LIPC_HUMAN
ID LIPC_HUMAN Reviewed; 499 AA.
AC P11150; A2RUB4; A8K9B6; O43571; P78529; Q99465;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Hepatic triacylglycerol lipase;
DE Short=HL;
DE Short=Hepatic lipase;
DE EC=3.1.1.3 {ECO:0000269|PubMed:12032167, ECO:0000269|PubMed:26193433, ECO:0000269|PubMed:7592706, ECO:0000269|PubMed:8798474};
DE AltName: Full=Lipase member C;
DE AltName: Full=Lysophospholipase;
DE EC=3.1.1.5 {ECO:0000250|UniProtKB:P07867};
DE AltName: Full=Phospholipase A1;
DE EC=3.1.1.32 {ECO:0000269|PubMed:12032167, ECO:0000269|PubMed:26193433, ECO:0000269|PubMed:7592706};
DE Flags: Precursor;
GN Name=LIPC; Synonyms=HTGL;
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], SUBCELLULAR LOCATION, AND VARIANTS SER-215 AND
RP LEU-356.
RC TISSUE=Liver;
RX PubMed=2828141; DOI=10.1111/j.1432-0436.1987.tb00150.x;
RA Stahnke G., Sprengel R., Augustin J., Will H.;
RT "Human hepatic triglyceride lipase: cDNA cloning, amino acid sequence and
RT expression in a cultured cell line.";
RL Differentiation 35:45-52(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS SER-215 AND LEU-356.
RC TISSUE=Liver;
RX PubMed=2447084; DOI=10.1016/s0021-9258(19)57271-4;
RA Datta S., Luo C.C., Li W.H., VanTuinen P., Ledbetter D.H., Brown M.A.,
RA Chen S.H., Liu S., Chan L.;
RT "Human hepatic lipase. Cloned cDNA sequence, restriction fragment length
RT polymorphisms, chromosomal localization, and evolutionary relationships
RT with lipoprotein lipase and pancreatic lipase.";
RL J. Biol. Chem. 263:1107-1110(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF N-TERMINUS, PARTIAL PROTEIN
RP SEQUENCE, AND VARIANT LEU-356.
RC TISSUE=Liver;
RX PubMed=2839510; DOI=10.1016/s0021-9258(18)38056-6;
RA Martin G.A., Busch S.J., Meredith G.D., Cardin A.D., Blankenship D.T.,
RA Mao S.J.T., Rechtin A.E., Woods C.W., Racke M.M., Schafer M.P.,
RA Fitzgerald M.C., Burke D.M., Flanagan M.A., Jackson R.L.;
RT "Isolation and cDNA sequence of human postheparin plasma hepatic
RT triglyceride lipase.";
RL J. Biol. Chem. 263:10907-10914(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-356.
RX PubMed=2605236; DOI=10.1021/bi00449a002;
RA Cai S.J., Wong D.M., Chen S.H., Chan L.;
RT "Structure of the human hepatic triglyceride lipase gene.";
RL Biochemistry 28:8966-8971(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-215 AND LEU-356.
RX PubMed=2324091; DOI=10.1016/s0021-9258(19)39182-3;
RA Ameis D., Stahnke G., Kobayashi J., McLean J., Lee G., Buscher M.,
RA Schotz M.C., Will H.;
RT "Isolation and characterization of the human hepatic lipase gene.";
RL J. Biol. Chem. 265:6552-6555(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS SER-215 AND LEU-356.
RC TISSUE=Kidney, and Thymus;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-356.
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 [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 92-152, AND VARIANT HL DEFICIENCY
RP HIS-TYR-THR-VAL-ALA-VAL-134 INS.
RX PubMed=10660332;
RA Tiebel O., Gehrisch S., Pietzsch J., Gromeier S., Jaross W.;
RT "18 bp insertion/duplication with internal missense mutation in human
RT hepatic lipase gene exon 3.";
RL Hum. Mutat. 12:216-216(1998).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 464-499.
