Affinage

PPP1R3C

Protein phosphatase 1 regulatory subunit 3C · UniProt Q9UQK1

Length
317 aa
Mass
36.4 kDa
Annotated
2026-06-10
44 papers in source corpus 22 papers cited in narrative 22 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

PPP1R3C (PTG/R5) is a glycogen-targeting scaffolding subunit of protein phosphatase 1 (PP1) that drives glycogen synthesis by spatially organizing PP1 with the enzymes of glycogen metabolism (PMID:9045612). It binds PP1C and recruits it to glycogen granules, while simultaneously assembling phosphorylase kinase, phosphorylase a, and glycogen synthase into a multiprotein complex; the crystal structure of the PP1/PTG/carbohydrate ternary complex shows that PTG uses an unusual combination of PP1-recruitment sites to capture the phosphatase at the glycogen particle (PMID:9045612, PMID:36261419). Mechanistically PTG acts by lowering the Km of PP1 for glycogen-bound substrates rather than altering Vmax, thereby net-activating glycogen synthase and inactivating glycogen phosphorylase to promote glycogen accumulation (PMID:9242697, PMID:9756875). Heterozygous deletion in mice reduces glycogen synthase activity and glycogen stores across adipose, liver, heart, and skeletal muscle, establishing PTG as required for normal in vivo glycogen synthesis (PMID:12727934). PTG abundance is controlled by a laforin/malin axis: laforin binds PTG through its central glycogen/glycogen-synthase-binding region and recruits the E3 ligase malin to ubiquitinate PTG for proteasomal degradation, a step accelerated by AMPK phosphorylation at Ser-8 (PMID:14532330, PMID:18070875, PMID:19171932). Transcriptionally, PTG is induced by HIF1 through a proximal hypoxia response element and by FoxA2/cAMP, PER2, and IRF4 in liver and muscle (PMID:20888814, PMID:16627590, PMID:24049741, PMID:33042761). Genetic removal of PTG eliminates pathogenic polyglucosan (Lafora body) formation and rescues neurodegeneration and myoclonic epilepsy in both laforin- and malin-deficient Lafora disease models, identifying PTG-driven glycogen synthesis as the proximal cause of disease (PMID:21552327, PMID:24419970). Beyond glycogen storage, PTG contributes to hepatic gluconeogenesis via TORC2 dephosphorylation (PMID:31181215), to osmotic-stress signaling through PP1γ-mediated dephosphorylation of SHP-1 to dampen NFAT5 (PMID:23720348), and acts as a tumor suppressor in endometrial cancer through glycogen-synthesis-dependent cell cycle arrest and apoptosis (PMID:41781186).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1997 High

    Established what PTG is at the molecular level: a scaffolding PP1 subunit that physically links the phosphatase to glycogen and to glycogen-metabolizing enzymes, defining a mechanism for spatially coordinated regulation.

    Evidence Cloning from 3T3-L1 adipocytes, co-IP/pulldown with PP1C and metabolic enzymes, and overexpression in CHO cells

    PMID:9045612

    Open questions at the time
    • Stoichiometry and architecture of the multienzyme complex not resolved
    • Did not show how scaffolding alters catalytic kinetics
  2. 1997 High

    Defined the catalytic basis of PTG action, showing it activates PP1 against phosphorylase a by lowering substrate Km rather than altering Vmax, with substrate selectivity (no effect on hormone-sensitive lipase).

    Evidence In vitro phosphatase activity assays with 32P-phosphorylase a, kinase assays, and DARPP-32 competition

    PMID:9242697

    Open questions at the time
    • Whether PTG itself is regulated by phosphorylation left open (none detected here)
    • Kinetics measured for one substrate only
  3. 1998 High

    Showed PTG is sufficient to drive glycogen synthesis and to suppress glycogenolysis in primary hepatocytes even without insulin or carbohydrate, demonstrating dominant control over glycogen flux.

    Evidence Adenoviral PTG overexpression in primary rat hepatocytes with glycogen synthase/phosphorylase activity and cAMP measurements

    PMID:9756875

    Open questions at the time
    • Did not establish physiological requirement (gain-of-function only)
    • Mechanism of resistance to glycogenolytic agents not fully defined
  4. 2000 Medium

    Distinguished PTG from other glycogen-targeting PP1 subunits, showing it retains insulin responsiveness but blunts the glycogenolytic response to forskolin relative to GL and GM.

