P38571 (LICH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lysosomal acid lipase/cholesteryl ester hydrolase
Short name=Acid cholesteryl ester hydrolase
Short name=LAL
EC=3.1.1.13

Alternative name(s):
Cholesteryl esterase
Lipase A
Sterol esterase

Gene names

Name:

LIPA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	399 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Crucial for the intracellular hydrolysis of cholesteryl esters and triglycerides that have been internalized via receptor-mediated endocytosis of lipoprotein particles. Important in mediating the effect of LDL (low density lipoprotein) uptake on suppression of hydroxymethylglutaryl-CoA reductase and activation of endogenous cellular cholesteryl ester formation.
Catalytic activity	A steryl ester + H2O = a sterol + a fatty acid.
Subcellular location	Lysosome.
Involvement in disease	Defects in LIPA are the cause of Wolman disease (WOD) [MIM:278000]. WOD is a severe manifestation of LIPA deficiency, leading to the accumulation of cholesteryl esters and triglycerides in most tissues of the body. WOD occurs in infancy and is nearly always fatal before the age of 1 year. Defects in LIPA are the cause of cholesteryl ester storage disease (CESD) [MIM:278000]. CESD is a mild manifestation of LIPA deficiency, leading to the accumulation of cholesteryl esters and triglycerides in most tissues of the body. It is characterized by late-onset. Ref.11 Ref.12
Sequence similarities	Belongs to the AB hydrolase superfamily. Lipase family.

Ontologies

Keywords
Biological process	Lipid degradation
Cellular component	Lysosome
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	lysosome Traceable author statement. Source: ProtInc
Molecular function	lipase activity Inferred from direct assay Ref.1. Source: UniProtKB sterol esterase activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P38571-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P38571-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: Missing.
     57-76: DGYILCLNRIPHGRKNHSDK → MACLEFVPFDVQMCLEFLPS

