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    MGLL monoglyceride lipase [ Homo sapiens (human) ]

    Gene ID: 11343, updated on 2-Nov-2024

    Summary

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    Official Symbol
    MGLLprovided by HGNC
    Official Full Name
    monoglyceride lipaseprovided by HGNC
    Primary source
    HGNC:HGNC:17038
    See related
    Ensembl:ENSG00000074416 MIM:609699; AllianceGenome:HGNC:17038
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MGL; HUK5; MAGL; HU-K5
    Summary
    This gene encodes a serine hydrolase of the AB hydrolase superfamily that catalyzes the conversion of monoacylglycerides to free fatty acids and glycerol. The encoded protein plays a critical role in several physiological processes including pain and nociperception through hydrolysis of the endocannabinoid 2-arachidonoylglycerol. Expression of this gene may play a role in cancer tumorigenesis and metastasis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]
    Expression
    Broad expression in fat (RPKM 103.8), esophagus (RPKM 51.9) and 19 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MGLL in Genome Data Viewer
    Location:
    3q21.3
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (127689066..127823185, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (130423721..130557760, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (127407909..127542028, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14692 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14693 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20458 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:127357688-127358188 Neighboring gene podocalyxin like 2 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:127386638-127386819 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14694 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14695 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14696 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:127401604-127402139 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20459 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20460 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:127408045-127408550 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:127408551-127409056 Neighboring gene ankyrin repeat and BTB domain containing 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:127420713-127421460 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:127421461-127422206 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:127425278-127425778 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:127425995-127426138 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:127452841-127453756 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:127456818-127457380 Neighboring gene uncharacterized LOC107986127 Neighboring gene MGLL intron CAGE-defined high expression enhancer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20463 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20464 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:127472805-127474004 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20468 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20469 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20470 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20471 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20472 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20473 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:127509215-127509818 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr3:127509819-127510421 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr3:127536190-127537389 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14697 Neighboring gene uncharacterized LOC107986129 Neighboring gene uncharacterized LOC105374096 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20475 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:127616018-127616222 Neighboring gene uncharacterized LOC124909427

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. [Effect of monoacylglycerol lipase with proliferation of MHCC97H human liver cancer cells in vivo]. Zhu WP, et al. Zhonghua Gan Zang Bing Za Zhi, 2019 Jul 20. PMID 31357777
    2. Crystal structure of a soluble form of human monoglyceride lipase in complex with an inhibitor at 1.35 Å resolution. Schalk-Hihi C, et al. Protein Sci, 2011 Apr. PMID 21308848, Free PMC Article
    3. Specific Inter-residue Interactions as Determinants of Human Monoacylglycerol Lipase Catalytic Competency: A ROLE FOR GLOBAL CONFORMATIONAL CHANGES. Tyukhtenko S, et al. J Biol Chem, 2016 Feb 5. PMID 26555264, Free PMC Article
    4. Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis. Carey CE, et al. J Abnorm Psychol, 2015 Nov. PMID 26595473, Free PMC Article
    5. Peroxide-Dependent MGL Sulfenylation Regulates 2-AG-Mediated Endocannabinoid Signaling in Brain Neurons. Dotsey EY, et al. Chem Biol, 2015 May 21. PMID 26000748, Free PMC Article

    See all (79) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Inhibition of MAGL attenuates Intervertebral Disc Degeneration by Delaying nucleus pulposus senescence through STING.
      Title: Inhibition of MAGL attenuates Intervertebral Disc Degeneration by Delaying nucleus pulposus senescence through STING.
    2. MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity.
      Title: MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity.
    3. IL-8-induced CXCR2 down-regulation in circulating monocytes in hepatocellular carcinoma is partially dependent on MAGL.
      Title: IL-8-induced CXCR2 down-regulation in circulating monocytes in hepatocellular carcinoma is partially dependent on MAGL.
    4. Decreased serum levels of glycerol-3- phosphate dehydrogenase 1 and monoacylglycerol lipase act as diagnostic biomarkers for breast cancer.
      Title: Decreased serum levels of glycerol-3- phosphate dehydrogenase 1 and monoacylglycerol lipase act as diagnostic biomarkers for breast cancer.
    5. Research progress on FASN and MGLL in the regulation of abnormal lipid metabolism and the relationship between tumor invasion and metastasis.
      Title: Research progress on FASN and MGLL in the regulation of abnormal lipid metabolism and the relationship between tumor invasion and metastasis.
    6. Brain structural changes in cannabis dependence: association with MAGL.
      Title: Brain structural changes in cannabis dependence: association with MAGL.
    7. Dysregulated expression of monoacylglycerol lipase is a marker for anti-diabetic drug metformin-targeted therapy to correct impaired neurogenesis and spatial memory in Alzheimer's disease.
      Title: Dysregulated expression of monoacylglycerol lipase is a marker for anti-diabetic drug metformin-targeted therapy to correct impaired neurogenesis and spatial memory in Alzheimer's disease.
    8. Conformational gating, dynamics and allostery in human monoacylglycerol lipase.
      Title: Conformational gating, dynamics and allostery in human monoacylglycerol lipase.
    9. ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages.
      Title: ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages.
    10. Low mRNA expression and activity of monoacylglycerol lipase in human SH-SY5Y neuroblastoma cells
      Title: Low mRNA expression and activity of monoacylglycerol lipase in human SH-SY5Y neuroblastoma cells.
    Submit: New GeneRIF Correction See all GeneRIFs (51)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables lysophospholipase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables monoacylglycerol lipase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables monoacylglycerol lipase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables monoacylglycerol lipase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables monoacylglycerol lipase activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in acylglycerol catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in acylglycerol catabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in arachidonate metabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in arachidonate metabolic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in fatty acid biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in inflammatory response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in lipid metabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in monoacylglycerol catabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of endocannabinoid signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of inflammatory response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of sensory perception of pain ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in triglyceride catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		  
    is_active_in membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    monoglyceride lipase
    Names
    lysophospholipase homolog
    monoacylglycerol lipase
    NP_001003794.1
    NP_001243514.1
    NP_001375241.1
    NP_001375242.1
    NP_001375243.1
    NP_001375244.1
    NP_001375245.1
    NP_001375246.1
    NP_001375247.1
    NP_009214.1
    XP_016861154.1
    XP_047303339.1
    XP_047303340.1
    XP_054201093.1
    XP_054201094.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001003794.3 → NP_001003794.1  monoglyceride lipase isoform 2