    Evidence Comparative adenoviral overexpression of PTG, GL, and GM in hepatocytes with enzymatic readouts

    PMID:10862764

    Open questions at the time
    • Mechanistic basis for differential glycogenolysis control only partly explained
    • Single-lab comparative study
  5. 2003 High

    Provided the in vivo requirement for PTG, showing genetic loss reduces glycogen synthase activity and glycogen stores across multiple tissues.

    Evidence Heterozygous PTG knockout mice with tissue glycogen and enzymatic phenotyping

    PMID:12727934

    Open questions at the time
    • Homozygous null phenotype not reported here
    • Tissue-specific contributions not dissected
  6. 2003 High

    Connected PTG to Lafora disease biology by showing laforin binds PTG via its central glycogen/GS-binding region, and that a disease-causing laforin mutation selectively disrupts this interaction.

    Evidence GST pulldowns, co-localization, and point mutagenesis of R5 and laforin

    PMID:14532330

    Open questions at the time
    • Functional consequence of the interaction not yet established here
    • In vivo relevance not tested
  7. 2007 High

    Defined the functional output of the laforin interaction: laforin enables malin to ubiquitinate PTG for proteasomal degradation, providing a mechanism to limit glycogen accumulation.

    Evidence Co-expression with in vitro/in vivo ubiquitination assays, proteasome inhibitor rescue, and glycogen accumulation readout

    PMID:18070875

    Open questions at the time
    • Upstream signals triggering this degradation not identified here
    • Ubiquitination site mapping not reported
  8. 2009 High

    Identified AMPK as the upstream regulator coupling energy status to PTG turnover, phosphorylating Ser-8/Ser-268 to accelerate laforin/malin-dependent degradation.

    Evidence Co-IP, MS site mapping, in vitro kinase assay, and degradation/glycogenic activity assays

    PMID:19171932

    Open questions at the time
    • Relative contributions of Ser-8 vs Ser-268 not fully resolved
    • In vivo physiological context of this regulation not tested
  9. 2013 Medium

    Showed PTG/PP1γ has a non-glycogenic signaling role, dephosphorylating SHP-1 to dampen NFAT5 transcriptional activity under osmotic stress.

    Evidence Reciprocal Co-IP, siRNA knockdown, phospho-specific Western, SHP-1 S591A mutagenesis, and NFAT5 reporter

    PMID:23720348

    Open questions at the time
    • Single-lab finding for a novel non-glycogenic function
    • Physiological/in vivo relevance not established
  10. 2010 Medium

    Identified hypoxic transcriptional control of PTG, with HIF1 driving glycogen accumulation through a proximal hypoxia response element.

    Evidence HRE luciferase mutagenesis, siRNA knockdown of HIF1α/HIF2α/PPP1R3C, and glycogen measurement under hypoxia

    PMID:20888814

    Open questions at the time
    • Direct HIF1 occupancy not shown by ChIP here
    • Tissue specificity of this axis unclear
  11. 2006 Medium

    Defined hepatic transcriptional regulation by showing FoxA2 directly transactivates the PTG promoter and cAMP induces PTG protein.

    Evidence Reporter assays, EMSA, ChIP, and Western blot after cAMP treatment

    PMID:16627590

    Open questions at the time
    • Integration with insulin/glucagon signaling not resolved
    • Single cell-line context
  12. 2011 High

    Confirmed PTG-mediated glycogen synthesis activation as the proximal cause of Lafora body formation through genetic epistasis in laforin-deficient mice.

    Evidence PTG-knockout crossed into laforin-deficient Lafora mice, with polyglucosan histology, EEG, and behavior

    PMID:21552327

    Open questions at the time
    • Did not address whether residual glycogen synthase activity contributes
    • Therapeutic translatability not addressed
  13. 2011 Medium

    Mapped a functionally required region of PTG by characterizing the N249S variant, which reduces glycogenic activity and binding to glycogen phosphorylase and laforin.

