ID DGLB_HUMAN Reviewed; 672 AA. AC Q8NCG7; A4D2P3; B3KV90; B4DQU0; Q6PIX3; Q8N2N2; Q8N9S1; Q8TED3; Q8WXE6; DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot. DT 05-SEP-2006, sequence version 2. DT 27-MAR-2024, entry version 160. DE RecName: Full=Diacylglycerol lipase-beta {ECO:0000303|PubMed:14610053}; DE Short=DAGL-beta {ECO:0000303|PubMed:14610053}; DE Short=DGL-beta; DE EC=3.1.1.116 {ECO:0000269|PubMed:14610053}; DE AltName: Full=KCCR13L; DE AltName: Full=PUFA-specific triacylglycerol lipase {ECO:0000250|UniProtKB:Q91WC9}; DE EC=3.1.1.3 {ECO:0000250|UniProtKB:Q91WC9}; DE AltName: Full=Sn1-specific diacylglycerol lipase beta {ECO:0000303|PubMed:14610053}; GN Name=DAGLB; 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] (ISOFORM 1). RC TISSUE=Placenta; RA Morimura S., Yasumoto S.; RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4), AND VARIANT RP ARG-664. RC TISSUE=Trachea; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Embryo; RX PubMed=16303743; DOI=10.1093/dnares/12.2.117; RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y., RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., RA Isogai T.; RT "Signal sequence and keyword trap in silico for selection of full-length RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA RT libraries."; RL DNA Res. 12:117-126(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-664. 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 [8] RP FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, RP SUBCELLULAR LOCATION, MUTAGENESIS OF SER-443 AND ASP-495, CATALYTIC RP ACTIVITY, AND ACTIVE SITE. RX PubMed=14610053; DOI=10.1083/jcb.200305129; RA Bisogno T., Howell F., Williams G., Minassi A., Cascio M.G., Ligresti A., RA Matias I., Schiano-Moriello A., Paul P., Williams E.-J., Gangadharan U., RA Hobbs C., Di Marzo V., Doherty P.; RT "Cloning of the first sn1-DAG lipases points to the spatial and temporal RT regulation of endocannabinoid signaling in the brain."; RL J. Cell Biol. 163:463-468(2003). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-570, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-584, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-570 AND SER-574, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-570 AND SER-579, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-574 AND SER-579, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Lipase that catalyzes the hydrolysis of arachidonic acid CC (AA)-esterified diacylglycerols (DAGs) to produce the principal CC endocannabinoid, 2-arachidonoylglycerol (2-AG) which can be further CC cleaved by downstream enzymes to release arachidonic acid (AA) for CC cyclooxygenase (COX)-mediated eicosanoid production (PubMed:14610053). CC Preferentially hydrolyzes DAGs at the sn-1 position in a calcium- CC dependent manner and has negligible activity against other lipids CC including monoacylglycerols and phospholipids (PubMed:14610053). Plays CC a key role in the regulation of 2-AG and AA pools utilized by COX1/2 to CC generate lipid mediators of macrophage and microglia inflammatory CC responses. Functions also as a polyunsaturated fatty acids-specific CC triacylglycerol lipase in macrophages. Plays an important role to CC support the metabolic and signaling demands of macrophages (By CC similarity). {ECO:0000250|UniProtKB:Q91WC9, CC ECO:0000269|PubMed:14610053}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycerol + H2O = a 2-acylglycerol + a fatty CC acid + H(+); Xref=Rhea:RHEA:33275, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17389, ChEBI:CHEBI:17815, CC ChEBI:CHEBI:28868; EC=3.1.1.116; CC Evidence={ECO:0000269|PubMed:14610053}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33276; CC Evidence={ECO:0000305|PubMed:14610053}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol CC + H2O = 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H(+) + CC octadecanoate; Xref=Rhea:RHEA:38507, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:25629, ChEBI:CHEBI:52392, CC ChEBI:CHEBI:75728; Evidence={ECO:0000269|PubMed:14610053}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38508; CC