LPIN1_HUMAN
ID LPIN1_HUMAN Reviewed; 890 AA.
AC Q14693; A8MU38; B4DET9; B4DGS4; B4DGZ6; B5MC18; B7Z858; D6W506; E7ESE7;
AC F5GY24; Q53T25;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Phosphatidate phosphatase LPIN1 {ECO:0000305};
DE EC=3.1.3.4 {ECO:0000269|PubMed:20231281};
DE AltName: Full=Lipin-1 {ECO:0000250|UniProtKB:Q91ZP3};
GN Name=LPIN1 {ECO:0000312|HGNC:HGNC:13345}; Synonyms=KIAA0188;
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] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=8724849; DOI=10.1093/dnares/3.1.17;
RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. V. The
RT coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 3:17-24(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4), AND
RP NUCLEOTIDE SEQUENCE [MRNA] OF 481-890 (ISOFORM 3).
RC TISSUE=Brain, Cerebellum, Testis, and Thalamus;
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 GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 6), AND VARIANT
RP THR-637.
RC TISSUE=Hippocampus, and Uterus;
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 [6]
RP TISSUE SPECIFICITY.
RX PubMed=17158099; DOI=10.1074/jbc.m610745200;
RA Donkor J., Sariahmetoglu M., Dewald J., Brindley D.N., Reue K.;
RT "Three mammalian lipins act as phosphatidate phosphatases with distinct
RT tissue expression patterns.";
RL J. Biol. Chem. 282:3450-3457(2007).
RN [7]
RP IDENTIFICATION BY 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 [8]
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 [9]
RP BIOPHYSICOCHEMICAL PROPERTIES (ISOFORMS 1; 3 AND 4), ACTIVITY REGULATION,
RP COFACTOR, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=20231281; DOI=10.1074/jbc.m110.117747;
RA Han G.S., Carman G.M.;
RT "Characterization of the human LPIN1-encoded phosphatidate phosphatase
RT isoforms.";
RL J. Biol. Chem. 285:14628-14638(2010).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=22134922; DOI=10.1074/jbc.m111.324350;
RA Han S., Bahmanyar S., Zhang P., Grishin N., Oegema K., Crooke R.,
RA Graham M., Reue K., Dixon J.E., Goodman J.M.;
RT "Nuclear envelope phosphatase-regulatory subunit 1 (formerly TMEM188) is
RT the metazoan SPO7 ortholog and functions in the lipin activation pathway.";
RL J. Biol. Chem. 287:3123-3137(2012).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACETYLATION AT LYS-425
RP AND LYS-595, AND MUTAGENESIS OF LYS-425 AND LYS-595.
RX PubMed=29765047; DOI=10.1038/s41467-018-04363-w;
RA Li T.Y., Song L., Sun Y., Li J., Yi C., Lam S.M., Xu D., Zhou L., Li X.,
RA Yang Y., Zhang C.S., Xie C., Huang X., Shui G., Lin S.Y., Reue K.,
RA Lin S.C.;
RT "Tip60-mediated lipin 1 acetylation and ER translocation determine
RT triacylglycerol synthesis rate.";
RL Nat. Commun. 9:1916-1916(2018).
RN [12]
RP VARIANT SER-610.
RX PubMed=12111372; DOI=10.1007/s100380200052;
RA Cao H., Hegele R.A.;
RT "Identification of single-nucleotide polymorphisms in the human LPIN1
RT gene.";
RL J. Hum. Genet. 47:370-372(2002).
RN [13]
RP VARIANT [LARGE SCALE ANALYSIS] GLU-56.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [14]
RP INVOLVEMENT IN ARARM.
RX PubMed=18817903; DOI=10.1016/j.ajhg.2008.09.002;
RA Zeharia A., Shaag A., Houtkooper R.H., Hindi T., de Lonlay P., Erez G.,
RA Hubert L., Saada A., de Keyzer Y., Eshel G., Vaz F.M., Pines O.,
RA Elpeleg O.;
RT "Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood.";
RL Am. J. Hum. Genet. 83:489-494(2008).
RN [15]
RP ERRATUM OF PUBMED:18817903.
