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Alternative titles; symbolsMGLMONOACYLGLYCEROL LIPASE; MAGLHUK5HGNC Approved Gene Symbol: MGLLCytogenetic location: 3q21.3 Genomic coordinates (GRCh38): 3:12...

Alternative titles; symbols

  • MGL
  • HUK5

HGNC Approved Gene Symbol: MGLL

Cytogenetic location: 3q21.3 Genomic coordinates (GRCh38): 3:127,689,065-127,823,184 (from NCBI)

▼ Description
Monoglyceride lipase (MGLL; EC functions together with hormone-sensitive lipase (LIPE; 151750) to hydrolyze intracellular triglyceride stores in adipocytes and other cells to fatty acids and glycerol. MGLL may also complement lipoprotein lipase (LPL; 238600) in completing hydrolysis of monoglycerides resulting from degradation of lipoprotein triglycerides (Karlsson et al., 2001).

▼ Cloning and Expression
By searching an EST database for sequences similar to a lysophospholipase gene from ectromelia virus, Wall et al. (1997) identified human MGLL, which they designated HUK5. The deduced 313-amino acid protein shares 49.5% identity with the virus protein. Database analysis indicated that MGLL is expressed in wide variety of tissues and may be preferentially expressed in adipose.

By RT-PCR of adipocyte total RNA using primers based on mouse Mgl, followed by screening an adipocyte cDNA library, Karlsson et al. (2001) cloned human MGL. The deduced 303-amino acid protein shares 84% identity with mouse Mgl. Mouse and human MGL both have an N-terminal his-gly dipeptide, a characteristic of lipases, and a catalytic triad of ser122, asp239, and his269. By EST database analysis, Karlsson et al. (2001) identified mouse and human MGL transcripts containing 2 different 5-prime leader sequences. Northern blot analysis of human adipocyte total RNA detected a 4.2-kb MGL transcript. MGL expression was also detected in lung, liver, kidney, brain, and heart. Western blot analysis of mouse tissues showed ubiquitous expression, but the pattern was tissue specific with regard to both the size and number of Mgl proteins.

Using a fluorescent active-site probe, Navia-Paldanius et al. (2012) found that human MGLL cDNA encoding the predicted 313-amino acid protein was expressed as 2 protein bands with apparent molecular masses of approximately 33 and 35 kD by SDS-PAGE.

▼ Gene Function
Dinh et al. (2002) found that rat Mgl participates in inactivation of 2-arachidonoylglycerol (2-AG), an endogenous cannabinoid monoglyceride. Mgl was highly expressed in regions of rat brain that also expressed cannabinoid receptors (see CNR1; 114610), and it appeared to assume a presynaptic localization in hippocampus. Adenovirus-mediated transfer of Mgl cDNA into rat cortical neurons increased Mgl expression and attenuated 2-AG accumulation induced by N-methyl-D-aspartate/carbachol.

Nomura et al. (2010) found that KIAA1363 (NCEH1; 613234) and MAGL were consistently elevated in aggressive human cancer cells relative to their nonaggressive counterparts. The authors suggested that enrichment of protumorigenic lipid signaling molecules in aggressive cancer cells supports their malignant phenotype.

Nomura et al. (2011) demonstrated that a distinct pathway exists in brain, where MAGL hydrolyzes the endocannabinoid 2-arachidonoylglycerol to generate a major arachidonate precursor pool for neuroinflammatory prostaglandins. MAGL-disrupted animals showed neuroprotection in a parkinsonian mouse model. These animals were spared the hemorrhaging caused by COX inhibitors in the gut, where prostaglandins are instead regulated by cytosolic phospholipase A(2) (PLA(2); see 611651). Nomura et al. (2011) concluded that their findings identified MAGL as a distinct metabolic node that couples endocannabinoid to prostaglandin signaling networks in the nervous system.

Using a panel of saturated and unsaturated monoacylglycerols (MAGs), Navia-Paldanius et al. (2012) found that human MAGL preferentially hydrolyzed the saturated MAG C10:0. Unlike ABHD6 (616966) and ABHD12 (613599), MAGL showed no preference for 1(3)-isomers of linoleoyl (C18:2) and arachidonoyl (C20:4) glycerols. MAGL did not hydrolyze di- or triglycerides or lisophosphatidic acid.

▼ Gene Structure
Karlsson et al. (2001) determined that the mouse and human MGLL genes contain 7 exons. Exon 1 is noncoding.

▼ Mapping
By genomic sequence analysis, Karlsson et al. (2001) mapped the MGLL gene to chromosome 3q21. They mapped the mouse Mgll gene to a region of chromosome 6 that shares homology of synteny with human chromosome 3q21.

Hartz (2016) mapped the MGLL gene to chromosome 3q21.3 based on an alignment of the MGLL sequence (GenBank BC000551) with the genomic sequence (GRCh38).

Tags: 3q21.3