Affinage

YWHAQ

14-3-3 protein theta · UniProt P27348

Length
245 aa
Mass
27.8 kDa
Annotated
2026-06-11
100 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

YWHAQ (14-3-3 theta/zeta) is a phosphoserine/phosphothreonine-binding adaptor that recognizes phosphorylated motifs on diverse clients and thereby controls their activity, localization, stability, and complex assembly across kinase signaling, vesicular transport, and cell-survival pathways (PMID:7935795, PMID:9822578, PMID:32913128). Sequence-specific recognition depends on an intact phosphopeptide-binding pocket, and many clients are engaged through cooperative multi-site binding in which loss of a single phosphosite abolishes association, as shown for SIK kinases, CaMKK2, LRRK2, and IRSp53 (PMID:9822578, PMID:29211348, PMID:32913128, PMID:28202711, PMID:30696821). Functionally, 14-3-3 binding can either activate or restrain clients: it stimulates Raf-1 to promote MAPK signaling (PMID:7935795), holds CaMKK2 and SIK kinases in an inactivated state by occluding sites and blocking dephosphorylation (PMID:32913128, PMID:29211348), reduces LRRK2 kinase activity and rescues mutant LRRK2-induced neurite shortening (PMID:26546614), and drives conformational change in IRSp53 that inhibits its membrane and Cdc42 binding (PMID:30696821). As a molecular adaptor it couples cargoes to trafficking machinery — recruiting misfolded protein cargo and BAG3 to dynein for aggresome delivery, and SAC1 to the COPII subunit Sec24 for ER export — and it modulates CFTR biogenesis by competing with retrograde ER retrieval (PMID:23843611, PMID:26056309, PMID:22278744). 14-3-3 function requires dimerization, and PKC phosphorylation of Ser58 shifts the equilibrium toward monomers and alters subcellular localization (PMID:23843611, PMID:35321476). The protein mediates essential anti-apoptotic signaling: loss of 14-3-3/ligand interactions induces apoptosis and dilated cardiomyopathy in vivo, and displacement of pro-apoptotic Bax from 14-3-3 by BAP1 promotes intrinsic-pathway death (PMID:10654934, PMID:11577088, PMID:29686263).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1994 High

    Established that 14-3-3 is not merely a passive binder but a positive regulator of a signaling kinase, defining its role as an activator of Raf-1-dependent MAPK signaling.

    Evidence Yeast two-hybrid, Xenopus oocyte overexpression, and dominant-negative Raf-1 epistasis

    PMID:7935795

    Open questions at the time
    • Structural basis of Raf-1 activation not resolved
    • Did not define the phospho-motif on Raf-1 recognized by 14-3-3
  2. 1995 Medium

    Distinguished scaffolding from catalytic modulation by showing 14-3-3 binds CDC25 phosphatases without altering their activity, and mapped dimerization and membrane-binding determinants to the N-terminus while showing full-length protein is needed to inhibit PKC.

    Evidence Yeast two-hybrid, co-IP, in vitro phosphatase assay; N-terminal deletion mutagenesis, circular dichroism, PKC activity assay

    PMID:7644510 PMID:7837270

    Open questions at the time
    • Functional outcome of CDC25 binding in vivo not defined
    • Single-lab biochemistry without independent confirmation
  3. 1998 High

    Demonstrated that 14-3-3 acts as a scaffold for MEKK kinases without altering their catalytic activity, and that phosphopeptide-pocket binding is genetically required for participation in TOR/rapamycin signaling.

    Evidence Quantitative binding and co-IP for MEKK1/2/3; multicopy suppressor screen with pocket mutagenesis in yeast

    PMID:9452471 PMID:9822578

    Open questions at the time
    • Direct phospho-clients in the TOR pathway not identified
    • Selectivity for MEKK1/2/3 over MEKK4 mechanism unexplained
  4. 2000 High

    Showed in vivo that 14-3-3 differentially tunes MAPK cascades (promoting ERK, restraining JNK/p38) and is required to suppress apoptosis at the organ level.