RA Zeharia A., Shaag A., Houtkooper R.H., Hindi T., de Lonlay P., Erez G.,
RA Hubert L., Saada A., de Keyzer Y., Eshel G., Vaz F.M., Pines O.,
RA Elpeleg O.;
RL Am. J. Hum. Genet. 84:95-95(2008).
CC -!- FUNCTION: Acts as a magnesium-dependent phosphatidate phosphatase
CC enzyme which catalyzes the conversion of phosphatidic acid to
CC diacylglycerol during triglyceride, phosphatidylcholine and
CC phosphatidylethanolamine biosynthesis and therefore controls the
CC metabolism of fatty acids at different levels (PubMed:20231281,
CC PubMed:29765047). Is involved in adipocyte differentiation (By
CC similarity). Acts also as nuclear transcriptional coactivator for
CC PPARGC1A/PPARA regulatory pathway to modulate lipid metabolism gene
CC expression (By similarity). Recruited at the mitochondrion outer
CC membrane and is involved in mitochondrial fission by converting
CC phosphatidic acid to diacylglycerol (By similarity).
CC {ECO:0000250|UniProtKB:Q91ZP3, ECO:0000269|PubMed:20231281,
CC ECO:0000269|PubMed:29765047}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphate + H2O = a 1,2-diacyl-sn-
CC glycerol + phosphate; Xref=Rhea:RHEA:27429, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17815, ChEBI:CHEBI:43474, ChEBI:CHEBI:58608; EC=3.1.3.4;
CC Evidence={ECO:0000269|PubMed:20231281, ECO:0000269|PubMed:29765047};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27430;
CC Evidence={ECO:0000305|PubMed:20231281, ECO:0000305|PubMed:29765047};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycero-3-phosphate + H2O = 1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-
CC docosahexaenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43296,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:77129,
CC ChEBI:CHEBI:77130; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43297;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphate + H2O = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43292,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:75728,
CC ChEBI:CHEBI:77091; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43293;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phosphate + H2O = 1-octadecanoyl-2-(9Z,12Z)-octadecadienoyl-sn-
CC glycerol + phosphate; Xref=Rhea:RHEA:43288, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:77097, ChEBI:CHEBI:77098;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43289;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate +
CC H2O = 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + phosphate;
CC Xref=Rhea:RHEA:43284, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:74560, ChEBI:CHEBI:75468;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43285;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycero-3-phosphate + H2O = 1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-
CC docosahexaenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43280,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:82928,
CC ChEBI:CHEBI:82949; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43281;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1,2-dioctadecanoyl-sn-glycero-3-phosphate + H2O = 1,2-
CC dioctadecanoyl-sn-glycerol + phosphate; Xref=Rhea:RHEA:33335,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:41847, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:82921; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33336;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphate + H2O = 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43260,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:72864,
CC ChEBI:CHEBI:77096; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43261;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phosphate + H2O = 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-
CC glycerol + phosphate; Xref=Rhea:RHEA:43256, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:72860, ChEBI:CHEBI:82927;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43257;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate +
CC H2O = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + phosphate;
CC Xref=Rhea:RHEA:41255, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:64839, ChEBI:CHEBI:75466;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41256;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1,2-di-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-
CC phosphate + H2O = 1,2-di-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycerol + phosphate; Xref=Rhea:RHEA:43252, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:82924, ChEBI:CHEBI:82925;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43253;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1,2-di-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphate
CC + H2O = 1,2-di-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycerol +
CC phosphate; Xref=Rhea:RHEA:43248, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:77125, ChEBI:CHEBI:77126;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43249;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphate + H2O =
CC 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycerol + phosphate;
CC Xref=Rhea:RHEA:43240, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:77127, ChEBI:CHEBI:77128;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43241;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1,2-
CC di-(9Z-octadecenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43244,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:52333,
CC ChEBI:CHEBI:74546; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43245;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphate + H2O = 1,2-
CC dihexadecanoyl-sn-glycerol + phosphate; Xref=Rhea:RHEA:43236,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:72859,
CC ChEBI:CHEBI:82929; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43237;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
CC Reaction=1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycero-3-phosphate + H2O = 1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-
CC docosahexaenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43296,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:77129,
CC ChEBI:CHEBI:77130; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43297;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphate + H2O = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43292,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:75728,
CC ChEBI:CHEBI:77091; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43293;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
CC Reaction=1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phosphate + H2O = 1-octadecanoyl-2-(9Z,12Z)-octadecadienoyl-sn-
CC glycerol + phosphate; Xref=Rhea:RHEA:43288, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:77097, ChEBI:CHEBI:77098;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43289;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
CC Reaction=1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate +
CC H2O = 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + phosphate;
CC Xref=Rhea:RHEA:43284, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:74560, ChEBI:CHEBI:75468;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43285;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
CC Reaction=1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycero-3-phosphate + H2O = 1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-
CC docosahexaenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43280,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:82928,
CC ChEBI:CHEBI:82949; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43281;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
CC Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphate + H2O = 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43260,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:72864,
CC ChEBI:CHEBI:77096; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43261;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
CC Reaction=1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phosphate + H2O = 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-
CC glycerol + phosphate; Xref=Rhea:RHEA:43256, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:72860, ChEBI:CHEBI:82927;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43257;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate +
CC H2O = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + phosphate;
CC Xref=Rhea:RHEA:41255, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:64839, ChEBI:CHEBI:75466;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41256;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
CC Reaction=1,2-di-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-
CC phosphate + H2O = 1,2-di-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycerol + phosphate; Xref=Rhea:RHEA:43252, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:82924, ChEBI:CHEBI:82925;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43253;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
CC Reaction=1,2-di-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphate
CC + H2O = 1,2-di-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycerol +
CC phosphate; Xref=Rhea:RHEA:43248, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:77125, ChEBI:CHEBI:77126;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43249;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
CC Reaction=1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphate + H2O =
CC 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycerol + phosphate;
CC Xref=Rhea:RHEA:43240, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:77127, ChEBI:CHEBI:77128;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43241;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1,2-
CC di-(9Z-octadecenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43244,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:52333,
CC ChEBI:CHEBI:74546; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43245;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycero-3-phosphate + H2O = 1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-
CC docosahexaenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43296,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:77129,
CC ChEBI:CHEBI:77130; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43297;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphate + H2O = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43292,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:75728,
CC ChEBI:CHEBI:77091; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43293;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phosphate + H2O = 1-octadecanoyl-2-(9Z,12Z)-octadecadienoyl-sn-
CC glycerol + phosphate; Xref=Rhea:RHEA:43288, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:77097, ChEBI:CHEBI:77098;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43289;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate +
CC H2O = 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + phosphate;
CC Xref=Rhea:RHEA:43284, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:74560, ChEBI:CHEBI:75468;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43285;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycero-3-phosphate + H2O = 1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-
CC docosahexaenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43280,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:82928,
CC ChEBI:CHEBI:82949; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43281;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphate + H2O = 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43260,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:72864,
CC ChEBI:CHEBI:77096; Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43261;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phosphate + H2O = 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-
CC glycerol + phosphate; Xref=Rhea:RHEA:43256, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:72860, ChEBI:CHEBI:82927;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43257;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate +
CC H2O = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + phosphate;
CC Xref=Rhea:RHEA:41255, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:64839, ChEBI:CHEBI:75466;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41256;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=1,2-di-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-
CC phosphate + H2O = 1,2-di-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycerol + phosphate; Xref=Rhea:RHEA:43252, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:82924, ChEBI:CHEBI:82925;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43253;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=1,2-di-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphate
CC + H2O = 1,2-di-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycerol +
CC phosphate; Xref=Rhea:RHEA:43248, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:77125, ChEBI:CHEBI:77126;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43249;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphate + H2O =
CC 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycerol + phosphate;
CC Xref=Rhea:RHEA:43240, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:77127, ChEBI:CHEBI:77128;
CC Evidence={ECO:0000269|PubMed:20231281};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43241;
CC Evidence={ECO:0000305|PubMed:20231281};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1,2-
CC di-(9Z-octadecenoyl)-sn-glycerol + phosphate; Xref=Rhea:RHEA:43244,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:52333,
CC ChEBI:CHEBI:74546; Evidence={ECO:0000269|PubMed:20231281};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:20231281};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:20231281};
CC Note=Mg(2+) and, at a lesser extent, Mn(2+).