RX PubMed=8865180; DOI=10.1006/mcpr.1996.0041;
RA Takagi A., Ikeda Y., Mori A., Ashida Y., Yamamoto A.;
RT "Identification of a BstNI polymorphism in exon 9 of the human hepatic
RT triglyceride lipase gene.";
RL Mol. Cell. Probes 10:313-314(1996).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, REGION, AND MUTAGENESIS OF 255-HIS--ILE-275
RP AND 255-HIS--LYS-276.
RX PubMed=7592706; DOI=10.1074/jbc.270.43.25396;
RA Dugi K.A., Dichek H.L., Santamarina-Fojo S.;
RT "Human hepatic and lipoprotein lipase: the loop covering the catalytic site
RT mediates lipase substrate specificity.";
RL J. Biol. Chem. 270:25396-25401(1995).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=8798474; DOI=10.1074/jbc.271.37.22931;
RA Hill J.S., Davis R.C., Yang D., Wen J., Philo J.S., Poon P.H.,
RA Phillips M.L., Kempner E.S., Wong H.;
RT "Human hepatic lipase subunit structure determination.";
RL J. Biol. Chem. 271:22931-22936(1996).
RN [13]
RP ASSOCIATION WITH NIDDM SUSCEPTIBILITY.
RX PubMed=15126514; DOI=10.1210/jc.2003-031325;
RA Todorova B., Kubaszek A., Pihlajamaki J., Lindstrom J., Eriksson J.,
RA Valle T.T., Hamalainen H., Ilanne-Parikka P., Keinanen-Kiukaanniemi S.,
RA Tuomilehto J., Uusitupa M., Laakso M.;
RT "The G-250A promoter polymorphism of the hepatic lipase gene predicts the
RT conversion from impaired glucose tolerance to type 2 diabetes mellitus: the
RT Finnish diabetes prevention study.";
RL J. Clin. Endocrinol. Metab. 89:2019-2023(2004).
RN [14]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12032167;
RA McCoy M.G., Sun G.-S., Marchadier D., Maugeais C., Glick J.M., Rader D.J.;
RT "Characterization of the lipolytic activity of endothelial lipase.";
RL J. Lipid Res. 43:921-929(2002).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=26193433; DOI=10.1016/j.bbalip.2015.07.003;
RA Yang P., Subbaiah P.V.;
RT "Regulation of hepatic lipase activity by sphingomyelin in plasma
RT lipoproteins.";
RL Biochim. Biophys. Acta 1851:1327-1336(2015).
RN [16]
RP INVOLVEMENT IN HDLCQ12.
RX PubMed=18364377; DOI=10.1210/jc.2007-2815;
RA Grarup N., Andreasen C.H., Andersen M.K., Albrechtsen A., Sandbaek A.,
RA Lauritzen T., Borch-Johnsen K., Jorgensen T., Schmitz O., Hansen T.,
RA Pedersen O.;
RT "The -250G>A promoter variant in hepatic lipase associates with elevated
RT fasting serum high-density lipoprotein cholesterol modulated by interaction
RT with physical activity in a study of 16,156 Danish subjects.";
RL J. Clin. Endocrinol. Metab. 93:2294-2299(2008).
RN [17]
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).
RN [18]
RP VARIANTS HL DEFICIENCY PHE-289 AND MET-405.
RX PubMed=1301939; DOI=10.1002/humu.1380010410;
RA Hegele R.A., Tu L., Connelly P.W.;
RT "Human hepatic lipase mutations and polymorphisms.";
RL Hum. Mutat. 1:320-324(1992).
RN [19]
RP REVIEW ON POLYMORPHISM.
RA Hayden M.R., Ma Y., Brunzell J., Henderson H.E.;
RT "Genetic variants affecting human lipoprotein and hepatic lipases.";
RL Curr. Opin. Lipidol. 2:104-109(1991).
RN [20]
RP VARIANTS MET-95; SER-215 AND ASN-440.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [21]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [22]
RP VARIANTS MET-95; SER-215; PHE-289; ILE-342; LEU-356; MET-405 AND ALA-409.