    Evidence Dominant-negative 14-3-3 transfection and cardiac transgenic mouse with MAPK assays and histology

    PMID:10654934

    Open questions at the time
    • Specific apoptotic clients responsible for the cardiac phenotype not pinpointed
    • Isoform-specific contributions not separated
  5. 2001 Medium

    Established that 14-3-3/ligand interactions are necessary for cell survival, using a generic interaction inhibitor to trigger apoptosis.

    Evidence Difopein inhibitor expression with cell death and drug-sensitization assays

    PMID:11577088

    Open questions at the time
    • Does not identify which client displacement drives death
    • Single-lab loss-of-function
  6. 2002 Medium

    Linked 14-3-3 to growth control by showing phospho-dependent binding to TSC2, providing a node for Akt-dependent regulation.

    Evidence Co-IP and Ser1210 phospho-site mutagenesis

    PMID:12364343

    Open questions at the time
    • Inhibition of TSC2 function inferred, not reconstituted
    • Effect on downstream mTOR output not measured here
  7. 2003 High

    Defined a mechanism by which 14-3-3 stabilizes a client by blocking its ubiquitination and nuclear export, illustrated by p53.

    Evidence Co-IP, ubiquitination assay, nuclear export assay, transcriptional reporter

    PMID:14517281

    Open questions at the time
    • Demonstrated for the sigma isoform; YWHAQ-specific contribution not isolated
  8. 2009 Medium

    Showed 14-3-3 controls nucleo-cytoplasmic trafficking of a signaling effector, coupling Akt phosphorylation of Chibby to beta-catenin nuclear export.

    Evidence Co-IP, phosphorylation assay, nuclear export assay

    PMID:19158508

    Open questions at the time
    • Direct transport mechanism of the 14-3-3/Cby/beta-catenin complex not resolved
    • Single-lab
  9. 2012 High

    Defined 14-3-3 as a regulator of membrane protein biogenesis, increasing CFTR maturation by competing with COPI-mediated ER retrieval.

    Evidence Co-IP, NMR mapping, pulse-chase, siRNA, surface biotinylation, anion efflux

    PMID:22278744

    Open questions at the time
    • Isoform redundancy at the CFTR R-region not dissected
    • Quantitative contribution of synthesis vs degradation effects not separated
  10. 2013 High

    Established 14-3-3 as a dimerization-dependent adaptor linking chaperone-bound misfolded cargo to dynein for aggresome transport.

    Evidence Reciprocal co-IP of a DIC/14-3-3/BAG3 ternary complex, dimerization mutants, aggresome assays in yeast and mammalian cells

    PMID:23843611

    Open questions at the time
    • Phospho-recognition basis of cargo selection not defined
    • Stoichiometry of the dynein-cargo bridge unresolved
  11. 2015 High

    Demonstrated by reconstitution that 14-3-3 directly drives COPII packaging of cargo (SAC1) via a minimal sorting motif and Sec24 interaction.

    Evidence Cell-free COPII budding with recombinant protein, sorting-motif mutagenesis, co-IP; plus LRRK2 protective gain/loss-of-function in neurons

    PMID:26056309 PMID:26546614

    Open questions at the time
    • Generality of 14-3-3-dependent COPII sorting beyond SAC1 untested
    • LRRK2 binding sites not yet mapped structurally at this stage
  12. 2017 High

    Provided the structural basis for multivalent 14-3-3/LRRK2 recognition and linked Parkinson's mutations to impaired 14-3-3 binding.

    Evidence X-ray crystallography of 14-3-3/LRRK2 phosphopeptides with binding assays

    PMID:28202711

    Open questions at the time
    • Functional consequence of each individual site in cells not quantified
  13. 2018 High

    Established cooperative multi-site phospho-recognition as the mechanism by which 14-3-3 inhibits kinase activity (SIK1/2/3) and revealed how 14-3-3 displacement releases pro-apoptotic Bax.

    Evidence In vitro kinase assays with multi-site mutagenesis and cAMP stimulation; co-IP/apoptosis/Bax-release assays and xenograft for BAP1

    PMID:29211348 PMID:29686263

    Open questions at the time
    • Whether 14-3-3 sterically occludes the SIK catalytic site or blocks dephosphorylation not fully separated
    • BAP1 study is single-lab Medium-confidence
  14. 2019 High

    Showed that 14-3-3 binding allosterically reshapes a client conformation, inhibiting IRSp53 membrane association and Cdc42 binding in opposition to activating inputs.