CC {ECO:0000269|PubMed:20231281};
CC -!- ACTIVITY REGULATION: Potently inhibited by sphingolipids, in
CC particular, the sphingoid bases sphinganine and sphingosine and
CC ceramide-1-phosphate. Inhibited by concentrations of Mg(2+) and Mn(2+)
CC above their optimums and by Ca(2+), Zn(2+), N-ethylmaleimide and
CC propranolol. {ECO:0000269|PubMed:20231281}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.35 mM for phosphatidate (isoform 1)
CC {ECO:0000269|PubMed:20231281};
CC KM=0.24 mM for phosphatidate (isoform 3)
CC {ECO:0000269|PubMed:20231281};
CC KM=0.11 mM for phosphatidate (isoform 4)
CC {ECO:0000269|PubMed:20231281};
CC Temperature dependence:
CC Optimum temperature is 40 degrees Celsius. Thermolabile above 40
CC degrees Celsius and essentially inactive at 60 degrees Celsius.
CC {ECO:0000269|PubMed:20231281};
CC -!- SUBUNIT: Interacts (via LXXIL motif) with PPARA (By similarity).
CC Interacts with PPARGC1A. Interaction with PPARA and PPARGC1A leads to
CC the formation of a complex that modulates gene transcription (By
CC similarity). Interacts with MEF2C (By similarity).
CC {ECO:0000250|UniProtKB:Q91ZP3}.
CC -!- INTERACTION:
CC Q14693; Q9UBB4: ATXN10; NbExp=3; IntAct=EBI-5278370, EBI-702390;
CC Q14693; P09172: DBH; NbExp=3; IntAct=EBI-5278370, EBI-8589586;
CC Q14693; Q01658: DR1; NbExp=3; IntAct=EBI-5278370, EBI-750300;
CC Q14693; P21333-2: FLNA; NbExp=3; IntAct=EBI-5278370, EBI-9641086;
CC Q14693; P01100: FOS; NbExp=3; IntAct=EBI-5278370, EBI-852851;
CC Q14693; P50440: GATM; NbExp=3; IntAct=EBI-5278370, EBI-2552594;
CC Q14693; P14136: GFAP; NbExp=3; IntAct=EBI-5278370, EBI-744302;
CC Q14693; P62993: GRB2; NbExp=3; IntAct=EBI-5278370, EBI-401755;
CC Q14693; P28799: GRN; NbExp=3; IntAct=EBI-5278370, EBI-747754;
CC Q14693; Q00403: GTF2B; NbExp=3; IntAct=EBI-5278370, EBI-389564;
CC Q14693; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-5278370, EBI-1054873;
CC Q14693; Q00613: HSF1; NbExp=3; IntAct=EBI-5278370, EBI-719620;
CC Q14693; P04792: HSPB1; NbExp=3; IntAct=EBI-5278370, EBI-352682;
CC Q14693; P42858: HTT; NbExp=12; IntAct=EBI-5278370, EBI-466029;
CC Q14693; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-5278370, EBI-1055254;
CC Q14693; O60333-2: KIF1B; NbExp=3; IntAct=EBI-5278370, EBI-10975473;
CC Q14693; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-5278370, EBI-473160;
CC Q14693; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-5278370, EBI-396669;
CC Q14693; P12931: SRC; NbExp=3; IntAct=EBI-5278370, EBI-621482;
CC Q14693; O76024: WFS1; NbExp=3; IntAct=EBI-5278370, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:29765047}.
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:29765047}. Nucleus
CC membrane {ECO:0000250|UniProtKB:Q91ZP3}. Note=Translocates from the
CC cytosol to the endoplasmic reticulum following acetylation by KAT5.
