Gene Report

Basic Information

Approved Symbol	LIPE
Approved Name	lipase, hormone-sensitive
Symbol Alias	HSL
Location	19q13.1-q13.2
Position	chr19:42931302-42931565 (-)
External Links	Entrez Gene: 3991 Ensembl: ENSG00000079435 UCSC: uc002otr.3 HGNC ID: 6621
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between LIPE and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
LIPE	Aston, 2005	patients and normal controls		Genes altered in major depressive disorder Genes altered in major depressive disorder

Positive relationships between LIPE and other components at different levels (count: 0)

Positive relationship network of LIPE in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between LIPE and MDD (count: 0)

Negative relationships between LIPE and other components at different levels (count: 0)

LIPE related SNPs in MK4MDD (count: 0)

LIPE related proteins in MK4MDD (count: 0)

LIPE related GO terms (count: 14)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0008203	cholesterol metabolic process	biological process	IEA
GO:0044281	small molecule metabolic process	biological process	TAS
GO:0004806	triglyceride lipase activity	molecular function	IEA
GO:0016042	lipid catabolic process	biological process	ISS
GO:0005829	cytosol	cellular component	IEA
GO:0005811	lipid particle	cellular component	ISS
GO:0005515	protein binding	molecular function	IPI[17026959]
GO:0005901	caveola	cellular component	IEA
GO:0019433	triglyceride catabolic process	biological process	IEA; TAS
GO:0006468	protein phosphorylation	biological process	TAS[3420405]
GO:0033878	hormone-sensitive lipase activity	molecular function	IEA
GO:0042758	long-chain fatty acid catabolic process	biological process	IEA
GO:0046340	diacylglycerol catabolic process	biological process	IEA
GO:0019901	protein kinase binding	molecular function	IEA

LIPE related KEGG pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04910	insulin signaling_pathway	Insulin signaling pathway	Insulin binding to its receptor results in the tyrosine phos...... Insulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the regulatory subunit of phosphoinositide 3-kinase (PI3K). PI3K activates 3-phosphoinositide-dependent protein kinase 1 (PDK1), which activates Akt, a serine kinase. Akt in turn deactivates glycogen synthase kinase 3 (GSK-3), leading to activation of glycogen synthase (GYS) and thus glycogen synthesis. Activation of Akt also results in the translocation of GLUT4 vesicles from their intracellular pool to the plasma membrane, where they allow uptake of glucose into the cell. Akt also leads to mTOR-mediated activation of protein synthesis by eIF4 and p70S6K. The translocation of GLUT4 protein is also elicited through the CAP/Cbl/TC10 pathway, once Cbl is phosphorylated by INSR. Other signal transduction proteins interact with IRS including GRB2. GRB2 is part of the cascade including SOS, RAS, RAF and MEK that leads to activation of mitogen-activated protein kinase (MAPK) and mitogenic responses in the form of gene transcription. SHC is another substrate of INSR. When tyrosine phosphorylated, SHC associates with GRB2 and can thus activate the RAS/MAPK pathway independently of IRS-1. More...

LIPE related BioCarta pathways (count: 0)

LIPE related Reactome pathways (count: 2)

ID	Name	Description
Gene mapped Reactome pathways
REACT_494	hormone sensitive_lipase_hsl_mediated_triacylglycerol_hydrolysis	Triacylglycerol is a major energy store in the body and its ...... Triacylglycerol is a major energy store in the body and its hydrolysis to yield fatty acids and glycerol is a tightly regulated part of energy metabolism. A central part in this regulation is played by hormone-sensitive lipase. The processes of triacylglycerol and cholesterol ester hydrolysis are also regulated by subcellular compartmentalization: these lipids are packaged in cytosolic particles and the enzymes responsible for their hydrolysis, and perhaps for additional steps in their metabolism, are organized at the surfaces of these particles. This organization is dynamic: the inactive form of HSL is not associated with the particles, but is translocated there after being phosphorylated. Conversely, perilipin, a major constituent of the particle surface, appears to block access of enzymes to the lipids within the particle; its phosphorylation allows greater access. Here, HSL-mediated triacylglycerol hydrolysis is described as a pathway containing twelve reactions. The first six of these involve activation: phosphorylation of HSL, dimerization of HSL, disruption of CGI-58:perilipin complexes at the surfaces of cytosolic lipid particles, phosphorylation of perilipin, association of phosphorylated HSL with FABP, and translocation of HSL from the cytosol to the surfaces of lipid particles. The next four reactions are the hydrolysis reactions themselves: the hydrolysis of cholesterol esters, and the successive removal of three fatty acids from triacylglycerol. The last two reactions, dephosphorylation of perilipin and HSL, negatively regulate the pathway. These events are outlined in the figure below. Inputs (substrates) and outputs (products) of individual reactions are connected by black arrows; blue lines connect output activated enzymes to the other reactions that they catalyze. Despite the undoubted importance of these reactions in normal human energy metabolism and in the pathology of diseases such as type II diabetes, they have been studied only to a limited extent in human cells and tissues. Most experimental data are derived instead from two rodent model systems: primary adipocytes from rats, and mouse 3T3-L1 cells induced to differentiate into adipocytes. More...
REACT_602	metabolism of_lipids_and_lipoproteins	Lipids are hydrophobic but otherwise chemically diverse mole...... Lipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphingolipids, eicosanoids, cholesterol, bile salts, steroid hormones, and fat-soluble vitamins, and function as a major source of energy (fatty acids, triacylglycerols, and ketone bodies), are major constituents of cell membranes (cholesterol and phospholipids), play a major role in their own digestion and uptake (bile salts), and participate in numerous signaling and regulatory processes (steroid hormones, eicosanoids, and sphingolipids). Because of their poor solubility in water, most lipids in extracellular spaces in the human body are found as complexes with specific carrier proteins. Regulation of the formation and movement of these lipoprotein complexes is a critical aspect of human lipid metabolism, and lipoprotein abnormalities are associated with major human disease processes including atherosclerosis and diabetes. Aspects of lipid metabolism currently annotated in Reactome include lipid digestion, trafficking of dietary sterols, triacylglycerol synthesis (fatty acid synthesis and triacylglycerol assembly), hormone-sensitive lipase-mediated triacylglycerol breakdown, and beta-oxidation of fatty acids, ketone body metabolism (synthesis and utilization), the synthesis of cholesterol, bile salts, and steroid hormones, and sphingolipid metabolism. Three aspects of lipoprotein function are currently annotated: chylomicron-mediated lipid transport, HDL (high density lipoprotein)-mediated lipid transport, and LDL (low density lipoprotein) endocytosis and degradation. More...

LIPE related interactors from protein-protein interaction data in HPRD (count: 7)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
LIPE	MAPK3	No	in vitro	11581251
LIPE	MAPK1	Yes	in vitro	11581251
LIPE	NSFL1C	No	yeast 2-hybrid	16169070
LIPE	STAR	No	in vitro;in vivo	12925534
LIPE	FABP4	No	in vitro;in vivo;yeast 2-hybrid	10318917
LIPE	PRKACA	No	in vitro;in vivo	9417067 , 14641008
LIPE	KATNA1	No	in vitro;in vivo	10445032

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped Reactome pathways