RX PubMed=12966036; DOI=10.1093/hmg/ddg314;
RA Morabia A., Cayanis E., Costanza M.C., Ross B.M., Flaherty M.S.,
RA Alvin G.B., Das K., Gilliam T.C.;
RT "Association of extreme blood lipid profile phenotypic variation with 11
RT reverse cholesterol transport genes and 10 non-genetic cardiovascular
RT disease risk factors.";
RL Hum. Mol. Genet. 12:2733-2743(2003).
CC -!- FUNCTION: Catalyzes the hydrolysis of triglycerides and phospholipids
CC present in circulating plasma lipoproteins, including chylomicrons,
CC intermediate density lipoproteins (IDL), low density lipoproteins (LDL)
CC of large size and high density lipoproteins (HDL), releasing free fatty
CC acids (FFA) and smaller lipoprotein particles (PubMed:7592706,
CC PubMed:8798474, PubMed:12032167, PubMed:26193433). Also exhibits
CC lysophospholipase activity (By similarity). Can hydrolyze both neutral
CC lipid and phospholipid substrates but shows a greater binding affinity
CC for neutral lipid substrates than phospholipid substrates (By
CC similarity). In native LDL, preferentially hydrolyzes the
CC phosphatidylcholine species containing polyunsaturated fatty acids at
CC sn-2 position (PubMed:26193433). {ECO:0000250|UniProtKB:P07867,
CC ECO:0000269|PubMed:12032167, ECO:0000269|PubMed:26193433,
CC ECO:0000269|PubMed:7592706, ECO:0000269|PubMed:8798474}.
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:0000269|PubMed:12032167, ECO:0000269|PubMed:26193433,
CC ECO:0000269|PubMed:7592706, ECO:0000269|PubMed:8798474};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-sn-glycero-3-phosphocholine + H2O = a fatty acid +
CC H(+) + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:15177,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870,
CC ChEBI:CHEBI:28868, ChEBI:CHEBI:58168; EC=3.1.1.5;
CC Evidence={ECO:0000250|UniProtKB:P07867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 2-acyl-sn-
CC glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:18689,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:57875; EC=3.1.1.32;
CC Evidence={ECO:0000269|PubMed:12032167, ECO:0000269|PubMed:26193433,
CC ECO:0000269|PubMed:7592706};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-
CC octadecenoate + di-(9Z)-octadecenoylglycerol + H(+);
CC Xref=Rhea:RHEA:38575, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75945;
CC Evidence={ECO:0000269|PubMed:12032167, ECO:0000269|PubMed:7592706,
CC ECO:0000269|PubMed:8798474};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38576;
CC Evidence={ECO:0000305|PubMed:7592706};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O =
CC (9Z)-octadecenoate + (9Z-octadecenoyl)-sn-glycero-3-phosphocholine +
CC H(+); Xref=Rhea:RHEA:38699, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:74669, ChEBI:CHEBI:76083;
CC Evidence={ECO:0000269|PubMed:7592706};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38700;
CC Evidence={ECO:0000305|PubMed:7592706};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2,3-tributanoylglycerol + H2O = butanoate +
CC dibutanoylglycerol + H(+); Xref=Rhea:RHEA:40475, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17968, ChEBI:CHEBI:35020,
CC ChEBI:CHEBI:76478; Evidence={ECO:0000269|PubMed:7592706};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40476;
CC Evidence={ECO:0000305|PubMed:7592706};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) +
CC hexadecanoate + hexadecanoyl-sn-glycero-3-phosphocholine;
CC Xref=Rhea:RHEA:41384, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:64563, ChEBI:CHEBI:72999;
CC Evidence={ECO:0000269|PubMed:12032167};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41385;
CC Evidence={ECO:0000305|PubMed:12032167};