    Evidence Functional glycogen synthesis assays and interaction assays of the natural variant

    PMID:21738631

    Open questions at the time
    • Clinical significance of the variant not established
    • Structural basis defined only later
  14. 2011 Medium

    Characterized the glycogen product driven by PTG, showing it activates glycogen synthase and produces enlarged cytosolic glycogen particles distinct from other PP1 subunits.

    Evidence Myotube overexpression with GS phosphorylation, glycogen content, and EM particle-size/localization analyses

    PMID:22054094

    Open questions at the time
    • Determinants of particle morphology unknown
    • Single-lab descriptive comparison
  15. 2013 Medium

    Placed PTG within circadian metabolic control, showing PER2 binds PTG genomic regions and contributes to rhythmic hepatic glycogen accumulation.

    Evidence PER2 ChIP and Per2-mutant mouse glycogen/enzymatic phenotyping

    PMID:24049741

    Open questions at the time
    • Direct vs indirect transcriptional effect not fully separated
    • Mechanism of PER2 recruitment unclear
  16. 2014 High

    Replicated and extended the Lafora epistasis to malin-deficient mice, confirming PTG-mediated glycogen synthesis as the key pathogenic mechanism downstream of malin.

    Evidence PTG-knockout crossed into malin-deficient mice with Lafora body, seizure, and behavioral readouts

    PMID:24419970

    Open questions at the time
    • Did not test partial PTG inhibition as a therapeutic strategy directly
    • Neuronal vs astrocytic contributions not dissected
  17. 2019 Medium

    Identified a gluconeogenic role for PTG, linking it to hepatic glucose production via TORC2 dephosphorylation and nuclear localization.

    Evidence Adenoviral gain/loss-of-function in hepatocytes and mouse liver with TORC2 phospho/localization and glucose production assays

    PMID:31181215

    Open questions at the time
    • Whether PP1 catalytic activity mediates TORC2 dephosphorylation not directly shown
    • Single-lab finding
  18. 2020 Medium

    Generalized PTG's pathogenic glycogen-synthesis role to a second polyglucosan disease, showing PTG knockout reduces muscle polyglucosan bodies and improves outcomes in an APBD model.

    Evidence PTG knockout crossed into GBE-deficient APBD mice with histology, lifespan, and neuromuscular testing

    PMID:33034425

    Open questions at the time
    • Brain vs muscle relative benefit not fully resolved
    • Single study
  19. 2020 Medium

    Defined IRF4 as a transcriptional regulator acting through PTG to control muscle glycogen and exercise capacity, demonstrated by epistatic rescue.

    Evidence Muscle-specific IRF4 knockout/overexpression with adenoviral PTG knockdown rescue

    PMID:33042761

    Open questions at the time
    • Direct IRF4 binding to PTG promoter not detailed
    • Single-lab finding
  20. 2022 High

    Provided the structural basis of PTG function, revealing how multiple PP1-recruitment sites assemble the PP1/PTG/carbohydrate ternary complex.

    Evidence X-ray crystallography, in-solution SAXS, and per-site binding affinity measurements

    PMID:36261419

    Open questions at the time
    • Substrate enzymes not captured in the structure
    • Conformational heterogeneity not mechanistically resolved
  21. 2026 Medium

    Established PTG as a glycogen-synthesis-dependent tumor suppressor in endometrial cancer, with glycogen synthase activity required for its growth-inhibitory effect.

    Evidence Ectopic expression in UCEC cell lines, glycogen synthase inhibition rescue, xenografts, and cell cycle/apoptosis assays

    PMID:41781186

    Open questions at the time
    • Link between glycogen accumulation and apoptosis mechanism unclear
    • Single-lab finding
  22. 2026 Low

    Proposed a non-canonical adipose role for PTG in browning via an ADRB3-PTG-VEGFB axis, linking glycogen metabolism to thermogenesis.