CC {ECO:0000269|PubMed:29765047}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q14693-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14693-2; Sequence=VSP_045533;
CC Name=3; Synonyms=Beta;
CC IsoId=Q14693-3; Sequence=VSP_053970;
CC Name=4; Synonyms=Gamma;
CC IsoId=Q14693-4; Sequence=VSP_053971;
CC Name=5;
CC IsoId=Q14693-5; Sequence=VSP_045533, VSP_053970;
CC Name=6;
CC IsoId=Q14693-6; Sequence=VSP_045533, VSP_053970, VSP_055361,
CC VSP_055362;
CC Name=7;
CC IsoId=Q14693-7; Sequence=VSP_055384, VSP_053970;
CC -!- TISSUE SPECIFICITY: Specifically expressed in skeletal muscle. Also
CC abundant in adipose tissue. Lower levels in some portions of the
CC digestive tract. {ECO:0000269|PubMed:17158099,
CC ECO:0000269|PubMed:22134922}.
CC -!- DOMAIN: Contains one Leu-Xaa-Xaa-Ile-Leu (LXXIL), a transcriptional
CC binding motif, which mediates interaction with PPARA.
CC {ECO:0000250|UniProtKB:Q91ZP3}.
CC -!- DOMAIN: Contains 1 Asp-Xaa-Asp-Xaa-Thr (DXDXT) motif, a catalytic motif
CC essential for phosphatidate phosphatase activity.
CC {ECO:0000250|UniProtKB:Q91ZP3}.
CC -!- PTM: Phosphorylated at multiple sites in response to insulin.
CC Phosphorylation is controlled by the mTOR signaling pathway.
CC Phosphorylation is decreased by epinephrine. Phosphorylation may not
CC directly affect the catalytic activity but may regulate the
CC localization. Dephosphorylated by the CTDNEP1-CNEP1R1 complex (By
CC similarity). {ECO:0000250|UniProtKB:Q91ZP3}.
CC -!- PTM: Acetylation at Lys-425 and Lys-595 by KAT5 in response to fatty
CC acids promotes translocation to the endoplasmic reticulum and synthesis
CC of diacylglycerol. {ECO:0000269|PubMed:29765047}.
CC -!- PTM: Sumoylated. {ECO:0000250|UniProtKB:Q91ZP3}.
CC -!- DISEASE: Myoglobinuria, acute recurrent, autosomal recessive (ARARM)
CC [MIM:268200]: Recurrent myoglobinuria is characterized by recurrent
CC attacks of rhabdomyolysis (necrosis or disintegration of skeletal
CC muscle) associated with muscle pain and weakness and followed by
CC excretion of myoglobin in the urine. Renal failure may occasionally
CC occur. {ECO:0000269|PubMed:18817903}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: May represent a candidate gene for human lipodysytropy
CC syndromes.
CC -!- SIMILARITY: Belongs to the lipin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA11505.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG57200.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG57885.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG57957.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BC018071; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; D80010; BAA11505.1; ALT_INIT; mRNA.
DR EMBL; AK290235; BAF82924.1; -; mRNA.
DR EMBL; AK293787; BAG57200.1; ALT_INIT; mRNA.
DR EMBL; AK294742; BAG57885.1; ALT_INIT; mRNA.
DR EMBL; AK294853; BAG57957.1; ALT_INIT; mRNA.
DR EMBL; AK302922; BAH13844.1; -; mRNA.
DR EMBL; AC012456; AAY14695.1; -; Genomic_DNA.
DR EMBL; AC106875; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAX00918.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00920.1; -; Genomic_DNA.
DR EMBL; BC018071; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC030537; AAH30537.1; -; mRNA.
DR CCDS; CCDS1682.1; -. [Q14693-1]
DR CCDS; CCDS58699.1; -. [Q14693-7]
DR CCDS; CCDS58701.1; -. [Q14693-2]
DR RefSeq; NP_001248356.1; NM_001261427.1. [Q14693-2]
DR RefSeq; NP_001248357.1; NM_001261428.1. [Q14693-7]
DR RefSeq; NP_001248358.1; NM_001261429.1.
DR RefSeq; NP_663731.1; NM_145693.2. [Q14693-1]
DR RefSeq; XP_006711933.1; XM_006711870.3. [Q14693-5]
DR RefSeq; XP_006711934.1; XM_006711871.2.
