1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1

Function

Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, EGFR, FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Plays a role in actin reorganization and cell migration. Guanine nucleotide exchange factor that binds the GTPase DNM1 and catalyzes the dissociation of GDP, allowing a GTP molecule to bind in its place, therefore enhancing DNM1-dependent endocytosis (By similarity).

Classification

Family (Pfam)

PF00168 C2, PF23329 EF_HAND_1_PLCG, PF23583 EF_HAND_2_PLCG, PF00169 PH, PF00388 PI-PLC-X, PF00387 PI-PLC-Y, PF00017 SH2, PF00018 SH3_1

InterPro

C2_dom, C2_domain_sf, EF-hand-dom_pair, EF-hand_PLCG1, EF_Hand_1_Ca_BS, EF_hand_dom, PH-like_dom_sf, PH_domain, PI-PLC_fam, PLC-gamma, PLC-gamma_C-SH2, PLC-gamma_N-SH2, PLC-like_Pdiesterase_TIM-brl, PLCG_EF-hand_2, PLCgamma1_SH3, PLipase_C_PInositol-sp_X_dom, PLipase_C_Pinositol-sp_Y, SH2, SH2_dom_sf, SH3-like_dom_sf, SH3_domain

Functional cluster

Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 5

• 1HSQ NMR
• 2HSP NMR
• 4EY0 X-ray 2.80A
• 4FBN X-ray 2.40A
• 7NXE X-ray 2.10A

A predicted model is available from AlphaFold.

Gene Ontology · 33

• GO:0042995 cell projection
• GO:0008180 COP9 signalosome
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0030027 lamellipodium
• GO:0005886 plasma membrane
• GO:0001726 ruffle
• GO:0032587 ruffle membrane
• GO:0004629 C-type glycerophospholipase activity
• GO:0005509 calcium ion binding
• GO:0005085 guanyl-nucleotide exchange factor activity
• GO:0140324 lysophospholipase C activity
• GO:0005168 neurotrophin TRKA receptor binding
• GO:0120548 phosphatidylinositol phospholipase C activity
• GO:0004435 phosphatidylinositol-4,5-bisphosphate phospholipase C activity
• GO:0019901 protein kinase binding
• GO:0019722 calcium-mediated signaling
• GO:0016477 cell migration
• GO:0071364 cellular response to epidermal growth factor stimulus
• GO:0007173 epidermal growth factor receptor signaling pathway
• GO:0038095 Fc-epsilon receptor signaling pathway
• GO:0002862 negative regulation of inflammatory response to antigenic stimulus
• GO:0046488 phosphatidylinositol metabolic process
• GO:0048015 phosphatidylinositol-mediated signaling
• GO:0009395 phospholipid catabolic process
• GO:0045766 positive regulation of angiogenesis
• GO:0043536 positive regulation of blood vessel endothelial cell migration
• GO:2000353 positive regulation of endothelial cell apoptotic process
• GO:0010634 positive regulation of epithelial cell migration
• GO:0051281 positive regulation of release of sequestered calcium ion into cytosol
• GO:1905564 positive regulation of vascular endothelial cell proliferation
• GO:0051209 release of sequestered calcium ion into cytosol
• GO:0050852 T cell receptor signaling pathway

Disease associations

• immune dysregulation, autoimmunity, and autoinflammation MONDO:0957790

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 1.00
• 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 1.00
• 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 1.00
• 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 0.93
• 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 0.93
• 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 0.93
• 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma plc-3 0.88
• Tyrosine-protein kinase ITK/TSK 0.76
• Tyrosine-protein kinase BTK 0.75
• Tyrosine-protein kinase BTK 0.75
• Tyrosine-protein kinase ITK/TSK 0.75
• Tyrosine-protein kinase BTK 0.74

Co-cited proteins · studied together in the literature

• Non-receptor tyrosine-protein kinase TNK1 1 shared papers
• Villin-1 1 shared papers
• Tyrosine-protein kinase TXK 1 shared papers
• Linker for activation of T-cells family member 1 4 shared papers
• B-cell linker protein 1 shared papers
• Vascular endothelial growth factor receptor 2 2 shared papers
• Fibroblast growth factor receptor 3 3 shared papers
• Fibroblast growth factor receptor 1 3 shared papers
• Phosphatidylinositol 3-kinase regulatory subunit alpha 8 shared papers
• Fibroblast growth factor receptor 2 2 shared papers
• Tyrosine-protein kinase SYK 1 shared papers
• Receptor-type tyrosine-protein phosphatase eta 2 shared papers

Literature · 43 cited papers

• A gain-of-function variation in PLCG1 causes a new immune dysregulation disease. J. Allergy Clin. Immunol. · 2023
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Tespa1 is involved in late thymocyte development through the regulation of TCR-mediated signaling. Nat. Immunol. · 2012
• Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function. EMBO J. · 2011
• System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Mutation of tyrosine residue 857 in the PDGF beta-receptor affects cell proliferation but not migration. Cell. Signal. · 2010
• Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
• Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
• Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
• A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells. Hum. Mol. Genet. · 2009
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• … and 31 more in the literature graph