Q99685 (MGLL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Monoglyceride lipase
Short name=MGL
EC=3.1.1.23

Alternative name(s):
HU-K5
Lysophospholipase homolog
Lysophospholipase-like
Monoacylglycerol lipase
Short name=MAGL

Gene names

Name:

MGLL

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	303 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain By similarity. Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth. Ref.8
Catalytic activity	Hydrolyzes glycerol monoesters of long-chain fatty acids.
Pathway	Glycerolipid metabolism; triacylglycerol degradation.
Subunit structure	Homodimer. Ref.9
Tissue specificity	Detected in adipose tissue, lung, liver, kidney, brain and heart. Ref.2
Miscellaneous	Short-term inhibition causes analgesia, while long-term inhibition causes tolerance to endocannabinoids acting on brain cannabinoid receptor CNR1, and a reduction in brain cannabinoid receptor CNR1 activity By similarity.
Sequence similarities	Belongs to the AB hydrolase superfamily. Monoacylglycerol lipase family.
Sequence caution	The sequence AAB39616.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAH00551.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAH06230.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence BAG37910.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAG33116.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence EAW79330.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence EAW79331.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Lipid degradation Lipid metabolism Lipid synthesis
Molecular function	Hydrolase Serine esterase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	arachidonic acid metabolic process Inferred from sequence or structural similarity. Source: UniProtKB fatty acid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW inflammatory response Traceable author statement. Source: ProtInc platelet activation Traceable author statement. Source: Reactome regulation of endocannabinoid signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB regulation of inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB regulation of sensory perception of pain Inferred from sequence or structural similarity. Source: UniProtKB triglyceride catabolic process Traceable author statement. Source: Reactome
Cellular component	plasma membrane Traceable author statement. Source: Reactome
Molecular function	acylglycerol lipase activity Inferred from sequence or structural similarity. Source: UniProtKB carboxylesterase activity Inferred from electronic annotation. Source: UniProtKB-KW lysophospholipase activity Traceable author statement. Source: ProtInc protein homodimerization activity Inferred from physical interaction Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 303

303

Monoglyceride lipase

PRO_0000191265

Sites

Active site

122

1

Nucleophile Ref.9 Ref.10

Active site

239

1

Charge relay system Probable

Active site

269

1

Charge relay system Probable

Secondary structure

1

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303

Helix Strand Turn

Details...