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:0000250|UniProtKB:P07867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38512;
CC Evidence={ECO:0000250|UniProtKB:P07867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-
CC octadecenoate + 2,3-di-(9Z)-octadecenoyl-sn-glycerol + H(+);
CC Xref=Rhea:RHEA:38391, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75824;
CC Evidence={ECO:0000250|UniProtKB:P07867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38392;
CC Evidence={ECO:0000250|UniProtKB:P07867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + H2O =
CC (9Z)-octadecenoate + H(+) + sn-glycero-3-phospho-L-serine;
CC Xref=Rhea:RHEA:40499, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:64765, ChEBI:CHEBI:74617;
CC Evidence={ECO:0000250|UniProtKB:P07867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40500;
CC Evidence={ECO:0000250|UniProtKB:P07867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) +
CC hexadecanoate + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40435,
CC ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16870, ChEBI:CHEBI:72998;
CC Evidence={ECO:0000250|UniProtKB:P07867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436;
CC Evidence={ECO:0000250|UniProtKB:P07867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,3-di-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate +
CC 3-(9Z-octadecenoyl)-sn-glycerol + H(+); Xref=Rhea:RHEA:38651,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:75735, ChEBI:CHEBI:75938;
CC Evidence={ECO:0000250|UniProtKB:P07867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38652;
CC Evidence={ECO:0000250|UniProtKB:P07867};
CC -!- ACTIVITY REGULATION: Phospholipase A1 and triacylglycerol lipase are
CC inhibited by sphingomyelin. {ECO:0000269|PubMed:26193433}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=16 mM for 1,2,3-tri-(9Z-octadecenoyl)-glycerol
CC {ECO:0000269|PubMed:8798474};
CC Vmax=1.4 umol/min/ug enzyme with 1,2,3-tri-(9Z-octadecenoyl)-glycerol
CC as substrate {ECO:0000269|PubMed:8798474};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:8798474}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2828141}.
CC -!- POLYMORPHISM: Genetic variations in LIPC define the high density
CC lipoprotein cholesterol level quantitative trait locus 12 (HDLCQ12)
CC [MIM:612797]. {ECO:0000269|PubMed:18364377}.
CC -!- POLYMORPHISM: Genetic variations in LIPC are associated with non-
CC insulin-dependent diabetes mellitus susceptibility (NIDDM
CC susceptibility) [MIM:125853]. {ECO:0000269|PubMed:15126514}.
CC -!- DISEASE: Hepatic lipase deficiency (HL deficiency) [MIM:614025]: A
CC disorder characterized by elevated levels of beta-migrating very low
CC density lipoproteins, and abnormally triglyceride-rich low and high
CC density lipoproteins. {ECO:0000269|PubMed:10660332,
CC ECO:0000269|PubMed:1301939}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
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DR EMBL; D83548; BAA12014.1; -; mRNA.
DR EMBL; X07228; CAA30188.1; -; mRNA.
DR EMBL; J03540; AAA59520.1; -; mRNA.
DR EMBL; J03895; AAA61165.1; -; mRNA.
DR EMBL; M29194; AAB60702.1; -; Genomic_DNA.
DR EMBL; M29186; AAB60702.1; JOINED; Genomic_DNA.
DR EMBL; M29187; AAB60702.1; JOINED; Genomic_DNA.
DR EMBL; M29188; AAB60702.1; JOINED; Genomic_DNA.
DR EMBL; M29189; AAB60702.1; JOINED; Genomic_DNA.
DR EMBL; M29190; AAB60702.1; JOINED; Genomic_DNA.
DR EMBL; M29191; AAB60702.1; JOINED; Genomic_DNA.
DR EMBL; M29192; AAB60702.1; JOINED; Genomic_DNA.
DR EMBL; M29193; AAB60702.1; JOINED; Genomic_DNA.
DR EMBL; D83062; BAA11760.1; -; Genomic_DNA.
DR EMBL; M35433; AAA59521.1; -; Genomic_DNA.
DR EMBL; M35425; AAA59521.1; JOINED; Genomic_DNA.