DR RefSeq; XP_006711935.1; XM_006711872.2. [Q14693-3]
DR RefSeq; XP_006711937.1; XM_006711874.2.
DR RefSeq; XP_011508636.1; XM_011510334.2. [Q14693-5]
DR RefSeq; XP_011508637.1; XM_011510335.2. [Q14693-3]
DR RefSeq; XP_011508638.1; XM_011510336.2. [Q14693-3]
DR RefSeq; XP_016859113.1; XM_017003624.1. [Q14693-3]
DR RefSeq; XP_016859114.1; XM_017003625.1. [Q14693-3]
DR RefSeq; XP_016859117.1; XM_017003628.1. [Q14693-1]
DR RefSeq; XP_016859118.1; XM_017003629.1. [Q14693-1]
DR RefSeq; XP_016859119.1; XM_017003630.1. [Q14693-1]
DR AlphaFoldDB; Q14693; -.
DR SMR; Q14693; -.
DR BioGRID; 116787; 23.
DR CORUM; Q14693; -.
DR IntAct; Q14693; 30.
DR STRING; 9606.ENSP00000397908; -.
DR SwissLipids; SLP:000000881; -. [Q14693-1]
DR SwissLipids; SLP:000000882; -. [Q14693-3]
DR SwissLipids; SLP:000000883; -. [Q14693-4]
DR DEPOD; LPIN1; -.
DR iPTMnet; Q14693; -.
DR PhosphoSitePlus; Q14693; -.
DR BioMuta; LPIN1; -.
DR DMDM; 23831266; -.
DR EPD; Q14693; -.
DR jPOST; Q14693; -.
DR MassIVE; Q14693; -.
DR MaxQB; Q14693; -.
DR PaxDb; Q14693; -.
DR PeptideAtlas; Q14693; -.
DR PRIDE; Q14693; -.
DR ProteomicsDB; 15159; -.
DR ProteomicsDB; 17975; -.
DR ProteomicsDB; 2078; -.
DR ProteomicsDB; 24603; -.
DR ProteomicsDB; 3982; -.
DR ProteomicsDB; 4174; -.
DR ProteomicsDB; 60131; -. [Q14693-1]
DR Antibodypedia; 26865; 486 antibodies from 37 providers.
DR DNASU; 23175; -.
DR Ensembl; ENST00000256720.6; ENSP00000256720.2; ENSG00000134324.12. [Q14693-1]
DR Ensembl; ENST00000396097.5; ENSP00000379404.2; ENSG00000134324.12. [Q14693-5]
DR Ensembl; ENST00000396098.5; ENSP00000379405.1; ENSG00000134324.12. [Q14693-6]
DR Ensembl; ENST00000425416.6; ENSP00000401522.2; ENSG00000134324.12. [Q14693-2]
DR Ensembl; ENST00000449576.6; ENSP00000397908.2; ENSG00000134324.12. [Q14693-7]
DR Ensembl; ENST00000674199.1; ENSP00000501331.1; ENSG00000134324.12. [Q14693-3]
DR GeneID; 23175; -.
DR KEGG; hsa:23175; -.
DR MANE-Select; ENST00000674199.1; ENSP00000501331.1; NM_001349206.2; NP_001336135.1. [Q14693-3]
DR UCSC; uc002rbs.5; human. [Q14693-1]
DR CTD; 23175; -.
DR DisGeNET; 23175; -.
DR GeneCards; LPIN1; -.
DR HGNC; HGNC:13345; LPIN1.
DR HPA; ENSG00000134324; Tissue enhanced (skeletal muscle, tongue).
DR MalaCards; LPIN1; -.
DR MIM; 268200; phenotype.
DR MIM; 605518; gene.
DR neXtProt; NX_Q14693; -.
DR OpenTargets; ENSG00000134324; -.
DR Orphanet; 99845; Genetic recurrent myoglobinuria.
DR PharmGKB; PA30436; -.
DR VEuPathDB; HostDB:ENSG00000134324; -.
DR eggNOG; KOG2116; Eukaryota.
DR GeneTree; ENSGT00940000157219; -.
