UniProtKB - P38571 (LICH_HUMAN)
Lysosomal acid lipase/cholesteryl ester hydrolase
LIPA
Functioni
Catalyzes the deacylation of triacylglyceryl and cholesteryl ester core lipids of endocytosed low density lipoproteins to generate free fatty acids and cholesterol.
5 PublicationsCatalytic activityi
Kineticsi
- KM=0.142 mM for cholesteryl oleate1 Publication
- KM=0.8 mM for cholesteryl oleate1 Publication
- KM=0.138 mM for trioleoylglycerol1 Publication
- KM=0.8 mM for trioleoylglycerol1 Publication
- KM=899 µM for trioleoylglycerol1 Publication
- KM=0.9 mM for 1,2-dioleoylglycerol1 Publication
- KM=1.2 mM for 1,3-dioleoylglycerol1 Publication
- Vmax=4390 nmol/min/mg enzyme with cholesteryl oleate as substrate1 Publication
- Vmax=1400 nmol/min/mg enzyme with cholesteryl oleate as substrate1 Publication
- Vmax=4756 mmol/min/mg enzyme with trioleoylglycerol as substrate1 Publication
- Vmax=5400 nmol/min/mg enzyme with trioleoylglycerol as substrate1 Publication
- Vmax=19400 nmol/min/mg enzyme with 1,2-dioleoylglycerol as substrate1 Publication
- Vmax=22100 nmol/min/mg enzyme with 1,3-dioleoylglycerol as substrate1 Publication
pH dependencei
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 174 | Charge relay systemPROSITE-ProRule annotation | 1 | |
Active sitei | 374 | Charge relay systemPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- lipase activity Source: UniProtKB
- sterol esterase activity Source: UniProtKB
GO - Biological processi
- cell morphogenesis Source: Ensembl
- cell population proliferation Source: Ensembl
- homeostasis of number of cells within a tissue Source: Ensembl
- inflammatory response Source: Ensembl
- lipid catabolic process Source: UniProtKB-KW
- low-density lipoprotein particle clearance Source: Reactome
- lung development Source: Ensembl
- sterol metabolic process Source: GO_Central
- tissue remodeling Source: Ensembl
Keywordsi
Molecular function | Hydrolase |
Biological process | Lipid degradation, Lipid metabolism |
Enzyme and pathway databases
PathwayCommonsi | P38571 |
Reactomei | R-HSA-8964038, LDL clearance |
SABIO-RKi | P38571 |
Protein family/group databases
ESTHERi | human-LIPA, Acidic_Lipase |
MEROPSi | S33.017 |
Chemistry databases
SwissLipidsi | SLP:000001261 |
Names & Taxonomyi
Protein namesi | Recommended name: Lysosomal acid lipase/cholesteryl ester hydrolase (EC:3.1.1.133 Publications)Short name: Acid cholesteryl ester hydrolase Short name: LAL Alternative name(s): Cholesteryl esterase Lipase A Sterol esterase |
Gene namesi | Name:LIPA |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6617, LIPA |
MIMi | 613497, gene |
neXtProti | NX_P38571 |
VEuPathDBi | HostDB:ENSG00000107798 |
Subcellular locationi
Lysosome
- Lysosome By similarity
Cytosol
- cytosol Source: HPA
Lysosome
- lysosomal lumen Source: Reactome
- lysosome Source: UniProtKB
Nucleus
- fibrillar center Source: HPA
- nucleoplasm Source: HPA
Other locations
- intracellular membrane-bounded organelle Source: HPA
Keywords - Cellular componenti
LysosomePathology & Biotechi
Involvement in diseasei
Wolman disease (WOD)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_004250 | 200 | L → P in CESD and WOD. 1 PublicationCorresponds to variant dbSNP:rs121965086EnsemblClinVar. | 1 |
Cholesteryl ester storage disease (CESD)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_004248 | 129 | H → P in CESD; significant loss of enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs1423914418EnsemblClinVar. | 1 | |
