DGLB_HUMAN
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 03-AUG-2022, entry version 151.
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 + a 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:147309;
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 + a 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:147310, ChEBI:CHEBI:147311;
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};
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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; 66.
DR IntAct; Q8NCG7; 26.
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; Q8NCG7; -.
DR PeptideAtlas; Q8NCG7; -.
DR PRIDE; Q8NCG7; -.
DR ProteomicsDB; 72891; -. [Q8NCG7-1]
DR ProteomicsDB; 72892; -. [Q8NCG7-2]
DR ProteomicsDB; 72893; -. [Q8NCG7-3]
DR ProteomicsDB; 72894; -. [Q8NCG7-4]
DR Antibodypedia; 24853; 101 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 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; ARYIYRR; -.
DR OrthoDB; 191418at2759; -.
DR PhylomeDB; Q8NCG7; -.
DR TreeFam; TF312928; -.
DR BioCyc; MetaCyc:ENSG00000164535-MON; -.
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; 12 hits in 1074 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 165 other tissues.
DR ExpressionAtlas; Q8NCG7; baseline and differential.
DR Genevisible; Q8NCG7; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:UniProtKB.
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:0071926; P:endocannabinoid signaling pathway; IBA:GO_Central.
DR GO; GO:0016042; P:lipid catabolic process; IBA:GO_Central.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0022008; P:neurogenesis; IBA:GO_Central.
DR GO; GO:0042136; P:neurotransmitter biosynthetic process; 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 Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR002921; Fungal_lipase-like.
DR Pfam; PF01764; Lipase_3; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00120; LIPASE_SER; 1.
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
