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P38571 (LICH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length399 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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

Wolman disease (WOD) [MIM:278000]: A severe manifestation of LIPA deficiency, leading to the accumulation of cholesteryl esters and triglycerides in most tissues of the body. WD occurs in infancy and is nearly always fatal before the age of 1 year.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Cholesteryl ester storage disease (CESD) [MIM:278000]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12

Sequence similarities

Belongs to the AB hydrolase superfamily. Lipase family.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 399376Lysosomal acid lipase/cholesteryl ester hydrolase
PRO_0000017799

Sites

Active site1741Charge relay system By similarity
Active site3741Charge relay system By similarity

Amino acid modifications

Glycosylation361N-linked (GlcNAc...) Potential
Glycosylation721N-linked (GlcNAc...) Potential
Glycosylation1011N-linked (GlcNAc...) Potential
Glycosylation1611N-linked (GlcNAc...) Ref.9
Glycosylation2731N-linked (GlcNAc...) Potential
Glycosylation3211N-linked (GlcNAc...) Ref.9

Natural variations

Alternative sequence1 – 5656Missing in isoform 2.
VSP_018596
Alternative sequence57 – 7620DGYIL…NHSDK → MACLEFVPFDVQMCLEFLPS in isoform 2.
VSP_018597
Natural variant161T → P. Ref.1 Ref.4 Ref.8
Corresponds to variant rs1051338 [ dbSNP | Ensembl ].
VAR_004247
Natural variant231G → R. Ref.3
Corresponds to variant rs1051339 [ dbSNP | Ensembl ].
VAR_026523
Natural variant291V → L. Ref.8
Corresponds to variant rs17850891 [ dbSNP | Ensembl ].
VAR_026524
Natural variant1291H → P in CESD. Ref.12
VAR_004248
Natural variant1291H → R in CESD. Ref.12
VAR_004249
Natural variant2001L → P in CESD and WOD. Ref.11
VAR_004250
Natural variant2281F → S.
Corresponds to variant rs2228159 [ dbSNP | Ensembl ].
VAR_049821

Experimental info

Sequence conflict3971K → R in BAD96480. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 21, 2005. Version 2.
Checksum: AC75A7909DA9195A

FASTA39945,419
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 67B2EB1703A732FC
Show »

FASTA34339,112

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-161 AND ASN-321.
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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: VARIANTS CESD ARG-129 AND PRO-129.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M74775 mRNA. Translation: AAA59519.1.
U04285 expand/collapse EMBL AC list , 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.
PIRG01416.
S41408.
RefSeqNP_000226.2. NM_000235.3.
NP_001121077.1. NM_001127605.2.
NP_001275908.1. NM_001288979.1.
UniGeneHs.643030.

3D structure databases

ProteinModelPortalP38571.
SMRP38571. Positions 24-395.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110176. 3 interactions.
STRING9606.ENSP00000337354.

Chemistry

BindingDBP38571.
ChEMBLCHEMBL4184.

Protein family/group databases

MEROPSS33.017.

PTM databases

PhosphoSiteP38571.

Polymorphism databases

DMDM68067636.

Proteomic databases

PaxDbP38571.
PRIDEP38571.

Protocols and materials databases

DNASU3988.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000336233; ENSP00000337354; ENSG00000107798. [P38571-1]
ENST00000371837; ENSP00000360903; ENSG00000107798. [P38571-2]
ENST00000456827; ENSP00000413019; ENSG00000107798. [P38571-1]
GeneID3988.
KEGGhsa:3988.
UCSCuc001kga.4. human. [P38571-1]
uc001kgb.4. human. [P38571-2]

Organism-specific databases

CTD3988.
GeneCardsGC10M090963.
HGNCHGNC:6617. LIPA.
HPACAB034892.
MIM278000. phenotype.
613497. gene.
neXtProtNX_P38571.
Orphanet75234. Cholesteryl ester storage disease.
75233. Wolman disease.
PharmGKBPA30391.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0596.
HOVERGENHBG006265.
KOK01052.
OMASTHVCTH.
OrthoDBEOG71RXJN.
PhylomeDBP38571.
TreeFamTF315485.

Enzyme and pathway databases

SABIO-RKP38571.

Gene expression databases

ArrayExpressP38571.
BgeeP38571.
CleanExHS_LIPA.
GenevestigatorP38571.

Family and domain databases

InterProIPR000073. AB_hydrolase_1.
IPR006693. AB_hydrolase_lipase.
IPR025483. Lipase_euk.
[Graphical view]
PfamPF04083. Abhydro_lipase. 1 hit.
PF00561. Abhydrolase_1. 1 hit.
[Graphical view]
PIRSFPIRSF000862. Steryl_ester_lip. 1 hit.
PROSITEPS00120. LIPASE_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLIPA. human.
GenomeRNAi3988.
NextBio15646.
PROP38571.
SOURCESearch...

Entry information

Entry nameLICH_HUMAN
AccessionPrimary (citable) accession number: P38571
Secondary accession number(s): B2RBH5 expand/collapse secondary AC list , D3DR29, Q16529, Q53H21, Q5T074, Q5T771, Q96EJ0
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: June 21, 2005
Last modified: March 19, 2014
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM