ABD12_HUMAN
ID ABD12_HUMAN Reviewed; 398 AA.
AC Q8N2K0; A6NED4; A6NJ90; A8K450; B4DE71; Q5T710; Q5T711; Q96CR1; Q9BX05;
AC Q9NPX7; Q9UFV6;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2003, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Lysophosphatidylserine lipase ABHD12 {ECO:0000305};
DE EC=3.1.-.- {ECO:0000269|PubMed:30237167};
DE AltName: Full=2-arachidonoylglycerol hydrolase ABHD12 {ECO:0000305};
DE AltName: Full=Abhydrolase domain-containing protein 12 {ECO:0000305};
DE Short=hABHD12 {ECO:0000303|PubMed:30237167, ECO:0000303|PubMed:30643283};
DE AltName: Full=Monoacylglycerol lipase ABHD12 {ECO:0000305};
DE EC=3.1.1.23 {ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:30237167};
DE AltName: Full=Oxidized phosphatidylserine lipase ABHD12 {ECO:0000305};
DE EC=3.1.-.- {ECO:0000269|PubMed:30643283};
GN Name=ABHD12 {ECO:0000303|PubMed:20797687, ECO:0000312|HGNC:HGNC:15868};
GN Synonyms=C20orf22 {ECO:0000312|HGNC:HGNC:15868};
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Cerebellum, Kidney, and Ovarian carcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Pancreas;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 152-398 (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP INVOLVEMENT IN PHARC, AND VARIANT PHARC 352-ARG--HIS-398 DEL.
RX PubMed=20797687; DOI=10.1016/j.ajhg.2010.08.002;
RA Fiskerstrand T., H'mida-Ben Brahim D., Johansson S., M'zahem A.,
RA Haukanes B.I., Drouot N., Zimmermann J., Cole A.J., Vedeler C., Bredrup C.,
RA Assoum M., Tazir M., Klockgether T., Hamri A., Steen V.M., Boman H.,
RA Bindoff L.A., Koenig M., Knappskog P.M.;
RT "Mutations in ABHD12 cause the neurodegenerative disease PHARC: An inborn
RT error of endocannabinoid metabolism.";
RL Am. J. Hum. Genet. 87:410-417(2010).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF SER-246; ASP-333 AND HIS-372.
RX PubMed=22969151; DOI=10.1194/jlr.m030411;
RA Navia-Paldanius D., Savinainen J.R., Laitinen J.T.;
RT "Biochemical and pharmacological characterization of human alpha/beta-
RT hydrolase domain containing 6 (ABHD6) and 12 (ABHD12).";
RL J. Lipid Res. 53:2413-2424(2012).
RN [9]
RP INVOLVEMENT IN PHARC, AND VARIANT PHARC 65-ARG--HIS-398 DEL.
RX PubMed=22938382; DOI=10.1186/1750-1172-7-59;
RA Eisenberger T., Slim R., Mansour A., Nauck M., Nurnberg G., Nurnberg P.,
RA Decker C., Dafinger C., Ebermann I., Bergmann C., Bolz H.J.;
RT "Targeted next-generation sequencing identifies a homozygous nonsense
RT mutation in ABHD12, the gene underlying PHARC, in a family clinically
RT diagnosed with Usher syndrome type 3.";
RL Orphanet J. Rare Dis. 7:59-59(2012).
RN [10]
RP FUNCTION, INVOLVEMENT IN PHARC, AND VARIANT PHARC 377-LYS--HIS-398 DEL.
RX PubMed=24027063; DOI=10.1002/humu.22437;
RA Chen D.H., Naydenov A., Blankman J.L., Mefford H.C., Davis M., Sul Y.,
RA Barloon A.S., Bonkowski E., Wolff J., Matsushita M., Smith C.,
RA Cravatt B.F., Mackie K., Raskind W.H., Stella N., Bird T.D.;
RT "Two novel mutations in ABHD12: expansion of the mutation spectrum in PHARC
RT and assessment of their functional effects.";
RL Hum. Mutat. 34:1672-1678(2013).
