LICH_MOUSE
ID LICH_MOUSE Reviewed; 397 AA.
AC Q9Z0M5; Q8C2G7;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Lysosomal acid lipase/cholesteryl ester hydrolase;
DE Short=Acid cholesteryl ester hydrolase;
DE Short=LAL;
DE EC=3.1.1.13 {ECO:0000250|UniProtKB:P38571};
DE AltName: Full=Cholesteryl esterase;
DE AltName: Full=Lipase A;
DE AltName: Full=Sterol esterase;
DE Flags: Precursor;
GN Name=Lipa; Synonyms=Lip1;
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], AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RX PubMed=8725147;
RA Du H., Witte D.P., Grabowski G.A.;
RT "Tissue and cellular specific expression of murine lysosomal acid lipase
RT mRNA and protein.";
RL J. Lipid Res. 37:937-949(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Liver, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the deacylation of triacylglyceryl and cholesteryl
CC ester core lipids of endocytosed low density lipoproteins to generate
CC free fatty acids and cholesterol. {ECO:0000250|UniProtKB:P38571}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sterol ester + H2O = a fatty acid + a sterol + H(+);
CC Xref=Rhea:RHEA:10100, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15889, ChEBI:CHEBI:28868, ChEBI:CHEBI:35915; EC=3.1.1.13;
CC Evidence={ECO:0000250|UniProtKB:P38571};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesteryl (9Z-octadecenoate) + H2O = (9Z)-octadecenoate +
CC cholesterol + H(+); Xref=Rhea:RHEA:33875, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16113, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:46898; Evidence={ECO:0000250|UniProtKB:P38571};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876;
CC Evidence={ECO:0000250|UniProtKB:P38571};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P38571}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:Q64194}.
CC -!- TISSUE SPECIFICITY: Expressed at low levels in most tissues. High level
CC expression is found in hepatocytes and splenic and thymic cells. Very
CC high level expression is observed in cells of the small intestinal
CC villi, the zona fasciculata and reticularis of the adrenal cortex,
CC pancreatic acini, and renal tubular epithelium.
CC {ECO:0000269|PubMed:8725147}.
CC -!- PTM: Glycosylation is not essential for catalytic activity.
CC {ECO:0000250|UniProtKB:P38571}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
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DR EMBL; Z31689; CAA83494.1; -; mRNA.
DR EMBL; AK088659; BAC40484.1; -; mRNA.
DR EMBL; AK149791; BAE29088.1; -; mRNA.
DR EMBL; AK164007; BAE37585.1; -; mRNA.
DR EMBL; CH466534; EDL41750.1; -; Genomic_DNA.
DR CCDS; CCDS29760.1; -.
DR RefSeq; NP_001104570.1; NM_001111100.1.
DR RefSeq; NP_067435.3; NM_021460.3.
DR AlphaFoldDB; Q9Z0M5; -.
DR SMR; Q9Z0M5; -.
DR BioGRID; 201168; 1.
DR STRING; 10090.ENSMUSP00000053270; -.
DR ESTHER; mouse-1llip; Acidic_Lipase.
DR GlyGen; Q9Z0M5; 5 sites.
DR iPTMnet; Q9Z0M5; -.
DR PhosphoSitePlus; Q9Z0M5; -.
DR EPD; Q9Z0M5; -.
DR jPOST; Q9Z0M5; -.
DR MaxQB; Q9Z0M5; -.
DR PaxDb; Q9Z0M5; -.
DR PRIDE; Q9Z0M5; -.
DR ProteomicsDB; 286196; -.
DR Antibodypedia; 30242; 273 antibodies from 29 providers.
DR DNASU; 16889; -.
DR Ensembl; ENSMUST00000049572; ENSMUSP00000053270; ENSMUSG00000024781.
DR Ensembl; ENSMUST00000178114; ENSMUSP00000136967; ENSMUSG00000024781.
DR GeneID; 16889; -.
DR KEGG; mmu:16889; -.
DR UCSC; uc008hgm.2; mouse.
DR CTD; 3988; -.
DR MGI; MGI:96789; Lipa.
DR VEuPathDB; HostDB:ENSMUSG00000024781; -.
DR eggNOG; KOG2624; Eukaryota.
DR GeneTree; ENSGT00940000154696; -.
DR HOGENOM; CLU_010974_0_0_1; -.
DR InParanoid; Q9Z0M5; -.
DR OMA; DGEHVDC; -.
DR OrthoDB; 651396at2759; -.
DR PhylomeDB; Q9Z0M5; -.
DR TreeFam; TF315485; -.
DR Reactome; R-MMU-8964038; LDL clearance.
DR BioGRID-ORCS; 16889; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Lipa; mouse.
DR PRO; PR:Q9Z0M5; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9Z0M5; protein.
DR Bgee; ENSMUSG00000024781; Expressed in left lobe of liver and 249 other tissues.
DR Genevisible; Q9Z0M5; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0016298; F:lipase activity; ISO:MGI.
DR GO; GO:0004771; F:sterol esterase activity; ISS:UniProtKB.
DR GO; GO:0000902; P:cell morphogenesis; IMP:MGI.
DR GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI.
DR GO; GO:0006631; P:fatty acid metabolic process; ISO:MGI.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IMP:MGI.
DR GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0061519; P:macrophage homeostasis; IMP:MGI.
DR GO; GO:0016125; P:sterol metabolic process; ISO:MGI.
DR GO; GO:0048771; P:tissue remodeling; IMP:MGI.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR InterPro; IPR025483; Lipase_euk.
DR Pfam; PF00561; Abhydrolase_1; 1.
DR PIRSF; PIRSF000862; Steryl_ester_lip; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00120; LIPASE_SER; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Hydrolase; Lipid degradation; Lipid metabolism; Lysosome;
KW Reference proteome; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT PROPEP 26..74
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P38571"
FT /id="PRO_0000450227"
FT CHAIN 75..397
FT /note="Lysosomal acid lipase/cholesteryl ester hydrolase"
FT /id="PRO_0000017800"
FT DOMAIN 78..378
FT /note="AB hydrolase-1"
FT /evidence="ECO:0000255"
FT ACT_SITE 172
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT ACT_SITE 372
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 159
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 271
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 68
FT /note="R -> W (in Ref. 1; CAA83494)"
FT /evidence="ECO:0000305"
FT CONFLICT 109
FT /note="A -> R (in Ref. 1; CAA83494)"
FT /evidence="ECO:0000305"
FT CONFLICT 285..287
FT /note="GTS -> ELL (in Ref. 1; CAA83494)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 397 AA; 45325 MW; 866B123A1A058134 CRC64;
MQLQGLVFVF TIGILLSRVP TGTVSAVDPE VNMNVTEIIM RWGYPGEEHS VLTGDGYILS
IHRIPRGRKN HFGKGPRPVV YLQHGLLADS SNWVTNIDNS SLGFLLADAG FDVWMGNSRG
NTWSLKHKTL SVSQDEFWAF SFDEMAKYDL PASINYILNK TGQEQIYYVG HSQGCTIGFI
AFSQMPELAK KIKMFLVLAP VLSLNFASGP LLQLGRLPDP LLKDMFGQKQ FLPQSAMLKW
LSIHVCTHVI MKELCANVFF LLCGFNEKNL NMSRVDVYTT HCPAGTSVQN MLHWGQVFKY
RKLQAFDWGS SEKNYFHYNQ SFPPSYNIKN MRLPTALWSG GRDWLADIND ITILLTQIPK
LVYHKNIPEW DHLDFIWGLD APWKLYDEII SLMKKYQ
