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FLASH GENE

Symbol

ENTPD1

contributors: mct - updated : 05-12-2016

HGNC name	ectonucleoside triphosphate diphosphohydrolase 1
HGNC id	3363

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE	head to head
text	vascular ATP diphosphohydrolase
STRUCTURE	165.49 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map

see WNT8B

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001776 10 - 12887 NP_001767 - 510 - 2015 26226423 NM_001098175 9 - 12615 NP_001091645 - 517 - 2015 26226423 NM_001164178 10 - 12515 NP_001157650 - 522 - 2015 26226423 NM_001164179 10 - 12617 NP_001157651 - 469 - 2015 26226423 NM_001164181 9 - 12387 NM_001164182 - 402 - 2015 26226423 NM_001164182 9 - 12589 NP_001157654 - 372 - 2015 26226423 NM_001164183 8 - 12471 NP_001157655 - 372 - 2015 26226423 NM_001312654 10 - 12561 NP_001299583 - 402 - 2015 26226423 NM_001320916 10 - 2171 NP_001307845 - 482 - 2015 26226423

EXPRESSION

Type	ubiquitous

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 Endocrine parathyroid       highly Hearing/Equilibrium ear       highly Homo sapiens Reproductive female system placenta     highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune lymphocyte

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	basic leucine zipper (bZIP) like structure
	four apyrase conserved regions in N terminal region (ACR)
	site of binding to RANBP9

conjugated

GlycoP

HOMOLOGY

interspecies

homolog to rattus brain E type ecto ATPase

Homologene

FAMILY	GDA1/CD39 NTPase family
	ectonucleoside triphosphate diphosphohydrolase (ENTPDase) family

CATEGORY

adhesion , enzyme , transcription factor , antigen

SUBCELLULAR LOCALIZATION	plasma membrane
text	localized in caveolae, which are plasma membrane invaginations with distinct lipid composition, similar to dynamic lipid microdomains, called rafts
	expressed at the sympathetic neuromuscular junction, where ATP is co-released with norepinephrine

basic FUNCTION	ectoenzyme that degrades ATP to AMP
	modulating P2 receptor signaling by controlling nucleotides concentrations at the cell surface
	ecto-nucleotidase influencing P2 receptor activation to regulate vascular and immune cell adhesion and signaling events pivotal in inflammation
	regulates purinergic receptor signaling by controlling the levels of extracellular nucleotides
	having a role in thromboregulation (through its localization in cholesterol-rich domains of the membrane)
	by hydrolyzing ATP and ADP to AMP, regulates ligand availability to a large family of P2 (purinergic) receptors (Friedman 2007)
	vascular protective factor in diabetic nephropathy that modulates glomerular inflammation and thromboregulation (Friedman 2007)
	controls IL8 production by human neutrophils via the regulation of P2Y(2) activation
	has anti-inflammatory properties as it hydrolyzes proinflammatory extracellular ATP, generates anti-inflammatory adenosine, and also protects regulatory T cells from ATP-induced cell death
	is an integral component of regulatory T cells (Treg), which are central to immunological tolerance and maintenance of normal pregnancy
	cellular homeostasis and fibrotic response involve the integration of signaling that is pro-fibrotic by ATP and anti-fibrotic by adenosine and that is regulated by ENTPD1 and ENTPD2
	is a key "molecular switch" that allows macrophages to self-limit their activation state
	extracellular adenosine, generated in tandem by ecto-enzymes ENTPD1 and NT5E, promotes dermal fibrogenesis
	ENTPD1 modulates local renin release and thus, RAS activation, ultimately exerting a cardioprotective effect
	expression of ENTPD1 in Tregs is primarily genetically driven, and this may determine interindividual differences in the control of inflammatory responses
	marker of regulatory immune cells and catalyzes extracellular hydrolysis of nucleotides to generate AMP and, in tandem with NT5E, adenosine
	ENTPD1, NT5E are two ectonucleotidases that cooperate in the generation of extracellular adenosine through ATP hydrolysis, thus tilting the balance towards immunosuppressive microenvironments
	nucleotide-converting ectoenzymes, such as ENTPD1, ENTPD7, and ENPP3, inhibit ATP-dependent immune responses by hydrolyzing ATP, thereby contributing to immune response regulation
	catalyzes the phosphohydrolysis of extracellular ATP (eATP) and ADP (eADP) released under conditions of inflammatory stress and cell injury
	plays a dominant role in the purinergic regulation of inflammation and the immune response because its expression is influenced by genetic and environmental factors

CELLULAR PROCESS	cell life, cell death/apoptosis
	nucleotide, transcription

PHYSIOLOGICAL PROCESS

coagulation/hemostasis , immunity/defense

text	prevention of platelet aggregation

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	associations with RANBP9 having the potential to regulate NTPDase catalytic activity( this intermolecular interaction may have important implications for the regulation of extracellular nucleotide-mediated signaling)
	is a negative regulator of P2RX7-mediated inflammatory cell death in mast cells
	KLRB1 and ENTPD1 have direct interactions that are further linked with acid sphingomyelinase (ASM)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

SPG64

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   correlated with better long-term survival after tumor resection in patients with pancreatic cancer tumoral     --over   in malignant epithelial cells of human rectal adenocarcinoma constitutional     --low   decreased in the late-onset preeclamptic (PE) placenta

Susceptibility

Variant & Polymorphism

Candidate gene	marker of a Treg subset likely involved in the control of the inflammatory autoimmune disease
Marker	dysregulated levels of ENTPD1 genes may be involved in sepsis pathophysiology and may be utilized as potential diagnostic biomarker
	ENTPD1 may act as potential markers for the clinical diagnosis of PE
Therapy target
	System Type Disorder Pubmed dermatology skin   biochemical or biological inhibitors of ENTPD1 and/or NT5E may hold promise in the treatment of dermal fibrosis in diseases such as scleroderma cancer hemopathy   may serve as a future target for the development of novel therapies with immune-modulating antitumor agents in chronic lymphocytic leukemia reproduction pregnancy placenta CD39 is a target for the clinical treatment of PE

ANIMAL & CELL MODELS

	Entpd1 null mice exhibit decreased synaptic efficacy, presumably due to desensitization P2X1 receptors
	in rat models of DNA damage, inhibiting Entpd1-driven ATP hydrolysis with POM-1 protected the heart and lung tissues against chemically induced DNA damage