ID LICH_HUMAN Reviewed; 399 AA. AC P38571; B2RBH5; D3DR29; Q16529; Q53H21; Q5T074; Q5T771; Q96EJ0; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 21-JUN-2005, sequence version 2. DT 27-MAR-2024, entry version 207. 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:0000269|PubMed:15269241, ECO:0000269|PubMed:7204383, ECO:0000269|PubMed:8112342}; DE AltName: Full=Cholesteryl esterase; DE AltName: Full=Lipase A; DE AltName: Full=Sterol esterase; DE Flags: Precursor; GN Name=LIPA; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 196-212; RP 277-297 AND 305-315, FUNCTION, CATALYTIC ACTIVITY, AND VARIANT PRO-16. RX PubMed=1718995; DOI=10.1016/s0021-9258(18)54597-x; RA Anderson R.A., Sando G.N.; RT "Cloning and expression of cDNA encoding human lysosomal acid RT lipase/cholesteryl ester hydrolase. Similarities to gastric and lingual RT lipases."; RL J. Biol. Chem. 266:22479-22484(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 28-33 AND RP 77-93, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, BIOPHYSICOCHEMICAL RP PROPERTIES, TISSUE SPECIFICITY, AND GLYCOSYLATION. RC TISSUE=Liver; RX PubMed=8112342; DOI=10.1111/j.1432-1033.1994.tb18572.x; RA Ameis D., Merkel M., Eckerskorn C., Greten H.; RT "Purification, characterization and molecular cloning of human hepatic RT lysosomal acid lipase."; RL Eur. J. Biochem. 219:905-914(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ARG-23. RC 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-16. RC TISSUE=Umbilical cord blood; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Liver; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS PRO-16 AND RP LEU-29. RC TISSUE=Placenta; 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 FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=7204383; DOI=10.1016/s0021-9258(19)69707-3; RA Warner T.G., Dambach L.M., Shin J.H., O'Brien J.S.; RT "Purification of the lysosomal acid lipase from human liver and its role in RT lysosomal lipid hydrolysis."; RL J. Biol. Chem. 256:2952-2957(1981). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, PROTEOLYTIC PROCESSING, MUTAGENESIS OF LYS-76 RP AND GLY-77, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=15269241; DOI=10.1093/jb/mvh093; RA Zschenker O., Oezden D., Ameis D.; RT "Lysosomal acid lipase as a preproprotein."; RL J. Biochem. 136:65-72(2004). RN [11] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-161 AND ASN-321. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [14] RP VARIANT WOLD PRO-200. RX PubMed=8146180; DOI=10.1073/pnas.91.7.2718; RA Anderson R.A., Byrum R.S., Coates P.M., Sando G.N.; RT "Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in RT Wolman disease."; RL Proc. Natl. Acad. Sci. U.S.A. 91:2718-2722(1994). RN [15] RP VARIANT CESD PRO-200. RX PubMed=8598644; DOI=10.1007/bf02436008; RA Maslen C.L., Babcock D., Illingworth D.R.; RT "Occurrence of a mutation associated with Wolman disease in a family with RT cholesteryl ester storage disease."; RL J. Inherit. Metab. Dis. 18:620-623(1995). RN [16] RP VARIANT WOLD 43-TYR--GLN-399 DEL. RX PubMed=8956047; RX DOI=10.1002/(sici)1098-1004(1996)8:4<377::aid-humu15>3.0.co;2-#; RA Fujiyama J., Sakuraba H., Kuriyama M., Fujita T., Nagata K., Nakagawa H., RA Osame M.; RT "A new mutation (LIPA Tyr22X) of lysosomal acid lipase gene in a Japanese RT patient with Wolman disease."; RL Hum. Mutat. 