Natural variantiVAR_004249 | 129 | H → R in CESD; significant loss of enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs1423914418EnsemblClinVar. | 1 | |
Natural variantiVAR_004250 | 200 | L → P in CESD and WOD. 1 PublicationCorresponds to variant dbSNP:rs121965086EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 76 | K → R: No effect on enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 77 | G → A: Significant loss of enzyme activity. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 3988 |
GeneReviewsi | LIPA |
MalaCardsi | LIPA |
MIMi | 278000, phenotype |
OpenTargetsi | ENSG00000107798 |
Orphaneti | 75234, Cholesteryl ester storage disease 406, NON RARE IN EUROPE: Heterozygous familial hypercholesterolemia 75233, Wolman disease |
PharmGKBi | PA30391 |
Miscellaneous databases
Pharosi | P38571, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4184 |
Genetic variation databases
BioMutai | LIPA |
DMDMi | 68067636 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 27 | 1 PublicationAdd BLAST | 27 | |
PropeptideiPRO_0000450225 | 28 – 76 | Removed in mature form2 PublicationsAdd BLAST | 49 | |
ChainiPRO_0000017799 | 77 – 399 | Lysosomal acid lipase/cholesteryl ester hydrolaseAdd BLAST | 323 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 36 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 72 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 101 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 161 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 273 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 321 | N-linked (GlcNAc...) asparagine1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
GlycoproteinProteomic databases
EPDi | P38571 |
jPOSTi | P38571 |
MassIVEi | P38571 |
MaxQBi | P38571 |
PaxDbi | P38571 |
PeptideAtlasi | P38571 |
PRIDEi | P38571 |
ProteomicsDBi | 55301 [P38571-1] 55302 [P38571-2] |
PTM databases
GlyConnecti | 1475, 12 N-Linked glycans (3 sites) |
GlyGeni | P38571, 7 sites, 11 N-linked glycans (3 sites) |
iPTMneti | P38571 |
PhosphoSitePlusi | P38571 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000107798, Expressed in visceral pleura and 243 other tissues |
ExpressionAtlasi | P38571, baseline and differential |
Genevisiblei | P38571, HS |
Organism-specific databases
HPAi | ENSG00000107798, Tissue enhanced (lymphoid) |
Interactioni
Subunit structurei
Monomer.
1 PublicationProtein-protein interaction databases
BioGRIDi | 110176, 29 interactors |
STRINGi | 9606.ENSP00000337354 |
Chemistry databases
BindingDBi | P38571 |
Miscellaneous databases
RNActi | P38571, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P38571 |
SMRi | P38571 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 80 – 380 | AB hydrolase-1Sequence analysisAdd BLAST | 301 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG2624, Eukaryota |
GeneTreei | ENSGT00940000154696 |
HOGENOMi | CLU_010974_0_0_1 |
InParanoidi | P38571 |
OMAi | DGEHVDC |
OrthoDBi | 651396at2759 |
PhylomeDBi | P38571 |
TreeFami | TF315485 |
Family and domain databases
Gene3Di | 3.40.50.1820, 1 hit |
InterProi | View protein in InterPro IPR029058, AB_hydrolase IPR000073, AB_hydrolase_1 IPR025483, Lipase_euk |
Pfami | View protein in Pfam PF00561, Abhydrolase_1, 1 hit |
PIRSFi | PIRSF000862, Steryl_ester_lip, 1 hit |
SUPFAMi | SSF53474, SSF53474, 1 hit |
PROSITEi | View protein in PROSITE PS00120, LIPASE_SER, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MKMRFLGLVV CLVLWTLHSE GSGGKLTAVD PETNMNVSEI ISYWGFPSEE