RN [11]
RP ACTIVITY REGULATION.
RX PubMed=24879289; DOI=10.1371/journal.pone.0098286;
RA Parkkari T., Haavikko R., Laitinen T., Navia-Paldanius D., Rytilahti R.,
RA Vaara M., Lehtonen M., Alakurtti S., Yli-Kauhaluoma J., Nevalainen T.,
RA Savinainen J.R., Laitinen J.T.;
RT "Discovery of triterpenoids as reversible inhibitors of alpha/beta-
RT hydrolase domain containing 12 (ABHD12).";
RL PLoS ONE 9:E98286-E98286(2014).
RN [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=25290914; DOI=10.1371/journal.pone.0109869;
RA Savinainen J.R., Patel J.Z., Parkkari T., Navia-Paldanius D.,
RA Marjamaa J.J., Laitinen T., Nevalainen T., Laitinen J.T.;
RT "Biochemical and pharmacological characterization of the human lymphocyte
RT antigen B-associated transcript 5 (BAT5/ABHD16A).";
RL PLoS ONE 9:E109869-E109869(2014).
RN [13]
RP INVOLVEMENT IN PHARC.
RX PubMed=25743180; DOI=10.1177/0003489415574513;
RA Yoshimura H., Hashimoto T., Murata T., Fukushima K., Sugaya A.,
RA Nishio S.Y., Usami S.;
RT "Novel ABHD12 mutations in PHARC patients: the differential diagnosis of
RT deaf-blindness.";
RL Ann. Otol. Rhinol. Laryngol. 124:77-83(2015).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, AND
RP MUTAGENESIS OF SER-246.
RX PubMed=30237167; DOI=10.1074/jbc.ra118.005640;
RA Joshi A., Shaikh M., Singh S., Rajendran A., Mhetre A., Kamat S.S.;
RT "Biochemical characterization of the PHARC-associated serine hydrolase
RT ABHD12 reveals its preference for very-long-chain lipids.";
RL J. Biol. Chem. 293:16953-16963(2018).
RN [16]
RP INVOLVEMENT IN PHARC.
RX PubMed=29571850; DOI=10.1016/j.jns.2018.02.021;
RA Frasquet M., Lupo V., Chumillas M.J., Vazquez-Costa J.F., Espinos C.,
RA Sevilla T.;
RT "Phenotypical features of two patients diagnosed with PHARC syndrome and
RT carriers of a new homozygous mutation in the ABHD12 gene.";
RL J. Neurol. Sci. 387:134-138(2018).
RN [17]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=30420694; DOI=10.1038/s41589-018-0155-8;
RA Ogasawara D., Ichu T.A., Vartabedian V.F., Benthuysen J., Jing H., Reed A.,
RA Ulanovskaya O.A., Hulce J.J., Roberts A., Brown S., Rosen H., Teijaro J.R.,
RA Cravatt B.F.;
RT "Selective blockade of the lyso-PS lipase ABHD12 stimulates immune
RT responses in vivo.";
RL Nat. Chem. Biol. 14:1099-1108(2018).
RN [18]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=30720278; DOI=10.1021/acs.jmedchem.8b01958;
RA Ogasawara D., Ichu T.A., Jing H., Hulce J.J., Reed A., Ulanovskaya O.A.,
RA Cravatt B.F.;
RT "Discovery and optimization of selective and in vivo active inhibitors of
RT the lysophosphatidylserine lipase alpha/beta-hydrolase domain-containing 12
RT (ABHD12).";
RL J. Med. Chem. 62:1643-1656(2019).
RN [19]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF SER-246.
RX PubMed=30643283; DOI=10.1038/s41589-018-0195-0;
RA Kelkar D.S., Ravikumar G., Mehendale N., Singh S., Joshi A., Sharma A.K.,
RA Mhetre A., Rajendran A., Chakrapani H., Kamat S.S.;
RT "A chemical-genetic screen identifies ABHD12 as an oxidized-
RT phosphatidylserine lipase.";
RL Nat. Chem. Biol. 15:169-178(2019).