    Evidence PTG overexpression in iWAT, VEGFB knockdown rescue, and ADRB3 agonist treatment in PM2.5-exposed mice

    PMID:41514494

    Open questions at the time
    • Mechanistic chain from PTG to VEGFB not established
    • Novel function reported in a single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PTG's diverse non-glycogenic functions (TORC2 dephosphorylation, SHP-1/NFAT5, VEGFB regulation) mechanistically depend on PP1 catalytic activity and how they are coordinated with its canonical glycogenic role across tissues.
  • Direct PP1 substrate identification for non-glycogenic roles missing
  • Tissue-specific regulatory integration not defined
  • Structural basis for substrate enzyme recruitment unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-1643685 Disease 4
Partners
EPM2A (LAFORIN)GYS1NHLRC1 (MALIN)PHKBPPP1CCPRKAA (AMPK)PTPN6 (SHP-1)PYGL
Complex memberships
PP1/PTG/glycogen complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 PTG (PPP1R3C) was identified as a glycogen-targeting subunit of PP1 that acts as a molecular scaffold: it binds PP1C, localizes it to glycogen, and also forms complexes with phosphorylase kinase, phosphorylase a, and glycogen synthase. Overexpression of PTG in CHO cells markedly increased basal and insulin-stimulated glycogen synthesis. Cloning from 3T3-L1 adipocytes, co-immunoprecipitation/pulldown of PTG with PP1C and glycogen metabolism enzymes, overexpression in CHO cells with insulin receptor Science High 9045612
1997 PTG increases PP1 activity against phosphorylase a by decreasing the Km of PP1 for this substrate 5-fold without affecting Vmax; PTG did not affect PP1 activity against hormone-sensitive lipase. PTG was not phosphorylated in vivo or in vitro by insulin- or forskolin-activated kinases. PTG decreased the ability of DARPP-32 to inhibit PP1 activity. GST-PTG pulldown from 3T3-L1 lysates, in vitro phosphatase activity assay with 32P-labeled phosphorylase a, in vivo and in vitro kinase assays, PP1 inhibitor (DARPP-32) competition assay The Journal of biological chemistry High 9242697
1998 Adenovirus-mediated overexpression of PTG in primary rat hepatocytes potently activates glycogen synthesis even in the absence of carbohydrates or insulin, increases glycogen synthase activation state 3.6-fold, and decreases glycogen phosphorylase activity 40%. Glycogenolytic agents (forskolin, glucagon) are largely ineffective at activating glycogen degradation in PTG-overexpressing hepatocytes despite large cAMP increases. Recombinant adenovirus-mediated PTG overexpression in primary rat hepatocytes; glycogen synthase activity assay; glycogen phosphorylase activity assay; cAMP measurement The Journal of biological chemistry High 9756875
2003 PTG (PPP1R3C) knockout mice (heterozygous deletion) have reduced glycogen stores in adipose tissue, liver, heart, and skeletal muscle, with decreased glycogen synthase activity and glycogen synthesis rate, demonstrating PTG is required for normal glycogen synthesis in vivo. Heterozygous PTG gene deletion in mice; tissue glycogen measurement; glycogen synthase activity assay; metabolic phenotyping including glucose tolerance and insulin resistance The Journal of clinical investigation High 12727934
2003 Laforin interacts with the glycogen-targeting regulatory subunit R5/PTG. The interaction requires full-length laforin, and a minimal central region of R5 (amino acids 116-238) including the glycogen and glycogen synthase binding sites is sufficient. Point mutagenesis of the glycogen synthase-binding site of R5 completely blocks interaction with laforin. Lafora disease-associated laforin mutation G240S disrupts the interaction with R5 without affecting phosphatase or glycogen binding activities. Pulldown assays (GST-fusion proteins), co-localization experiments, point mutagenesis of R5 and laforin Human molecular genetics High 14532330
2007 Malin (E3 ubiquitin ligase) ubiquitinates PTG in a laforin-dependent manner both in vivo and in vitro, targeting PTG for proteasome-dependent degradation. Co-expression of malin and laforin abolished PTG-stimulated glycogen accumulation in tissue culture cells. Co-expression of PTG, malin, and laforin in tissue culture cells; in vitro and in vivo ubiquitination assays; proteasome inhibitor rescue experiments; glycogen accumulation assay The Journal of biological chemistry High 18070875
