ABHD2_HUMAN
ID ABHD2_HUMAN Reviewed; 425 AA.
AC P08910; Q53G48; Q53GU0; Q5FVD9; Q8TC79;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Monoacylglycerol lipase ABHD2 {ECO:0000305};
DE EC=3.1.1.23 {ECO:0000269|PubMed:26989199};
DE AltName: Full=2-arachidonoylglycerol hydrolase {ECO:0000305};
DE AltName: Full=Abhydrolase domain-containing protein 2 {ECO:0000305};
DE AltName: Full=Acetylesterase {ECO:0000305};
DE EC=3.1.1.6 {ECO:0000269|PubMed:27247428};
DE AltName: Full=Lung alpha/beta hydrolase 2 {ECO:0000250|UniProtKB:Q9QXM0};
DE AltName: Full=Progesterone-sensitive lipase {ECO:0000305};
DE EC=3.1.1.79 {ECO:0000269|PubMed:27247428};
DE AltName: Full=Protein PHPS1-2 {ECO:0000303|PubMed:2843827};
GN Name=ABHD2 {ECO:0000312|HGNC:HGNC:18717};
GN Synonyms=LABH2 {ECO:0000250|UniProtKB:Q9QXM0};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=2843827; DOI=10.1093/nar/16.17.8721;
RA Rapiejko P.J., George S.T., Malbon C.C.;
RT "Primary structure of a human protein which bears structural similarities
RT to members of the rhodopsin/beta-adrenergic receptor family.";
RL Nucleic Acids Res. 16:8721-8721(1988).
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 TISSUE=Gastric carcinoma, and Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-253.
RC TISSUE=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 CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND FUNCTION.
RX PubMed=27247428; DOI=10.1042/bsr20160033;
RA M N.K., V B S C T., G K V., B C.S., Guntupalli S., J S B.;
RT "Molecular characterization of human ABHD2 as TAG lipase and ester
RT hydrolase.";
RL Biosci. Rep. 36:0-0(2016).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND IDENTIFICATION BY MASS SPECTROMETRY.
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 (PubMed:26989199). Acts as a progesterone receptor:
CC progesterone-binding activates the acylglycerol lipase activity,
CC mediating degradation of 1-arachidonoylglycerol (1AG) and 2-
CC arachidonoylglycerol (2AG) to glycerol and arachidonic acid (AA)
CC (PubMed:26989199). Also displays an ester hydrolase activity against
CC acetyl ester, butanoate ester and hexadecanoate ester
CC (PubMed:27247428). Plays a key role in sperm capacitation in response
CC to progesterone by mediating degradation of 2AG, an inhibitor of the
CC sperm calcium channel CatSper, leading to calcium influx via CatSper
CC and sperm activation (PubMed:26989199). May also play a role in smooth
CC muscle cells migration (By similarity). {ECO:0000250|UniProtKB:Q9QXM0,
CC ECO:0000269|PubMed:26989199, ECO:0000269|PubMed:27247428}.
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:0000269|PubMed:27247428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12958;
CC Evidence={ECO:0000305|PubMed:27247428};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.;
CC EC=3.1.1.23; Evidence={ECO:0000269|PubMed:26989199};
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:0000269|PubMed:27247428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12045;
CC Evidence={ECO:0000305|PubMed:27247428};
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:0000269|PubMed:26989199};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC Evidence={ECO:0000305|PubMed:26989199};
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:0000269|PubMed:27247428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47349;
CC Evidence={ECO:0000305|PubMed:27247428};
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:0000269|PubMed:27247428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47393;
CC Evidence={ECO:0000305|PubMed:27247428};
CC -!- ACTIVITY REGULATION: Acylglycerol lipase activity is activated upon
CC binding to progesterone. {ECO:0000269|PubMed:26989199}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12.4 mM for p-nitrophenyl acetate {ECO:0000269|PubMed:27247428};
CC KM=11.76 mM for p-nitrophenyl butyrate {ECO:0000269|PubMed:27247428};
CC KM=17.66 mM for p-nitrophenyl palmitate
CC {ECO:0000269|PubMed:27247428};
CC Vmax=2.69 umol/sec/mg enzyme toward p-nitrophenyl acetate
CC {ECO:0000269|PubMed:27247428};
CC Vmax=3.71 umol/sec/mg enzyme toward p-nitrophenyl butyrate
CC {ECO:0000269|PubMed:27247428};
CC Vmax=1.27 umol/sec/mg enzyme toward p-nitrophenyl palmitate
CC {ECO:0000269|PubMed:27247428};
CC pH dependence:
CC Optimum pH is 8.5 for p-nitrophenyl palmitate and 7.5 for p-
CC nitrophenyl acetate and p-nitrophenyl butyrate.
CC {ECO:0000269|PubMed:27247428};
CC Temperature dependence:
CC Optimum temperature is 45 degrees Celsius with p-nitrophenyl
CC palmitate and 30 degrees Celsius with p-nitrophenyl acetate and p-
CC nitrophenyl butyrate. {ECO:0000269|PubMed:27247428};
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium, flagellum membrane
CC {ECO:0000305|PubMed:26989199}; Single-pass type II membrane protein
CC {ECO:0000305}. Cell membrane {ECO:0000305}; Single-pass type II
CC membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Present in sperm (at protein level).