    Evidence Phosphoproteomics, crystallography, bicistronic heterodimer expression, FRET-sensor and liposome assays

    PMID:30696821

    Open questions at the time
    • In vivo cytoskeletal consequence of IRSp53 conformational switching not addressed
  15. 2020 High

    Defined how dual PKA-driven canonical and non-canonical sites cooperate to recruit 14-3-3 and lock CaMKK2 inactive by protecting its activation-site phosphorylation from phosphatases.

    Evidence In vitro kinase assay, phosphosite mutagenesis, co-IP, crystal structure of 14-3-3 zeta with a diphospho-CaMKK2 peptide

    PMID:32913128

    Open questions at the time
    • Identity of the phosphatase shielded from phospho-Ser495 not established
  16. 2021 Medium

    Placed 14-3-3 inside a transmembrane receptor signaling complex (TNFR2) required for progranulin-driven ERK/Elk-1 output and disease protection.

    Evidence Copurification/proteomics, co-IP, transcription-factor screen, chondrocyte conditional knockout, OA model

    PMID:34226187

    Open questions at the time
    • Direct phospho-motif engaged within TNFR2 complex not mapped
    • Demonstrated for the epsilon isoform
  17. 2022 Medium

    Established a regulatory switch for 14-3-3 itself: PKC phosphorylation of Ser58 drives monomerization and relocalization, controlling adaptor availability.

    Evidence Site-specific phosphorylation with analytical ultracentrifugation, thermal stability, and microscopy in human cancer cells

    PMID:35321476

    Open questions at the time
    • Functional consequence of monomerization for specific clients not measured
    • Phosphomimetics incompletely recapitulate the effect