2009 AMPK physically interacts with R5/PTG and phosphorylates it at Ser-8 and Ser-268 (mapped by mass spectrometry). Phosphorylation of Ser-8 by AMPK accelerates laforin/malin-dependent ubiquitination and proteasomal degradation of R5/PTG, resulting in decreased glycogenic activity. Co-immunoprecipitation of AMPK with R5/PTG; mass spectrometry phosphorylation site mapping; in vitro AMPK kinase assay; ubiquitination and proteasome-dependent degradation assays; glycogenic activity measurement The Journal of biological chemistry High 19171932
2009 PTG (PP1 regulatory subunit) associates physically with PP1γ, and high NaCl reduces PTG-PP1γ association and remaining PTG-associated PP1γ activity. PTG and PP1γ bind to SHP-1, and knockdown of PTG or PP1γ increases high NaCl-induced phosphorylation of SHP-1-S591 (inhibitory), which in turn reduces SHP-1's inhibitory effect on NFAT5. Thus PTG/PP1γ dephosphorylates SHP-1 to dampen NFAT5 activity under high NaCl. Co-immunoprecipitation of PTG with PP1γ and SHP-1; siRNA knockdown of PTG and PP1γ; phospho-specific Western blot for SHP-1-S591; mutation of SHP-1-S591 to alanine; NFAT5 transcriptional activity assay American journal of physiology. Renal physiology Medium 23720348
2010 HIF1 directly regulates PPP1R3C expression through a functional hypoxia response element 229 bp upstream of the PPP1R3C gene. PPP1R3C induction by hypoxia correlates with glycogen accumulation in MCF7 cells; knockdown of either HIF1α or PPP1R3C attenuates hypoxia-induced glycogen accumulation. Mutation analysis of hypoxia response element by luciferase reporter assay; siRNA knockdown of HIF1α, HIF2α, and PPP1R3C; glycogen content measurement under hypoxia FEBS letters Medium 20888814
2011 Genetic removal of PTG from Lafora disease mice (laforin- or malin-deficient) results in near-complete disappearance of polyglucosan (Lafora body) accumulation and resolution of neurodegeneration and myoclonic epilepsy, demonstrating that PTG-driven PP1 activation of glycogen synthase is the proximal cause of Lafora body formation. Genetic cross of PTG-knockout mice with Lafora disease (laforin-deficient) mice; histological analysis of polyglucosan accumulation; EEG/behavioral assessment of myoclonic epilepsy PLoS genetics High 21552327
2011 A PTG variant (N249S, c.746A>G) results in decreased capacity to induce glycogen synthesis and reduced interaction with glycogen phosphorylase and laforin, establishing that the glycogen phosphorylase and laforin binding region of PTG is required for full glycogenic activity. Identification of N249S mutation; functional assay of glycogen synthesis; interaction assays with glycogen phosphorylase and laforin PloS one Medium 21738631
2014 Genetic reduction of PTG in malin-deficient Lafora disease mice nearly completely eliminates Lafora bodies and rescues neurodegeneration, myoclonus, seizure susceptibility, and behavioral abnormality, confirming that PTG-mediated glycogen synthesis activation is the key pathogenic mechanism downstream of malin. Genetic cross of PTG-knockout mice with malin-deficient mice; histological Lafora body quantification; seizure susceptibility and behavioral testing Annals of neurology High 24419970
2019 PPP1R3C overexpression in primary mouse hepatocytes and mouse liver promotes hepatic glucose production and gluconeogenic gene expression. Knockdown of PPP1R3C suppresses cAMP-stimulated gluconeogenic gene expression and blocks TORC2 dephosphorylation (nuclear localization). AMPK activation (by metformin) suppresses Ppp1r3c mRNA expression. PPP1R3C-mediated TORC2 dephosphorylation links PPP1R3C to gluconeogenic transcription. Adenovirus-mediated overexpression and knockdown of PPP1R3C in primary hepatocytes and mouse liver in vivo; Western blot and immunofluorescence for TORC2 phosphorylation/localization; hepatic glucose production assay; gluconeogenic gene expression Metabolism: clinical and experimental Medium 31181215
2020 PPP1R3C knockout reduces skeletal muscle polyglucosan bodies in an APBD (GBE-deficient) mouse model and improves lifespan, morphology, and neuromuscular function, confirming PTG's role in activating glycogen synthase (GYS1) in muscle in vivo. PPP1R3C knockout crossed into APBD mouse model; histological polyglucosan body quantification; lifespan and behavioral assays; brain and muscle glycogen quantification Annals of clinical and translational neurology Medium 33034425