CC {ECO:0000269|PubMed:26989199}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. AB hydrolase 4
CC family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a G-coupled receptor.
CC {ECO:0000305|PubMed:2843827}.
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DR EMBL; X12433; CAA30976.1; -; mRNA.
DR EMBL; AF546700; AAQ12021.1; -; mRNA.
DR EMBL; AK222841; BAD96561.1; -; mRNA.
DR EMBL; AK223083; BAD96803.1; -; mRNA.
DR EMBL; BC019248; AAH19248.1; -; mRNA.
DR EMBL; BC090052; AAH90052.1; -; mRNA.
DR CCDS; CCDS10348.1; -.
DR PIR; A31026; A31026.
DR RefSeq; NP_008942.3; NM_007011.7.
DR RefSeq; NP_690888.1; NM_152924.4.
DR RefSeq; XP_005254889.1; XM_005254832.1.
DR RefSeq; XP_005254890.1; XM_005254833.1.
DR RefSeq; XP_011519467.1; XM_011521165.1.
DR AlphaFoldDB; P08910; -.
DR BioGRID; 116242; 10.
DR STRING; 9606.ENSP00000268129; -.
DR SwissLipids; SLP:000001546; -.
DR ESTHER; human-ABHD2; abh_upf0017.
DR GlyGen; P08910; 1 site.
DR iPTMnet; P08910; -.
DR PhosphoSitePlus; P08910; -.
DR SwissPalm; P08910; -.
DR BioMuta; ABHD2; -.
DR DMDM; 123504; -.
DR MassIVE; P08910; -.
DR MaxQB; P08910; -.
DR PaxDb; P08910; -.
DR PeptideAtlas; P08910; -.
DR PRIDE; P08910; -.
DR ProteomicsDB; 52174; -.
DR Antibodypedia; 1104; 165 antibodies from 26 providers.
DR DNASU; 11057; -.
DR Ensembl; ENST00000352732.10; ENSP00000268129.5; ENSG00000140526.18.
DR Ensembl; ENST00000565973.5; ENSP00000455639.1; ENSG00000140526.18.
DR GeneID; 11057; -.
DR KEGG; hsa:11057; -.
DR MANE-Select; ENST00000352732.10; ENSP00000268129.5; NM_152924.5; NP_690888.1.
DR UCSC; uc002bnk.2; human.
DR CTD; 11057; -.
DR DisGeNET; 11057; -.
DR GeneCards; ABHD2; -.
DR HGNC; HGNC:18717; ABHD2.
DR HPA; ENSG00000140526; Low tissue specificity.
DR MIM; 612196; gene.
DR neXtProt; NX_P08910; -.
DR OpenTargets; ENSG00000140526; -.
DR PharmGKB; PA38658; -.
DR VEuPathDB; HostDB:ENSG00000140526; -.
DR eggNOG; KOG1838; Eukaryota.
DR GeneTree; ENSGT00950000182902; -.
DR HOGENOM; CLU_032487_5_0_1; -.
DR InParanoid; P08910; -.
DR OMA; DHCRRFY; -.
DR OrthoDB; 1033151at2759; -.
DR PhylomeDB; P08910; -.
DR TreeFam; TF313195; -.
DR PathwayCommons; P08910; -.
DR SignaLink; P08910; -.
DR BioGRID-ORCS; 11057; 8 hits in 1076 CRISPR screens.
DR ChiTaRS; ABHD2; human.
DR GeneWiki; ABHD2; -.
DR GenomeRNAi; 11057; -.
DR Pharos; P08910; Tbio.
DR PRO; PR:P08910; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P08910; protein.
DR Bgee; ENSG00000140526; Expressed in corpus epididymis and 197 other tissues.
DR ExpressionAtlas; P08910; baseline and differential.
DR Genevisible; P08910; HS.
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; IDA:UniProtKB.
DR GO; GO:0097524; C:sperm plasma membrane; IDA:UniProtKB.
DR GO; GO:0008126; F:acetylesterase activity; IDA:UniProtKB.
DR GO; GO:0047372; F:acylglycerol lipase activity; IDA:UniProtKB.
DR GO; GO:0042562; F:hormone binding; IDA:UniProtKB.
DR GO; GO:0033878; F:hormone-sensitive lipase activity; IDA:UniProtKB.
DR GO; GO:0003707; F:nuclear steroid receptor activity; IDA: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; IEA:Ensembl.
DR GO; GO:0046464; P:acylglycerol catabolic process; IDA: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; IEA:Ensembl.
DR GO; GO:0032570; P:response to progesterone; IDA: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; IDA:UniProtKB.
DR GO; GO:0043401; P:steroid hormone mediated signaling pathway; IDA: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; Cell projection; Cilium; Flagellum; 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_0000212457"
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 VARIANT 253
FT /note="R -> Q (in dbSNP:rs17851730)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_031203"
FT CONFLICT 27
FT /note="Y -> C (in Ref. 3; BAD96803)"
FT /evidence="ECO:0000305"
FT CONFLICT 388
FT /note="E -> G (in Ref. 3; BAD96561)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 425 AA; 48315 MW; 747C6AB2C99B3CC2 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 KLQCSDTEQV
EADLE