8:377-380(1996). RN [17] RP VARIANTS CESD ARG-129 AND PRO-129, CHARACTERIZATION OF VARIANTS CESD RP ARG-129 AND PRO-129, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=9633819; RX DOI=10.1002/(sici)1098-1004(1998)12:1<44::aid-humu7>3.0.co;2-o; RA Ries S., Buechler C., Schindler G., Aslanidis C., Ameis D., Gasche C., RA Jung N., Schambach A., Fehringer P., Vanier M.T., Belli D.C., Greten H., RA Schmitz G.; RT "Different missense mutations in histidine-108 of lysosomal acid lipase RT cause cholesteryl ester storage disease in unrelated compound heterozygous RT and hemizygous individuals."; RL Hum. Mutat. 12:44-51(1998). RN [18] RP INVOLVEMENT IN WOLD. RX PubMed=21963785; DOI=10.1016/j.ymgme.2011.09.006; RA Lee T.M., Welsh M., Benhamed S., Chung W.K.; RT "Intragenic deletion as a novel type of mutation in Wolman disease."; RL Mol. Genet. Metab. 104:703-705(2011). 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:0000269|PubMed:15269241, CC ECO:0000269|PubMed:1718995, ECO:0000269|PubMed:7204383, CC ECO:0000269|PubMed:8112342, ECO:0000269|PubMed:9633819}. 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:0000269|PubMed:15269241, ECO:0000269|PubMed:7204383, CC ECO:0000269|PubMed:8112342}; 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:0000269|PubMed:1718995, CC ECO:0000269|PubMed:9633819}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876; CC Evidence={ECO:0000305|PubMed:1718995}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.142 mM for cholesteryl oleate {ECO:0000269|PubMed:8112342}; CC KM=0.8 mM for cholesteryl oleate {ECO:0000269|PubMed:7204383}; CC KM=0.138 mM for trioleoylglycerol {ECO:0000269|PubMed:8112342}; CC KM=0.8 mM for trioleoylglycerol {ECO:0000269|PubMed:7204383}; CC KM=899 uM for trioleoylglycerol {ECO:0000269|PubMed:15269241}; CC KM=0.9 mM for 1,2-dioleoylglycerol {ECO:0000269|PubMed:7204383}; CC KM=1.2 mM for 1,3-dioleoylglycerol {ECO:0000269|PubMed:7204383}; CC Vmax=4390 nmol/min/mg enzyme with cholesteryl oleate as substrate CC {ECO:0000269|PubMed:8112342}; CC Vmax=1400 nmol/min/mg enzyme with cholesteryl oleate as substrate CC {ECO:0000269|PubMed:7204383}; CC Vmax=4756 mmol/min/mg enzyme with trioleoylglycerol as substrate CC {ECO:0000269|PubMed:8112342}; CC Vmax=5400 nmol/min/mg enzyme with trioleoylglycerol as substrate CC {ECO:0000269|PubMed:7204383}; CC Vmax=19400 nmol/min/mg enzyme with 1,2-dioleoylglycerol as substrate CC {ECO:0000269|PubMed:7204383}; CC Vmax=22100 nmol/min/mg enzyme with 1,3-dioleoylglycerol as substrate CC {ECO:0000269|PubMed:7204383}; CC pH dependence: CC Optimum pH is 4.5-5 (PubMed:8112342). Optimum pH is 4.4 with either CC cholesterol oleate or trioleoylglycerol as substrate CC (PubMed:7204383). {ECO:0000269|PubMed:7204383, CC ECO:0000269|PubMed:8112342}; CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:8112342}. CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:Q64194}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P38571-1; Sequence=Displayed; CC Name=2; CC IsoId=P38571-2; Sequence=VSP_018596, VSP_018597; CC -!- TISSUE SPECIFICITY: Most abundantly expressed in brain, lung, kidney CC and mammary gland, a moderate expression seen in placenta and expressed CC at low levels in the liver and heart. {ECO:0000269|PubMed:8112342}. CC -!- PTM: Glycosylation is not essential for catalytic activity. CC {ECO:0000269|PubMed:8112342}. CC -!