Evidence={ECO:0000305|PubMed:14610053}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycerol + H2O = (9Z)- CC octadecenoate + 2-(9Z-octadecenoyl)-glycerol + H(+); CC Xref=Rhea:RHEA:38511, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30823, ChEBI:CHEBI:52333, ChEBI:CHEBI:73990; CC Evidence={ECO:0000269|PubMed:14610053}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38512; CC Evidence={ECO:0000305|PubMed:14610053}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-(9Z-octadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn- CC glycerol + H2O = (9Z)-octadecenoate + 2-(5Z,8Z,11Z,14Z- CC eicosatetraenoyl)-glycerol + H(+); Xref=Rhea:RHEA:38515, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, CC ChEBI:CHEBI:52392, ChEBI:CHEBI:75449; CC Evidence={ECO:0000269|PubMed:14610053}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38516; CC Evidence={ECO:0000305|PubMed:14610053}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-(9Z-octadecenoyl)-2-octadecanoyl-sn-glycerol + H2O = (9Z)- CC octadecenoate + 2-octadecanoylglycerol + H(+); Xref=Rhea:RHEA:38519, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, CC ChEBI:CHEBI:75448, ChEBI:CHEBI:75456; CC Evidence={ECO:0000269|PubMed:14610053}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38520; CC Evidence={ECO:0000305|PubMed:14610053}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-(9Z-octadecenoyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycerol + CC H2O = (9Z)-octadecenoate + 2-(9Z,12Z-octadecadienoyl)-glycerol + CC H(+); Xref=Rhea:RHEA:38523, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30823, ChEBI:CHEBI:75450, ChEBI:CHEBI:75457; CC Evidence={ECO:0000269|PubMed:14610053}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38524; CC Evidence={ECO:0000305|PubMed:14610053}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-(9Z-octadecenoyl)-2-O-(5Z,8Z,11Z,14Z-eicosatetraenyl)-sn- CC glycerol + H2O = (9Z)-octadecenoate + 2-O-(5Z,8Z,11Z,14Z)- CC eicosatetraenylglycerol + H(+); Xref=Rhea:RHEA:38527, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, CC ChEBI:CHEBI:75913, ChEBI:CHEBI:75914; CC Evidence={ECO:0000269|PubMed:14610053}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38528; CC Evidence={ECO:0000305|PubMed:14610053}; 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=3.1.1.3; CC Evidence={ECO:0000250|UniProtKB:Q91WC9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12045; CC Evidence={ECO:0000250|UniProtKB:Q91WC9}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-tri-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = CC (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1,2-di-(5Z,8Z,11Z,14Z- CC eicosatetraenoyl)-glycerol + H(+); Xref=Rhea:RHEA:63432, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395, CC ChEBI:CHEBI:147308, ChEBI:CHEBI:228166; CC Evidence={ECO:0000250|UniProtKB:Q91WC9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63433; CC Evidence={ECO:0000250|UniProtKB:Q91WC9}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,2,3-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycerol + H2O = CC (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + 1,2-di- CC (4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycerol + H(+); CC Xref=Rhea:RHEA:63436, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:77016, ChEBI:CHEBI:147311, ChEBI:CHEBI:228170; CC Evidence={ECO:0000250|UniProtKB:Q91WC9}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:14610053}; CC -!- ACTIVITY REGULATION: Inhibited by the 1,2,3-triazole urea covalent CC inhibitors KT109 and KT172 (By similarity). Inhibited by p-hydroxy- CC mercuri-benzoate and HgCl(2), but not by PMSF. Also inhibited by CC RHC80267, a drug that blocks 2-AG formation. CC {ECO:0000250|UniProtKB:Q91WC9, ECO:0000269|PubMed:14610053}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=74.1 uM for diacylglycerol {ECO:0000269|PubMed:14610053}; CC Vmax=3.45 nmol/min/mg enzyme {ECO:0000269|PubMed:14610053}; CC pH dependence: CC Optimum pH is 7.0. {ECO:0000269|PubMed:14610053}; CC -!