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Protein

Hormone-sensitive lipase

Gene

LIPE

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

In adipose tissue and heart, it primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production.

Catalytic activityi

Diacylglycerol + H2O = monoacylglycerol + a carboxylate.
Triacylglycerol + H2O = diacylglycerol + a carboxylate.
Monoacylglycerol + H2O = glycerol + a carboxylate.

Enzyme regulationi

Rapidly activated by cAMP-dependent phosphorylation under the influence of catecholamines. Dephosphorylation and inactivation are controlled by insulin.

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei651 – 6511PROSITE-ProRule annotation
Active sitei725 – 7251PROSITE-ProRule annotation

GO - Molecular functioni

  1. hormone-sensitive lipase activity Source: UniProtKB-EC
  2. triglyceride lipase activity Source: Ensembl

GO - Biological processi

  1. cholesterol metabolic process Source: UniProtKB-KW
  2. diacylglycerol catabolic process Source: Ensembl
  3. lipid catabolic process Source: UniProtKB
  4. long-chain fatty acid catabolic process Source: Ensembl
  5. protein phosphorylation Source: ProtInc
  6. small molecule metabolic process Source: Reactome
  7. triglyceride catabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Cholesterol metabolism, Lipid degradation, Lipid metabolism, Steroid metabolism, Sterol metabolism

Enzyme and pathway databases

BioCyciMetaCyc:HS01328-MONOMER.
BRENDAi3.1.1.79. 2681.
ReactomeiREACT_494. Hormone-sensitive lipase (HSL)-mediated triacylglycerol hydrolysis.
SABIO-RKQ05469.
UniPathwayiUPA00256.

Protein family/group databases

MEROPSiS09.993.

Names & Taxonomyi

Protein namesi
Recommended name:
Hormone-sensitive lipase (EC:3.1.1.79)
Short name:
HSL
Gene namesi
Name:LIPE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:6621. LIPE.

Subcellular locationi

Cell membrane. Membranecaveola. Cytoplasmcytosol
Note: Found in the high-density caveolae. Translocates to the cytoplasm from the caveolae upon insulin stimulation.

GO - Cellular componenti

  1. caveola Source: UniProtKB-SubCell
  2. cytosol Source: UniProtKB-SubCell
  3. lipid particle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Abdominal obesity-metabolic syndrome 4 (AOMS4)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA form of abdominal obesity-metabolic syndrome, a disorder characterized by abdominal obesity, high triglycerides, low levels of high density lipoprotein cholesterol, high blood pressure, insulin resistance, and elevated fasting glucose levels. AOMS4 patients have dyslipidemia, hepatic steatosis, systemic insulin resistance, and diabetes.

See also OMIM:615980

Keywords - Diseasei

Diabetes mellitus, Obesity

Organism-specific databases

MIMi615980. phenotype.
PharmGKBiPA30393.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10761076Hormone-sensitive lipasePRO_0000071547Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei853 – 8531PhosphoserineBy similarity
Modified residuei855 – 8551Phosphoserine; by AMPKBy similarity
Modified residuei950 – 9501PhosphoserineBy similarity
Modified residuei951 – 9511PhosphoserineBy similarity

Post-translational modificationi

Phosphorylation by AMPK may block translocation to lipid droplets.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ05469.
PaxDbiQ05469.
PRIDEiQ05469.

PTM databases

PhosphoSiteiQ05469.

Expressioni

Gene expression databases

BgeeiQ05469.
CleanExiHS_LIPE.
ExpressionAtlasiQ05469. baseline and differential.
GenevestigatoriQ05469.

Organism-specific databases

HPAiCAB017700.

Interactioni

Subunit structurei

Interacts with PTRF in the adipocyte cytoplasm. Interacts with PLIN5 (By similarity).By similarity

Protein-protein interaction databases

BioGridi110179. 4 interactions.
IntActiQ05469. 1 interaction.
MINTiMINT-1370154.
STRINGi9606.ENSP00000244289.

