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FLASH GENE
Symbol PLD2 contributors: mct/shn/pgu - updated : 07-12-2015
HGNC name phospholipase D2
HGNC id 9068
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Digestiveliver   lowly
Endocrinepancreas   highly
Lymphoid/Immunethymus   highly
Nervousbrain   highly
Reproductivefemale systemuterus  highly
 male systemprostate  highly
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticleukocyte
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • putative pleckstrin homology (PH) domains, that mediates GEF effect of RAC2 and is dependent on an intact RAC2 GTPase activity
  • a catalytic domain
  • two PLD phosphodiesterase domains
  • a PX(phox homology) domain, the major catalytic domain for its GEF activity, whereas the pleckstrin homology domain assists in the PX-mediated activity
  • a specific binding site to RAC2, composed of two CRIB (Cdc42-and Rac-interactive binding) motifs CRIB-1 and CRIB-2 in and around the PH domain in PLD2
    • HOMOLOGY
    interspecies ortholog to Pld2, Rattus norvegicus
    ortholog to PLD2, Pan troglodytes
    ortholog to Pld2, Mus musculus
    ortholog to pld2, Danio rerio
    Homologene
    FAMILY
  • phospholipase D family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • major myocardial phospholipase and localizes primarily to sarcolemmal membranes
    • basic FUNCTION
  • may have a role in signal-induced cytoskeletal regulation and/or endocytosis
  • involved in metabolic regulation, cardiac and brain function, senescence regulated secretion, mitogenesis and cytoskeletal changes
  • implicated in the regulation of Ca(2+) mobilization and contractile performance in the heart
  • may have a role in signal-induced cytoskeletal regulation and/or endocytosis
  • play a key role in the regulation of agonist-induced endocytosis of the mu-opioid receptor
  • PLD1, PLD2 activity plays an important role in promoting IgE-dependent signaling events within lipid microdomains in mast cells
  • overexpression leads to an increased DNA synthesis in presence of CD45 phosphatase
  • required for the stimulation of lysophosphatidic acid production by EGF
  • agonist-selective activation plays a key role in the regulation of NADH/NADPH-mediated ROS formation by opioids
  • both PLD1 and PLD2 participate in regulated cellular secretion, cytoskeletal organization, gene expression regulation, cell cycle control, growth, proliferation, and differentiation
  • involved in the subcellular localization of formyl-peptide receptors
  • phosphorylated PLD2, aided by Grb2, mediates lipase activity, whereas dephosphorylated PLD2 mediates an induction of cell proliferation
  • in activated cells PLD2 affects RAC2 in an initial positive feedback, but as RAC2-GTP accumulates in the cell, this constitutes a termination signal leading to PLD2 inactivation
  • PLD2 and FES might be physically associated, which could be beneficial for a quick transduction of the activating signal within the cell
  • PLD1, PLD2 shortens the differentiation time of cells becoming mature neutrophils
  • producing phosphatidic acid (PA) that plays an important role in regulating cell morphology in mast cells
  • involvement of PLD2 and phosphatidic acid (PA) in mediating PARN-induced eukaryotic mRNA decay and the crosstalk between the two enzymes that is deregulated in breast cancer cells
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text
  • catalyzes the hydrolysis of phosphatidylcholine to produce phosphatidic acid and choline
    • PATHWAY
    metabolism
    signaling
  • new signaling pathway (JAK-FES-PLD2) that is enhanced in highly proliferative breast cancer cells
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • EGF receptor, EGFR
  • phosphoprotein enriched in astrocytes 15, PEA15
  • phosphatidylinositol-4-phosphate 5-kinase type I alpha, PIP5K1A
  • alpha-actinin, ACTA
  • caveolin 1, CAV1
  • beta-actin, ACTB (PMID;
  • aldolase A, ALOA, via its PH domain
  • collapsin response mediator protein 2, CRMP-2
  • protein kinase C delta, PRKCD
  • tyrosine phosphorylated by c-Src (SRC) tyrosine kinase via direct association
  • opioid receptor mu 1, OPRM1
  • phospholipase C gamma 1, PLCG1
  • Mammalian target-of-rapamycin (mTOR) and regulatory associated protein of MTOR complex 1, RPTOR
  • rowth factor receptor-bound protein 2, GBR2
  • importance of functional interactions between PLD and Rac in the biological response of cell migration
  • PLD2 interacts with and activates the oncogene FES, a protein-tyrosine kinase known to be involved in myeloid cell development
  • binds directly to RAC2, resulting in PLD2 functioning as a guanine nucleotide exchange factor (GEF), because it switches RAC2 from the GDP-bound to the GTP-bound states
  • guanine nucleotide exchange factor (GEF) for RAC2 and any domains and amino acid site(s)are responsible for its GEF activity
  • activation of PRKCH and PLD2 signaling pathway is an important mechanism for regulation of TLR2-induced ABCA1 expression
  • JAK3, FES and PLD2 interactions in transformed cells maintain PLD2 at an enhanced level that leads to abnormal cell growth
  • PARN downregulates PLD2 whereas PLD2 upregulates PARN
    • cell & other
    REGULATION
    activated by protein kinase C
    calcium Ca2+
    GRB2, mediating lipase activity
    ARF6and thus involved in the regulation of mu-opioid receptor trafficking and signalling
    inhibited by PTPRC, mediating an induction of cell proliferation
    Munc-18-1
    amphiphysins, synaptojanin, and AP180
    collapsin response mediator protein 2, CRMP-2
    Other positively regulated by PIP2 and ARF1
    phosphorylation of PLD2 by CDK5 is involved in EGF-dependent insulin secretion
    regulated in sarcolemmal membranes by alpha-actinin and ARF1
    stimulated by G(M2) activator
    induced by insulin
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    of the lipid-signaling enzymes phospholipase D1 and D2 alter cytoskeletal organization, macrophage phagocytosis, and cytokine-stimulated neutrophil recruitment
    Susceptibility
    Variant & Polymorphism SNP
  • rs2286672 correlates with risk for hypertension
    • Candidate gene
  • active PLD2 enhances processes favorable to lymphoma cell metastasis whereas expression of inactive PLD2 inhibits metastasis
    • Marker
    Therapy target
    ANIMAL & CELL MODELS