ABHD2_MACFA
ID ABHD2_MACFA Reviewed; 425 AA.
AC Q4R2Y9; Q4R7R8;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 76.
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=Triacylglycerol lipase {ECO:0000250|UniProtKB:P08910};
DE EC=3.1.1.79 {ECO:0000250|UniProtKB:P08910};
GN Name=ABHD2; ORFNames=QtsA-14549, QtsA-21018;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
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). May also play a role in smooth muscle cells migration (By
CC similarity). {ECO:0000250|UniProtKB:P08910,
CC ECO:0000250|UniProtKB:Q9QXM0}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q4R2Y9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q4R2Y9-2; Sequence=VSP_023917, VSP_023918;
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. AB hydrolase 4
CC family. {ECO:0000305}.
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DR EMBL; AB168745; BAE00854.1; -; mRNA.
DR EMBL; AB179479; BAE02530.1; -; mRNA.
DR RefSeq; NP_001270570.1; NM_001283641.1. [Q4R2Y9-1]
DR RefSeq; XP_005560519.1; XM_005560462.2. [Q4R2Y9-1]
DR RefSeq; XP_015308713.1; XM_015453227.1. [Q4R2Y9-1]
DR AlphaFoldDB; Q4R2Y9; -.
DR STRING; 9541.XP_005560518.1; -.
DR ESTHER; macfa-abhd2; abh_upf0017.
DR Ensembl; ENSMFAT00000028633; ENSMFAP00000000464; ENSMFAG00000034068. [Q4R2Y9-2]
DR Ensembl; ENSMFAT00000087775; ENSMFAP00000048606; ENSMFAG00000034068. [Q4R2Y9-1]
DR GeneID; 101867085; -.
DR KEGG; mcf:101867085; -.
DR CTD; 11057; -.
DR VEuPathDB; HostDB:ENSMFAG00000034068; -.
DR eggNOG; KOG1838; Eukaryota.
DR GeneTree; ENSGT00950000182902; -.
DR OMA; DHCRRFY; -.
DR Proteomes; UP000233100; Chromosome 7.
DR Bgee; ENSMFAG00000034068; Expressed in liver and 13 other tissues.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0036126; C:sperm flagellum; IEA:Ensembl.
DR GO; GO:0097524; C:sperm plasma membrane; IEA:Ensembl.
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:0004806; F:triglyceride lipase activity; IEA:RHEA.
DR GO; GO:0007340; P:acrosome reaction; IEA:Ensembl.
DR GO; GO:0046464; P:acylglycerol catabolic process; ISS:UniProtKB.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:0032570; P:response to progesterone; ISS:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR GO; GO:0014909; P:smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:0048240; P:sperm capacitation; IEA:Ensembl.
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 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; 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_0000280781"
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 VAR_SEQ 215..220
FT /note="KYLGET -> ARGTVH (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_023917"
FT VAR_SEQ 221..425
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_023918"
SQ SEQUENCE 425 AA; 48289 MW; 747C6AB2C9839FC2 CRC64;
MNAMLETPEL PAVFDGVKLA AVAAVLYVIV RCLNLKSPTA PPDLYFQDSG LSRFLLKSCP
LLTKEYIPPL IWGKSGHIQT ALYGKMGRVR SPHPYGHRKF ITMSDGATST FDLFEPLAEH
CVGDDITMVI CPGIANHSEK QYIRTFVDYA QKNGYRCAVL NHLGALPNIE LTSPRMFTYG
CTWEFGAMVN YIKKTYPLTQ LVVVGFSLGG NIVCKYLGET QANQEKVLCC VSVCQGYSAL
RAQETFMQWD QCRRFYNFLM ADNMKKIILS HRQALFGDHV KKPQSLEDTD LSRLYTATSL
MQIDDNVMRK FHGYNSLKEY YEEESCMRYL HRIYVPLMLV NAADDPLVHE SLLTIPKSLS
EKRENVMFVL PLHGGHLGFF EGSVLFPEPL TWMDKLVVEY ANAICQWERN KSQCSDTEQV
EADLE
