LICH_HUMAN
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 03-AUG-2022, entry version 198.
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 CESD/WOD 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 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).
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: Wolman disease (WOD) [MIM:278000]: A severe manifestation of
CC LIPA deficiency, leading to the accumulation of cholesteryl esters and
CC triglycerides in most tissues of the body. WD occurs in infancy and is
CC nearly always fatal before the age of 1 year.
CC {ECO:0000269|PubMed:8146180}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cholesteryl ester storage disease (CESD) [MIM:278000]: A mild
CC manifestation of LIPA deficiency, leading to the accumulation of
CC cholesteryl esters and triglycerides in most tissues of the body. It is
CC characterized by late-onset. {ECO:0000269|PubMed:8146180,
CC ECO:0000269|PubMed:9633819}. 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; 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; 29.
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 GlyGen; P38571; 7 sites, 11 N-linked glycans (3 sites).
DR iPTMnet; P38571; -.
DR PhosphoSitePlus; P38571; -.
DR BioMuta; LIPA; -.
DR DMDM; 68067636; -.
DR EPD; P38571; -.
DR jPOST; P38571; -.
DR MassIVE; P38571; -.
DR MaxQB; P38571; -.
DR PaxDb; P38571; -.
DR PeptideAtlas; P38571; -.
DR PRIDE; P38571; -.
DR ProteomicsDB; 55301; -. [P38571-1]
DR ProteomicsDB; 55302; -. [P38571-2]
DR Antibodypedia; 30242; 273 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 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 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; 651396at2759; -.
DR PhylomeDB; P38571; -.
DR TreeFam; TF315485; -.
DR PathwayCommons; P38571; -.
DR Reactome; R-HSA-8964038; LDL clearance.
DR SABIO-RK; P38571; -.
DR BioGRID-ORCS; 3988; 12 hits in 1077 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 205 other tissues.
DR ExpressionAtlas; P38571; baseline and differential.
DR Genevisible; P38571; HS.
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:0000902; P:cell morphogenesis; IEA:Ensembl.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0034383; P:low-density lipoprotein particle clearance; TAS:Reactome.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0061519; P:macrophage homeostasis; IEA:Ensembl.
DR GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central.
DR GO; GO:0048771; P:tissue remodeling; IEA:Ensembl.
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 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 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 CESD and WOD; dbSNP:rs121965086)"
FT /evidence="ECO:0000269|PubMed:8146180"
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
