ID   LIPC_MOUSE              Reviewed;         510 AA.
AC   P27656; Q8VC44;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   24-JAN-2024, entry version 184.
DE   RecName: Full=Hepatic triacylglycerol lipase;
DE            Short=HL;
DE            Short=Hepatic lipase;
DE            EC=3.1.1.3 {ECO:0000250|UniProtKB:P07867};
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:0000250|UniProtKB:P07867};
DE   Flags: Precursor;
GN   Name=Lipc; Synonyms=Hpl;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2025643; DOI=10.1016/0167-4781(91)90078-z;
RA   Oka K., Nakano T., Tkalcevic G.T., Scow R.O., Brown W.V.;
RT   "Molecular cloning of mouse hepatic triacylglycerol lipase: gene expression
RT   in combined lipase-deficient (cld/cld) mice.";
RL   Biochim. Biophys. Acta 1089:13-20(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RX   PubMed=1840530; DOI=10.1016/0014-5793(91)80910-u;
RA   Chang S.F., Netter H.J., Will H.;
RT   "Characterization of cDNA encoding the mouse hepatic triglyceride lipase
RT   and expression by in vitro translation.";
RL   FEBS Lett. 289:69-72(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Liver;
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).
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 (By similarity). Also
CC       exhibits lysophospholipase activity (By similarity). Can hydrolyze both
CC       neutral lipid and phospholipid substrates but shows a greater binding
CC       affinity 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 (By similarity). {ECO:0000250|UniProtKB:P07867,
CC       ECO:0000250|UniProtKB:P11150}.
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:P07867};
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:0000250|UniProtKB:P07867};
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:0000250|UniProtKB:P11150};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38576;
CC         Evidence={ECO:0000250|UniProtKB:P11150};
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:0000250|UniProtKB:P11150};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38700;
CC         Evidence={ECO:0000250|UniProtKB:P11150};
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:0000250|UniProtKB:P11150};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40476;
CC         Evidence={ECO:0000250|UniProtKB:P11150};
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:0000250|UniProtKB:P11150};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41385;
CC         Evidence={ECO:0000250|UniProtKB:P11150};
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   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P11150}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P11150}.
CC   -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC       {ECO:0000305}.
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DR   EMBL; AY228765; AAO73443.1; -; mRNA.
DR   EMBL; X58426; CAA41329.1; -; mRNA.
DR   EMBL; CH466522; EDL26212.1; -; Genomic_DNA.
DR   EMBL; BC021841; AAH21841.1; -; mRNA.
DR   EMBL; BC094050; AAH94050.1; -; mRNA.
DR   CCDS; CCDS23324.1; -.
DR   PIR; S15893; S15893.
DR   RefSeq; NP_001311401.1; NM_001324472.1.
DR   RefSeq; NP_001311402.1; NM_001324473.1.
DR   RefSeq; NP_032306.2; NM_008280.2.
DR   AlphaFoldDB; P27656; -.
DR   SMR; P27656; -.
DR   BioGRID; 200409; 28.
DR   STRING; 10090.ENSMUSP00000034731; -.
DR   ESTHER; mouse-1hlip; Hepatic_Lipase.
DR   GlyCosmos; P27656; 2 sites, No reported glycans.
DR   GlyGen; P27656; 2 sites.
DR   PhosphoSitePlus; P27656; -.
DR   MaxQB; P27656; -.
DR   PaxDb; 10090-ENSMUSP00000034731; -.
DR   ProteomicsDB; 290030; -.
DR   Antibodypedia; 4249; 408 antibodies from 30 providers.
DR   DNASU; 15450; -.
DR   Ensembl; ENSMUST00000034731.10; ENSMUSP00000034731.9; ENSMUSG00000032207.11.
DR   GeneID; 15450; -.
DR   KEGG; mmu:15450; -.
DR   UCSC; uc009qos.1; mouse.
DR   AGR; MGI:96216; -.
DR   CTD; 3990; -.
DR   MGI; MGI:96216; Lipc.
DR   VEuPathDB; HostDB:ENSMUSG00000032207; -.
DR   eggNOG; ENOG502QVTG; Eukaryota.
DR   GeneTree; ENSGT00940000157602; -.
DR   HOGENOM; CLU_027171_1_1_1; -.
DR   InParanoid; P27656; -.
DR   OMA; FVRCKED; -.
DR   OrthoDB; 3428256at2759; -.
DR   PhylomeDB; P27656; -.
DR   TreeFam; TF324997; -.
DR   Reactome; R-MMU-8963889; Assembly of active LPL and LIPC lipase complexes.
DR   Reactome; R-MMU-8964026; Chylomicron clearance.
DR   BioGRID-ORCS; 15450; 6 hits in 80 CRISPR screens.
DR   PRO; PR:P27656; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   RNAct; P27656; Protein.
DR   Bgee; ENSMUSG00000032207; Expressed in left lobe of liver and 45 other cell types or tissues.
DR   ExpressionAtlas; P27656; baseline and differential.
DR   GO; GO:0009986; C:cell surface; ISO:MGI.
DR   GO; GO:0005769; C:early endosome; ISO:MGI.
DR   GO; GO:0005615; C:extracellular space; IDA:MGI.
DR   GO; GO:0034364; C:high-density lipoprotein particle; IEA:UniProtKB-KW.
DR   GO; GO:0005770; C:late endosome; ISO:MGI.
DR   GO; GO:0005902; C:microvillus; ISO:MGI.
DR   GO; GO:0052740; F:1-acyl-2-lysophosphatidylserine acylhydrolase activity; IEA:UniProtKB-EC.
DR   GO; GO:0008126; F:acetylesterase activity; ISO:MGI.
DR   GO; GO:0047372; F:acylglycerol lipase activity; ISO:MGI.
DR   GO; GO:0016746; F:acyltransferase activity; ISO:MGI.
DR   GO; GO:0034185; F:apolipoprotein binding; ISO:MGI.
DR   GO; GO:0035478; F:chylomicron binding; ISO:MGI.
DR   GO; GO:0043395; F:heparan sulfate proteoglycan binding; ISO:MGI.
DR   GO; GO:0008201; F:heparin binding; ISO:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0016298; F:lipase activity; IDA:MGI.
DR   GO; GO:0008289; F:lipid binding; ISO:MGI.
DR   GO; GO:0004465; F:lipoprotein lipase activity; IBA:GO_Central.
DR   GO; GO:0030169; F:low-density lipoprotein particle binding; ISO:MGI.
DR   GO; GO:0004622; F:lysophospholipase activity; ISO:MGI.
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; ISS:UniProtKB.
DR   GO; GO:0004620; F:phospholipase activity; IBA:GO_Central.
DR   GO; GO:0004806; F:triglyceride lipase activity; ISS:UniProtKB.
DR   GO; GO:0042632; P:cholesterol homeostasis; IGI:MGI.
DR   GO; GO:0008203; P:cholesterol metabolic process; IGI:MGI.
DR   GO; GO:0030301; P:cholesterol transport; IMP:MGI.
DR   GO; GO:0034382; P:chylomicron remnant clearance; ISO:MGI.
DR   GO; GO:0034371; P:chylomicron remodeling; ISO:MGI.
DR   GO; GO:0006633; P:fatty acid biosynthetic process; ISO:MGI.
DR   GO; GO:0006631; P:fatty acid metabolic process; ISO:MGI.
DR   GO; GO:0046475; P:glycerophospholipid catabolic process; ISO:MGI.
DR   GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; ISO:MGI.
DR   GO; GO:0034375; P:high-density lipoprotein particle remodeling; ISO:MGI.
DR   GO; GO:0034383; P:low-density lipoprotein particle clearance; ISO:MGI.
DR   GO; GO:0034374; P:low-density lipoprotein particle remodeling; ISO:MGI.
DR   GO; GO:0046461; P:neutral lipid catabolic process; ISO:MGI.
DR   GO; GO:0046473; P:phosphatidic acid metabolic process; ISO:MGI.
DR   GO; GO:0046470; P:phosphatidylcholine metabolic process; ISO:MGI.
DR   GO; GO:0046337; P:phosphatidylethanolamine metabolic process; ISO:MGI.
DR   GO; GO:0006658; P:phosphatidylserine metabolic process; ISO:MGI.
DR   GO; GO:0097006; P:regulation of plasma lipoprotein particle levels; ISO:MGI.
DR   GO; GO:0019433; P:triglyceride catabolic process; ISO:MGI.
DR   GO; GO:0070328; P:triglyceride homeostasis; ISO:MGI.
DR   GO; GO:0006641; P:triglyceride metabolic process; ISO:MGI.
DR   GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; ISO:MGI.
DR   CDD; cd00707; Pancreat_lipase_like; 1.
DR   CDD; cd01758; PLAT_LPL; 1.
DR   Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1.
DR   Gene3D; 2.60.60.20; PLAT/LH2 domain; 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:SF2; HEPATIC TRIACYLGLYCEROL LIPASE; 1.
DR   PANTHER; PTHR11610; LIPASE; 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; SSF53474; alpha/beta-Hydrolases; 1.
DR   SUPFAM; SSF49723; Lipase/lipooxygenase domain (PLAT/LH2 domain); 1.
DR   PROSITE; PS00120; LIPASE_SER; 1.
DR   PROSITE; PS50095; PLAT; 1.
DR   Genevisible; P27656; MM.
PE   2: Evidence at transcript level;
KW   Glycoprotein; HDL; Heparin-binding; Hydrolase; Lipid degradation;
KW   Lipid metabolism; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000250|UniProtKB:P11150"
FT   CHAIN           22..510
FT                   /note="Hepatic triacylglycerol lipase"
FT                   /id="PRO_0000017770"
FT   DOMAIN          353..487
FT                   /note="PLAT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT   REGION          255..278
FT                   /note="Essential for determining substrate specificity"
FT                   /evidence="ECO:0000250|UniProtKB:P11150"
FT   ACT_SITE        169
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        195
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT   ACT_SITE        280
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT   CARBOHYD        79
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        398
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        286
FT                   /note="L -> P (in Ref. 2; CAA41329)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   510 AA;  57389 MW;  E30222652D782A05 CRC64;
     MGNPLQISIF LVFCIFIQSS ACGQGVGTEP FGRSLGATEA SKPLKKPETR FLLFQDENDR
     LGCRLRPQHP ETLQECGFNS SQPLIMIIHG WSVDGLLENW IWKIVSALKS RQSQPVNVGL
     VDWISLAYQH YTIAVQNTRI VGQDVAALLL WLEESAKFSR SKVHLIGYSL GAHVSGFAGS
     SMDGKNKIGR ITGLDPAGPM FEGTSPNERL SPDDANFVDA IHTFTREHMG LSVGIKQPIA
     HYDFYPNGGS FQPGCHFLEL YKHIAEHGLN AITQTIKCAH ERSVHLFIDS LQHSDLQSIG
     FQCSDMGSFS QGLCLSCKKG RCNTLGYDIR KDRSGKSKRL FLITRAQSPF KVYHYQFKIQ
     FINQIEKPVE PTFTMSLLGT KEEIKRIPIT LGEGITSNKT YSFLITLDKD IGELILLKFK
     WENSAVWANV WNTVQTIMLW GIEPHHSGLI LKTIWVKAGE TQQRMTFCPE NLDDLQLHPS
     QEKVFVNCEV KSKRLTESKE QMSQETHAKK
//