ABHD2_MOUSE
ID ABHD2_MOUSE Reviewed; 425 AA.
AC Q9QXM0; Q3U5E8; Q5FWC6; Q9D7Y8;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Monoacylglycerol lipase ABHD2 {ECO:0000305};
DE EC=3.1.1.23 {ECO:0000250|UniProtKB:P08910};
DE AltName: Full=2-arachidonoylglycerol hydrolase {ECO:0000305};
DE AltName: Full=Abhydrolase domain-containing protein 2 {ECO:0000305};
DE AltName: Full=Acetylesterase {ECO:0000250|UniProtKB:P08910};
DE EC=3.1.1.6 {ECO:0000250|UniProtKB:P08910};
DE AltName: Full=Lung alpha/beta hydrolase 2 {ECO:0000303|PubMed:11922611};
DE Short=MmLABH2 {ECO:0000303|PubMed:11922611};
DE AltName: Full=Triacylglycerol lipase {ECO:0000250|UniProtKB:P08910};
DE EC=3.1.1.79 {ECO:0000250|UniProtKB:P08910};
GN Name=Abhd2;
GN Synonyms=Labh-2 {ECO:0000303|PubMed:11922611},
GN Labh2 {ECO:0000303|PubMed:11922611};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Lung;
RX PubMed=11922611; DOI=10.1006/bbrc.2002.6692;
RA Edgar A.J., Polak J.M.;
RT "Cloning and tissue distribution of three murine alpha/beta hydrolase fold
RT protein cDNAs.";
RL Biochem. Biophys. Res. Commun. 292:617-625(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Utleg A., White J., Lin B.;
RT "Cloning of an androgen-regulated a/b hydrolase.";
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Egg, Stomach, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=15721306; DOI=10.1016/j.bbrc.2005.01.127;
RA Miyata K., Oike Y., Hoshii T., Maekawa H., Ogawa H., Suda T., Araki K.,
RA Yamamura K.;
RT "Increase of smooth muscle cell migration and of intimal hyperplasia in
RT mice lacking the alpha/beta hydrolase domain containing 2 gene.";
RL Biochem. Biophys. Res. Commun. 329:296-304(2005).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=19250629; DOI=10.1016/j.bbrc.2009.01.098;
RA Jin S., Zhao G., Li Z., Nishimoto Y., Isohama Y., Shen J., Ito T.,
RA Takeya M., Araki K., He P., Yamamura K.;
RT "Age-related pulmonary emphysema in mice lacking alpha/beta hydrolase
RT domain containing 2 gene.";
RL Biochem. Biophys. Res. Commun. 380:419-424(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26989199; DOI=10.1126/science.aad6887;
RA Miller M.R., Mannowetz N., Iavarone A.T., Safavi R., Gracheva E.O.,
RA Smith J.F., Hill R.Z., Bautista D.M., Kirichok Y., Lishko P.V.;
RT "Unconventional endocannabinoid signaling governs sperm activation via sex
RT hormone progesterone.";
RL Science 352:555-559(2016).
CC -!- FUNCTION: Progesterone-dependent acylglycerol lipase that catalyzes
CC hydrolysis of endocannabinoid arachidonoylglycerol (AG) from cell
CC membrane. Acts as a progesterone receptor: progesterone-binding
CC activates the acylglycerol lipase activity, mediating degradation of 1-
CC arachidonoylglycerol (1AG) and 2-arachidonoylglycerol (2AG) to glycerol
CC and arachidonic acid (AA). Also displays an ester hydrolase activity
CC against acetyl ester, butanoate ester and hexadecanoate ester. Plays a
CC key role in sperm capacitation in response to progesterone by mediating
CC degradation of 2AG, an inhibitor of the sperm calcium channel CatSper,
CC leading to calcium influx via CatSper and sperm activation (By
CC similarity). Involved in acrosomal reaction (Probable). May also play a
CC role in smooth muscle cells migration (PubMed:15721306).