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how isoform-specific (YWHAQ vs other 14-3-3 paralogs) client engagement and the Ser58 dimer-monomer switch are integrated to set context-dependent activating versus inhibitory outcomes on shared clients.
  • No systematic isoform-resolved client map
  • Cellular triggers of Ser58 phosphorylation in physiological settings undefined
  • How a single adaptor selects activation vs inhibition of a given client not mechanistically unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 3 GO:0140313 molecular sequestering activity 2
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-5653656 Vesicle-mediated transport 3
Partners
BAG3BAP1CAMKK2CFTRLRRK2RAF1SAC1TSC2
Complex memberships
14-3-3/Sec24 COPII sorting complex14-3-3/dynein-DIC/BAG3 transport complexTNFR2 receptor complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 14-3-3 zeta (YWHAQ) and 14-3-3 beta interact with the amino-terminal region of Raf-1, and expression of 14-3-3 proteins in Xenopus oocytes enhanced Raf-1 kinase activity and promoted Raf-1-dependent oocyte maturation; a dominant-negative Raf-1 mutant blocked these effects, establishing 14-3-3 as an activator of Raf-1 signaling. Yeast two-hybrid, Xenopus oocyte overexpression, dominant-negative epistasis Nature High 7935795
1995 14-3-3 epsilon and 14-3-3 beta physically interact with the human CDC25A and CDC25B phosphatases both in vitro and in vivo, as established by yeast two-hybrid and co-immunoprecipitation; however, 14-3-3 does not affect CDC25A phosphatase activity or CDC25A-stimulated Raf-1 kinase activity, suggesting 14-3-3 may scaffold CDC25-Raf-1 association. Yeast two-hybrid, co-immunoprecipitation, in vitro phosphatase activity assay Proceedings of the National Academy of Sciences of the United States of America Medium 7644510
1995 The N-terminal 26 amino acids of 14-3-3 are required for dimerization; the N-terminal 12 kDa domain mediates binding to synaptic plasma membranes; intact 14-3-3 potently inhibits protein kinase C (PKC) activity, whereas the isolated N-terminal domain does not, indicating the full-length protein is required for PKC inhibition. N-terminal deletion mutagenesis, circular dichroism, PKC activity assay, membrane fractionation Journal of molecular biology Medium 7837270
1998 14-3-3 zeta and epsilon isoforms interact with the N-terminal regulatory domain of MEKK3 with ~90 nM affinity, and also bind MEKK1 and MEKK2 but not MEKK4; 14-3-3 does not directly influence MEKK1/2/3 kinase activity but functions as a scaffold for protein-protein interactions; caspase-3 cleavage of MEKK1 releases the kinase domain from the N-terminal 14-3-3-binding region. Yeast two-hybrid, quantitative binding assay, co-immunoprecipitation, confocal colocalization, in vitro kinase assay The Journal of biological chemistry High 9452471
1998 Yeast 14-3-3 homologs BMH1 and BMH2 are multicopy suppressors of rapamycin-induced growth arrest; mutations in the phosphopeptide-binding pocket of 14-3-3 abolish rapamycin resistance, establishing that phosphoserine/threonine binding is required for 14-3-3 participation in TOR/rapamycin-sensitive signaling. Multicopy suppressor screen, deletion analysis, phosphopeptide-binding pocket mutagenesis, growth assay Current biology : CB High 9822578
2000 Dominant-negative 14-3-3 zeta (R56A/R60A double mutant) inhibits serum-stimulated ERK MAPK activation and increases basal JNK1 and p38 MAPK activation in fibroblasts; targeted expression of dominant-negative 14-3-3 eta in cardiac tissue increases JNK1/p38 activation, causes dilated cardiomyopathy, and massive cardiomyocyte apoptosis, demonstrating that 14-3-3 differentially regulates MAPK cascades and inhibits apoptosis in vivo. Dominant-negative transfection, transgenic mouse model, MAPK activity assays, histology The EMBO journal High 10654934
2001 Expression of difopein, a specific inhibitor of 14-3-3/ligand interactions, is sufficient to induce apoptosis in cells and sensitizes cells to cisplatin-induced death, establishing that 14-3-3/ligand interactions are required for cell survival signaling downstream of pro-survival kinases. Difopein inhibitor expression, cell death assay, drug sensitization assay The Journal of biological chemistry Medium 11577088
2002 TSC2 (but not TSC1) associates with 14-3-3 in vivo, and phosphorylation of Ser1210 in TSC2 is required for this association; 14-3-3 binding may inhibit TSC2 function and represents a mechanism of Akt-dependent TSC2 regulation. Co-immunoprecipitation, phosphorylation site mutagenesis The Journal of biological chemistry Medium 12364343
2003 14-3-3 sigma interacts with p53 in response to the DNA-damaging agent adriamycin; 14-3-3 sigma expression stabilizes p53 by blocking Mdm2-mediated p53 ubiquitination and nuclear export, and facilitates p53 oligomerization and enhances p53 transcriptional activity. Co-immunoprecipitation, ubiquitination assay, nuclear export assay, transcriptional reporter assay Molecular and cellular biology High 14517281
2009 Akt kinase-dependent phosphorylation of Chibby (Cby) enables 14-3-3 binding to Cby, and the resulting 14-3-3/Cby complex facilitates nuclear export of beta-catenin, providing a mechanism for cross-talk between Wnt and Akt signaling pathways in regulating beta-catenin nucleo-cytoplasmic trafficking. Co-immunoprecipitation, phosphorylation assay, nuclear export assay Cell cycle (Georgetown, Tex.) Medium 19158508