DR HOGENOM; CLU_595738_0_0_1; -.
DR InParanoid; Q14693; -.
DR OMA; XIKHESS; -.
DR OrthoDB; 866929at2759; -.
DR PhylomeDB; Q14693; -.
DR TreeFam; TF314095; -.
DR BRENDA; 3.1.3.4; 2681.
DR PathwayCommons; Q14693; -.
DR Reactome; R-HSA-1483191; Synthesis of PC.
DR Reactome; R-HSA-1483213; Synthesis of PE.
DR Reactome; R-HSA-4419969; Depolymerisation of the Nuclear Lamina.
DR Reactome; R-HSA-75109; Triglyceride biosynthesis.
DR SignaLink; Q14693; -.
DR SIGNOR; Q14693; -.
DR BioGRID-ORCS; 23175; 17 hits in 1083 CRISPR screens.
DR ChiTaRS; LPIN1; human.
DR GeneWiki; LPIN1; -.
DR GenomeRNAi; 23175; -.
DR Pharos; Q14693; Tbio.
DR PRO; PR:Q14693; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q14693; protein.
DR Bgee; ENSG00000134324; Expressed in sperm and 213 other tissues.
DR ExpressionAtlas; Q14693; baseline and differential.
DR Genevisible; Q14693; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005741; C:mitochondrial outer membrane; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; TAS:Reactome.
DR GO; GO:0031965; C:nuclear membrane; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0008195; F:phosphatidate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IBA:GO_Central.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0044255; P:cellular lipid metabolic process; IBA:GO_Central.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IBA:GO_Central.
DR GO; GO:0009062; P:fatty acid catabolic process; ISS:UniProtKB.
DR GO; GO:0007077; P:mitotic nuclear membrane disassembly; TAS:Reactome.
DR GO; GO:0031642; P:negative regulation of myelination; IEA:Ensembl.
DR GO; GO:1903741; P:negative regulation of phosphatidate phosphatase activity; IEA:Ensembl.
DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; IEA:Ensembl.
DR GO; GO:0046473; P:phosphatidic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0045740; P:positive regulation of DNA replication; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0019432; P:triglyceride biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006642; P:triglyceride mobilization; ISS:UniProtKB.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR026058; LIPIN.
DR InterPro; IPR031703; Lipin_mid.
DR InterPro; IPR007651; Lipin_N.
DR InterPro; IPR013209; LNS2.
DR InterPro; IPR031315; LNS2/PITP.
DR InterPro; IPR028794; LPIN1.
DR PANTHER; PTHR12181; PTHR12181; 2.
DR PANTHER; PTHR12181:SF10; PTHR12181:SF10; 2.
DR Pfam; PF16876; Lipin_mid; 1.
DR Pfam; PF04571; Lipin_N; 1.
DR Pfam; PF08235; LNS2; 1.
DR SMART; SM00775; LNS2; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Endoplasmic reticulum;
KW Fatty acid metabolism; Hydrolase; Isopeptide bond; Lipid metabolism;
KW Membrane; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..890
FT /note="Phosphatidate phosphatase LPIN1"
FT /id="PRO_0000209879"
FT REGION 1..108
FT /note="N-LIP"
FT REGION 125..183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 228..300
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 365..392
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 421..456
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 566..616
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 624..830
FT /note="C-LIP"
FT MOTIF 153..158
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 678..682
FT /note="DXDXT motif"
FT MOTIF 689..693
FT /note="LXXIL motif"
FT COMPBIAS 228..267
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 430..452
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT MOD_RES 254
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT MOD_RES 260
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT MOD_RES 264
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT MOD_RES 425
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:29765047"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT MOD_RES 438
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT MOD_RES 595
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:29765047"
FT MOD_RES 600
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT MOD_RES 601
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT MOD_RES 887
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT MOD_RES 889
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT CROSSLNK 565
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT CROSSLNK 595
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP3"
FT VAR_SEQ 1
FT /note="M -> MSRVQTM (in isoform 2, isoform 5 and isoform
FT 6)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_045533"
FT VAR_SEQ 1
FT /note="M -> MGEQDGIRSSSWETSQGKSSPDSAWSWIPIMRDPGWIRNVWSSNINV
FT QTM (in isoform 7)"
FT /evidence="ECO:0000305"
FT /id="VSP_055384"
FT VAR_SEQ 241
FT /note="S -> SSLVDCKRTAPHLAVAAEGGLSSSCPPQSSLFHPSES (in
FT isoform 3, isoform 5, isoform 6 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_053970"
FT VAR_SEQ 417
FT /note="N -> K (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055361"
FT VAR_SEQ 418..890
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055362"
FT VAR_SEQ 535
FT /note="K -> KSSCLSYLHVILDAIRFCFSKIFNAQI (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_053971"
FT VARIANT 56
FT /note="G -> E (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035874"
FT VARIANT 610
FT /note="P -> S (in dbSNP:rs4669781)"
FT /evidence="ECO:0000269|PubMed:12111372"
FT /id="VAR_013885"
FT VARIANT 637
FT /note="S -> T (in dbSNP:rs17852755)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_054878"
FT MUTAGEN 425
FT /note="K->R: Decreased acetylation by KAT5."