- DISEASE: Cholesteryl ester storage disease (CESD) [MIM:278000]: An CC autosomal recessive, mild form of lysosomal acid lipase deficiency CC characterized by accumulation of cholesteryl esters and triglycerides CC primarily in the liver. The clinical presentation is highly variable CC depending on residual levels of lysosomal acid lipase activity, and CC ranges from early onset of severe cirrhosis to later onset of more CC slowly progressive hepatic disease with survival into adulthood. Age at CC onset varies from childhood to adulthood. {ECO:0000269|PubMed:8598644, CC ECO:0000269|PubMed:9633819}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Wolman disease (WOLD) [MIM:620151]: An autosomal recessive, CC fulminant form of lysosomal acid lipase deficiency manifesting in early CC infancy. It is characterized by massive infiltration of the liver, CC spleen, and other organs by macrophages filled with cholesteryl esters CC and triglycerides. In addition, accumulation of cholesteryl esters in CC the zona reticularis of the adrenal gland leads to adrenal CC calcification and cortical insufficiency. Death occurs early in life CC from inanition. {ECO:0000269|PubMed:21963785, CC ECO:0000269|PubMed:8146180, ECO:0000269|PubMed:8956047}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M74775; AAA59519.1; -; mRNA. DR EMBL; U04285; AAB60327.1; -; Genomic_DNA. DR EMBL; U04286; AAB60327.1; JOINED; Genomic_DNA. DR EMBL; U04287; AAB60327.1; JOINED; Genomic_DNA. DR EMBL; U04288; AAB60327.1; JOINED; Genomic_DNA. DR EMBL; U04290; AAB60327.1; JOINED; Genomic_DNA. DR EMBL; U04291; AAB60327.1; JOINED; Genomic_DNA. DR EMBL; U04292; AAB60327.1; JOINED; Genomic_DNA. DR EMBL; U04293; AAB60327.1; JOINED; Genomic_DNA. DR EMBL; X76488; CAA54026.1; -; mRNA. DR EMBL; Z31690; CAA83495.1; -; mRNA. DR EMBL; U08464; AAB60328.1; -; mRNA. DR EMBL; AK314665; BAG37222.1; -; mRNA. DR EMBL; AK222760; BAD96480.1; -; mRNA. DR EMBL; AL353751; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL353146; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL513533; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW50140.1; -; Genomic_DNA. DR EMBL; CH471066; EAW50141.1; -; Genomic_DNA. DR EMBL; CH471066; EAW50142.1; -; Genomic_DNA. DR EMBL; BC012287; AAH12287.1; -; mRNA. DR CCDS; CCDS7401.1; -. [P38571-1] DR PIR; G01416; G01416. DR PIR; S41408; S41408. DR RefSeq; NP_000226.2; NM_000235.3. [P38571-1] DR RefSeq; NP_001121077.1; NM_001127605.2. [P38571-1] DR RefSeq; NP_001275908.1; NM_001288979.1. DR PDB; 6V7N; X-ray; 2.62 A; A/B=22-399. DR PDBsum; 6V7N; -. DR AlphaFoldDB; P38571; -. DR SMR; P38571; -. DR BioGRID; 110176; 47. DR STRING; 9606.ENSP00000337354; -. DR BindingDB; P38571; -. DR ChEMBL; CHEMBL4184; -. DR SwissLipids; SLP:000001261; -. DR ESTHER; human-LIPA; Acidic_Lipase. DR MEROPS; S33.017; -. DR GlyConnect; 1475; 12 N-Linked glycans (3 sites). DR GlyCosmos; P38571; 6 sites, 11 glycans. DR GlyGen; P38571; 7 sites, 11 N-linked glycans (3 sites). DR iPTMnet; P38571; -. DR PhosphoSitePlus; P38571; -. DR SwissPalm; P38571; -. DR BioMuta; LIPA; -. DR DMDM; 68067636; -. DR EPD; P38571; -. DR jPOST; P38571; -. DR MassIVE; P38571; -. DR MaxQB; P38571; -. DR PaxDb; 9606-ENSP00000337354; -. DR PeptideAtlas; P38571; -. DR ProteomicsDB; 55301; -. [P38571-1] DR ProteomicsDB; 55302; -. [P38571-2] DR Pumba; P38571; -. DR Antibodypedia; 30242; 302 antibodies from 29 providers. DR DNASU; 3988; -. DR Ensembl; ENST00000336233.10; ENSP00000337354.5; ENSG00000107798.18. [P38571-1] DR Ensembl; ENST00000371837.5; ENSP00000360903.1; ENSG00000107798.18. [P38571-2] DR GeneID; 3988; -. DR KEGG; hsa:3988; -. DR MANE-Select; ENST00000336233.10; ENSP00000337354.5; NM_000235.4; NP_000226.2. DR UCSC; uc001kga.6; human. [P38571-1] DR AGR; HGNC:6617; -. DR CTD; 3988; -. DR DisGeNET; 3988; -. DR GeneCards; LIPA; -. DR GeneReviews; LIPA; -. DR HGNC; HGNC:6617; LIPA. DR HPA; ENSG00000107798; Tissue enhanced (lymphoid). DR MalaCards; LIPA; -. DR MIM; 278000; phenotype. DR MIM; 613497; gene. DR MIM; 620151; phenotype. DR