DR EMBL; M35426; AAA59521.1; JOINED; Genomic_DNA.
DR EMBL; M35427; AAA59521.1; JOINED; Genomic_DNA.
DR EMBL; M35429; AAA59521.1; JOINED; Genomic_DNA.
DR EMBL; M35430; AAA59521.1; JOINED; Genomic_DNA.
DR EMBL; M35431; AAA59521.1; JOINED; Genomic_DNA.
DR EMBL; M35432; AAA59521.1; JOINED; Genomic_DNA.
DR EMBL; AK292631; BAF85320.1; -; mRNA.
DR EMBL; AK315306; BAG37710.1; -; mRNA.
DR EMBL; AC018904; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC084781; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC132825; AAI32826.1; -; mRNA.
DR EMBL; BC136495; AAI36496.1; -; mRNA.
DR EMBL; AF037404; AAC34206.1; -; Genomic_DNA.
DR CCDS; CCDS10166.1; -.
DR PIR; A28997; A28997.
DR RefSeq; NP_000227.2; NM_000236.2.
DR RefSeq; XP_005254429.1; XM_005254372.1.
DR AlphaFoldDB; P11150; -.
DR SMR; P11150; -.
DR BioGRID; 110178; 13.
DR IntAct; P11150; 3.
DR STRING; 9606.ENSP00000299022; -.
DR BindingDB; P11150; -.
DR ChEMBL; CHEMBL2127; -.
DR SwissLipids; SLP:000000569; -.
DR ESTHER; human-LIPC; Hepatic_Lipase.
DR GlyGen; P11150; 4 sites.
DR iPTMnet; P11150; -.
DR PhosphoSitePlus; P11150; -.
DR BioMuta; LIPC; -.
DR DMDM; 317373430; -.
DR MassIVE; P11150; -.
DR PaxDb; P11150; -.
DR PeptideAtlas; P11150; -.
DR PRIDE; P11150; -.
DR ProteomicsDB; 52700; -.
DR Antibodypedia; 4249; 382 antibodies from 30 providers.
DR DNASU; 3990; -.
DR Ensembl; ENST00000299022.10; ENSP00000299022.5; ENSG00000166035.11.
DR Ensembl; ENST00000356113.10; ENSP00000348425.6; ENSG00000166035.11.
DR GeneID; 3990; -.
DR KEGG; hsa:3990; -.
DR MANE-Select; ENST00000299022.10; ENSP00000299022.5; NM_000236.3; NP_000227.2.
DR UCSC; uc002afa.3; human.
DR CTD; 3990; -.
DR DisGeNET; 3990; -.
DR GeneCards; LIPC; -.
DR HGNC; HGNC:6619; LIPC.
DR HPA; ENSG00000166035; Tissue enriched (liver).
DR MalaCards; LIPC; -.
DR MIM; 125853; phenotype.
DR MIM; 151670; gene.
DR MIM; 612797; phenotype.
DR MIM; 614025; phenotype.
DR neXtProt; NX_P11150; -.
DR OpenTargets; ENSG00000166035; -.
DR Orphanet; 140905; Hyperlipidemia due to hepatic triacylglycerol lipase deficiency.
DR PharmGKB; PA230; -.
DR VEuPathDB; HostDB:ENSG00000166035; -.
DR eggNOG; ENOG502QVTG; Eukaryota.
DR GeneTree; ENSGT00940000157602; -.
DR InParanoid; P11150; -.
DR OMA; YIGGKHK; -.
DR OrthoDB; 534956at2759; -.
DR PhylomeDB; P11150; -.
DR TreeFam; TF324997; -.
DR PathwayCommons; P11150; -.
DR Reactome; R-HSA-8963889; Assembly of active LPL and LIPC lipase complexes.
DR Reactome; R-HSA-8964026; Chylomicron clearance.
DR SignaLink; P11150; -.
DR BioGRID-ORCS; 3990; 5 hits in 1062 CRISPR screens.
DR ChiTaRS; LIPC; human.