FT /evidence="ECO:0000269|PubMed:29765047"
FT MUTAGEN 595
FT /note="K->R: Decreased acetylation by KAT5."
FT /evidence="ECO:0000269|PubMed:29765047"
FT CONFLICT 171
FT /note="D -> G (in Ref. 5; BC018071)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="D -> G (in Ref. 2; BAG57885)"
FT /evidence="ECO:0000305"
FT CONFLICT 316
FT /note="D -> Y (in Ref. 2; BAH13844)"
FT /evidence="ECO:0000305"
FT CONFLICT 535
FT /note="K -> R (in Ref. 2; BAH13844)"
FT /evidence="ECO:0000305"
FT CONFLICT 592
FT /note="T -> I (in Ref. 2; BAG57885)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 890 AA; 98664 MW; 781761FC47E9CEE7 CRC64;
MNYVGQLAGQ VFVTVKELYK GLNPATLSGC IDIIVIRQPN GNLQCSPFHV RFGKMGVLRS
REKVVDIEIN GESVDLHMKL GDNGEAFFVQ ETDNDQEVIP MHLATSPILS EGASRMECQL
KRGSVDRMRG LDPSTPAQVI APSETPSSSS VVKKRRKRRR KSQLDSLKRD DNMNTSEDED
MFPIEMSSDE AMELLESSRT LPNDIPPFQD DIPEENLSLA VIYPQSASYP NSDREWSPTP
SPSGSRPSTP KSDSELVSKS TERTGQKNPE MLWLWGELPQ AAKSSSPHKM KESSPLSSRK
ICDKSHFQAI HSESSDTFSD QSPTLVGGAL LDQNKPQTEM QFVNEEDLET LGAAAPLLPM
IEELKPPSAS VVQTANKTDS PSRKRDKRSR HLGADGVYLD DLTDMDPEVA ALYFPKNGDP
SGLAKHASDN GARSANQSPQ SVGSSGVDSG VESTSDGLRD LPSIAISLCG GLSDHREITK
DAFLEQAVSY QQFVDNPAII DDPNLVVKIG SKYYNWTTAA PLLLAMQAFQ KPLPKATVES
IMRDKMPKKG GRWWFSWRGR NTTIKEESKP EQCLAGKAHS TGEQPPQLSL ATRVKHESSS
SDEERAAAKP SNAGHLPLLP NVSYKKTLRL TSEQLKSLKL KNGPNDVVFS VTTQYQGTCR
CEGTIYLWNW DDKVIISDID GTITRSDTLG HILPTLGKDW THQGIAKLYH KVSQNGYKFL
YCSARAIGMA DMTRGYLHWV NERGTVLPQG PLLLSPSSLF SALHREVIEK KPEKFKVQCL
TDIKNLFFPN TEPFYAAFGN RPADVYSYKQ VGVSLNRIFT VNPKGELVQE HAKTNISSYV
RLCEVVDHVF PLLKRSHSSD FPCSDTFSNF TFWREPLPPF ENQDIHSASA