Structurei

3D structure databases

ProteinModelPortaliQ05469.
SMRiQ05469. Positions 636-826, 970-1059.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi651 – 6533Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion holeBy similarity

Sequence similaritiesi

Belongs to the 'GDXG' lipolytic enzyme family.Curated

Phylogenomic databases

eggNOGiCOG0657.
GeneTreeiENSGT00730000111056.
HOGENOMiHOG000047722.
HOVERGENiHBG000187.
InParanoidiQ05469.
KOiK07188.
OMAiMHKGCFY.
OrthoDBiEOG7KSX7S.
PhylomeDBiQ05469.
TreeFamiTF314423.

Family and domain databases

Gene3Di3.40.50.1820. 2 hits.
InterProiIPR029058. AB_hydrolase.
IPR013094. AB_hydrolase_3.
IPR010468. HSL_N.
IPR002168. Lipase_GDXG_AS.
[Graphical view]
PfamiPF07859. Abhydrolase_3. 2 hits.
PF06350. HSL_N. 1 hit.
[Graphical view]
SUPFAMiSSF53474. SSF53474. 2 hits.
PROSITEiPS01173. LIPASE_GDXG_HIS. 1 hit.
PS01174. LIPASE_GDXG_SER. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q05469-1) [UniParc]FASTAAdd to basket

Also known as: Testicular

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.

« Hide

        10         20         30         40         50
MEPGSKSVSR SDWQPEPHQR PITPLEPGPE KTPIAQPESK TLQGSNTQQK
60 70 80 90 100
PASNQRPLTQ QETPAQHDAE SQKEPRAQQK SASQEEFLAP QKPAPQQSPY
110 120 130 140 150
IQRVLLTQQE AASQQGPGLG KESITQQEPA LRQRHVAQPG PGPGEPPPAQ
160 170 180 190 200
QEAESTPAAQ AKPGAKREPS APTESTSQET PEQSDKQTTP VQGAKSKQGS
210 220 230 240 250
LTELGFLTKL QELSIQRSAL EWKALSEWVT DSESESDVGS SSDTDSPATM
260 270 280 290 300
GGMVAQGVKL GFKGKSGYKV MSGYSGTSPH EKTSARNHRH YQDTASRLIH
310 320 330 340 350
NMDLRTMTQS LVTLAEDNIA FFSSQGPGET AQRLSGVFAG VREQALGLEP
360 370 380 390 400
ALGRLLGVAH LFDLDPETPA NGYRSLVHTA RCCLAHLLHK SRYVASNRRS
410 420 430 440 450
IFFRTSHNLA ELEAYLAALT QLRALVYYAQ RLLVTNRPGV LFFEGDEGLT
460 470 480 490 500
ADFLREYVTL HKGCFYGRCL GFQFTPAIRP FLQTISIGLV SFGEHYKRNE
510 520 530 540 550
TGLSVAASSL FTSGRFAIDP ELRGAEFERI TQNLDVHFWK AFWNITEMEV
560 570 580 590 600
LSSLANMASA TVRVSRLLSL PPEAFEMPLT ADPTLTVTIS PPLAHTGPGP
610 620 630 640 650
VLVRLISYDL REGQDSEELS SLIKSNGQRS LELWPRPQQA PRSRSLIVHF
660 670 680 690 700
HGGGFVAQTS RSHEPYLKSW AQELGAPIIS IDYSLAPEAP FPRALEECFF
710 720 730 740 750
AYCWAIKHCA LLGSTGERIC LAGDSAGGNL CFTVALRAAA YGVRVPDGIM
760 770 780 790 800
AAYPATMLQP AASPSRLLSL MDPLLPLSVL SKCVSAYAGA KTEDHSNSDQ
810 820 830 840 850
KALGMMGLVR RDTALLLRDF RLGASSWLNS FLELSGRKSQ KMSEPIAEPM
860 870 880 890 900
RRSVSEAALA QPQGPLGTDS LKNLTLRDLS LRGNSETSSD TPEMSLSAET
910 920 930 940 950
LSPSTPSDVN FLLPPEDAGE EAEAKNELSP MDRGLGVRAA FPEGFHPRRS
960 970 980 990 1000
SQGATQMPLY SSPIVKNPFM SPLLAPDSML KSLPPVHIVA CALDPMLDDS
1010 1020 1030 1040 1050
VMLARRLRNL GQPVTLRVVE DLPHGFLTLA ALCRETRQAA ELCVERIRLV
1060 1070
LTPPAGAGPS GETGAAGVDG GCGGRH
Length:1,076
Mass (Da):116,598
Last modified:April 16, 2007 - v4
Checksum:i1CC0E3880FF64D74
GO
Isoform 2 (identifier: Q05469-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-301: Missing.