RN [20]
RP VARIANTS PHARC 159-TRP--HIS-398 DEL; PRO-186; ILE-202 AND GLN-372.
RX PubMed=24697911; DOI=10.1016/j.ophtha.2014.02.008;
RA Nishiguchi K.M., Avila-Fernandez A., van Huet R.A., Corton M.,
RA Perez-Carro R., Martin-Garrido E., Lopez-Molina M.I., Blanco-Kelly F.,
RA Hoefsloot L.H., van Zelst-Stams W.A., Garcia-Ruiz P.J., Del Val J.,
RA Di Gioia S.A., Klevering B.J., van de Warrenburg B.P., Vazquez C.,
RA Cremers F.P., Garcia-Sandoval B., Hoyng C.B., Collin R.W., Rivolta C.,
RA Ayuso C.;
RT "Exome sequencing extends the phenotypic spectrum for ABHD12 mutations:
RT from syndromic to nonsyndromic retinal degeneration.";
RL Ophthalmology 121:1620-1627(2014).
RN [21]
RP VARIANT PHARC ARG-253, AND CHARACTERIZATION OF VARIANTS PHARC ILE-202;
RP ARG-253 AND 352-ARG--HIS-398 DEL.
RX PubMed=27890673; DOI=10.1016/j.nbd.2016.11.008;
RA Tingaud-Sequeira A., Raldua D., Lavie J., Mathieu G., Bordier M.,
RA Knoll-Gellida A., Rambeau P., Coupry I., Andre M., Malm E., Moeller C.,
RA Andreasson S., Rendtorff N.D., Tranebjaerg L., Koenig M., Lacombe D.,
RA Goizet C., Babin P.J.;
RT "Functional validation of ABHD12 mutations in the neurodegenerative disease
RT PHARC.";
RL Neurobiol. Dis. 98:36-51(2017).
CC -!- FUNCTION: Lysophosphatidylserine (LPS) lipase that mediates the
CC hydrolysis of lysophosphatidylserine, a class of signaling lipids that
CC regulates immunological and neurological processes (PubMed:25290914,
CC PubMed:30237167, PubMed:30420694, PubMed:30720278, PubMed:30643283).
CC Represents a major lysophosphatidylserine lipase in the brain, thereby
CC playing a key role in the central nervous system (By similarity). Also
CC able to hydrolyze oxidized phosphatidylserine; oxidized
CC phosphatidylserine is produced in response to severe inflammatory
CC stress and constitutes a proapoptotic 'eat me' signal
CC (PubMed:30643283). Also has monoacylglycerol (MAG) lipase activity:
CC hydrolyzes 2-arachidonoylglycerol (2-AG), thereby acting as a regulator
CC of endocannabinoid signaling pathways (PubMed:22969151,
CC PubMed:24027063). Has a strong preference for very-long-chain lipid
CC substrates; substrate specificity is likely due to improved catalysis
CC and not improved substrate binding (PubMed:30237167).