60 70 80 90 100
YLVETEDGYI LCLNRIPHGR KNHSDKGPKP VVFLQHGLLA DSSNWVTNLA
110 120 130 140 150
NSSLGFILAD AGFDVWMGNS RGNTWSRKHK TLSVSQDEFW AFSYDEMAKY
160 170 180 190 200
DLPASINFIL NKTGQEQVYY VGHSQGTTIG FIAFSQIPEL AKRIKMFFAL
210 220 230 240 250
GPVASVAFCT SPMAKLGRLP DHLIKDLFGD KEFLPQSAFL KWLGTHVCTH
260 270 280 290 300
VILKELCGNL CFLLCGFNER NLNMSRVDVY TTHSPAGTSV QNMLHWSQAV
310 320 330 340 350
KFQKFQAFDW GSSAKNYFHY NQSYPPTYNV KDMLVPTAVW SGGHDWLADV
360 370 380 390
YDVNILLTQI TNLVFHESIP EWEHLDFIWG LDAPWRLYNK IINLMRKYQ
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ5T073 | Q5T073_HUMAN | Lysosomal acid lipase/cholesteryl e... | LIPA | 290 | Annotation score: | ||
A0A0A0MT32 | A0A0A0MT32_HUMAN | Lysosomal acid lipase/cholesteryl e... | LIPA | 283 | Annotation score: | ||
Q5T770 | Q5T770_HUMAN | Lysosomal acid lipase/cholesteryl e... | LIPA | 219 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 397 | K → R in BAD96480 (Ref. 5) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_004247 | 16 | T → P3 PublicationsCorresponds to variant dbSNP:rs1051338EnsemblClinVar. | 1 | |
Natural variantiVAR_026523 | 23 | G → R1 PublicationCorresponds to variant dbSNP:rs1051339EnsemblClinVar. | 1 | |
Natural variantiVAR_026524 | 29 | V → L1 PublicationCorresponds to variant dbSNP:rs17850891Ensembl. | 1 | |
Natural variantiVAR_004248 | 129 | H → P in CESD; significant loss of enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs1423914418EnsemblClinVar. | 1 | |
Natural variantiVAR_004249 | 129 | H → R in CESD; significant loss of enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs1423914418EnsemblClinVar. | 1 | |
Natural variantiVAR_004250 | 200 | L → P in CESD and WOD. 1 PublicationCorresponds to variant dbSNP:rs121965086EnsemblClinVar. | 1 | |
Natural variantiVAR_049821 | 228 | F → S. Corresponds to variant dbSNP:rs2228159EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_018596 | 1 – 56 | Missing in isoform 2. CuratedAdd BLAST | 56 | |
Alternative sequenceiVSP_018597 | 57 – 76 | DGYIL…NHSDK → MACLEFVPFDVQMCLEFLPS in isoform 2. CuratedAdd BLAST | 20 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 Genomic DNA No translation available. AL353146 Genomic DNA No translation available. AL513533 Genomic DNA No translation available. CH471066 Genomic DNA Translation: EAW50140.1 CH471066 Genomic DNA Translation: EAW50141.1 CH471066 Genomic DNA Translation: EAW50142.1 BC012287 mRNA Translation: AAH12287.1 |
CCDSi | CCDS7401.1 [P38571-1] |
PIRi | G01416 S41408 |
RefSeqi | NP_000226.2, NM_000235.3 [P38571-1] NP_001121077.1, NM_001127605.2 [P38571-1] NP_001275908.1, NM_001288979.1 |
Genome annotation databases
Ensembli | ENST00000336233.10; ENSP00000337354.5; ENSG00000107798.18 ENST00000371837.5; ENSP00000360903.1; ENSG00000107798.18 [P38571-2] |
GeneIDi | 3988 |
KEGGi | hsa:3988 |
MANE-Selecti | ENST00000336233.10; ENSP00000337354.5; NM_000235.4; NP_000226.2 |
UCSCi | uc001kga.6, human [P38571-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 Genomic DNA No translation available. AL353146 Genomic DNA No translation available. AL513533 Genomic DNA No translation available. CH471066 Genomic DNA Translation: EAW50140.1 CH471066 Genomic DNA Translation: EAW50141.1 CH471066 Genomic DNA Translation: EAW50142.1 BC012287 mRNA Translation: AAH12287.1 |
CCDSi | CCDS7401.1 [P38571-1] |
PIRi | G01416 S41408 |