2020 IRF4 in skeletal muscle regulates glycogen metabolism via transcriptional control of PTG. Skeletal muscle-specific IRF4 knockout increases glycogen content and exercise capacity; IRF4 overexpression decreases both. Knockdown of PTG reverses the phenotype of IRF4 knockout, placing PTG downstream of IRF4 in a glycogen regulatory pathway. Skeletal muscle-specific IRF4 knockout and overexpression mice; glycogen content measurement; exercise capacity testing; adenovirus-mediated PTG knockdown as epistasis test Advanced science Medium 33042761
2022 Crystal structure of the ternary PP1/PTG/carbohydrate complex was determined, revealing an unusual combination of PP1-recruitment sites on PTG. PTG uses multiple binding interfaces to recruit PP1 to glycogen granules. In-solution SAXS analyses revealed conformational heterogeneity of the complex. Individual contributions of recruitment sites to overall binding affinity were characterized. X-ray crystallography of PP1/PTG/carbohydrate ternary complex; SAXS (small-angle X-ray scattering) in solution analysis; binding affinity measurements of individual recruitment sites Nature communications High 36261419
2000 Among glycogen-targeting PP1 subunits expressed in hepatocytes, PTG overexpression retains dose-dependent regulation of glycogen synthesis and glycogen synthase activity by insulin, whereas PTG-overexpressing cells show reduced glycogenolytic response to forskolin compared to GL- or GM/RGl-overexpressing cells. This is partly explained by lesser forskolin-induced increase in glycogen phosphorylase activity in PTG cells. Adenovirus-mediated overexpression of PTG, GL, and GM/RGl in hepatocytes; glycogen synthase activity ratio measurement; glycogen phosphorylase activity assay; glycogenolytic response to forskolin The Journal of biological chemistry Medium 10862764
2006 The PTG promoter contains functional FoxA2 binding sites. FoxA2 transactivates the PTG promoter in H4IIE hepatoma cells. FoxA2 binds the PTG promoter in vivo (shown by ChIP). cAMP analog treatment activates the PTG promoter and increases PTG protein levels in H4IIE cells. Luciferase reporter assays with PTG promoter constructs; electrophoretic mobility shift assay with nuclear extracts; chromatin immunoprecipitation (ChIP); Western blot of PTG levels after cAMP treatment Endocrinology Medium 16627590
2011 PPP1R3C/PTG overexpression in skeletal muscle myotubes activates glycogen synthase (reduces phosphorylation at Ser-641/0), increases glycogen content, and produces larger glycogen particles (mean diameter 36.9 nm) compared to PPP1R6 (14.4 nm) or GM (28.3 nm). PTG-derived glycogen is found in membrane- and organelle-devoid cytosolic glycogen-rich areas. Overexpression in skeletal muscle myotubes; glycogen synthase activity and phosphorylation assay; glycogen content measurement; electron microscopy of glycogen particle size and subcellular localization BMC biochemistry Medium 22054094
2013 PER2 promotes expression of PTG (and GL) by binding to genomic regions of PTG in liver. Per2-deficient mice show reduced hepatic glycogen content, altered rhythms of glycogen accumulation, and altered glycogen phosphorylase activity. These effects are at least partly mediated through PER2's transcriptional control of PTG. Chromatin immunoprecipitation (ChIP) of PER2 at PTG genomic regions; Per2 mutant mice phenotyped for glycogen content, glycogen synthase protein levels, and glycogen phosphorylase activity under fasting/refeeding Molecular metabolism Medium 24049741
2026 PPP1R3C acts as a tumor suppressor in endometrial cancer cells through promotion of glycogen synthesis: ectopic PPP1R3C expression induces cell cycle arrest and apoptosis in UCEC-derived cells (HEC1A, HEC1B) and inhibits xenograft tumor growth. Inhibition of glycogen synthase abrogates the growth inhibitory effect of PPP1R3C, establishing that glycogen synthesis activation is required for its tumor suppressor function. Ectopic expression of PPP1R3C in UCEC cell lines; glycogen synthase inhibition rescue experiment; xenograft tumor growth in BALB/c nude mice; cell cycle and apoptosis assays BMB reports Medium 41781186
2026 PTG overexpression in inguinal white adipose tissue restores glycogen metabolism, thermogenesis, and mitochondrial function impaired by PM2.5 exposure. Mechanistically, PTG negatively regulates VEGFB, and VEGFB knockdown rescues browning. ADRB3 activation restores PTG and normalizes VEGFB, defining an ADRB3-PTG-VEGFB axis. PTG overexpression in iWAT via adenovirus/AAV in PM2.5-exposed mice; VEGFB knockdown rescue experiment; ADRB3 agonist treatment; thermogenesis and mitochondrial function assays; glycogen content measurement Advanced science Low 41514494