CC {ECO:0000250|UniProtKB:Q99LR1, ECO:0000269|PubMed:22969151,
CC ECO:0000269|PubMed:24027063, ECO:0000269|PubMed:25290914,
CC ECO:0000269|PubMed:30237167, ECO:0000269|PubMed:30420694,
CC ECO:0000269|PubMed:30643283, ECO:0000269|PubMed:30720278}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + H2O =
CC (9Z)-octadecenoate + H(+) + sn-glycero-3-phospho-L-serine;
CC Xref=Rhea:RHEA:40499, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:64765, ChEBI:CHEBI:74617;
CC Evidence={ECO:0000269|PubMed:25290914, ECO:0000269|PubMed:30237167};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40500;
CC Evidence={ECO:0000269|PubMed:25290914, ECO:0000269|PubMed:30237167};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1'-sn-glycerol) +
CC H2O = (9Z)-octadecenoate + H(+) + sn-glycero-3-phospho-(1'-sn-
CC glycerol); Xref=Rhea:RHEA:44584, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:64717,
CC ChEBI:CHEBI:72828; Evidence={ECO:0000250|UniProtKB:Q99LR1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1D-myo-inositol) +
CC H2O = (9Z)-octadecenoate + H(+) + sn-glycero-3-phospho-1D-myo-
CC inositol; Xref=Rhea:RHEA:44588, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:58444, ChEBI:CHEBI:78762;
CC Evidence={ECO:0000250|UniProtKB:Q99LR1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O =
CC (9Z)-octadecenoate + H(+) + sn-glycero-3-phosphoethanolamine;
CC Xref=Rhea:RHEA:40895, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:74971, ChEBI:CHEBI:143890;
CC Evidence={ECO:0000250|UniProtKB:Q99LR1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-(9Z-
CC octadecenoyl)-sn-glycerol + H(+) + phosphocholine;
CC Xref=Rhea:RHEA:41091, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28610, ChEBI:CHEBI:75757, ChEBI:CHEBI:295975;
CC Evidence={ECO:0000250|UniProtKB:Q99LR1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate +
CC glycerol + H(+); Xref=Rhea:RHEA:38491, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:73990; Evidence={ECO:0000269|PubMed:22969151,
CC ECO:0000269|PubMed:30237167};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38492;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:30237167};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phospho-L-serine + H2O = H(+) +
CC hexadecanoate + sn-glycero-3-phospho-L-serine; Xref=Rhea:RHEA:44552,
CC ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:64765, ChEBI:CHEBI:75020;
CC Evidence={ECO:0000269|PubMed:30237167};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44553;
CC Evidence={ECO:0000269|PubMed:30237167};
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:22969151, ECO:0000269|PubMed:30237167};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:30237167};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.;
CC EC=3.1.1.23; Evidence={ECO:0000269|PubMed:22969151,
CC ECO:0000269|PubMed:30237167};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-decanoylglycerol + H2O = decanoate + glycerol + H(+);
CC Xref=Rhea:RHEA:44320, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:27689, ChEBI:CHEBI:75547;
CC Evidence={ECO:0000269|PubMed:22969151};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44321;
CC Evidence={ECO:0000269|PubMed:22969151};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-dodecanoylglycerol + H2O = dodecanoate + glycerol + H(+);
CC Xref=Rhea:RHEA:44316, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:18262, ChEBI:CHEBI:75539;
CC Evidence={ECO:0000269|PubMed:22969151};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44317;
CC Evidence={ECO:0000269|PubMed:22969151};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-tetradecanoylglycerol + H2O = glycerol + H(+) +
CC tetradecanoate; Xref=Rhea:RHEA:44312, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30807,
CC ChEBI:CHEBI:75562; Evidence={ECO:0000269|PubMed:22969151};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44313;
CC Evidence={ECO:0000269|PubMed:22969151};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hexadecanoylglycerol + H2O = glycerol + H(+) +
CC hexadecanoate; Xref=Rhea:RHEA:39963, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754,
CC ChEBI:CHEBI:75455; Evidence={ECO:0000269|PubMed:22969151,
CC ECO:0000269|PubMed:30237167};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39964;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:30237167};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate +
CC glycerol + H(+); Xref=Rhea:RHEA:38487, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:75342; Evidence={ECO:0000269|PubMed:22969151,
CC ECO:0000269|PubMed:30237167};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:30237167};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-
