of the National Academy of Sciences of the United States of America 5 40424130
2019 Live imaging screen reveals that TYRO3 and GAK ensure accurate spindle positioning in human cells. Nature communications 5 31253758
2017 GAK is phosphorylated by c-Src and translocated from the centrosome to chromatin at the end of telophase. Cell cycle (Georgetown, Tex.) 5 28135906
2022 The cyclin G-associated kinase (GAK) inhibitor SGC-GAK-1 inhibits neurite outgrowth and synapse formation. Molecular brain 4 35883152
1984 [A newly established melanoma cell line (GAK) with 5-S-cysteinyldopa phenotype]. Nihon Sanka Fujinka Gakkai zasshi 4 6431036
2024 Synthesis and evaluation of isothiazolo[4,5-b]pyridines as cyclin G-associated kinase (GAK) inhibitors. Organic & biomolecular chemistry 1 39171941
2026 Genome-wide association study identifies GAK and KLF12 associated with curve severity of adolescent idiopathic scoliosis. PeerJ 0 41584833
2026 GAK antagonises ROCK-dependent regulation of actomyosin dynamics. Journal of cell science 0 41995027
2026 Loss of Cyclin G-Associated Kinase (Gak) Leads to Lysosome Dysfunction and Immune Modulation in Podocytes. Journal of the American Society of Nephrology : JASN 0 42149668
2026 Development of a novel GAK solution for efficient hypothermic preservation of NK cell viability and anti-tumor function. Stem cell research & therapy 0 42226278
2025 Low-frequency genetic variants in GAK enhance Golgi function and protect against Parkinson's disease. medRxiv : the preprint server for health sciences 0 40832425
2024 Back-pocket optimization of 2-aminopyrimidine-based macrocycles leads to potent dual EPHA2/GAK kinase inhibitors with antiviral activity. bioRxiv : the preprint server for biology 0 38405908
2024 The cyclin-G associated kinase (GAK) is a novel mitotic kinase and therapeutic target in diffuse large B-cell lymphoma. bioRxiv : the preprint server for biology 0 39484514

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