Show »
Length:775
Mass (Da):84,128
Checksum:i3462D4A99945661B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti230 – 2301T → A in AAA69810 (PubMed:8506334).Curated
Sequence conflicti230 – 2301T → A in AAC50666 (PubMed:8812477).Curated
Sequence conflicti230 – 2301T → A in ABA03168 (Ref. 3) Curated
Sequence conflicti486 – 4861S → Y in AAH70041 (PubMed:15489334).Curated
Sequence conflicti608 – 6081Y → C in AAH70041 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti100 – 1001Y → H.1 Publication
Corresponds to variant rs16975750 [ dbSNP | Ensembl ].
VAR_025108
Natural varianti127 – 1271Q → H.1 Publication
Corresponds to variant rs34080774 [ dbSNP | Ensembl ].
VAR_025109
Natural varianti146 – 1461P → Q in a breast cancer sample; somatic mutation. 1 Publication
VAR_036539
Natural varianti146 – 1461P → S.1 Publication
Corresponds to variant rs34348028 [ dbSNP | Ensembl ].
VAR_025110
Natural varianti177 – 1771S → T.1 Publication
Corresponds to variant rs16975748 [ dbSNP | Ensembl ].
VAR_025111
Natural varianti194 – 1941A → V.1 Publication
Corresponds to variant rs34996020 [ dbSNP | Ensembl ].
VAR_025112
Natural varianti217 – 2171R → Q.1 Publication
Corresponds to variant rs3745238 [ dbSNP | Ensembl ].
VAR_025113
Natural varianti497 – 4971K → N.1 Publication
Corresponds to variant rs35938529 [ dbSNP | Ensembl ].
VAR_025114
Natural varianti499 – 4991N → H.1 Publication
Corresponds to variant rs33921216 [ dbSNP | Ensembl ].
VAR_025115
Natural varianti938 – 9381R → S.1 Publication
Corresponds to variant rs7246232 [ dbSNP | Ensembl ].
VAR_025116

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 301301Missing in isoform 2. CuratedVSP_017116Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11706 Genomic DNA. Translation: AAA69810.1.
U40001 mRNA. Translation: AAC50666.1.
DQ188033 Genomic DNA. Translation: ABA03168.1.
BC070041 mRNA. Translation: AAH70041.1.
CCDSiCCDS12607.1. [Q05469-1]
RefSeqiNP_005348.2. NM_005357.3. [Q05469-1]
XP_005258997.1. XM_005258940.2. [Q05469-2]
XP_005258998.1. XM_005258941.2. [Q05469-2]
XP_006723281.1. XM_006723218.1. [Q05469-2]
UniGeneiHs.656980.

Genome annotation databases

EnsembliENST00000244289; ENSP00000244289; ENSG00000079435. [Q05469-1]
GeneIDi3991.
KEGGihsa:3991.
UCSCiuc002otr.3. human. [Q05469-1]

Polymorphism databases

DMDMi145559491.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11706 Genomic DNA. Translation: AAA69810.1.
U40001 mRNA. Translation: AAC50666.1.
DQ188033 Genomic DNA. Translation: ABA03168.1.
BC070041 mRNA. Translation: AAH70041.1.
CCDSiCCDS12607.1. [Q05469-1]
RefSeqiNP_005348.2. NM_005357.3. [Q05469-1]
XP_005258997.1. XM_005258940.2. [Q05469-2]
XP_005258998.1. XM_005258941.2. [Q05469-2]
XP_006723281.1. XM_006723218.1. [Q05469-2]
UniGeneiHs.656980.

3D structure databases

ProteinModelPortaliQ05469.
SMRiQ05469. Positions 636-826, 970-1059.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110179. 4 interactions.
IntActiQ05469. 1 interaction.
MINTiMINT-1370154.
STRINGi9606.ENSP00000244289.

Chemistry

BindingDBiQ05469.
ChEMBLiCHEMBL3590.
GuidetoPHARMACOLOGYi2593.