CC octadecadienoate + glycerol + H(+); Xref=Rhea:RHEA:44732,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:75457;
CC Evidence={ECO:0000269|PubMed:22969151};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44733;
CC Evidence={ECO:0000269|PubMed:22969151};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O =
CC (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H(+);
CC Xref=Rhea:RHEA:44728, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:32395, ChEBI:CHEBI:75612;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:25290914,
CC ECO:0000269|PubMed:30237167};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44729;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:25290914,
CC ECO:0000269|PubMed:30237167};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-
CC octadecadienoate + glycerol + H(+); Xref=Rhea:RHEA:48428,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:75568;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:25290914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48429;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:25290914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoylglycerol + H2O = glycerol + H(+) +
CC hexadecanoate; Xref=Rhea:RHEA:39959, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754,
CC ChEBI:CHEBI:69081; Evidence={ECO:0000269|PubMed:30237167};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39960;
CC Evidence={ECO:0000269|PubMed:30237167};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoylglycerol + H2O = glycerol + H(+) +
CC octadecanoate; Xref=Rhea:RHEA:38363, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:25629,
CC ChEBI:CHEBI:75555; Evidence={ECO:0000269|PubMed:30237167};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38364;
CC Evidence={ECO:0000269|PubMed:30237167};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(9,10-epoxyoctadecanoyl)-sn-glycero-3-
CC phospho-L-serine + H2O = 1-octadecanoyl-sn-glycero-3-phosphoserine +
CC 9,10-epoxyoctadecanoate + H(+); Xref=Rhea:RHEA:59364,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:84467,
CC ChEBI:CHEBI:85195, ChEBI:CHEBI:143087;
CC Evidence={ECO:0000269|PubMed:30643283};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59365;
CC Evidence={ECO:0000269|PubMed:30643283};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(10-hydroxyoctadecanoyl)-sn-glycero-3-
CC phospho-L-serine + H2O = 1-octadecanoyl-sn-glycero-3-phosphoserine +
CC 10-hydroxyoctadecanoate + H(+); Xref=Rhea:RHEA:59368,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:84467,
CC ChEBI:CHEBI:143088, ChEBI:CHEBI:143089;
CC Evidence={ECO:0000269|PubMed:30643283};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59369;
CC Evidence={ECO:0000269|PubMed:30643283};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(10-hydroxyoctadecanoyl)-sn-glycero-3-
CC phospho-L-serine + H2O = 1-hexadecanoyl-sn-glycero-3-phospho-L-serine
CC + 10-hydroxyoctadecanoate + H(+); Xref=Rhea:RHEA:59372,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:75020,
CC ChEBI:CHEBI:143089, ChEBI:CHEBI:143094;
CC Evidence={ECO:0000269|PubMed:30643283};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59373;
CC Evidence={ECO:0000269|PubMed:30643283};
CC -!- ACTIVITY REGULATION: Selectively inhibited by DO264 (N-3-pyridyl-N'-(1-
CC [3-chloro-4-{2-chloro-4-(trifluoromethoxy)phenoxy}pyridine-2-
CC yl]piperidin-4-yl)thiourea) (PubMed:30420694, PubMed:30720278).
CC Reversibly inhibited by triterpenoids, but with rather low potency
CC (PubMed:24879289). {ECO:0000269|PubMed:24879289,
CC ECO:0000269|PubMed:30420694, ECO:0000269|PubMed:30720278}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=117 uM for 2-arachidonoyglycerol {ECO:0000269|PubMed:22969151};
CC Vmax=42 nmol/min/mg enzyme toward 2-arachidonoyglycerol
CC {ECO:0000269|PubMed:22969151};
CC pH dependence:
CC Optimum pH is 7.2-9 with 2-arachidonoyglycerol as substrate.
CC {ECO:0000269|PubMed:22969151};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:30237167}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8N2K0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N2K0-2; Sequence=VSP_009097;
CC Name=3;
CC IsoId=Q8N2K0-3; Sequence=VSP_037372;
CC -!- PTM: Glycosylated; glycosylation is required for optimal activity.
CC {ECO:0000269|PubMed:30237167}.
CC -!- DISEASE: Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa,
CC and cataract (PHARC) [MIM:612674]: A slowly progressive neurologic
CC disorder with a variable phenotype resembling Refsum disease. Clinical
CC features include sensorineural hearing loss, visual problems related to
CC cataracts, retinitis pigmentosa, pes cavus, ataxic and/or spastic gait
CC disturbances with a progressive sensorimotor peripheral neuropathy.