Helix

16 – 18

3

Beta strand

19 – 23

5

Beta strand

29 – 35

7

Beta strand

42 – 47

6

Helix

59 – 65

7

Beta strand

70 – 75

6

Helix

94 – 110

17

Beta strand

116 – 119

4

Helix

127 – 134

8

Beta strand

143 – 146

4

Turn

153 – 156

4

Helix

158 – 170

13

Helix

181 – 183

3

Helix

188 – 196

9

Helix

212 – 223

12

Helix

224 – 226

3

Beta strand

231 – 235

5

Beta strand

240 – 242

3

Helix

248 – 253

6

Beta strand

257 – 263

7

Helix

271 – 273

3

Helix

276 – 292

17

Sequences

	Sequence		Length	Mass (Da)
	Q99685 [UniParc]. Last modified May 10, 2004. Version 2. Checksum: 80E754F126EE64DE	FASTA	303	33,261
	10 20 30 40 50 60 MPEESSPRRT PQSIPYQDLP HLVNADGQYL FCRYWKPTGT PKALIFVSHG AGEHSGRYEE 70 80 90 100 110 120 LARMLMGLDL LVFAHDHVGH GQSEGERMVV SDFHVFVRDV LQHVDSMQKD YPGLPVFLLG 130 140 150 160 170 180 HSMGGAIAIL TAAERPGHFA GMVLISPLVL ANPESATTFK VLAAKVLNLV LPNLSLGPID 190 200 210 220 230 240 SSVLSRNKTE VDIYNSDPLI CRAGLKVCFG IQLLNAVSRV ERALPKLTVP FLLLQGSADR 250 260 270 280 290 300 LCDSKGAYLL MELAKSQDKT LKIYEGAYHV LHKELPEVTN SVFHEINMWV SQRTATAGTA SPP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel poxvirus gene and its human homolog are similar to an E. coli lysophospholipase." Wall E.M., Cao J.X., Chen N., Buller R.M.L., Upton C. Virus Res. 52:157-167(1997) [PubMed: 9495531] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[2]	"Exon-intron organization and chromosomal localization of the mouse monoglyceride lipase gene." Karlsson M., Reue K., Xia Y.-R., Lusis A.J., Langin D., Tornqvist H., Holm C. Gene 272:11-18(2001) [PubMed: 11470505] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Adipose tissue.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Lung.
[7]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 175-303. Tissue: Rectum tumor.
[8]	"Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis." Nomura D.K., Long J.Z., Niessen S., Hoover H.S., Ng S.W., Cravatt B.F. Cell 140:49-61(2010) [PubMed: 20079333] [Abstract] Cited for: FUNCTION.
[9]	"Crystal structure of the human monoacylglycerol lipase, a key actor in endocannabinoid signaling." Labar G., Bauvois C., Borel F., Ferrer J.L., Wouters J., Lambert D.M. ChemBioChem 11:218-227(2010) [PubMed: 19957260] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 2-303, SUBUNIT, ACTIVE SITE, MASS SPECTROMETRY.
[10]	"Structural basis for human monoglyceride lipase inhibition." Bertrand T., Auge F., Houtmann J., Rak A., Vallee F., Mikol V., Berne P.F., Michot N., Cheuret D., Hoornaert C., Mathieu M. J. Mol. Biol. 396:663-673(2010) [PubMed: 19962385] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR SAR629, ACTIVE SITE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U67963 mRNA. Translation: AAB39616.1. Different initiation.
AJ270950 mRNA. Translation: CAC43316.1.
BC000551 mRNA. Translation: AAH00551.1. Different initiation.
BC006230 mRNA. Translation: AAH06230.1. Different initiation.
BX640777 mRNA. Translation: CAE45873.1.
AK315529 mRNA. Translation: BAG37910.1. Different initiation.
CR456835 mRNA. Translation: CAG33116.1. Different initiation.
CH471052 Genomic DNA. Translation: EAW79330.1. Different initiation.
CH471052 Genomic DNA. Translation: EAW79331.1. Different initiation.

IPI

IPI00293590.
IPI00455206.

RefSeq

NP_001003794.1. NM_001003794.1.
NP_009214.1. NM_007283.5.

UniGene

Hs.277035.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3HJU	X-ray	2.20	A/B	2-303	[»]
3JW8	X-ray	2.10	A/B	1-303	[»]
3JWE	X-ray	2.70	A/B	1-303	[»]
3PE6	X-ray	1.35	A	1-303	[»]

ProteinModelPortal

Q99685.

SMR

Q99685. Positions 6-295.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q99685. 3 interactions.

MINT

MINT-1414843.

STRING

Q99685.

Protein family/group databases

MEROPS

S33.980.

PTM databases

PhosphoSite

Q99685.

Polymorphism databases

DMDM

47117287.

Proteomic databases

PRIDE

Q99685.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265052; ENSP00000265052; ENSG00000074416.
ENST00000398104; ENSP00000381176; ENSG00000074416.
ENST00000434178; ENSP00000402798; ENSG00000074416.

GeneID

11343.

KEGG

hsa:11343.

NMPDR

fig|9606.3.peg.23134.

UCSC

uc003ejw.1. human.

Organism-specific databases

CTD

11343.

GeneCards

GC03M127407.

HGNC

HGNC:17038. MGLL.

HPA

HPA011993.
HPA011994.

MIM

609699. gene.

neXtProt

NX_Q99685.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00390000011364.

HOVERGEN

HBG049220.

InParanoid

Q99685.

OrthoDB

EOG4HMJ9X.

PhylomeDB

Q99685.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_22258. Metabolism of lipids and lipoproteins.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

Q99685.

Bgee

Q99685.

CleanEx

HS_MGLL.

Genevestigator

Q99685.

GermOnline

ENSG00000074416. Homo sapiens.

Family and domain databases

InterPro

IPR000073. AB_hydrolase_1.
[Graphical view]

KO

K01054.

PRINTS

PR00111. ABHYDROLASE.

PROSITE

PS00120. LIPASE_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

43106.

SOURCE

Search...

Entry information

Entry name

MGLL_HUMAN

Accession

Primary (citable) accession number: Q99685
Secondary accession number(s): Q6IBG9, Q96AA5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	May 10, 2004
Last modified:	January 25, 2012
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.