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Symbol PLD2 contributors: mct/shn/pgu - updated : 07-12-2015
HGNC name phospholipase D2
HGNC id 9068
Location 17p13.2      Physical location : 4.710.420 - 4.726.727
Synonym name
  • choline phosphatase 2
  • phosphatidylcholine-hydrolyzing phospholipase D2
  • Synonym symbol(s) PLD1C, hPLD2
    TYPE functioning gene
    STRUCTURE 16.33 kb     25 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence cytosine-phosphate-guanine/HTF
    text structure
  • promoter is a TATA-less one, rich in CpG islands and with at least two core promoter sites located 362 and 77 bp upstream of the TSS
  • MAPPING cloned Y linked N status provisional
    Map pter - D17S1828 - D17S1584 - PLD2 - D17S1810 - D17S1854 - cen
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    25 - 3489 106 933 - 2006 16837165
    25 - 3481 - 922 - -
    Type ubiquitous
       expressed in (based on citations)
    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
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
  • 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
    interspecies ortholog to Pld2, Rattus norvegicus
    ortholog to PLD2, Pan troglodytes
    ortholog to Pld2, Mus musculus
    ortholog to pld2, Danio rerio
  • phospholipase D family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • 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
  • catalyzes the hydrolysis of phosphatidylcholine to produce phosphatidic acid and choline
  • new signaling pathway (JAK-FES-PLD2) that is enhanced in highly proliferative breast cancer cells
  • a component
    small molecule
  • 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
    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
    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
    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
    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