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 399	378	Lysosomal acid lipase/cholesteryl ester hydrolase		PRO_0000017799
Sites
	Active site	174	1	Charge relay system By similarity
	Active site	374	1	Charge relay system By similarity
Amino acid modifications
	Glycosylation	36	1	N-linked (GlcNAc...) Potential
	Glycosylation	72	1	N-linked (GlcNAc...) Potential
	Glycosylation	101	1	N-linked (GlcNAc...) Potential
	Glycosylation	161	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	273	1	N-linked (GlcNAc...) Potential
	Glycosylation	321	1	N-linked (GlcNAc...) Ref.9
Natural variations
	Alternative sequence	1 – 56	56	Missing in isoform 2.		VSP_018596
	Alternative sequence	57 – 76	20	DGYIL…NHSDK → MACLEFVPFDVQMCLEFLPS in isoform 2.		VSP_018597
	Natural variant	16	1	T → P. Ref.1 Ref.4 Ref.8 Corresponds to variant rs1051338 [ dbSNP | Ensembl ].		VAR_004247
	Natural variant	23	1	G → R. Ref.3 Corresponds to variant rs1051339 [ dbSNP | Ensembl ].		VAR_026523
	Natural variant	29	1	V → L. Ref.8 Corresponds to variant rs17850891 [ dbSNP | Ensembl ].		VAR_026524
	Natural variant	129	1	H → P in CESD. Ref.12		VAR_004248
	Natural variant	129	1	H → R in CESD. Ref.12		VAR_004249
	Natural variant	200	1	L → P in CESD and WOD. Ref.11		VAR_004250
	Natural variant	228	1	F → S. Corresponds to variant rs2228159 [ dbSNP | Ensembl ].		VAR_049821
Experimental info
	Sequence conflict	397	1	K → R in BAD96480. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 21, 2005. Version 2. Checksum: AC75A7909DA9195A	FASTA	399	45,419
	10 20 30 40 50 60 MKMRFLGLVV CLVLWTLHSE GSGGKLTAVD PETNMNVSEI ISYWGFPSEE YLVETEDGYI 70 80 90 100 110 120 LCLNRIPHGR KNHSDKGPKP VVFLQHGLLA DSSNWVTNLA NSSLGFILAD AGFDVWMGNS 130 140 150 160 170 180 RGNTWSRKHK TLSVSQDEFW AFSYDEMAKY DLPASINFIL NKTGQEQVYY VGHSQGTTIG 190 200 210 220 230 240 FIAFSQIPEL AKRIKMFFAL GPVASVAFCT SPMAKLGRLP DHLIKDLFGD KEFLPQSAFL 250 260 270 280 290 300 KWLGTHVCTH VILKELCGNL CFLLCGFNER NLNMSRVDVY TTHSPAGTSV QNMLHWSQAV 310 320 330 340 350 360 KFQKFQAFDW GSSAKNYFHY NQSYPPTYNV KDMLVPTAVW SGGHDWLADV YDVNILLTQI 370 380 390 TNLVFHESIP EWEHLDFIWG LDAPWRLYNK IINLMRKYQ
	Isoform 2 [UniParc]. Checksum: 67B2EB1703A732FC	FASTA	343	39,112
	10 20 30 40 50 60 MACLEFVPFD VQMCLEFLPS GPKPVVFLQH GLLADSSNWV TNLANSSLGF ILADAGFDVW 70 80 90 100 110 120 MGNSRGNTWS RKHKTLSVSQ DEFWAFSYDE MAKYDLPASI NFILNKTGQE QVYYVGHSQG 130 140 150 160 170 180 TTIGFIAFSQ IPELAKRIKM FFALGPVASV AFCTSPMAKL GRLPDHLIKD LFGDKEFLPQ 190 200 210 220 230 240 SAFLKWLGTH VCTHVILKEL CGNLCFLLCG FNERNLNMSR VDVYTTHSPA GTSVQNMLHW 250 260 270 280 290 300 SQAVKFQKFQ AFDWGSSAKN YFHYNQSYPP TYNVKDMLVP TAVWSGGHDW LADVYDVNIL 310 320 330 340 LTQITNLVFH ESIPEWEHLD FIWGLDAPWR LYNKIINLMR KYQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of cDNA encoding human lysosomal acid lipase/cholesteryl ester hydrolase. Similarities to gastric and lingual lipases." Anderson R.A., Sando G.N. J. Biol. Chem. 266:22479-22484(1991) [PubMed: 1718995] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 196-212; 277-297 AND 305-315, VARIANT PRO-16.
[2]	"Purification, characterization and molecular cloning of human hepatic lysosomal acid lipase." Ameis D., Merkel M., Eckerskorn C., Greten H. Eur. J. Biochem. 219:905-914(1994) [PubMed: 8112342] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[3]	"Tissue and cellular specific expression of murine lysosomal acid lipase mRNA and protein." Du H., Witte D.P., Grabowski G.A. J. Lipid Res. 37:937-949(1996) [PubMed: 8725147] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-23. Tissue: Liver.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT PRO-16. Tissue: Umbilical cord blood.
[5]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Liver.
[6]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS PRO-16 AND LEU-29. Tissue: Placenta.
[9]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-161 AND ASN-321, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman disease." Anderson R.A., Byrum R.S., Coates P.M., Sando G.N. Proc. Natl. Acad. Sci. U.S.A. 91:2718-2722(1994) [PubMed: 8146180] [Abstract] Cited for: VARIANT CESD/WOD PRO-200.
[12]	"Different missense mutations in histidine-108 of lysosomal acid lipase cause cholesteryl ester storage disease in unrelated compound heterozygous and hemizygous individuals." Ries S., Buechler C., Schindler G., Aslanidis C., Ameis D., Gasche C., Jung N., Schambach A., Fehringer P., Vanier M.T., Belli D.C., Greten H., Schmitz G. Hum. Mutat. 12:44-51(1998) [PubMed: 9633819] [Abstract] Cited for: VARIANTS CESD ARG-129 AND PRO-129.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	M74775 mRNA. Translation: AAA59519.1. U04285 , U04286, U04287, U04288, U04290, U04291, U04292, U04293 Genomic DNA. Translation: AAB60327.1. X76488 mRNA. Translation: CAA54026.1. Z31690 mRNA. Translation: CAA83495.1. U08464 mRNA. Translation: AAB60328.1. AK314665 mRNA. Translation: BAG37222.1. AK222760 mRNA. Translation: BAD96480.1. AL353751, AL353146, AL513533 Genomic DNA. Translation: CAI12234.1. AL353751, AL513533 Genomic DNA. Translation: CAI12236.1. AL353146, AL353751, AL513533 Genomic DNA. Translation: CAI12380.1. AL513533, AL353146, AL353751 Genomic DNA. Translation: CAI13515.1. AL513533, AL353751 Genomic DNA. Translation: CAI13516.1. CH471066 Genomic DNA. Translation: EAW50140.1. CH471066 Genomic DNA. Translation: EAW50141.1. CH471066 Genomic DNA. Translation: EAW50142.1. BC012287 mRNA. Translation: AAH12287.1.
IPI	IPI00007207. IPI00446007.
PIR	G01416. S41408.
RefSeq	NP_000226.2. NM_000235.2. NP_001121077.1. NM_001127605.1.
UniGene	Hs.643030.
3D structure databases
ProteinModelPortal	P38571.
SMR	P38571. Positions 24-395.
ModBase	Search...
Protein-protein interaction databases
STRING	P38571.
Protein family/group databases
MEROPS	S33.017.
Polymorphism databases
DMDM	68067636.
Proteomic databases
PRIDE	P38571.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000336233; ENSP00000337354; ENSG00000107798. ENST00000371829; ENSP00000360894; ENSG00000107798. ENST00000456827; ENSP00000413019; ENSG00000107798.
GeneID	3988.
KEGG	hsa:3988.
UCSC	uc001kga.2. human. uc001kgb.2. human.
Organism-specific databases
CTD	3988.
GeneCards	GC10M090963.
H-InvDB	HIX0009020.
HGNC	HGNC:6617. LIPA.
HPA	CAB034892.
MIM	278000. phenotype. 613497. gene.
neXtProt	NX_P38571.
Orphanet	75233. Wolman disease.
PharmGKB	PA30391.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG14778.
HOVERGEN	HBG006265.
OMA	WLSTHVC.
OrthoDB	EOG4K6G45.
PhylomeDB	P38571.
Gene expression databases
ArrayExpress	P38571.
Bgee	P38571.
CleanEx	HS_LIPA.
Genevestigator	P38571.
GermOnline	ENSG00000107798. Homo sapiens.
Family and domain databases
InterPro	IPR000073. AB_hydrolase_1. IPR006693. AB_hydrolase_lipase. [Graphical view]
KO	K01052.
Pfam	PF04083. Abhydro_lipase. 1 hit. PF00561. Abhydrolase_1. 1 hit. [Graphical view]
PROSITE	PS00120. LIPASE_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	15646.
SOURCE	Search...

Entry information

Entry name

LICH_HUMAN

Accession

Primary (citable) accession number: P38571
Secondary accession number(s): B2RBH5 , D3DR29, Q16529, Q53H21, Q5T074, Q5T771, Q96EJ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	June 21, 2005
Last modified:	January 25, 2012
This is version 119 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.