2012 14-3-3 isoforms (including beta and epsilon) interact with CFTR at PKA-phosphorylated sites in the regulatory region; 14-3-3 binding increases CFTR biogenesis by reducing retrograde ER retrieval (competing with COP1 binding), increasing CFTR synthesis, reducing degradation, and promoting maturation to cell surface. Co-immunoprecipitation, NMR, pulse-chase, siRNA knockdown, cell surface biotinylation, anion efflux assay Molecular biology of the cell High 22278744
2013 14-3-3 functions as a molecular adaptor to recruit chaperone-associated misfolded protein cargoes to dynein motors for transport to aggresomes; 14-3-3 simultaneously binds both dynein intermediate chain (DIC) and the Hsp70 co-chaperone BAG3, and functional 14-3-3 dimerization is required for this process in both yeast and mammalian cells. Co-immunoprecipitation, dimerization-defective mutant analysis, aggresome formation assay, yeast and mammalian cell models Journal of cell science High 23843611
2015 14-3-3 proteins act as cytosolic adaptors mediating ER export of SAC1 (a PI4P phosphatase) in COPII-coated vesicles; 14-3-3 directly binds a minimal 7-aa sorting motif (RLSNTSP) in SAC1 and interacts with the COPII sorting subunit Sec24; recombinant 14-3-3 stimulates SAC1 packaging into COPII vesicles in a cell-free budding reaction. Cell-free COPII vesicle budding assay, recombinant protein, co-immunoprecipitation, homology modeling, sorting motif mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 26056309
2015 14-3-3 theta (YWHAQ) overexpression reduces LRRK2 kinase activity and reverses mutant LRRK2 (G2019S and R1441G)-induced neurite shortening in primary neurons; this protective effect requires direct physical binding of 14-3-3 theta to LRRK2; pan-14-3-3 inhibitor difopein conversely promotes LRRK2 kinase activity and exacerbates neurite shortening. Overexpression in BAC transgenic neurons, LRRK2 kinase activity assay, neurite length measurement, difopein inhibition, LRRK2 kinase inhibitor rescue Human molecular genetics High 26546614
2017 Crystal structures of 14-3-3 bound to phosphopeptides from LRRK2 characterize the multivalent interaction interface; LRRK2 possesses multiple phosphorylation sites that each can bind 14-3-3, and many Parkinson's disease-relevant LRRK2 mutations impair 14-3-3 binding. X-ray crystallography, biochemical binding assays The Biochemical journal High 28202711
2018 PKA-dependent phosphorylation of SIK1, SIK2, and SIK3 induces 14-3-3 binding and inhibits their catalytic activity; SIK1 and SIK3 have two functional PKA/14-3-3 sites while SIK2 has four; loss of a single site in SIK1/3 abolishes 14-3-3 association and cAMP responsiveness, demonstrating multi-site cooperativity in 14-3-3-mediated kinase inhibition. In vitro kinase assay, phosphorylation site mutagenesis, co-immunoprecipitation, cAMP stimulation The FEBS journal High 29211348
2018 BAP1 (BRCA1-associated protein 1) interacts with 14-3-3 protein; this interaction releases the pro-apoptotic protein Bax from 14-3-3, promoting apoptosis through the intrinsic pathway in neuroblastoma cells. Co-immunoprecipitation, apoptosis assay, Bax release assay, xenograft Cell death & disease Medium 29686263
2019 14-3-3 binds to two pairs of phosphorylation sites in IRSp53 (established by phosphoproteomics and quantitative binding); each subunit of an IRSp53 homodimer independently binds one 14-3-3 dimer; a FRET-sensor assay shows that 14-3-3 binding induces opposite conformational changes in IRSp53 compared to activatory inputs (Cdc42, Eps8); 14-3-3 inhibits IRSp53 binding to membranes and its interaction with Cdc42. Phosphoproteomics, quantitative binding assay, X-ray crystallography, bicistronic expression of heterodimer, FRET-sensor assay, liposome binding assay Nature communications High 30696821
2020 PKA phosphorylates CaMKK2 at Ser100 and Ser511, which mediates recruitment of 14-3-3 adaptor proteins; 14-3-3 binding holds CaMKK2 in an inactivated state by preventing dephosphorylation of phospho-Ser495 (the Ca2+/CaM activation site); crystal structure of 14-3-3 zeta bound to a diphosphorylated CaMKK2 peptide reveals how canonical (Ser511) and non-canonical (Ser100) 14-3-3 consensus sites cooperate to bind 14-3-3. In vitro kinase assay, phosphosite mutagenesis, X-ray crystallography, co-immunoprecipitation The Journal of biological chemistry High 32913128
2021 14-3-3 epsilon was biochemically identified as an intracellular component of TNFR2 receptor complexes in chondrocytes in response to progranulin (PGRN); 14-3-3 epsilon is required for PGRN/TNFR2 signaling through ERK-dependent Elk-1 activation while suppressing NF-κB; chondrocyte-specific deletion of 14-3-3 epsilon abolishes PGRN's therapeutic effects against osteoarthritis in vivo. Biochemical copurification, proteomics, co-immunoprecipitation, transcription factor activity screen, conditional knockout mouse, OA disease model Annals of the rheumatic diseases Medium 34226187
2022 Phosphorylation of 14-3-3 zeta at Ser58 by PKC shifts the dimer-monomer equilibrium strongly toward monomers at physiological concentrations; phosphomimicking mutations (S58E/D) incompletely recapitulate this shift; Ser58 phosphorylation changes the subcellular localization of 14-3-3 zeta in HeLa and U251 cells. Site-specific phosphorylation, analytical ultracentrifugation/biophysics, thermal stability assay, fluorescence microscopy in human cancer cells Frontiers in chemistry Medium 35321476