CC Other features include hyporeflexia, hyperreflexia, extensor plantar
CC responses. {ECO:0000269|PubMed:20797687, ECO:0000269|PubMed:22938382,
CC ECO:0000269|PubMed:24027063, ECO:0000269|PubMed:24697911,
CC ECO:0000269|PubMed:25743180, ECO:0000269|PubMed:27890673,
CC ECO:0000269|PubMed:29571850}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the serine esterase family. {ECO:0000305}.
CC -!- CAUTION: A family suffering from Polyneuropathy, hearing loss, ataxia,
CC retinitis pigmentosa, and cataract (PHARC) was initially clinically
CC diagnosed with Usher syndrome type 3 (PubMed:22938382). Reexamination
CC of one affected member of this family revealed ataxia but not
CC polyneuropathy, demonstrating the phenotypic heterogeneity in PHARC and
CC the need for careful neurological assessments to distinguish this
CC disease from other neuropathic disorders (PubMed:22938382).
CC {ECO:0000269|PubMed:22938382}.
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DR EMBL; AK075023; BAC11357.1; -; mRNA.
DR EMBL; AK290815; BAF83504.1; -; mRNA.
DR EMBL; AK293495; BAG56982.1; -; mRNA.
DR EMBL; AL121772; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353812; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10089.1; -; Genomic_DNA.
DR EMBL; BC014049; AAH14049.1; -; mRNA.
DR EMBL; AL117442; CAB55927.1; -; mRNA.
DR CCDS; CCDS13172.1; -. [Q8N2K0-2]
DR CCDS; CCDS42857.1; -. [Q8N2K0-1]
DR PIR; T17237; T17237.
DR RefSeq; NP_001035937.1; NM_001042472.2. [Q8N2K0-1]
DR RefSeq; NP_056415.1; NM_015600.4. [Q8N2K0-2]
DR AlphaFoldDB; Q8N2K0; -.
DR SMR; Q8N2K0; -.
DR BioGRID; 117541; 105.
DR IntAct; Q8N2K0; 31.
DR MINT; Q8N2K0; -.
DR STRING; 9606.ENSP00000365725; -.
DR BindingDB; Q8N2K0; -.
DR ChEMBL; CHEMBL5516; -.
DR DrugCentral; Q8N2K0; -.
DR GuidetoPHARMACOLOGY; 3070; -.
DR SwissLipids; SLP:000001043; -.
DR ESTHER; human-ABHD12; ABHD12-PHARC.
DR MEROPS; S09.939; -.
DR GlyConnect; 1517; 3 N-Linked glycans (1 site).
DR GlyGen; Q8N2K0; 2 sites, 3 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q8N2K0; -.
DR PhosphoSitePlus; Q8N2K0; -.
DR BioMuta; ABHD12; -.
DR DMDM; 38604894; -.
DR EPD; Q8N2K0; -.
DR jPOST; Q8N2K0; -.
DR MassIVE; Q8N2K0; -.
DR MaxQB; Q8N2K0; -.
DR PaxDb; Q8N2K0; -.
DR PeptideAtlas; Q8N2K0; -.
DR PRIDE; Q8N2K0; -.
DR ProteomicsDB; 71711; -. [Q8N2K0-1]
DR ProteomicsDB; 71712; -. [Q8N2K0-2]
DR ProteomicsDB; 71713; -. [Q8N2K0-3]
DR Antibodypedia; 10033; 182 antibodies from 28 providers.
DR DNASU; 26090; -.
DR Ensembl; ENST00000339157.10; ENSP00000341408.5; ENSG00000100997.20. [Q8N2K0-1]
DR Ensembl; ENST00000376542.8; ENSP00000365725.3; ENSG00000100997.20. [Q8N2K0-2]
DR GeneID; 26090; -.
DR KEGG; hsa:26090; -.
DR MANE-Select; ENST00000339157.10; ENSP00000341408.5; NM_001042472.3; NP_001035937.1.