neXtProt; NX_P38571; -. DR OpenTargets; ENSG00000107798; -. DR Orphanet; 75234; Cholesteryl ester storage disease. DR Orphanet; 406; NON RARE IN EUROPE: Heterozygous familial hypercholesterolemia. DR Orphanet; 75233; Wolman disease. DR PharmGKB; PA30391; -. DR VEuPathDB; HostDB:ENSG00000107798; -. DR eggNOG; KOG2624; Eukaryota. DR GeneTree; ENSGT00940000154696; -. DR HOGENOM; CLU_010974_0_0_1; -. DR InParanoid; P38571; -. DR OMA; DGEHVDC; -. DR OrthoDB; 5474043at2759; -. DR PhylomeDB; P38571; -. DR TreeFam; TF315485; -. DR PathwayCommons; P38571; -. DR Reactome; R-HSA-8964038; LDL clearance. DR SABIO-RK; P38571; -. DR BioGRID-ORCS; 3988; 13 hits in 1157 CRISPR screens. DR ChiTaRS; LIPA; human. DR GenomeRNAi; 3988; -. DR Pharos; P38571; Tchem. DR PRO; PR:P38571; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; P38571; Protein. DR Bgee; ENSG00000107798; Expressed in jejunal mucosa and 207 other cell types or tissues. DR ExpressionAtlas; P38571; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0001650; C:fibrillar center; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome. DR GO; GO:0005764; C:lysosome; ISS:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0016298; F:lipase activity; IDA:UniProtKB. DR GO; GO:0004771; F:sterol esterase activity; IDA:UniProtKB. DR GO; GO:0002526; P:acute inflammatory response; IEA:Ensembl. DR GO; GO:1990845; P:adaptive thermogenesis; IEA:Ensembl. DR GO; GO:0060612; P:adipose tissue development; IEA:Ensembl. DR GO; GO:0006754; P:ATP biosynthetic process; IEA:Ensembl. DR GO; GO:0060837; P:blood vessel endothelial cell differentiation; IEA:Ensembl. DR GO; GO:0048539; P:bone marrow development; IEA:Ensembl. DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl. DR GO; GO:0071838; P:cell proliferation in bone marrow; IEA:Ensembl. DR GO; GO:0097384; P:cellular lipid biosynthetic process; IEA:Ensembl. DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:Ensembl. DR GO; GO:0033344; P:cholesterol efflux; IEA:Ensembl. DR GO; GO:0010878; P:cholesterol storage; IEA:Ensembl. DR GO; GO:0035726; P:common myeloid progenitor cell proliferation; IEA:Ensembl. DR GO; GO:0030421; P:defecation; IEA:Ensembl. DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl. DR GO; GO:0006897; P:endocytosis; IEA:Ensembl. DR GO; GO:0008333; P:endosome to lysosome transport; IEA:Ensembl. DR GO; GO:0001935; P:endothelial cell proliferation; IEA:Ensembl. DR GO; GO:0070341; P:fat cell proliferation; IEA:Ensembl. DR GO; GO:0006631; P:fatty acid metabolic process; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; IEA:Ensembl. DR GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl. DR GO; GO:0006096; P:glycolytic process; IEA:Ensembl. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl. DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl. DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW. DR GO; GO:0055088; P:lipid homeostasis; IEA:Ensembl. DR GO; GO:0140354; P:lipid import into cell; IEA:Ensembl. DR GO; GO:0042159; P:lipoprotein catabolic process; IEA:Ensembl. DR GO; GO:0072576; P:liver morphogenesis; IEA:Ensembl. DR GO; GO:0034383; P:low-density lipoprotein particle clearance; TAS:Reactome. DR GO; GO:0030324; P:lung development; IEA:Ensembl. DR GO; GO:0007040; P:lysosome organization; IEA:Ensembl. DR GO; GO:0061519; P:macrophage homeostasis; IEA:Ensembl. DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl. DR GO; GO:0000278; P:mitotic cell cycle; IEA:Ensembl. DR GO; GO:0140962; P:multicellular organismal-level chemical homeostasis; IEA:Ensembl. DR GO; GO:0033028; P:myeloid cell apoptotic