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FLASH GENE
Symbol PLCG1 contributors: mct/ - updated : 26-11-2015
HGNC name phospholipase C, gamma 1
HGNC id 9065
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestinecolon moderately
 intestinesmall intestine  moderately
 mouthtongue  moderately
Lymphoid/Immunethymus   highly
Nervousbrain   highly Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Nervousneuron Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one C2 domain
  • one EF-hand calcium-binding domain
  • two pleckstrin homology (PH) domains
  • one PI-PLC X-box catalytic domain
  • one PI-PLC Y-box catalytic domain
  • two SH2 domains
  • one SH3 domain, Src homology 3 (SH3) domain which possesses mitogenic activity, mediating EGF-induced squamous cell carcinoma cell mitogenesis
  • HOMOLOGY
    interspecies ortholog to murine Plcg1
    ortholog to rattus Plcg1
    homolog to C. elegans T01E8.3 and 2K519
    ortholog to xenopus AF090112.1
    Homologene
    FAMILY
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • nuclear localization is increased by high NaCl
  • basic FUNCTION
  • phospholipase C, gamma 1 (subtype 148), phosphatidylinositol specific
  • catalyzing the hydrolysis of phosphatidylinositol 4,5 biphosphate to generate diacylglycerol and inositol 1,4,5 triphosphate
  • mediating a wide variety of cellular stimuli
  • being a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase
  • promoting adhesion-dependent association of the two molecules and increase inositol-phosphate production by direct interaction with phosphorylated PTK2 (mouse fibroblasts)
  • regulating TRPC3 channels
  • couple immune recognition receptors to important calcium- and protein kinase C-dependent cellular functions
  • may be involved in tumor progression and in the metastatic potential of cancer cells
  • involved with PDGFA in phosphorylation of PEA15
  • PDPK1 and PLCG1 are two key enzymes in signal transduction that control several intracellular processes
  • participates in neuronal cell functions mediated by neurotrophins
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism lipid/lipoprotein
    signaling signal transduction
  • lipid degradation
  • transducer
  • PDPK1-PLCG1 pathway is important for cancer cell invasion
  • a component
  • with PLCG1, is part of the protein complex that associates with NFAT5 at its DNA binding site
  • GRB14 was recruited to FGFR1 into a trimeric complex containing also phospholipase C gamma (PLCG1)
  • complexes with cofilin, ERBB2 and PLCG1
  • INTERACTION
    DNA
    RNA
    small molecule metal binding, cofactor,
  • Ca2+
  • protein
  • directly interacting with phosphorylated PTK2 (mouse fibroblasts)
  • Pro-rich domain of TNK1 via its SH3 domain
  • TRPC3 channels
  • substrate for parkin (PARK2 deficiency disrupts calcium homeostasis by modulating phospholipase C1 signaling)
  • association with complexes containing GIT1 and ARHGEF7 is essential for its role in integrin-mediated cell spreading and motility (as a component of this complex, PLCG1 is also involved in the activation of Cdc42 and Rac1)
  • by regulating the localization of PLCG1, APBB1IP plays a central role in TCR signaling and the transcription of target genes
  • interacting with NFAT5 (when NaCl is elevated, NFAT5 becomes phosphorylated at Y143, resulting in binding of PLCG1 to that site, which contributes to NFAT5 transcriptional activity, transactivating activity, and nuclear localization)
  • interacting with NTRK2 (NTRK2-dependent activation of PLCG1 signaling is an important molecular mechanism of limbic epileptogenesis)
  • CBL is a negative regulator of PLCG1 in endothelial cells
  • STK11 predominately interacted with LAT and PLCG1 following TCR stimulation
  • PDPK1 regulates PLCG1 activation in a mechanism involving association of the two enzymes and modulation of PLCG1 tyrosine phosphorylation
  • interaction of VAV1 with PLCG1 (oncogenic truncation of VAV1 N-terminus elicits conformational changes that interfere with the VAV1-mediated activation of PLCG1 and inhibit calcium mobilization) (PMKID: 22474331)
  • ITK modulates T-cell signaling by activating PLCG1 and regulating the extent of Ca2+ flux
  • RASGRF1/2 associates with PLCG1
  • a specific docking interaction between the kinase domain of ITK and the C-terminal Src homology 2 (SH2C) domain of PLCG1 that promotes substrate specificity for this enzyme/substrate pair
  • SOCS7 interact with PLCG1, one of the insulin-like growth factor-1 (IGF1) receptor downstream molecules
  • upon T cell activation, LAT is phosphorylated and associates with GRB2, GRAP2, and PLCG1 through its four distal tyrosine residues
  • CISH physically interacts with the TCR intermediate PLCG1, targeting it for proteasomal degradation after TCR stimulation
  • cell & other
    REGULATION
    activated by hypoxia, that activates PLCG1 by increasing RISP-dependent mitochondrial ROS production in the complex III, which causes inositol 1,4,5-trisphosphate (IP3) production, ITPR opening, and Ca(2+) release, playing an important role in hypoxic Ca(2+) and contractile responses in pulmonary arterial smooth muscle cells (PASMCs)
    Other regulated by PARK2 (Parkin-mediated ubiquitination regulates PLCG1)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyepilepsy 
    disruption of NTRK2-mediated PLCG1 signaling inhibits limbic epileptogenesis, and is a novel target for specific and effective therapeutic intervention
    ANIMAL & CELL MODELS