Source papers

Stage 0 corpus · 44 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 PTG, a protein phosphatase 1-binding protein with a role in glycogen metabolism. Science (New York, N.Y.) 248 9045612
2007 Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG). The Journal of biological chemistry 125 18070875
2011 PTG depletion removes Lafora bodies and rescues the fatal epilepsy of Lafora disease. PLoS genetics 110 21552327
2003 Laforin, the dual-phosphatase responsible for Lafora disease, interacts with R5 (PTG), a regulatory subunit of protein phosphatase-1 that enhances glycogen accumulation. Human molecular genetics 89 14532330
2003 PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance. The Journal of clinical investigation 87 12727934
2009 Prophylactic total gastrectomy (PTG) for hereditary diffuse gastric cancer (HDGC): the Newfoundland experience with 23 patients. Annals of surgical oncology 82 19408054
2010 Hypoxia-inducible factor 1-mediated regulation of PPP1R3C promotes glycogen accumulation in human MCF-7 cells under hypoxia. FEBS letters 81 20888814
2000 Distinctive regulatory and metabolic properties of glycogen-targeting subunits of protein phosphatase-1 (PTG, GL, GM/RGl) expressed in hepatocytes. The Journal of biological chemistry 72 10862764
1997 Role of protein targeting to glycogen (PTG) in the regulation of protein phosphatase-1 activity. The Journal of biological chemistry 72 9242697
2014 PTG protein depletion rescues malin-deficient Lafora disease in mouse. Annals of neurology 68 24419970
1998 Overexpression of protein targeting to glycogen (PTG) in rat hepatocytes causes profound activation of glycogen synthesis independent of normal hormone- and substrate-mediated regulatory mechanisms. The Journal of biological chemistry 67 9756875
2013 PER2 promotes glucose storage to liver glycogen during feeding and acute fasting by inducing Gys2 PTG and G L expression. Molecular metabolism 62 24049741
2009 AMP-activated protein kinase phosphorylates R5/PTG, the glycogen targeting subunit of the R5/PTG-protein phosphatase 1 holoenzyme, and accelerates its down-regulation by the laforin-malin complex. The Journal of biological chemistry 49 19171932
2014 Aberrant promoter methylation of PPP1R3C and EFHD1 in plasma of colorectal cancer patients. Cancer medicine 37 24861485
2021 PTG-100, an Oral α4β7 Antagonist Peptide: Preclinical Development and Phase 1 and 2a Studies in Ulcerative Colitis. Gastroenterology 35 34474038
2020 PTG-0861: A novel HDAC6-selective inhibitor as a therapeutic strategy in acute myeloid leukaemia. European journal of medicinal chemistry 34 32615502
2019 The traditional Chinese formulae Ling-gui-zhu-gan decoction alleviated non-alcoholic fatty liver disease via inhibiting PPP1R3C mediated molecules. BMC complementary and alternative medicine 30 30616587
2020 IRF4 in Skeletal Muscle Regulates Exercise Capacity via PTG/Glycogen Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 24 33042761
2019 PPP1R3C mediates metformin-inhibited hepatic gluconeogenesis. Metabolism: clinical and experimental 23 31181215
2011 A PTG variant contributes to a milder phenotype in Lafora disease. PloS one 22 21738631
2020 GYS1 or PPP1R3C deficiency rescues murine adult polyglucosan body disease. Annals of clinical and translational neurology 21 33034425
2015 The effect of high glucose levels on the hypermethylation of protein phosphatase 1 regulatory subunit 3C (PPP1R3C) gene in colorectal cancer. Journal of genetics 21 25846879
1999 Retro Models of Pt Anticancer Drug DNA Adducts: Chirality-Controlling Chelate Ligand Restriction of Guanine Dynamic Motion in (2,2'-Bipiperidine)PtG(2) Complexes (G = Guanine Derivative). Inorganic chemistry 21 11671050