process; IEA:Ensembl. DR GO; GO:0030099; P:myeloid cell differentiation; IEA:Ensembl. DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; IEA:Ensembl. DR GO; GO:1903409; P:reactive oxygen species biosynthetic process; IEA:Ensembl. DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IEA:Ensembl. DR GO; GO:0002536; P:respiratory burst involved in inflammatory response; IEA:Ensembl. DR GO; GO:0009409; P:response to cold; IEA:Ensembl. DR GO; GO:0002021; P:response to dietary excess; IEA:Ensembl. DR GO; GO:1901355; P:response to rapamycin; IEA:Ensembl. DR GO; GO:0033189; P:response to vitamin A; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:Ensembl. DR GO; GO:0048536; P:spleen development; IEA:Ensembl. DR GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central. DR GO; GO:0070231; P:T cell apoptotic process; IEA:Ensembl. DR GO; GO:0030217; P:T cell differentiation; IEA:Ensembl. DR GO; GO:0042098; P:T cell proliferation; IEA:Ensembl. DR GO; GO:0048771; P:tissue remodeling; IEA:Ensembl. DR GO; GO:0031929; P:TOR signaling; IEA:Ensembl. DR GO; GO:0006641; P:triglyceride metabolic process; IEA:Ensembl. DR GO; GO:0071830; P:triglyceride-rich lipoprotein particle clearance; IEA:Ensembl. DR GO; GO:0006776; P:vitamin A metabolic process; IEA:Ensembl. DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1. DR InterPro; IPR029058; AB_hydrolase. DR InterPro; IPR000073; AB_hydrolase_1. DR InterPro; IPR025483; Lipase_euk. DR PANTHER; PTHR11005; LYSOSOMAL ACID LIPASE-RELATED; 1. DR PANTHER; PTHR11005:SF26; LYSOSOMAL ACID LIPASE_CHOLESTERYL ESTER HYDROLASE; 1. DR Pfam; PF00561; Abhydrolase_1; 1. DR PIRSF; PIRSF000862; Steryl_ester_lip; 1. DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1. DR PROSITE; PS00120; LIPASE_SER; 1. DR Genevisible; P38571; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Direct protein sequencing; KW Disease variant; Glycoprotein; Hydrolase; Lipid degradation; KW Lipid metabolism; Lysosome; Reference proteome; Signal. FT SIGNAL 1..27 FT /evidence="ECO:0000269|PubMed:8112342" FT PROPEP 28..76 FT /note="Removed in mature form" FT /evidence="ECO:0000269|PubMed:15269241, FT ECO:0000269|PubMed:8112342" FT /id="PRO_0000450225" FT CHAIN 77..399 FT /note="Lysosomal acid lipase/cholesteryl ester hydrolase" FT /id="PRO_0000017799" FT DOMAIN 80..380 FT /note="AB hydrolase-1" FT /evidence="ECO:0000255" FT ACT_SITE 174 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037" FT ACT_SITE 374 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037" FT CARBOHYD 36 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 72 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 101 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 161 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 273 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 321 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT VAR_SEQ 1..56 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_018596" FT VAR_SEQ 57..76 FT /note="DGYILCLNRIPHGRKNHSDK -> MACLEFVPFDVQMCLEFLPS (in FT isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_018597" FT VARIANT 16 FT /note="T -> P (in dbSNP:rs1051338)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:1718995" FT /id="VAR_004247" FT VARIANT 23 FT /note="G -> R (in dbSNP:rs1051339)" FT /evidence="ECO:0000269|PubMed:8725147" FT /id="VAR_026523" FT VARIANT 29 FT /note="V -> L (in dbSNP:rs17850891)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_026524" FT VARIANT 43..399 FT /note="Missing (in WOLD; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:8956047" FT /id="VAR_088546" FT VARIANT 129 FT /note="H -> P (in CESD; significant loss of enzyme FT activity; dbSNP:rs1423914418)" FT /evidence="ECO:0000269|PubMed:9633819" FT /id="VAR_004248" FT VARIANT 129 FT /note="H -> R (in CESD; significant loss of enzyme FT activity; dbSNP:rs1423914418)" FT /evidence="ECO:0000269|PubMed:9633819" FT /id="VAR_004249" FT VARIANT 200 FT /note="L -> P (in WOLD and CESD; likely pathogenic; FT dbSNP:rs121965086)" FT /evidence="ECO:0000269|PubMed:8146180, FT ECO:0000269|PubMed:8598644" FT /id="VAR_004250" FT VARIANT 228 FT /note="F -> S (in dbSNP:rs2228159)" FT /id="VAR_049821" FT MUTAGEN 76 FT /note="K->R: No effect on enzyme activity." FT /evidence="ECO:0000269|PubMed:15269241" FT MUTAGEN 77 FT /note="G->A: Significant loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:15269241" FT CONFLICT 397 FT /note="K -> R (in Ref. 5; BAD96480)" FT /evidence="ECO:0000305" FT TURN 31..34 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 37..43 FT /evidence="ECO:0007829|PDB:6V7N" FT STRAND 49..54 FT /evidence="ECO:0007829|PDB:6V7N" FT STRAND 58..66 FT /evidence="ECO:0007829|PDB:6V7N" FT STRAND 81..85 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 92..95 FT /evidence="ECO:0007829|PDB:6V7N" FT TURN 100..102 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 104..110 FT /evidence="ECO:0007829|PDB:6V7N" FT STRAND 114..118 FT /evidence="ECO:0007829|PDB:6V7N" FT STRAND 123..126 FT /evidence="ECO:0007829|PDB:6V7N" FT STRAND 128..131 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 137..140 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 144..149 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 151..163 FT /evidence="ECO:0007829|PDB:6V7N" FT STRAND 168..173 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 175..186 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 188..191 FT /evidence="ECO:0007829|PDB:6V7N" FT STRAND 194..201 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 212..217 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 221..228 FT /evidence="ECO:0007829|PDB:6V7N" FT STRAND 230..232 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 237..244 FT /evidence="ECO:0007829|PDB:6V7N" FT TURN 245..247 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 255..258 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 260..265 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 269..271 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 277..283 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 290..302 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 313..320 FT /evidence="ECO:0007829|PDB:6V7N" FT STRAND 321..324 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 330..332 FT /evidence="ECO:0007829|PDB:6V7N" FT STRAND 337..342 FT /evidence="ECO:0007829|PDB:6V7N" FT STRAND 346..348 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 350..357 FT /evidence="ECO:0007829|PDB:6V7N" FT STRAND 363..369 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 376..379 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 383..386 FT /evidence="ECO:0007829|PDB:6V7N" FT HELIX 388..399 FT /evidence="ECO:0007829|PDB:6V7N" SQ SEQUENCE 399 AA; 45419 MW; AC75A7909DA9195A CRC64; MKMRFLGLVV CLVLWTLHSE GSGGKLTAVD PETNMNVSEI ISYWGFPSEE YLVETEDGYI LCLNRIPHGR KNHSDKGPKP VVFLQHGLLA DSSNWVTNLA NSSLGFILAD AGFDVWMGNS RGNTWSRKHK TLSVSQDEFW AFSYDEMAKY DLPASINFIL NKTGQEQVYY VGHSQGTTIG FIAFSQIPEL AKRIKMFFAL GPVASVAFCT SPMAKLGRLP DHLIKDLFGD KEFLPQSAFL KWLGTHVCTH VILKELCGNL CFLLCGFNER NLNMSRVDVY TTHSPAGTSV QNMLHWSQAV KFQKFQAFDW GSSAKNYFHY NQSYPPTYNV KDMLVPTAVW SGGHDWLADV YDVNILLTQI TNLVFHESIP EWEHLDFIWG LDAPWRLYNK IINLMRKYQ //