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FLASH GENE

Symbol

LPL

contributors: mct - updated : 26-05-2020

HGNC name	lipoprotein lipase
HGNC id	6677

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	LPL hyperlipoproteinemia, types I SBPQ human blood pressure QTL
Location	8p21.3      Physical location : 19.796.581 - 19.824.769
Synonym symbol(s)	LIPD, LIPL, HDLCQ11
EC.number	3.1.1.34

DNA

TYPE	anonymous DNA segment
STRUCTURE	28.19 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000237 10 - 3747 NP_000228 - 475 - 2002 11893776

EXPRESSION

Rna function	mRNA expression in normal human testis
Type	widely

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 Cardiovascular heart       highly Homo sapiens   vessels         Endocrine pancreas       highly Mus musculus   placenta       highly Homo sapiens Nervous brain       highly Homo sapiens Reproductive male system testis       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose white   highly Homo sapiens Connective adipose brown     Homo sapiens Muscular striatum skeletal   highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell Endocrine islet cell (alpha,beta...) Mus musculus Reproductive spermatid Homo sapiens Reproductive spermatocyte Homo sapiens

cell lineage
cell lines
fluid/secretion	milk

at STAGE

physiological period

perinatal, pregnancy

Text	increased in the mammary gland and decreased in the adipose tissue during lactation

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	one PLAT domain
	C-terminal LPL sequences, distinct from the heparin-binding domain, are crucial for GPIHBP1 binding , and C terminus of LPL, detached from the N terminus, is sufficient for specific binding to GPIHBP1

conjugated

GlycoP

mono polymer

homomer , monomer , dimer

HOMOLOGY

interspecies

homolog to murine Lpl

intraspecies

homolog to LIPC,highly

Homologene

FAMILY	AB hydrolase superfamily
	lipase family

CATEGORY

enzyme , transport

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
text	located on the luminal surface of capillary
	attached to the membrane by a GPI-anchor

basic FUNCTION	serine esterase
	involved in plasma lipid transport
	rate limiting for the hydrolysis and clearance of circulating triglyceride (TG), hydrolyzing triglycerides in chylomicrons and very low-density lipoproteins
	catalysing the hydrolysis of the triacylglycerol component of circulating chylomicrons and very low density lipoproteins
	AHR paradoxically regulates IGFBP1 and LPL expressions in the liver
	both LIPG and LPL participate in the supply of nutrients and steroidogenesis in the testes, and especially LIPG may be important for the supply of cholesterol for testosterone production in the Leydig cells
	plays a role in the binding of lipoprotein particles to cell-surface molecules, including sulfated glycosaminoglycans (GAGs)
	Abeta-binding protein promoting cellular uptake and subsequent degradation of Abeta
	its expression in placenta facilitates uptake of retinoids by this organ and their transfer to the embryo, mainly through its catalytic activity
	is involved in regulation of fatty acid metabolism, and facilitates cellular uptake of lipoproteins, lipids and lipid-soluble vitamins
	is a triglyceride-hydrolyzing enzyme that is synthesized within the cardiomyocyte and secreted towards the lumen under various conditions
	neuronal LPL is an important regulator of lipid homeostasis in neurons and that alterations in LPL levels may have important effects on systemic metabolism and neuronal lipid biology
	LPL expression is likely a novel feature of a microglial phenotype that supports remyelination and repair through the clearance of lipid debris
	catalyzes the breakdown of circulating triglycerides in muscle and fat
	is a secreted enzyme that hydrolyzes triglycerides from circulating lipoproteins
	LPL is responsible for the intravascular processing of triglyceride-rich lipoproteins
	catalytically active LPL can exist in a monomeric state, not only as a homodimer

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text	lipid transport

PATHWAY

metabolism

lipid/lipoprotein

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacts with apolipoprotein C2
	bound avidly to GPIHBP1
	GPIHBP1 is an endothelial cell protein that transports lipoprotein lipase (LPL) from the subendothelial spaces to the capillary lumen (
	binding of LPL to GPIHBP1 requires only the C-terminal portion of LPL and does not depend on full-length LPL homodimers
	is transported and attached to the capillary endothelium by the protein GPIHBP1
	LPL inhibition is made possible by a free fatty acids, FA-induced activation of PPARB/PPARD, which augments angiopoietin-like 4 (ANGPTL4), an inhibitor of LPL activity
	ANGPTL4 can both bind and inactivate LPL complexed to GPIHBP1 and that inactivation of LPL by ANGPTL4 greatly reduces the affinity of LPL for GPIHBP1
	ANGPTL8 has a functional LPL inhibitory motif, but only inhibits LPL and increases plasma TG levels in the presence of ANGPTL3
	ANGPTL4 promotes PCSK-mediated intracellular cleavage of LPL in adipocytes, likely contributing to regulation of LPL in adipose tissue
	GPIHBP1's LU domain binds to LPL's C-terminal domain, largely by hydrophobic interactions
	ANGPTL4 binds LPL near the active site at the lid domain and a nearby alpha-helix
	ANGPTL3, much like ANGPTL4, is a physiologically relevant regulator of LPL activity, which causes irreversible inactivation of the enzyme
	TCF21 is a novel regulator of preadipocyte differentiation, in part by directly promoting LPL expression
	GPIHBP1 is LPL's essential partner: it binds LPL and transports it to the capillary lumen; it is essential for lipoprotein margination along capillaries, allowing lipolysis to proceed
	ZHX2 protects hepatocytes from abnormal lipid deposition in Non-alcoholic fatty liver disease (NAFLD) through transcriptional repression of LPL, which subsequently retards cell growth and NAFLD-HCC progression

cell & other

REGULATION

activated by

GIP thatbincreases adipocyte LPL expression through CREB1 and CRTC2-mediated trans-activation of the LPL gene)

induced by

cortisol

inhibited by

PRL and GH

repressed by

ANGPTL3, that inhibit LPL activity and plays important roles in modulating lipoprotein metabolism

Other	activated when heterodimerization occurred in a head-to-tail orientation
	regulated by by extracellular proteins divided into two main groups: the liver-derived apolipoproteins APOC1, APOC2, APOC3, APOA5, and APOE, and the angiopoietin-like proteins

ASSOCIATED DISORDERS

corresponding disease(s)

LPL , SBPQ

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     in prostate carcinoma constitutional germinal mutation       associated with the severity of Alzheimer disease pathophysiological features constitutional germinal mutation       in a Chinese infant with severe hypertriglyceridemia constitutional     --low   in the dentate gyrus of Alzheimer's disease brains

Susceptibility

to overweight in post menopausal women to familial combined hyperlipidemia, atherosclerosis, chylomicronaemia, and dyslipidaemia associated with diabetes, insulin resistance, and infection Alzheimer's disease to preeclampsia to coronary heart disease to ischemic heart disease

Variant & Polymorphism SNP

Candidate gene	furin-resistant LPL is a useful reagent for both biochemical and biomedical studies
Marker	LPL expression is the strongest RNA-based prognostic marker in chronic lymphocytic leukemia that could potentially be applied to predict outcome in the clinical setting, particularly in the large group of patients with favorable prognosis
Therapy target

ANIMAL & CELL MODELS