CC {ECO:0000250|UniProtKB:P08910, ECO:0000269|PubMed:15721306,
CC ECO:0000305|PubMed:26989199}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.;
CC EC=3.1.1.23; Evidence={ECO:0000250|UniProtKB:P08910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an acetyl ester + H2O = acetate + an aliphatic alcohol + H(+);
CC Xref=Rhea:RHEA:12957, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:47622; EC=3.1.1.6;
CC Evidence={ECO:0000250|UniProtKB:P08910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12958;
CC Evidence={ECO:0000250|UniProtKB:P08910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a triacylglycerol + H2O = a diacylglycerol + a fatty acid +
CC H(+); Xref=Rhea:RHEA:12044, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17855, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.79;
CC Evidence={ECO:0000250|UniProtKB:P08910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12045;
CC Evidence={ECO:0000250|UniProtKB:P08910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O =
CC (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H(+);
CC Xref=Rhea:RHEA:26132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:32395, ChEBI:CHEBI:52392;
CC Evidence={ECO:0000250|UniProtKB:P08910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC Evidence={ECO:0000250|UniProtKB:P08910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a butanoate ester + H2O = an aliphatic alcohol + butanoate +
CC H(+); Xref=Rhea:RHEA:47348, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17968, ChEBI:CHEBI:50477;
CC Evidence={ECO:0000250|UniProtKB:P08910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47349;
CC Evidence={ECO:0000250|UniProtKB:P08910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + hexadecanoate ester = an aliphatic alcohol + H(+) +
CC hexadecanoate; Xref=Rhea:RHEA:47392, ChEBI:CHEBI:2571,
CC ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:25835; Evidence={ECO:0000250|UniProtKB:P08910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47393;
CC Evidence={ECO:0000250|UniProtKB:P08910};
CC -!- ACTIVITY REGULATION: Acylglycerol lipase activity is activated upon
CC binding to progesterone. {ECO:0000250|UniProtKB:P08910}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P08910};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:P08910}.
CC Cytoplasmic vesicle, secretory vesicle, acrosome membrane
CC {ECO:0000269|PubMed:26989199}. Note=Absent from the sperm flagellum.
CC {ECO:0000269|PubMed:26989199}.
CC -!- TISSUE SPECIFICITY: Widely expressed with higher expression in testis.
CC Expressed by vascular smooth muscle cells, non vascular smooth muscle
CC cells and heart. {ECO:0000269|PubMed:11922611,
CC ECO:0000269|PubMed:15721306}.
CC -!- DEVELOPMENTAL STAGE: Detected in embryos from 7 dpc to 17 dpc. Weakly
CC expressed in heart at 9.5 dpc. Expression is detected in endothelial
CC cells of the dorsal aorta at 10.5 dpc and disappear at 12.5 dpc.
CC Expression in smooth muscle cells is first detected at 11.5 dpc.
CC Strongly expressed in vitelline vessels at 12.5 dpc. Expressed in all
CC smooth muscle cells at 16.5 dpc. {ECO:0000269|PubMed:11922611,
CC ECO:0000269|PubMed:15721306}.
CC -!- DISRUPTION PHENOTYPE: Neointimal hyperplasia (PubMed:15721306). In
CC lungs, decreased level of phosphatidylcholine in the bronchoalveolar
CC lavage is observed (PubMed:19250629). Mice develop spontaneous gradual
CC progression of emphysema (PubMed:19250629).
CC {ECO:0000269|PubMed:15721306, ECO:0000269|PubMed:19250629}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. AB hydrolase 4
CC family. {ECO:0000305}.
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DR EMBL; AF201730; AAF17566.1; -; mRNA.
DR EMBL; AF546701; AAQ12022.1; -; mRNA.
DR EMBL; AK008690; BAB25836.1; -; mRNA.
DR EMBL; AK139526; BAE24049.1; -; mRNA.
DR EMBL; AK153642; BAE32131.1; -; mRNA.
DR EMBL; BC027098; AAH27098.1; -; mRNA.
DR EMBL; BC089477; AAH89477.1; -; mRNA.
DR CCDS; CCDS21380.1; -.
DR RefSeq; NP_061281.3; NM_018811.6.
DR AlphaFoldDB; Q9QXM0; -.
DR STRING; 10090.ENSMUSP00000038361; -.
DR BindingDB; Q9QXM0; -.
DR ESTHER; mouse-ABHD2; abh_upf0017.
DR MEROPS; S33.A56; -.
DR GlyGen; Q9QXM0; 2 sites.
DR iPTMnet; Q9QXM0; -.
DR PhosphoSitePlus; Q9QXM0; -.
DR EPD; Q9QXM0; -.
DR MaxQB; Q9QXM0; -.
DR PaxDb; Q9QXM0; -.
DR PeptideAtlas; Q9QXM0; -.
DR PRIDE; Q9QXM0; -.
DR ProteomicsDB; 285826; -.
DR Antibodypedia; 1104; 165 antibodies from 26 providers.
DR DNASU; 54608; -.
DR Ensembl; ENSMUST00000037315; ENSMUSP00000038361; ENSMUSG00000039202.
DR GeneID; 54608; -.
DR KEGG; mmu:54608; -.
DR UCSC; uc009hyc.1; mouse.
DR CTD; 11057; -.
DR MGI; MGI:1914344; Abhd2.
DR VEuPathDB; HostDB:ENSMUSG00000039202; -.
