PLD2

Phospholipase D2 is an enzyme that in humans is encoded by the PLD2 gene.^[5][6]

PLD2
Identifiers
Aliases	PLD2, phospholipase D2, PLD1C
External IDs	OMIM: 602384; MGI: 892877; HomoloGene: 55672; GeneCards: PLD2; OMA:PLD2 - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p13.2 Start 4,807,152 bp[1] End 4,823,434 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 B3|11 42.99 cM Start 70,430,890 bp[2] End 70,448,936 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of leg right hemisphere of cerebellum ectocervix right ovary skin of abdomen minor salivary glands left ovary tibial nerve apex of heart ventricular zone Top expressed in lip esophagus zygote secondary oocyte ankle primary oocyte vestibular membrane of cochlear duct choroid plexus of fourth ventricle dentate gyrus of hippocampal formation granule cell skeletal muscle tissue More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phospholipase D activity N-acylphosphatidylethanolamine-specific phospholipase D activity protein binding catalytic activity phosphatidylinositol binding hydrolase activity Cellular component Golgi apparatus endoplasmic reticulum membrane membrane plasma membrane presynapse Biological process Fc-gamma receptor signaling pathway involved in phagocytosis lipid metabolism cell motility small GTPase mediated signal transduction lipid catabolic process synaptic vesicle recycling cytoskeleton organization phosphatidic acid biosynthetic process inositol lipid-mediated signaling Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5338 18806 Ensembl ENSG00000129219 ENSMUSG00000020828 UniProt O14939 P97813 RefSeq (mRNA) NM_001243108 NM_002663 NM_008876 NM_001302475 NM_001302476 NM_001361935 RefSeq (protein) NP_001230037 NP_002654 NP_001289404 NP_001289405 NP_032902 NP_001348864 Location (UCSC) Chr 17: 4.81 – 4.82 Mb Chr 11: 70.43 – 70.45 Mb PubMed search [3] [4]
Wikidata
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Function

Phosphatidylcholine (PC)-specific phospholipases D (PLDs) catalyze the hydrolysis of PC to produce phosphatidic acid and choline. Activation of PC-specific PLDs occurs as a consequence of agonist stimulation of both tyrosine kinase and G protein-coupled receptors. PC-specific PLDs have been proposed to function in regulated secretion, cytoskeletal reorganization, transcriptional regulation, and cell cycle control.[supplied by OMIM]^[7]

Mechanism of activation

PLD2 is activated by substrate presentation.^[8] The enzyme is palmitoylated, which drives PLD2 to lipid rafts. PC substrate is polyunsaturated and resides in the membrane separately from lipid rafts near phosphatidylinositol 4,5-bisphosphate (PIP2). When PIP2 levels increase, PLD2 trafficks to PIP2 where it encounters its substrate PC. Scaffolding proteins that interact with PLD2 likely changes its preference of lipid rafts vs PIP2.

Interactions

PLD2 has been shown to interact with:

• ARF1,^[9][10]
• Aldolase A,^[11]
• Amphiphysin,^[12]
• BIN1,^[12]
• Caveolin 1,^[13][14]
• Glyceraldehyde 3-phosphate dehydrogenase,^[15]
• PLCG1,^[16]
• PRKCD,^[17]
• Src,^[18] and
• Wiskott-Aldrich syndrome protein.^[19]

Inhibitors

• N-(2-(1-(3-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)-2-naphthamide: 75-fold selective versus PLD1, IC₅₀ = 20 nM.^[20]