LIPE (lipase E, hormone sensitive type)

Alias_names	lipase, hormone-sensitive
Alias_symbol (synonym)	HSL
Other alias	lipase
	AOMS4
	FPLD6
	LHS
HGNC (Hugo)	LIPE
LocusID (NCBI)	3991
Atlas_Id	43466
Location	The human LIPE gene is located on 19q13.2 [Link to chromosome band 19q13]  [Link to chromosome band 19q13]
Location_base_pair	Starts at 42401507 and ends at 42427426 bp from pter ( according to hg19-Feb_2009)  [Mapping LIPE.png]
Local_order	LIPE spans 25,920bp, starts at 42401507 and ends at 42427426 bp from pter (according to hg38-Dec_2013).
	Figure 1. Gene neighbours of LIPE on chromosome 19q13.2 (NCBI Annotation Release 108)

Note	LIPE plays a crucial role in acylglycerol and cholesteryl ester hydrolysis in adipose tissue and exhibits cholesterol hydrolase activity in steroidogenic tissue and macrophages.
Description	LIPE is highly expressed in adipose tissue as well as in heart and skeletal muscle, pancreatic β-cells, placenta, adrenal glands, ovary and testis (Haemmerle et al., 2003). 2 isoforms produced by alternative splicing (Yeamen et, al., 2004; Holst et al., 1996). Isoform 1 : Testicular form also known as canonical sequence, composed of 1,076 amino acids, has 116,598 Da molecular mass. Two testicular forms of LIPE have been characterized (Stenson et al., 1996 ; Mairal et al., 2002). The 3.9 kb mRNA encodes a 1,076 amino acid protein that contains a unique NH2-terminal region encoded by exon T1. The 3.3 kb mRNA encodes a protein that is identical to the adipocyte LIPE form. However, the mRNA species differ in their 5' ends. Exon usage is mutually exclusive; exon T2 is only transcribed in testis, and exon B is only transcribed in Adipose tissue (Lucas et al., 2003). Isoform 2 : Adipocyte form, composed of 775 amino acids encoded by 9 exons, has 84,128 Da molecular mass.
	Figure 2. Genomic organization of the LIPE gene coding sequences (red boxes) and untranslated regions (grey boxes). Exons T1 and T2 are used in testis. Exons A and B are used in the colon adenocarcinoma cell line HT29 and adipose tissue, respectively. Exons 1 to 9 are used in all tissues expressing LIPE (adapted from Lucas et al., 2003).
Expression	A 3.3-kb transcript was detected in mammary gland, adrenal gland, adipose tissue and muscle, and both a 3.3 and 3.9 kb transcripts were found in testis (Holst et al. 1996). RNA-seq data from 95 human individuals representing 27 different tissues reveal biased expression in fat and testis (BioProject: PRJEB4337) (Figure 2).
	Figure 3. LIPE tissue expression. RNA-seq data from 27 tissues are reported as mean RPKM (Reads Per Kilobase Million), corresponding to mean values of the different individual samples from each tissue type.
Localisation	Found in cell membrane (UniProtKB-SubCell), cytosol (HPA), lipid droplet (UniProtKB-SubCell) and high density caveolae (UniProtKB-SubCell). Translocates to the cytoplasm from the caveolae upon insulin stimulation for lipolysis activation (Egan et al., 1992).
Function	Hormone sensitive lipase is a lipolytic enzyme of the 'GDXG' family catalyzing the rate limiting step of diacylglycerol and monoacylglycerol lipolysis (Stralfors et al., 1978). In adipose tissue and heart, it primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production. LIPE is a multifunctional enzyme catalyzing (GO_REF:0000003); Diacylglycerol + H2O = monoacylglycerol + a carboxylate. Triacylglycerol + H2O = diacylglycerol + a carboxylate. Monoacylglycerol + H2O = glycerol + a carboxylate. Enzyme is regulated post-transcriptionally. LIPE is rapidly activated by cAMP-dependent phosphorylation under the influence of catecholamines. Dephosphorylation and inactivation via protein phosphatases or inhibition of protein kinases, are controlled by insulin (Yeamen et al., 1994). Ser 659 and Ser 660 have been shown as phosphorylation sites, for in vitro activation of LIPE (Anthonsen et al., 1998). Also it has protein binding and protein kinase binding function interacting selectively and non-covalently with any protein of protein complex (Aboulaich et al., 2006).
Homology	LIPE gene is conserved in chimpanzee, dog, cow, mouse, rat, zebrafish and frog (Table 3). Table 3.    Pairwise alignment of LIPE gene and protein sequences (in distance from human)  Gene Identity % Species Symbol Protein DNA H. Sapiens LIPE vs. P.troglodytes LIPE 99.0 99.3 vs. C.lupus LIPE 80.2 84.0 vs. B.taurus LIPE 85.9 86.2 vs. M.musculus Lipe 84.3 82.0 vs. R.norvegicus Lipe 74.9 78.1 vs. X.tropicalis lipe 62.7 62.3 vs. D.reriro lipeb 61.7 61.5

Note	198 missense, 12 truncating and 2 inframe mutations of LIPE (cBioPortal).
	Figure 4. Mutation types observed in LIPE expression in literature and corresponding color codes are as follows: Green: Missense Mutations, Black: Truncating Mutations: Nonsense, Nonstop, Frameshift deletion, Frameshift insertion, Splice site, Brown: Inframe Mutations: Inframe deletion, Inframe insertion, Purple: Other Mutations: All other types of mutations
Somatic	LIPE has 3543 SNPs (Ensembl). Arg 309 Cyc polymorphism is associated with an increased serum cholesterol levels and type 2 diabetes (Shimada et al. 1996). LIPE i6(CA)n repeat polymorphism is associated with type 2 diabetes and obesity (Magré et al. 1998). The C-60 G polymorphism is located in the promoter region of the LIPE and it is possible that the substitution of C with G nucleotide result in a decrease in gene expression (Talmud et al. 2001). The C-60 G polymorphism in the promoter of LIPE is associated with body composition and waist circumference (Garenc et al. 2002; Carlsson et al. 2006). In addition, the C-60 G allele male carriers present lower levels of fasting non-esterified fatty acid and higher levels of low density lipoprotein cholesterol (Talmud et al. 2001).

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