DR UCSC; uc002wuq.4; human. [Q8N2K0-1]
DR CTD; 26090; -.
DR DisGeNET; 26090; -.
DR GeneCards; ABHD12; -.
DR GeneReviews; ABHD12; -.
DR HGNC; HGNC:15868; ABHD12.
DR HPA; ENSG00000100997; Low tissue specificity.
DR MalaCards; ABHD12; -.
DR MIM; 612674; phenotype.
DR MIM; 613599; gene.
DR neXtProt; NX_Q8N2K0; -.
DR OpenTargets; ENSG00000100997; -.
DR Orphanet; 171848; Polyneuropathy-hearing loss-ataxia-retinitis pigmentosa-cataract syndrome.
DR PharmGKB; PA25738; -.
DR VEuPathDB; HostDB:ENSG00000100997; -.
DR eggNOG; KOG1552; Eukaryota.
DR GeneTree; ENSGT00940000160517; -.
DR HOGENOM; CLU_029375_1_0_1; -.
DR InParanoid; Q8N2K0; -.
DR OMA; YELHNCL; -.
DR OrthoDB; 691954at2759; -.
DR PhylomeDB; Q8N2K0; -.
DR TreeFam; TF315122; -.
DR PathwayCommons; Q8N2K0; -.
DR Reactome; R-HSA-426048; Arachidonate production from DAG.
DR SignaLink; Q8N2K0; -.
DR BioGRID-ORCS; 26090; 16 hits in 1080 CRISPR screens.
DR ChiTaRS; ABHD12; human.
DR GenomeRNAi; 26090; -.
DR Pharos; Q8N2K0; Tchem.
DR PRO; PR:Q8N2K0; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q8N2K0; protein.
DR Bgee; ENSG00000100997; Expressed in C1 segment of cervical spinal cord and 182 other tissues.
DR ExpressionAtlas; Q8N2K0; baseline and differential.
DR Genevisible; Q8N2K0; HS.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; IEA:Ensembl.
DR GO; GO:0032839; C:dendrite cytoplasm; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0047372; F:acylglycerol lipase activity; IDA:UniProtKB.
DR GO; GO:0004622; F:lysophospholipase activity; IDA:UniProtKB.
DR GO; GO:0008474; F:palmitoyl-(protein) hydrolase activity; IBA:GO_Central.
DR GO; GO:0004620; F:phospholipase activity; IDA:UniProtKB.
DR GO; GO:0046464; P:acylglycerol catabolic process; IDA:UniProtKB.
DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
DR GO; GO:0019369; P:arachidonic acid metabolic process; TAS:Reactome.
DR GO; GO:0046475; P:glycerophospholipid catabolic process; IDA:BHF-UCL.
DR GO; GO:0052651; P:monoacylglycerol catabolic process; IDA:UniProtKB.
DR GO; GO:0006660; P:phosphatidylserine catabolic process; IDA:UniProtKB.
DR GO; GO:0009395; P:phospholipid catabolic process; IDA:UniProtKB.
DR GO; GO:0002084; P:protein depalmitoylation; IEA:Ensembl.
DR GO; GO:0050727; P:regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0010996; P:response to auditory stimulus; IEA:Ensembl.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR026605; ABHD12.
DR InterPro; IPR022742; Hydrolase_4.
DR PANTHER; PTHR12277:SF61; PTHR12277:SF61; 1.
DR Pfam; PF12146; Hydrolase_4; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cataract; Deafness; Disease variant;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Lipid metabolism; Membrane;
KW Neuropathy; Reference proteome; Retinitis pigmentosa; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..398
FT /note="Lysophosphatidylserine lipase ABHD12"
FT /id="PRO_0000079413"
FT TOPO_DOM 1..74
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q99LR1"
FT TRANSMEM 75..95
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q99LR1"
FT TOPO_DOM 96..398
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q99LR1"
FT ACT_SITE 246
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:22969151,
FT ECO:0000305|PubMed:30237167"
FT ACT_SITE 333
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:22969151"
FT ACT_SITE 372
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:22969151"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 11..48
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_037372"
FT VAR_SEQ 387..398
FT /note="EFLGKSEPEHQH -> PQQGPGSSPDPSMWSELV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009097"
FT VARIANT 65..398
FT /note="Missing (in PHARC)"
FT /evidence="ECO:0000269|PubMed:22938382"
FT /id="VAR_081587"
FT VARIANT 159..398
FT /note="Missing (in PHARC; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24697911"
FT /id="VAR_081588"
FT VARIANT 186
FT /note="R -> P (in PHARC; unknown pathological significance;
FT dbSNP:rs587777604)"
FT /evidence="ECO:0000269|PubMed:24697911"
FT /id="VAR_081589"
FT VARIANT 202
FT /note="T -> I (in PHARC; unknown pathological significance;
FT abolished monoacyglycerol lipase activity)"
FT /evidence="ECO:0000269|PubMed:24697911,
FT ECO:0000269|PubMed:27890673"
FT /id="VAR_081590"
FT VARIANT 253
FT /note="T -> R (in PHARC; abolished monoacyglycerol lipase
FT activity; dbSNP:rs772987424)"
FT /evidence="ECO:0000269|PubMed:27890673"
FT /id="VAR_081591"
FT VARIANT 349
FT /note="A -> T (in dbSNP:rs746748)"
FT /id="VAR_050630"
FT VARIANT 352..398
FT /note="Missing (in PHARC; abolished monoacyglycerol lipase
FT activity)"
FT /evidence="ECO:0000269|PubMed:20797687,
FT ECO:0000269|PubMed:27890673"
FT /id="VAR_081592"
FT VARIANT 372
FT /note="H -> Q (in PHARC; unknown pathological significance;
FT dbSNP:rs587777602)"
FT /evidence="ECO:0000269|PubMed:24697911"
FT /id="VAR_081593"
FT VARIANT 377..398
FT /note="Missing (in PHARC)"
FT /evidence="ECO:0000269|PubMed:24027063"
FT /id="VAR_081594"
FT MUTAGEN 246
FT /note="S->A: Loss of lipase activity."
FT /evidence="ECO:0000269|PubMed:22969151,
FT ECO:0000269|PubMed:30237167, ECO:0000269|PubMed:30643283"
FT MUTAGEN 333
FT /note="D->N: Loss of 2-arachidonoyglycerol hydrolase
FT activity."
FT /evidence="ECO:0000269|PubMed:22969151"
FT MUTAGEN 372
FT /note="H->A: Loss of 2-arachidonoyglycerol hydrolase
FT activity."
FT /evidence="ECO:0000269|PubMed:22969151"
FT CONFLICT 359
FT /note="V -> I (in Ref. 1; BAF83504)"
FT /evidence="ECO:0000305"
FT CONFLICT 376
FT /note="Y -> C (in Ref. 1; BAC11357)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 398 AA; 45097 MW; E21425C1412B5607 CRC64;
MRKRTEPVAL EHERCAAAGS SSSGSAAAAL DADCRLKQNL RLTGPAAAEP RCAADAGMKR
ALGRRKGVWL RLRKILFCVL GLYIAIPFLI KLCPGIQAKL IFLNFVRVPY FIDLKKPQDQ
GLNHTCNYYL QPEEDVTIGV WHTVPAVWWK NAQGKDQMWY EDALASSHPI ILYLHGNAGT
RGGDHRVELY KVLSSLGYHV VTFDYRGWGD SVGTPSERGM TYDALHVFDW IKARSGDNPV
YIWGHSLGTG VATNLVRRLC ERETPPDALI LESPFTNIRE EAKSHPFSVI YRYFPGFDWF
FLDPITSSGI KFANDENVKH ISCPLLILHA EDDPVVPFQL GRKLYSIAAP ARSFRDFKVQ
FVPFHSDLGY RHKYIYKSPE LPRILREFLG KSEPEHQH