DR GeneWiki; Hepatic_lipase; -.
DR GenomeRNAi; 3990; -.
DR Pharos; P11150; Tchem.
DR PRO; PR:P11150; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P11150; protein.
DR Bgee; ENSG00000166035; Expressed in right lobe of liver and 98 other tissues.
DR ExpressionAtlas; P11150; baseline and differential.
DR Genevisible; P11150; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0034364; C:high-density lipoprotein particle; IEA:UniProtKB-KW.
DR GO; GO:0052740; F:1-acyl-2-lysophosphatidylserine acylhydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0034185; F:apolipoprotein binding; ISS:BHF-UCL.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0016298; F:lipase activity; IBA:GO_Central.
DR GO; GO:0004465; F:lipoprotein lipase activity; IBA:GO_Central.
DR GO; GO:0030169; F:low-density lipoprotein particle binding; ISS:BHF-UCL.
DR GO; GO:0004622; F:lysophospholipase activity; IEA:UniProtKB-EC.
DR GO; GO:0102545; F:phosphatidyl phospholipase B activity; IEA:UniProtKB-EC.
DR GO; GO:0052739; F:phosphatidylserine 1-acylhydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0008970; F:phospholipase A1 activity; IDA:UniProtKB.
DR GO; GO:0004620; F:phospholipase activity; IBA:GO_Central.
DR GO; GO:0004806; F:triglyceride lipase activity; IDA:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:BHF-UCL.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:Ensembl.
DR GO; GO:0034382; P:chylomicron remnant clearance; TAS:BHF-UCL.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0034375; P:high-density lipoprotein particle remodeling; IMP:BHF-UCL.
DR GO; GO:0034373; P:intermediate-density lipoprotein particle remodeling; TAS:BHF-UCL.
DR GO; GO:0016042; P:lipid catabolic process; IBA:GO_Central.
DR GO; GO:0034374; P:low-density lipoprotein particle remodeling; IMP:BHF-UCL.
DR GO; GO:0034638; P:phosphatidylcholine catabolic process; TAS:BHF-UCL.
DR GO; GO:0043691; P:reverse cholesterol transport; IC:BHF-UCL.
DR GO; GO:0019433; P:triglyceride catabolic process; IDA:BHF-UCL.
DR GO; GO:0070328; P:triglyceride homeostasis; IMP:BHF-UCL.
DR GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; IDA:BHF-UCL.
DR CDD; cd00707; Pancreat_lipase_like; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR013818; Lipase.
DR InterPro; IPR002333; Lipase_hep.
DR InterPro; IPR016272; Lipase_LIPH.
DR InterPro; IPR033906; Lipase_N.
DR InterPro; IPR001024; PLAT/LH2_dom.
DR InterPro; IPR036392; PLAT/LH2_dom_sf.
DR InterPro; IPR000734; TAG_lipase.
DR PANTHER; PTHR11610; PTHR11610; 1.
DR PANTHER; PTHR11610:SF2; PTHR11610:SF2; 1.
DR Pfam; PF00151; Lipase; 1.
DR Pfam; PF01477; PLAT; 1.
DR PIRSF; PIRSF000865; Lipoprotein_lipase_LIPH; 1.
DR PRINTS; PR00824; HEPLIPASE.
DR PRINTS; PR00821; TAGLIPASE.
DR SMART; SM00308; LH2; 1.
DR SUPFAM; SSF49723; SSF49723; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00120; LIPASE_SER; 1.
