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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.9
Catalytic activity	Hydrolyzes glycerol monoesters of long-chain fatty acids.
Pathway	Glycerolipid metabolism; triacylglycerol degradation.
Subunit structure	Homodimer. Ref.10
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 Fatty acid metabolism Lipid biosynthesis Lipid degradation Lipid metabolism
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Serine esterase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	acylglycerol acyl-chain remodeling Traceable author statement. Source: Reactome arachidonic acid metabolic process Inferred from sequence or structural similarity. Source: UniProtKB fatty acid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW glycerophospholipid biosynthetic process Traceable author statement. Source: Reactome inflammatory response Traceable author statement Ref.1. Source: ProtInc long term synaptic depression Inferred from electronic annotation. Source: Compara 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	endoplasmic reticulum membrane Traceable author statement. Source: Reactome plasma membrane Traceable author statement. Source: Reactome synapse Inferred from electronic annotation. Source: Compara
Molecular_function	acylglycerol lipase activity Inferred from sequence or structural similarity. Source: UniProtKB carboxylesterase activity Inferred from electronic annotation. Source: UniProtKB-KW lipid binding Inferred from electronic annotation. Source: Compara lysophospholipase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q99685-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q99685-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → METGPEDPSSM
     161-190: Missing.

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.10 Ref.11

Active site

239

1

Charge relay system Probable

Active site

269

1

Charge relay system Probable

Natural variations

Alternative sequence

1

1

M → METGPEDPSSM in isoform 2.

VSP_045138

Alternative sequence

161 – 190

30

Missing in isoform 2.

VSP_045139

Secondary structure

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303

Helix Strand Turn

Details...

Helix

16 – 18

3

Beta strand

21 – 23

3

Beta strand

29 – 35

7

Beta strand

42 – 48

7

Helix

55 – 58

4

Helix

59 – 67

9

Beta strand

70 – 75

6

Helix

94 – 110

17

Beta strand

116 – 121

6

Helix

123 – 134

12

Turn

136 – 138

3

Beta strand

140 – 146

7

Beta strand

148 – 151

4

Helix

153 – 168

16

Helix

181 – 183

3

Helix

188 – 195

8

Helix

207 – 223

17

Helix

224 – 226

3

Beta strand

231 – 236

6

Beta strand

240 – 242

3

Helix

244 – 253

10

Beta strand

257 – 264

8

Helix

271 – 273

3

Helix

276 – 292

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [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
	Isoform 2 [UniParc]. Checksum: 5EE1BFA7CC9FBF26	FASTA	283	31,149
	10 20 30 40 50 60 METGPEDPSS MPEESSPRRT PQSIPYQDLP HLVNADGQYL FCRYWKPTGT PKALIFVSHG 70 80 90 100 110 120 AGEHSGRYEE LARMLMGLDL LVFAHDHVGH GQSEGERMVV SDFHVFVRDV LQHVDSMQKD 130 140 150 160 170 180 YPGLPVFLLG HSMGGAIAIL TAAERPGHFA GMVLISPLVL ANPESATTFK VDIYNSDPLI 190 200 210 220 230 240 CRAGLKVCFG IQLLNAVSRV ERALPKLTVP FLLLQGSADR LCDSKGAYLL MELAKSQDKT 250 260 270 280 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain and Uterus.
[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] (ISOFORM 1).
[5]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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].
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain and Lung.
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 175-303. Tissue: Rectum tumor.
[9]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 2-303, SUBUNIT, ACTIVE SITE, MASS SPECTROMETRY.
[11]	"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] [Europe PMC] [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.
AK315529 mRNA. Translation: BAG37910.1. Different initiation.
AK304844 mRNA. Translation: BAH14267.1.
CR456835 mRNA. Translation: CAG33116.1. Different initiation.
AC023593 Genomic DNA. No translation available.
AC117480 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW79330.1. Different initiation.
CH471052 Genomic DNA. Translation: EAW79331.1. Different initiation.
BC000551 mRNA. Translation: AAH00551.1. Different initiation.
BC006230 mRNA. Translation: AAH06230.1. Different initiation.
BX640777 mRNA. Translation: CAE45873.1.

IPI

IPI00293590.
IPI00455206.

RefSeq

NP_001003794.1. NM_001003794.2.
NP_001243514.1. NM_001256585.1.
NP_009214.1. NM_007283.6.

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.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q99685. 3 interactions.

MINT

MINT-1414843.

STRING

9606.ENSP00000265052.

Protein family/group databases

MEROPS

S33.980.

PTM databases

PhosphoSite

Q99685.

Polymorphism databases

DMDM

47117287.

Proteomic databases

PaxDb

Q99685.

PRIDE

Q99685.

Protocols and materials databases

DNASU

11343.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265052; ENSP00000265052; ENSG00000074416.
ENST00000398104; ENSP00000381176; ENSG00000074416.
ENST00000434178; ENSP00000402798; ENSG00000074416.
ENST00000453507; ENSP00000404146; ENSG00000074416.

GeneID

11343.

KEGG

hsa:11343.

UCSC

uc003ejw.3. human.
uc003ejx.3. human.
uc011bko.2. human.

Organism-specific databases

CTD

11343.

GeneCards

GC03M127407.

HGNC

HGNC:17038. MGLL.

HPA

HPA011993.
HPA011994.

MIM

609699. gene.

neXtProt

NX_Q99685.

PharmGKB

PA30789.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2267.

HOGENOM

HOG000003227.

HOVERGEN

HBG049220.

InParanoid

Q99685.

KO

K01054.

OrthoDB

EOG4HMJ9X.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_604. Hemostasis.

UniPathway

UPA00256.

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]

PRINTS

PR00111. ABHYDROLASE.

PROSITE

PS00120. LIPASE_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q99685.

ChEMBL

CHEMBL4191.

ChiTaRS

MGLL. human.

EvolutionaryTrace

Q99685.

GenomeRNAi

11343.

NextBio

43106.

SOURCE

Search...

Entry information

Entry name

MGLL_HUMAN

Accession

Primary (citable) accession number: Q99685
Secondary accession number(s): B7Z9D1, Q6IBG9, Q96AA5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	May 10, 2004
Last modified:	May 29, 2013
This is version 116 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.