RefSeqi | NP_000226.2, NM_000235.3 [P38571-1] NP_001121077.1, NM_001127605.2 [P38571-1] NP_001275908.1, NM_001288979.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6V7N | X-ray | 2.62 | A/B | 22-399 | [»] | |
AlphaFoldDBi | P38571 | |||||
SMRi | P38571 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110176, 29 interactors |
STRINGi | 9606.ENSP00000337354 |
Chemistry databases
BindingDBi | P38571 |
ChEMBLi | CHEMBL4184 |
SwissLipidsi | SLP:000001261 |
Protein family/group databases
ESTHERi | human-LIPA, Acidic_Lipase |
MEROPSi | S33.017 |
PTM databases
GlyConnecti | 1475, 12 N-Linked glycans (3 sites) |
GlyGeni | P38571, 7 sites, 11 N-linked glycans (3 sites) |
iPTMneti | P38571 |
PhosphoSitePlusi | P38571 |
Genetic variation databases
BioMutai | LIPA |
DMDMi | 68067636 |
Proteomic databases
EPDi | P38571 |
jPOSTi | P38571 |
MassIVEi | P38571 |
MaxQBi | P38571 |
PaxDbi | P38571 |
PeptideAtlasi | P38571 |
PRIDEi | P38571 |
ProteomicsDBi | 55301 [P38571-1] 55302 [P38571-2] |
Protocols and materials databases
Antibodypediai | 30242, 272 antibodies from 29 providers |
DNASUi | 3988 |
Genome annotation databases
Ensembli | ENST00000336233.10; ENSP00000337354.5; ENSG00000107798.18 ENST00000371837.5; ENSP00000360903.1; ENSG00000107798.18 [P38571-2] |
GeneIDi | 3988 |
KEGGi | hsa:3988 |
MANE-Selecti | ENST00000336233.10; ENSP00000337354.5; NM_000235.4; NP_000226.2 |
UCSCi | uc001kga.6, human [P38571-1] |
Organism-specific databases
CTDi | 3988 |
DisGeNETi | 3988 |
GeneCardsi | LIPA |
GeneReviewsi | LIPA |
HGNCi | HGNC:6617, LIPA |
HPAi | ENSG00000107798, Tissue enhanced (lymphoid) |
MalaCardsi | LIPA |
MIMi | 278000, phenotype 613497, gene |
neXtProti | NX_P38571 |
OpenTargetsi | ENSG00000107798 |
Orphaneti | 75234, Cholesteryl ester storage disease 406, NON RARE IN EUROPE: Heterozygous familial hypercholesterolemia 75233, Wolman disease |
PharmGKBi | PA30391 |
VEuPathDBi | HostDB:ENSG00000107798 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2624, Eukaryota |
GeneTreei | ENSGT00940000154696 |
HOGENOMi | CLU_010974_0_0_1 |
InParanoidi | P38571 |
OMAi | DGEHVDC |
OrthoDBi | 651396at2759 |
PhylomeDBi | P38571 |
TreeFami | TF315485 |
Enzyme and pathway databases
PathwayCommonsi | P38571 |
Reactomei | R-HSA-8964038, LDL clearance |
SABIO-RKi | P38571 |
Miscellaneous databases
BioGRID-ORCSi | 3988, 12 hits in 1077 CRISPR screens |
ChiTaRSi | LIPA, human |
GenomeRNAii | 3988 |
Pharosi | P38571, Tchem |
PROi | PR:P38571 |
RNActi | P38571, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000107798, Expressed in visceral pleura and 243 other tissues |
ExpressionAtlasi | P38571, baseline and differential |
Genevisiblei | P38571, HS |
Family and domain databases
Gene3Di | 3.40.50.1820, 1 hit |
InterProi | View protein in InterPro IPR029058, AB_hydrolase IPR000073, AB_hydrolase_1 IPR025483, Lipase_euk |
Pfami | View protein in Pfam PF00561, Abhydrolase_1, 1 hit |
PIRSFi | PIRSF000862, Steryl_ester_lip, 1 hit |
SUPFAMi | SSF53474, SSF53474, 1 hit |
PROSITEi | View protein in PROSITE PS00120, LIPASE_SER, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | LICH_HUMAN | |
Accessioni | P38571Primary (citable) accession number: P38571 Secondary accession number(s): B2RBH5 Q96EJ0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1994 |
Last sequence update: | June 21, 2005 | |
Last modified: | May 25, 2022 | |
This is version 197 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 10
Human chromosome 10: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families