2002 Factors influencing conformer equilibria in retro models of cisplatin-DNA adducts as revealed by moderately dynamic (N,N'-dimethyl-2,3-diaminobutane)PtG(2) retro models (G = a guanine derivative). Inorganic chemistry 20 12230397
2014 Arraying the post-translational glycoproteome (PTG). Current opinion in chemical biology 19 24487061
2011 Differential pattern of glycogen accumulation after protein phosphatase 1 glycogen-targeting subunit PPP1R6 overexpression, compared to PPP1R3C and PPP1R3A, in skeletal muscle cells. BMC biochemistry 19 22054094
1987 Genetic control of capsid length in bacteriophage T4: clustering of ptg mutations in gene 23. Journal of virology 13 3612952
2006 Regulation of the mouse protein targeting to glycogen (PTG) promoter by the FoxA2 forkhead protein and by 3',5'-cyclic adenosine 5'-monophosphate in H4IIE hepatoma cells. Endocrinology 12 16627590
2022 Molecular architecture of the glycogen- committed PP1/PTG holoenzyme. Nature communications 11 36261419
2020 MiR-4461 Inhibits Tumorigenesis of Renal Cell Carcinoma by Targeting PPP1R3C. Cancer biotherapy & radiopharmaceuticals 10 32915648
2013 High NaCl-induced inhibition of PTG contributes to activation of NFAT5 through attenuation of the negative effect of SHP-1. American journal of physiology. Renal physiology 10 23720348
1987 Genetic control of capsid length in bacteriophage T4: phenotypes displayed by ptg mutants. Journal of virology 10 3612954
2013 [Guidelines for application of molecular tests identyfying HR HPV DNA in the prevention of cervical cancer. Statement of experts from PGS (PTG) and NCLD (KIDL)]. Ginekologia polska 7 23819408
2023 Integration of in-situ and ex-situ power-to-gas (PtG) strategy for simultaneous bio-natural gas production and CO2 emission reduction. Chemosphere 6 37802480
2022 Protein Targeting to Glycogen (PTG): A Promising Player in Glucose and Lipid Metabolism. Biomolecules 6 36551183
2018 Prostaglandin (PTG) E and F receptors in the porcine corpus luteum; effect of tumor necrosis factor-α. Animal reproduction science 6 29908856
2013 Molecular characterization and expression analysis of PPP1R3C in hypoxia-tolerant Indian catfish, Clarias batrachus (Linnaeus, 1758) under hypoxia. Gene 6 23948083
2025 QKI-induced circ_0001766 inhibits colorectal cancer progression and rapamycin resistance by miR-1203/PPP1R3C/mTOR/Myc axis. Cell death discovery 5 40263288
1999 Protein targeting to glycogen/PPP1R5: screening of coding and flanking genomic regions for polymorphisms and association analysis with insulin action in Pima Indians. Biochemical and biophysical research communications 5 10222257
2024 sgRNA structure optimization and PTG/Cas9 system synergistically boost gene knockout efficiency in an insect. International journal of biological macromolecules 2 39270887
2026 PTG-Dependent Glycogen Metabolic Dysfunction Drives Impaired Adipose Browning: A Novel Mechanism Linking PM2.5 to Metabolic Disorders. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41514494
2026 PPP1R3C functions as a tumor suppressor in endometrial cancer through promotion of glycogen synthesis. BMB reports 0 41781186
2026 CRISP-PTG-Assembler Ver. 1.0: a primer design tool for polycistronic tRNA-gRNA (PTG) assembly for Cas9-based multiplex genome editing in plants. Planta 0 42043584
1992 Nude mouse interim host model for human parathyroid grafts. II. Alteration of MHC antigens in human PTG grafts in the nude mouse. Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih 0 1450400

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