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FLASH GENE
Symbol PPP1CC contributors: np/mct - updated : 11-02-2016
HGNC name protein phosphatase 1, catalytic subunit, gamma isozyme
HGNC id 9283
DNA
TYPE functioning gene
STRUCTURE 23.14 kb     7 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure
  • endogenous PPP1CC promoter normally functions in the testis to maintain a sufficient level of PPP1CC2 expression for normal spermatogenesis to occur, and production of spermatozoa capable of fertilization can take place in the complete absence of PPP1CC1 expression
  • MAPPING cloned Y linked N status confirmed
    Map cen - D12S1451 - D12S2275 - D12S2234 - D12S2351 - D12S2236 - D12S2038 - D12S2260 - D12S2252 - PPP1CC /D12S1327 ,D12S2038 - D12S2301 /D12S2257 - D12S2393 - D12S2266 - D12S2265 - D12S2237 - D12S2287 - D12S2212 - D12S2262 - D12S2313 - D12S2248 - D12S2312 - D12S2278 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 splicing 2483 37 323 ubiquitously expressed isoform 2014 25620225
    also called gamma 1, PPP1CC1
    8 - 1628 - 337 the most abundant isoform in the testis, and is a key regulator of sperm motility 2014 25620225
  • PP1gamma2, PPP1CC2
  • a key regulator of sperm motility
  • capability of PPP1CC2 to form a complex with TSSK1B mediated by the direct interaction of each with the kinase substrate protein TSKS (PMID: 24088291)
  • interaction between PPP1CC2 and DDOST that may have physiological implications in spermatogenesis (PMID: 23140390)
  • testis-enriched and sperm-specific isoform, PPP1CC2 which is essential for completion of spermatogenesis
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver    
    Nervousbrain    
    Reproductivemale systemtestis    Homo sapiens
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac  
    Muscularstriatumskeletal  
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    interspecies homolog to murine Ppp1cc
    homolog to C.elegans Fs6c9.1
    Homologene
    FAMILY
  • PPP phosphatase family
  • PP1 subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    intracellular,nucleus,chromatin/chromosome,heterochromosome
    intracellular,nucleus,nucleolus
    text
  • IKZF1 can target PPP1CC to the nucleus, and a fraction of PPP1CC
  • colocalizes with IKZF1 at pericentromeric heterochromatin (PC-HC)
  • co-localize with TCTEX1D4 in the microtubule organizing center (MTOC)
  • basic FUNCTION
  • serine/threonine protein phosphatase 1,catalytic subunit
  • possible mechanism involving PPP1CC and LBR for the regulation of nuclear membrane targeting to chromatin
  • involved in cell division and glycogen metabolism
  • dephosphorylate specific substrates in discrete subcellular compartments to modulate many cellular processes
  • role in maintaining GSK3B-serine9 phosphorylation downstream of thrombin signaling and promoting thrombus formation via fibrinogen binding and platelet aggregation
  • regulating muscle contractility,protein synthesis, ionic conductances and long term synaptic plasticity
  • potential role of the PTW/PP1 phosphatase complex in the regulation of chromatin structure during the transition from mitosis into interphase
  • role in the formation of the SMN complex and the maintenance of Cajal bodies (CBs) integrity
  • PPP1CA and PPP1CC are the primary phosphatases that are responsible for IFIH1 and DDX58 dephosphorylation
  • that lead to their activation
  • its phosphatase activity regulates overall TRAF6 E3 ubiquitin ligase function and promotes NFKB1-mediated innate signaling responses
  • CELLULAR PROCESS cell cycle, division
    protein, translation/synthesis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism carbohydrate
    signaling
    a component
  • stable multimeric complex composed of regulatory subunits PPP1R10, TOX4, and WDR82 , and PPP1CC catalytic subunit (denoted as the PTW/PP1 phosphatase complex)
  • TCTEX1D4/PPP1CC complex appears to be involved in microtubule dynamics, sperm motility, acrosome reaction and in the regulation of the blood-testis barrier
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Mn2+
  • protein
  • targeting of PPP1CC to F-actin by neurabins in intact cells requires both the canonical PP1-binding motif and an auxiliary PPP1CC-selectivity determinant
  • interact with, and dephosphorylate AXIN1, leading to its destabilization and DAB2 functions upstream of PPP1CC to block the interaction between AXIN1 and PPP1CC, inhibiting AXIN1 dephosphorylation and thereby stabilizing its expression, ultimately leading to inhibition of Wnt/beta-catenin
  • interacts with IKZF1 via a conserved PP1 binding motif, RVXF, in the C-terminal end of the IKZF1 protein
  • reciprocal relationship between the levels of the PPP1CC and its regulator PPP1R11, suggesing that complex formation between these polypeptides in testis may prevent proteolysis of PPP1R11 and thus, germ cell apoptosis
  • binding of PPP1CC to CENPE required for the stable attachmentof these chromosomes
  • PLK1 controls the NEK2-PPP1CC antagonism in centrosome disjunction
  • dependent manner
  • PPP1CC interacts with and dephosphorylates WWC1
  • SMN complex and its component GEMIN8 interact directly with protein phosphatase PPP1CC
  • binding of actin to PHACTR4 influences the activity of PPP1CC and the phosphorylation status of one of its downstream targets, cofilin
  • TCTEX1D4 interacts with the different spliced isoforms of PPP1CC
  • is a positive regulator of MYD88-dependent proinflammatory innate immune activation
  • physically interacts with the E3 ubiquitin ligase TRAF6, and enhances the activity of TRAF6 towards itself and substrates such as IKBKG
  • AHCTF1 docks the catalytic subunit of protein phosphatase 1 (PPP1CC) to direct kinetochore disassembly-dependent chromosome segregation during oocyte meiosis I and nuclear assembly during the transition from M phase to interphase
  • cell & other
    REGULATION
    inhibited by DAB2 (DAB2 acts as a competitive inhibitor of PPP1CC by binding to the same C-terminal domain of AXIN1)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    promotes vascular smooth muscle cell survival by interfering with MAPK8 and TP53 phosphorylation cascades involved in apoptosis
    constitutional   deletion    
    in male infertility
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neuromuscularspinal muscular atrophy 
    GEMIN8 interaction with PPP1CC is a target for therapeutic intervention in SMA
    ANIMAL & CELL MODELS
  • testicular sperm tails from Ppp1cc-null mice showed malformed mitochondrial sheaths and extra outer dense fibers in both the middle and principal pieces
  • male Ppp1cc mutant mice are sterile due to disruptions in spermatogenesis that begin during prepubertal testicular development, and continue into adulthood, often resulting in loss of germ cells to the point of Sertoli cell-only syndrome