Protein family/group databases

MEROPSiS09.993.

PTM databases

PhosphoSiteiQ05469.

Polymorphism databases

DMDMi145559491.

Proteomic databases

MaxQBiQ05469.
PaxDbiQ05469.
PRIDEiQ05469.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000244289; ENSP00000244289; ENSG00000079435. [Q05469-1]
GeneIDi3991.
KEGGihsa:3991.
UCSCiuc002otr.3. human. [Q05469-1]

Organism-specific databases

CTDi3991.
GeneCardsiGC19M042906.
H-InvDBHIX0040096.
HGNCiHGNC:6621. LIPE.
HPAiCAB017700.
MIMi151750. gene.
615980. phenotype.
neXtProtiNX_Q05469.
PharmGKBiPA30393.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0657.
GeneTreeiENSGT00730000111056.
HOGENOMiHOG000047722.
HOVERGENiHBG000187.
InParanoidiQ05469.
KOiK07188.
OMAiMHKGCFY.
OrthoDBiEOG7KSX7S.
PhylomeDBiQ05469.
TreeFamiTF314423.

Enzyme and pathway databases

UniPathwayiUPA00256.
BioCyciMetaCyc:HS01328-MONOMER.
BRENDAi3.1.1.79. 2681.
ReactomeiREACT_494. Hormone-sensitive lipase (HSL)-mediated triacylglycerol hydrolysis.
SABIO-RKQ05469.

Miscellaneous databases

GeneWikiiHormone-sensitive_lipase.
GenomeRNAii3991.
NextBioi15656.
PROiQ05469.
SOURCEiSearch...

Gene expression databases

BgeeiQ05469.
CleanExiHS_LIPE.
ExpressionAtlasiQ05469. baseline and differential.
GenevestigatoriQ05469.

Family and domain databases

Gene3Di3.40.50.1820. 2 hits.
InterProiIPR029058. AB_hydrolase.
IPR013094. AB_hydrolase_3.
IPR010468. HSL_N.
IPR002168. Lipase_GDXG_AS.
[Graphical view]
PfamiPF07859. Abhydrolase_3. 2 hits.
PF06350. HSL_N. 1 hit.
[Graphical view]
SUPFAMiSSF53474. SSF53474. 2 hits.
PROSITEiPS01173. LIPASE_GDXG_HIS. 1 hit.
PS01174. LIPASE_GDXG_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Gene organization and primary structure of human hormone-sensitive lipase: possible significance of a sequence homology with a lipase of Moraxella TA144, an antarctic bacterium."
    Langin D., Laurell H., Stenson Holst L., Belfrage P., Holm C.
    Proc. Natl. Acad. Sci. U.S.A. 90:4897-4901(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Molecular cloning, genomic organization, and expression of a testicular isoform of hormone-sensitive lipase."
    Holst L.S., Langin D., Mulder H., Laurell H., Grober J., Bergh A., Mohrenweiser H.W., Edgren G., Holm C.
    Genomics 35:441-447(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Testis.
  3. SeattleSNPs variation discovery resource
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-100; HIS-127; SER-146; THR-177; VAL-194; GLN-217; ASN-497; HIS-499 AND SER-938.
  4. "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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Testis.
  5. "Association and insulin regulated translocation of hormone-sensitive lipase with PTRF."
    Aboulaich N., Oertegren U., Vener A.V., Stralfors P.
    Biochem. Biophys. Res. Commun. 350:657-661(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PTRF, SUBCELLULAR LOCATION.
  6. "Separation and characterization of caveolae subclasses in the plasma membrane of primary adipocytes; segregation of specific proteins and functions."
    Oertegren U., Yin L., Oest A., Karlsson H., Nystrom F.H., Stralfors P.
    FEBS J. 273:3381-3392(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  7. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  8. Cited for: INVOLVEMENT IN AOMS4.
  9. Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-146.

Entry informationi

Entry nameiLIPS_HUMAN
AccessioniPrimary (citable) accession number: Q05469
Secondary accession number(s): Q3LRT2, Q6NSL7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 1994
Last sequence update: April 16, 2007
Last modified: March 3, 2015
This is version 139 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.