- INTERACTION: CC Q8NCG7; Q92989: CLP1; NbExp=3; IntAct=EBI-721948, EBI-2559831; CC Q8NCG7; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-721948, EBI-22310682; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14610053}; CC Multi-pass membrane protein {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q8NCG7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8NCG7-2; Sequence=VSP_020245; CC Name=3; CC IsoId=Q8NCG7-3; Sequence=VSP_020246, VSP_020247; CC Name=4; CC IsoId=Q8NCG7-4; Sequence=VSP_043309; CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB85017.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF450090; AAL47020.1; -; mRNA. DR EMBL; AK093958; BAC04258.1; -; mRNA. DR EMBL; AK074210; BAB85017.1; ALT_INIT; mRNA. DR EMBL; AK122748; BAG53702.1; -; mRNA. DR EMBL; AK298955; BAG61052.1; -; mRNA. DR EMBL; AK074584; BAC11073.1; -; mRNA. DR EMBL; AK074744; BAC11175.1; -; mRNA. DR EMBL; AK075128; BAC11420.1; -; mRNA. DR EMBL; AC009412; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC072052; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH878731; EAW55033.1; -; Genomic_DNA. DR EMBL; CH878731; EAW55035.1; -; Genomic_DNA. DR EMBL; CH236963; EAL23721.1; -; Genomic_DNA. DR EMBL; BC027603; AAH27603.1; -; mRNA. DR CCDS; CCDS47536.1; -. [Q8NCG7-4] DR CCDS; CCDS5350.1; -. [Q8NCG7-1] DR RefSeq; NP_001136408.1; NM_001142936.1. [Q8NCG7-4] DR RefSeq; NP_631918.3; NM_139179.3. [Q8NCG7-1] DR AlphaFoldDB; Q8NCG7; -. DR SMR; Q8NCG7; -. DR BioGRID; 128772; 69. DR IntAct; Q8NCG7; 27. DR STRING; 9606.ENSP00000297056; -. DR BindingDB; Q8NCG7; -. DR ChEMBL; CHEMBL5521; -. DR DrugCentral; Q8NCG7; -. DR GuidetoPHARMACOLOGY; 1397; -. DR SwissLipids; SLP:000000322; -. DR ESTHER; human-DAGLB; Lipase_3. DR iPTMnet; Q8NCG7; -. DR PhosphoSitePlus; Q8NCG7; -. DR SwissPalm; Q8NCG7; -. DR BioMuta; DAGLB; -. DR DMDM; 114149272; -. DR EPD; Q8NCG7; -. DR jPOST; Q8NCG7; -. DR MassIVE; Q8NCG7; -. DR MaxQB; Q8NCG7; -. DR PaxDb; 9606-ENSP00000297056; -. DR PeptideAtlas; Q8NCG7; -. DR ProteomicsDB; 72891; -. [Q8NCG7-1] DR ProteomicsDB; 72892; -. [Q8NCG7-2] DR ProteomicsDB; 72893; -. [Q8NCG7-3] DR ProteomicsDB; 72894; -. [Q8NCG7-4] DR Pumba; Q8NCG7; -. DR Antibodypedia; 24853; 122 antibodies from 21 providers. DR DNASU; 221955; -. DR Ensembl; ENST00000297056.11; ENSP00000297056.6; ENSG00000164535.15. [Q8NCG7-1] DR Ensembl; ENST00000425398.6; ENSP00000391171.2; ENSG00000164535.15. [Q8NCG7-4] DR GeneID; 221955; -. DR KEGG; hsa:221955; -. DR MANE-Select; ENST00000297056.11; ENSP00000297056.6; NM_139179.4; NP_631918.3. DR UCSC; uc003sqa.4; human. [Q8NCG7-1] DR AGR; HGNC:28923; -. DR CTD; 221955; -. DR DisGeNET; 221955; -. DR GeneCards; DAGLB; -. DR HGNC; HGNC:28923; DAGLB. DR HPA; ENSG00000164535; Low tissue specificity. DR MIM; 614016; gene. DR neXtProt; NX_Q8NCG7; -. DR OpenTargets; ENSG00000164535; -. DR PharmGKB; PA162383203; -. DR VEuPathDB; HostDB:ENSG00000164535; -. DR eggNOG; KOG2088; Eukaryota. DR GeneTree; ENSGT00940000156486; -. DR HOGENOM; CLU_008300_2_1_1; -. DR InParanoid; Q8NCG7; -. DR OMA; KVWECRL; -. DR OrthoDB; 373802at2759; -. DR PhylomeDB; Q8NCG7; -. DR TreeFam; TF312928; -. DR BioCyc; MetaCyc:ENSG00000164535-MONOMER; -. DR BRENDA; 3.1.1.116; 2681. DR PathwayCommons; Q8NCG7; -. DR Reactome; R-HSA-426048; Arachidonate production from DAG. DR SABIO-RK; Q8NCG7; -. DR SignaLink; Q8NCG7; -. DR SIGNOR; Q8NCG7; -. DR BioGRID-ORCS; 221955; 13 hits in 1153 CRISPR screens. DR ChiTaRS; DAGLB; human. DR GenomeRNAi; 221955; -. DR Pharos; Q8NCG7; Tchem. DR PRO; PR:Q8NCG7; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q8NCG7; Protein. DR Bgee; ENSG00000164535; Expressed in granulocyte and 167 other cell types or tissues. DR ExpressionAtlas; Q8NCG7; baseline and differential. DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0047372; F:acylglycerol lipase activity; TAS:Reactome. DR GO; GO:0016298; F:lipase activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004806; F:triglyceride lipase activity; ISS:UniProtKB. DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB. DR GO; GO:1901696; P:cannabinoid biosynthetic process; IEA:Ensembl. DR GO; GO:0046340; P:diacylglycerol catabolic process; IBA:GO_Central. DR GO; GO:0006640; P:monoacylglycerol biosynthetic