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 14-3-3 proteins: structure, function, and regulation. Annual review of pharmacology and toxicology 1339 10836149
2006 14-3-3 proteins: a historic overview. Seminars in cancer biology 701 16678438
2011 FoxO transcription factors; Regulation by AKT and 14-3-3 proteins. Biochimica et biophysica acta 597 21708191
2002 How do 14-3-3 proteins work?-- Gatekeeper phosphorylation and the molecular anvil hypothesis. FEBS letters 556 11911880
2001 14-3-3 proteins: key regulators of cell division, signalling and apoptosis. BioEssays : news and reviews in molecular, cellular and developmental biology 464 11598960
2004 Unlocking the code of 14-3-3. Journal of cell science 400 15090593
2000 14-3-3 proteins: regulation of subcellular localization by molecular interference. Cellular signalling 345 11152955
1994 Activation of Raf-1 by 14-3-3 proteins. Nature 334 7935795
2001 14-3-3 proteins mediate an essential anti-apoptotic signal. The Journal of biological chemistry 271 11577088
2006 14-3-3 proteins in cell cycle regulation. Seminars in cancer biology 262 16697662
2001 14-3-3 proteins; bringing new definitions to scaffolding. Oncogene 259 11607836
2005 14-3-3 proteins--an update. Cell research 253 15857577
2000 14-3-3 proteins block apoptosis and differentially regulate MAPK cascades. The EMBO journal 247 10654934
1995 14-3-3 proteins associate with cdc25 phosphatases. Proceedings of the National Academy of Sciences of the United States of America 240 7644510
2011 14-3-3 proteins as signaling integration points for cell cycle control and apoptosis. Seminars in cell & developmental biology 235 21945648
2011 Structural basis of 14-3-3 protein functions. Seminars in cell & developmental biology 234 21920446
2005 14-3-3 proteins: a number of functions for a numbered protein. Science's STKE : signal transduction knowledge environment 234 16091624
2017 Modulators of 14-3-3 Protein-Protein Interactions. Journal of medicinal chemistry 215 28968506
2011 14-3-3 Proteins: diverse functions in cell proliferation and cancer progression. Seminars in cell & developmental biology 206 21884813
2003 14-3-3 sigma positively regulates p53 and suppresses tumor growth. Molecular and cellular biology 201 14517281
2004 14-3-3 Proteins--a focus on cancer and human disease. Journal of molecular and cellular cardiology 199 15350836
2011 14-3-3 proteins in plant physiology. Seminars in cell & developmental biology 196 21907297
2006 14-3-3 proteins as potential oncogenes. Seminars in cancer biology 188 16725345
2003 14-3-3 proteins find new partners in plant cell signalling. Trends in plant science 152 12758039
2002 Specificity of 14-3-3 isoform dimer interactions and phosphorylation. Biochemical Society transactions 147 12196094
1998 14-3-3 proteins in neuronal development and function. Molecular neurobiology 146 9626666
2005 Role of 14-3-3 proteins in eukaryotic signaling and development. Current topics in developmental biology 136 16125003
2011 14-3-3 proteins as potential therapeutic targets. Seminars in cell & developmental biology 135 21983031
1998 14-3-3 proteins interact with specific MEK kinases. The Journal of biological chemistry 134 9452471
2011 The 14-3-3 proteins in regulation of cellular metabolism. Seminars in cell & developmental biology 130 21888985
2008 14-3-3 proteins: a family of versatile molecular regulators. Physiological research 129 18481918
2009 14-3-3 and FHA domains mediate phosphoprotein interactions. Annual review of plant biology 128 19575580
2002 14-3-3 proteins and the response to abiotic and biotic stress. Plant molecular biology 122 12516870
1995 Expression and structural analysis of 14-3-3 proteins. Journal of molecular biology 117 7837270
2017 14-3-3 Proteins in Brain Development: Neurogenesis, Neuronal Migration and Neuromorphogenesis. Frontiers in molecular neuroscience 106 29075177
2018 14-3-3 Proteins in Plant Hormone Signaling: Doing Several Things at Once. Frontiers in plant science 103 29593761
2005 14-3-3 proteins: regulators of numerous eukaryotic proteins. IUBMB life 101 16203681
2022 Structural insights into the functional roles of 14-3-3 proteins. Frontiers in molecular biosciences 94 36188227
2002 Survival-promoting functions of 14-3-3 proteins. Biochemical Society transactions 94 12196095
2012 Plant 14-3-3 proteins as spiders in a web of phosphorylation. Protoplasma 93 22926776
2002 Regulation of TSC2 by 14-3-3 binding. The Journal of biological chemistry 93 12364343
2013 14-3-3 protein targets misfolded chaperone-associated proteins to aggresomes. Journal of cell science 92 23843611
2002 Metabolic enzymes as targets for 14-3-3 proteins. Plant molecular biology 91 12516872
2015 14-3-3 proteins in plant-pathogen interactions. Molecular plant-microbe interactions : MPMI 89 25584723
1998 The 14-3-3 proteins positively regulate rapamycin-sensitive signaling. Current biology : CB 85 9822578
2013 Neuroprotective function of 14-3-3 proteins in neurodegeneration. BioMed research international 84 24364034
2012 14-3-3 zeta as novel molecular target for cancer therapy. Expert opinion on therapeutic targets 84 22512284
2006 Yeast 14-3-3 proteins. Yeast (Chichester, England) 83 16498703
2011 14-3-3 proteins in neurodegeneration. Seminars in cell & developmental biology 79 21920445
2009 Plant 14-3-3 proteins catch up with their mammalian orthologs. Current opinion in plant biology 73 19748819
2004 14-3-3 proteins: a number of functions for a numbered protein. Science's STKE : signal transduction knowledge environment 73 15266103
2015 14-3-3 Proteins regulate mutant LRRK2 kinase activity and neurite shortening. Human molecular genetics 71 26546614
2006 14-3-3 proteins in membrane protein transport. Biological chemistry 70 16972791
2021 14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis. Annals of the rheumatic diseases 69 34226187
2003 14-3-3 proteins in apoptosis. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 68 12700817
2012 Oligomeric structure of 14-3-3 protein: what do we know about monomers? FEBS letters 63 23159940
2020 14-3-3 modulation of the inflammatory response. Pharmacological research 62 33053447
2018 14-3-3 proteins mediate inhibitory effects of cAMP on salt-inducible kinases (SIKs). The FEBS journal 60 29211348
2016 14-3-3 protein mediates plant seed oil biosynthesis through interaction with AtWRI1. The Plant journal : for cell and molecular biology 60 27322486
2011 Membrane proteins as 14-3-3 clients in functional regulation and intracellular transport. Physiology (Bethesda, Md.) 60 21670164
2011 The role of protein disorder in the 14-3-3 interaction network. Molecular bioSystems 60 21947246
2021 14-3-3 Proteins: Novel Pharmacological Targets in Neurodegenerative Diseases. Trends in pharmacological sciences 58 33518287
2017 CDPKs and 14-3-3 Proteins: Emerging Duo in Signaling. Trends in plant science 58 28065409
2012 14-3-3 Proteins are Regulators of Autophagy. Cells 57 24710529
2010 14-3-3 proteins and regulation of cytoskeleton. Biochemistry. Biokhimiia 57 21417993
2004 14-3-3 proteins: regulation of signal-induced events. Physiologia plantarum 57 15032850
2020 The 14-3-3 Proteins as Important Allosteric Regulators of Protein Kinases. International journal of molecular sciences 56 33233473
2019 Intrinsic disorder associated with 14-3-3 proteins and their partners. Progress in molecular biology and translational science 55 31521232