DR eggNOG; KOG1838; Eukaryota.
DR GeneTree; ENSGT00950000182902; -.
DR HOGENOM; CLU_032487_5_0_1; -.
DR InParanoid; Q9QXM0; -.
DR OMA; DHCRRFY; -.
DR OrthoDB; 1033151at2759; -.
DR PhylomeDB; Q9QXM0; -.
DR TreeFam; TF313195; -.
DR BioGRID-ORCS; 54608; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Abhd2; mouse.
DR PRO; PR:Q9QXM0; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9QXM0; protein.
DR Bgee; ENSMUSG00000039202; Expressed in pigmented layer of retina and 221 other tissues.
DR Genevisible; Q9QXM0; MM.
DR GO; GO:0002080; C:acrosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0036126; C:sperm flagellum; ISO:MGI.
DR GO; GO:0097524; C:sperm plasma membrane; ISO:MGI.
DR GO; GO:0008126; F:acetylesterase activity; ISS:UniProtKB.
DR GO; GO:0047372; F:acylglycerol lipase activity; ISS:UniProtKB.
DR GO; GO:0042562; F:hormone binding; ISS:UniProtKB.
DR GO; GO:0033878; F:hormone-sensitive lipase activity; ISS:UniProtKB.
DR GO; GO:0003707; F:nuclear steroid receptor activity; ISS:UniProtKB.
DR GO; GO:0034338; F:short-chain carboxylesterase activity; IBA:GO_Central.
DR GO; GO:0004806; F:triglyceride lipase activity; IEA:RHEA.
DR GO; GO:0007340; P:acrosome reaction; IMP:UniProtKB.
DR GO; GO:0046464; P:acylglycerol catabolic process; ISS:UniProtKB.
DR GO; GO:0044255; P:cellular lipid metabolic process; IBA:GO_Central.
DR GO; GO:0051792; P:medium-chain fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0051793; P:medium-chain fatty acid catabolic process; IBA:GO_Central.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; IMP:MGI.
DR GO; GO:0032570; P:response to progesterone; ISS:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IMP:MGI.
DR GO; GO:0014909; P:smooth muscle cell migration; IMP:MGI.
DR GO; GO:0048240; P:sperm capacitation; ISO:MGI.
DR GO; GO:0043401; P:steroid hormone mediated signaling pathway; ISS:UniProtKB.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR InterPro; IPR000952; AB_hydrolase_4_CS.
DR InterPro; IPR012020; ABHD4.
DR Pfam; PF00561; Abhydrolase_1; 1.
DR PIRSF; PIRSF005211; Ab_hydro_YheT; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS01133; UPF0017; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasmic vesicle; Glycoprotein; Hydrolase;
KW Lipid degradation; Lipid metabolism; Membrane; Reference proteome;
KW Serine esterase; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..425
FT /note="Monoacylglycerol lipase ABHD2"
FT /id="PRO_0000280782"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 10..30
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..425
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT DOMAIN 128..382
FT /note="AB hydrolase-1"
FT /evidence="ECO:0000255"
FT ACT_SITE 207
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q86WA6"
FT ACT_SITE 345
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q86WA6"
FT ACT_SITE 376
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q86WA6"
FT CARBOHYD 136
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 410
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CONFLICT 21
FT /note="A -> V (in Ref. 3; BAB25836)"
FT /evidence="ECO:0000305"
FT CONFLICT 63
FT /note="T -> A (in Ref. 4; AAH89477)"
FT /evidence="ECO:0000305"
FT CONFLICT 338
FT /note="M -> L (in Ref. 3; BAE32131)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 425 AA; 48378 MW; 82CC000D4A90004F CRC64;
MNAMLETPEL PAVFDGVKLA AVAAVLYVIV RCLNLKSPTA PPDLYFQDSG LSRFLLKSCP
LLTKEYIPPL IWGKSGHIQT ALYGKMGRVR SPHPYGHRKF ITMSDGATST FDLFEPLAEH
CVGDDITMVI CPGIANHSEK QYIRTFVDYA QKNGYRCAVL NHLGALPNIE LTSPRMFTYG
CTWEFGAMVN YIKRTYPQTQ LVVVGFSLGG NIVCKYLGET QANQEKVLCC VSVCQGYSAL
RAQETFMQWD QCRRFYNFLM ADNMKKIILS HRQALFGDHV KKPQSLEDTD LSRLYTATSL
MQIDDNVMRK FHGYNSLKEY YEEESCMRYL HRIYVPLMLV NAADDPLVHE SLLTIPKSLS
EKRENVMFVL PLHGGHLGFF EGSVLFPEPL TWMDKLVVEY ANAICQWERN KSQCSDTEQM
EAELE