process; IEA:Ensembl. DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl. DR GO; GO:0022008; P:neurogenesis; IBA:GO_Central. DR GO; GO:0010898; P:positive regulation of triglyceride catabolic process; ISS:UniProtKB. DR GO; GO:0001516; P:prostaglandin biosynthetic process; ISS:UniProtKB. DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB. DR CDD; cd00519; Lipase_3; 1. DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1. DR InterPro; IPR029058; AB_hydrolase. DR InterPro; IPR002921; Fungal_lipase-like. DR PANTHER; PTHR45792; DIACYLGLYCEROL LIPASE HOMOLOG-RELATED; 1. DR PANTHER; PTHR45792:SF2; DIACYLGLYCEROL LIPASE-BETA; 1. DR Pfam; PF01764; Lipase_3; 1. DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1. DR PROSITE; PS00120; LIPASE_SER; 1. DR Genevisible; Q8NCG7; HS. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Cell membrane; Hydrolase; Lipid degradation; KW Lipid metabolism; Membrane; Metal-binding; Phosphoprotein; KW Reference proteome; Transmembrane; Transmembrane helix. FT CHAIN 1..672 FT /note="Diacylglycerol lipase-beta" FT /id="PRO_0000248350" FT TOPO_DOM 1..17 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 18..38 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 39..58 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 59..79 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 80..102 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 103..123 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 124..132 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 133..153 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 154..672 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT ACT_SITE 443 FT /note="Charge relay system" FT /evidence="ECO:0000305|PubMed:14610053" FT ACT_SITE 495 FT /note="Charge relay system" FT /evidence="ECO:0000305|PubMed:14610053" FT MOD_RES 570 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231" FT MOD_RES 574 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 579 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 583 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q91WC9" FT MOD_RES 584 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT VAR_SEQ 1..281 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_020245" FT VAR_SEQ 140..310 FT /note="SWIIIAATVVSIIIVFDPLGGKMAPYSSAGPSHLDSHDSSQLLNGLKTAATS FT VWETRIKLLCCCIGKDDHTRVAFSSTAELFSTYFSDTDLVPSDIAAGLALLHQQQDNIR FT NNQEPAQVVCHAPGSSQEADLDAELENCHHYMQFAAAAYGWPLYIYRNPLTGLCRIGGD FT C -> RTQIWCPATLRRASPCFISNRTISGTTKSLPRWSAMPQGAPS (in isoform FT 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043309" FT VAR_SEQ 249..267 FT /note="IRNNQEPAQVVCHAPGSSQ -> TRATGNCPRNDGLTLLSLN (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_020246" FT VAR_SEQ 268..672 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_020247" FT VARIANT 664 FT /note="Q -> R (in dbSNP:rs2303361)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334" FT /id="VAR_027275" FT MUTAGEN 443 FT /note="S->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:14610053" FT MUTAGEN 495 FT /note="D->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:14610053" FT CONFLICT 270 FT /note="D -> Y (in Ref. 3; BAC11175)" FT /evidence="ECO:0000305" FT CONFLICT 456 FT /note="L -> V (in Ref. 2; BAC04258)" FT /evidence="ECO:0000305" FT CONFLICT 545 FT /note="T -> K (in Ref. 7; AAH27603)" FT /evidence="ECO:0000305" SQ SEQUENCE 672 AA; 73732 MW; AA953D737E0EFF44 CRC64; MPGMVLFGRR WAIASDDLVF PGFFELVVRV LWWIGILTLY LMHRGKLDCA GGALLSSYLI VLMILLAVVI CTVSAIMCVS MRGTICNPGP RKSMSKLLYI RLALFFPEMV WASLGAAWVA DGVQCDRTVV NGIIATVVVS WIIIAATVVS IIIVFDPLGG KMAPYSSAGP SHLDSHDSSQ LLNGLKTAAT SVWETRIKLL CCCIGKDDHT RVAFSSTAEL FSTYFSDTDL VPSDIAAGLA LLHQQQDNIR NNQEPAQVVC HAPGSSQEAD LDAELENCHH YMQFAAAAYG WPLYIYRNPL TGLCRIGGDC CRSRTTDYDL VGGDQLNCHF GSILHTTGLQ YRDFIHVSFH DKVYELPFLV ALDHRKESVV VAVRGTMSLQ DVLTDLSAES EVLDVECEVQ DRLAHKGISQ AARYVYQRLI NDGILSQAFS IAPEYRLVIV GHSLGGGAAA LLATMLRAAY PQVRCYAFSP PRGLWSKALQ EYSQSFIVSL VLGKDVIPRL SVTNLEDLKR RILRVVAHCN KPKYKILLHG LWYELFGGNP NNLPTELDGG DQEVLTQPLL GEQSLLTRWS PAYSFSSDSP LDSSPKYPPL YPPGRIIHLQ EEGASGRFGC CSAAHYSAKW SHEAEFSKIL IGPKMLTDHM PDILMRALDS VVSDRAACVS CPAQGVSSVD VA //