2017 Structural interface between LRRK2 and 14-3-3 protein. The Biochemical journal 55 28202711
2012 Phosphorylation-dependent 14-3-3 protein interactions regulate CFTR biogenesis. Molecular biology of the cell 55 22278744
1992 Evolutionary conservation of the 14-3-3 protein. Biochemical and biophysical research communications 55 1375463
2022 Regain flood adaptation in rice through a 14-3-3 protein OsGF14h. Nature communications 51 36175427
2009 14-3-3 Proteins: insights from genome-wide studies in yeast. Genomics 51 19631734
2006 A stress response pathway involving sirtuins, forkheads and 14-3-3 proteins. Cell cycle (Georgetown, Tex.) 51 17172829
2019 Downregulation of 14-3-3 Proteins in Alzheimer's Disease. Molecular neurobiology 50 31487003
2000 14-3-3 proteins and growth control. Progress in cell cycle research 50 10740814
2021 B-Raf autoinhibition in the presence and absence of 14-3-3. Structure (London, England : 1993) 47 33711246
2016 Extracellular functions of 14-3-3 adaptor proteins. Cellular signalling 46 27993556
2021 Pathways to Parkinson's disease: a spotlight on 14-3-3 proteins. NPJ Parkinson's disease 45 34548498
2011 Probable participation of 14-3-3 in tau protein oligomerization and aggregation. Journal of Alzheimer's disease : JAD 44 21876254
2007 14-3-3 cruciform-binding proteins as regulators of eukaryotic DNA replication. Trends in biochemical sciences 44 18054234
2018 14-3-3: A Case Study in PPI Modulation. Molecules (Basel, Switzerland) 42 29890630
2016 14-3-3 Proteins in Guard Cell Signaling. Frontiers in plant science 42 26858725
2015 Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma. Cancers 42 26083935
2002 From cytosol to organelles: 14-3-3 proteins as multifunctional regulators of plant cell. IUBMB life 42 12018408
2019 Mechanism of IRSp53 inhibition by 14-3-3. Nature communications 40 30696821
2018 BAP1 induces cell death via interaction with 14-3-3 in neuroblastoma. Cell death & disease 40 29686263
2008 14-3-3 proteins in Echinococcus: their role and potential as protective antigens. Experimental parasitology 40 18316081
2002 14-3-3 protein regulation of proton pumps and ion channels. Plant molecular biology 39 12516871
2016 14-3-3 proteins regulate Tctp-Rheb interaction for organ growth in Drosophila. Nature communications 37 27151460
2014 14-3-3 and aggresome formation: implications in neurodegenerative diseases. Prion 37 24549097
2009 Fine-tuning of nuclear-catenin by Chibby and 14-3-3. Cell cycle (Georgetown, Tex.) 37 19158508
2015 Phosphoregulatory protein 14-3-3 facilitates SAC1 transport from the endoplasmic reticulum. Proceedings of the National Academy of Sciences of the United States of America 36 26056309
2009 14-3-3 and its binding partners are regulators of protein-protein interactions during spermatogenesis. The Journal of endocrinology 36 19366886
2020 CaMKK2 is inactivated by cAMP-PKA signaling and 14-3-3 adaptor proteins. The Journal of biological chemistry 34 32913128
2005 14-3-3 protein signaling in development and growth factor responses. Current topics in developmental biology 34 15949538
2022 Phosphorylated and Phosphomimicking Variants May Differ-A Case Study of 14-3-3 Protein. Frontiers in chemistry 32 35321476
2022 14-3-3 proteins contribute to autophagy by modulating SINAT-mediated degradation of ATG13. The Plant cell 32 36053201
2020 14-3-3 σ: A potential biomolecule for cancer therapy. Clinica chimica acta; international journal of clinical chemistry 31 32950519
2017 14-3-3 proteins: an important regulator of autophagy in diseases. American journal of translational research 30 29218076

Missed literature

Know a paper Affinage missed for YWHAQ? Flag it for the maintainers and the community.

No submissions yet.