DR PROSITE; PS50095; PLAT; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disease variant; Glycoprotein; HDL;
KW Heparin-binding; Hydrolase; Lipid degradation; Lipid metabolism;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:2839510"
FT CHAIN 23..499
FT /note="Hepatic triacylglycerol lipase"
FT /id="PRO_0000017769"
FT DOMAIN 352..486
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT REGION 254..277
FT /note="Essential for determining substrate specificity"
FT /evidence="ECO:0000269|PubMed:7592706"
FT ACT_SITE 168
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 194
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT ACT_SITE 279
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 397
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 95
FT /note="V -> M (in dbSNP:rs6078)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:12966036"
FT /id="VAR_004206"
FT VARIANT 134
FT /note="V -> VHYTVAV (in HL deficiency)"
FT /evidence="ECO:0000269|PubMed:10660332"
FT /id="VAR_004207"
FT VARIANT 215
FT /note="N -> S (in dbSNP:rs6083)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:12966036, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:2324091, ECO:0000269|PubMed:2447084,
FT ECO:0000269|PubMed:2828141"
FT /id="VAR_004208"
FT VARIANT 289
FT /note="S -> F (in HL deficiency; dbSNP:rs121912502)"
FT /evidence="ECO:0000269|PubMed:12966036,
FT ECO:0000269|PubMed:1301939"
FT /id="VAR_004209"
FT VARIANT 342
FT /note="V -> I (in dbSNP:rs145811475)"
FT /evidence="ECO:0000269|PubMed:12966036"
FT /id="VAR_017024"
FT VARIANT 356
FT /note="F -> L (in dbSNP:rs3829462)"
FT /evidence="ECO:0000269|PubMed:12966036,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:2324091, ECO:0000269|PubMed:2447084,
FT ECO:0000269|PubMed:2605236, ECO:0000269|PubMed:2828141,
FT ECO:0000269|PubMed:2839510"
FT /id="VAR_017025"
FT VARIANT 405
FT /note="T -> M (in HL deficiency; dbSNP:rs113298164)"
FT /evidence="ECO:0000269|PubMed:12966036,
FT ECO:0000269|PubMed:1301939"
FT /id="VAR_004210"
FT VARIANT 409
FT /note="D -> A (in dbSNP:rs142036980)"
FT /evidence="ECO:0000269|PubMed:12966036"
FT /id="VAR_017026"
FT VARIANT 440
FT /note="S -> N (in dbSNP:rs6079)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_014179"
FT MUTAGEN 255..276
FT /note="HFLELYRHIAQHGFNAITQTIK->CFHLEYLRIHQAHGFNATIQTKI:
FT Loss of triglyceride hydrolase and phospholipase activity."
FT /evidence="ECO:0000269|PubMed:7592706"
FT MUTAGEN 255..275
FT /note="HFLELYRHIAQHGFNAITQTI->NIGEAIRVIAERGLGDVDQLV:
FT Increased triglyceride hydrolase and reduced phospholipase
FT activity."
FT /evidence="ECO:0000269|PubMed:7592706"
FT CONFLICT 256
FT /note="F -> S (in Ref. 1; AAA61165)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 499 AA; 55914 MW; 1FC7567CAE3E514B CRC64;
MDTSPLCFSI LLVLCIFIQS SALGQSLKPE PFGRRAQAVE TNKTLHEMKT RFLLFGETNQ
GCQIRINHPD TLQECGFNSS LPLVMIIHGW SVDGVLENWI WQMVAALKSQ PAQPVNVGLV
DWITLAHDHY TIAVRNTRLV GKEVAALLRW LEESVQLSRS HVHLIGYSLG AHVSGFAGSS
IGGTHKIGRI TGLDAAGPLF EGSAPSNRLS PDDANFVDAI HTFTREHMGL SVGIKQPIGH
YDFYPNGGSF QPGCHFLELY RHIAQHGFNA ITQTIKCSHE RSVHLFIDSL LHAGTQSMAY
PCGDMNSFSQ GLCLSCKKGR CNTLGYHVRQ EPRSKSKRLF LVTRAQSPFK VYHYQFKIQF
INQTETPIQT TFTMSLLGTK EKMQKIPITL GKGIASNKTY SFLITLDVDI GELIMIKFKW
ENSAVWANVW DTVQTIIPWS TGPRHSGLVL KTIRVKAGET QQRMTFCSEN TDDLLLRPTQ
EKIFVKCEIK SKTSKRKIR