      See identical proteins and their annotated locations for NP_001003794.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream, in-frame start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AC023593, AJ270950, AL833254, BP307995, BX403703
      Consensus CDS
      CCDS43148.1
      UniProtKB/Swiss-Prot
      B3KRC2, B7Z9D1, Q6IBG9, Q96AA5, Q99685
      UniProtKB/TrEMBL
      A0A3B3ITT3
      Related
      ENSP00000381176.1, ENST00000398104.6
      Conserved Domains (1) summary
      cl21494
      Location:22 → 294
      Abhydrolase; alpha/beta hydrolases

    2. NM_001256585.2 → NP_001243514.1  monoglyceride lipase isoform 3

      See identical proteins and their annotated locations for NP_001243514.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an exon in the 3' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
      Source sequence(s)
      AC023593, AK304844, AL833254, BM051374, EU660904
      Consensus CDS
      CCDS58852.1
      UniProtKB/TrEMBL
      A0A3B3ITT3
      Related
      ENSP00000404146.2, ENST00000453507.7
      Conserved Domains (1) summary
      cl21494
      Location:32 → 274
      Abhydrolase; alpha/beta hydrolases

    3. NM_001388312.1 → NP_001375241.1  monoglyceride lipase isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC023593, AC117480
      Conserved Domains (1) summary
      cl21494
      Location:32 → 330
      Abhydrolase; alpha/beta hydrolases

    4. NM_001388313.1 → NP_001375242.1  monoglyceride lipase isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC023593, AC117480
      Conserved Domains (1) summary
      cl21494
      Location:22 → 320
      Abhydrolase; alpha/beta hydrolases

    5. NM_001388314.1 → NP_001375243.1  monoglyceride lipase isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC023593, AC117480
      UniProtKB/TrEMBL
      A0A3B3ITT3
      Related
      ENSP00000497905.1, ENST00000648300.1
      Conserved Domains (1) summary
      cl21494
      Location:22 → 263
      Abhydrolase; alpha/beta hydrolases

    6. NM_001388315.1 → NP_001375244.1  monoglyceride lipase isoform 7

      Status: REVIEWED

      Source sequence(s)
      AC023593, AC117480
      UniProtKB/TrEMBL
      Q2VYF8
      Conserved Domains (1) summary
      cl21494
      Location:52 → 294
      Abhydrolase; alpha/beta hydrolases

    7. NM_001388316.1 → NP_001375245.1  monoglyceride lipase isoform 8

      Status: REVIEWED

      Source sequence(s)
      AC023593, AC117480
      UniProtKB/TrEMBL
      A0A3B3ITT3, B2ZGL7
      Conserved Domains (1) summary
      cl21494
      Location:22 → 264
      Abhydrolase; alpha/beta hydrolases

    8. NM_001388317.1 → NP_001375246.1  monoglyceride lipase isoform 9

      Status: REVIEWED

      Source sequence(s)
      AC023593, AC117480
      UniProtKB/TrEMBL
      Q2VYF8
      Conserved Domains (1) summary
      cl21494
      Location:52 → 268
      Abhydrolase; alpha/beta hydrolases

    9. NM_001388318.1 → NP_001375247.1  monoglyceride lipase isoform 9

      Status: REVIEWED

      Source sequence(s)
      AC023593, AC117480
      UniProtKB/TrEMBL
      Q2VYF8
      Conserved Domains (1) summary
      cl21494
      Location:52 → 268
      Abhydrolase; alpha/beta hydrolases

    10. NM_007283.7 → NP_009214.1  monoglyceride lipase isoform 1

      See identical proteins and their annotated locations for NP_009214.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC023593, AL833254, BC006230
      Consensus CDS
      CCDS46902.1
      UniProtKB/TrEMBL
      A0A0C4DFN3, A0A3B3ITT3
      Related
      ENSP00000265052.5, ENST00000265052.10
      Conserved Domains (1) summary
      cl21494
      Location:32 → 304
      Abhydrolase; alpha/beta hydrolases

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      127689066..127823185 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047447384.1 → XP_047303340.1  monoglyceride lipase isoform X3

    2. XM_017005665.2 → XP_016861154.1  monoglyceride lipase isoform X2

      UniProtKB/TrEMBL
      Q2VYF8
      Conserved Domains (1) summary
      cl21494
      Location:52 → 268
      Abhydrolase; alpha/beta hydrolases

    3. XM_047447383.1 → XP_047303339.1  monoglyceride lipase isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      130423721..130557760 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054345118.1 → XP_054201093.1  monoglyceride lipase isoform X2

    2. XM_054345119.1 → XP_054201094.1  monoglyceride lipase isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q99685.2 GenPept UniProtKB/Swiss-Prot:Q99685

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