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FLASH GENE

Symbol

PLD1

contributors: mct - updated : 07-12-2016

HGNC name	phospholipase D1, phophatidylcholine-specific
HGNC id	9067

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002662 27 - 6025 NP_002653 124.2 1072 - Steel, Hammond longer form of PLD1 NM_001130081 26 splicing 5911 NP_001123553 - 1036 - Steel, Hammond lacking amino acids 585 to 624 shorter form of PLD1

EXPRESSION

Type

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       highly   mouth tongue     highly Endocrine adrenal gland       highly Nervous brain hindbrain     highly Rattus norvegicus Fetal Reproductive female system breast mammary gland   lowly   female system uterus     lowly Urinary kidney       moderately Visual eye       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     moderately Connective bone     moderately

cells

System Cell Pubmed Species Stage Rna symbol Nervous glia Rattus norvegicus Fetal Nervous neuron Rattus norvegicus Fetal Nervous Purkinje cell Rattus norvegicus Fetal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an effector regulatory region at the N terminus (modified for the PLD activation), and four hydrophobic residues present in the N-terminal HKD catalytic motif responsible for vesicular localization
	a putative pleckstrin homology (PH) domain
	a catalytic domain

HOMOLOGY

interspecies	homolog to rattus Pld1 (90.63 pc)
	homolog to murine Pld1 (91.41 pc)

Homologene

FAMILY

phospholipase D family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,organelle,lysosome
text	perinuclear
	PLD1 is translocated to the plasma membrane upon stimulation of endothelial secretion, and this process correlates with the generation of phosphatidic acid (PA) in the plasma membrane
	primarily localized in vesicular structures such as endosomes, lysosomes and autophagosomes

basic FUNCTION	phospholipase D1, phosphatidylcholine specific
	involved in inflammation, metabolic regulation, oncogenesis, neural and cardiac stimulation
	intravesicular membrane trafficking, cell morphology alterations
	having a protective effect against TNF-induced apoptosis
	implicated in the release process of a variety of hormones, most likely at a late stage of exocytosis through the production of lipids that are essential for the fusion process and seems to be also essential for fast neurotransmitter release
	both PLD1 and PLD2 participate in regulated cellular secretion, cytoskeletal organization, gene expression regulation, cell cycle control, growth, proliferation, and differentiation
	PLD1, PLD2 activity plays an important role in promoting IgE-dependent signaling events within lipid microdomains in mast cells
	its phosphorylation is important for the regulation of (14)C-glucose uptake
	role of phospholipase D1 in glucose-induced insulin secretion in pancreatic Beta cells
	its nuclear localization mediates the activation of nuclear PRKCA and extracellular signal-regulated kinase signaling pathways
	PLD1, PLD2 shortens the differentiation time of cells becoming mature neutrophils
	acts downstream of RHOA, one of the small Rho GTPases, to suppress dendritic branching
	in the tumor environment promotes tumor growth and metastasis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

	RHOA-PLD1-phosphatidic acid (PA) may represent a novel signaling pathway in the restriction of dendritic branching
	PIK3C3-PLD1 pathway acts independently of, and in parallel to, the Rag pathway in regulating amino acid activation of MTOR

a component

INTERACTION

DNA

RNA

small molecule

protein	is a specific regulator of VWF secretion
	PLD1 regulates PSEN1 trafficking and PLD1 overexpression promotes cell surface accumulation of PSEN1 in an APP-independent manner
	PEA15 positively regulates HRAS/ERK signaling and increases the proliferation of HRAS-transformed epithelial cells through enhanced PLD1 expression and activation
	interacting with FAM83B (elevated FAM83B expression and suppression of PLD1 activity prevents FAM83B-mediated transformation)
	ADRA1B contraction of vascular smooth muscle involves activation of PLD1, which controls a portion of the ADRA1B-induced CACNA1C channel activity
	HS1BP3 inhibits autophagy by regulation of PLD1
	RALA recruits PLD1 to lysosomes during nutrient deprivation to promote the localized production of phosphatidic acid (PA) and the recruitment of perilipin 3 to expanding lipid droplets (LDs)

cell & other

i5 membrane associated

REGULATION

activated by

ADP-ribosylation factor 1, by protein kinase C alpha, and Rho A

Other

regulated by RPS6KA3 (PLD1 phosphorylation by RPS6KA3 is essential for the function of PLD1 in exocytosis)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     potential use of PLD1 inhibitors as cancer therapeutics

ANIMAL & CELL MODELS