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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: triacylglycerol degradation

This protein is involved in the pathway triacylglycerol degradation, which is part of Glycerolipid metabolism.
View all proteins of this organism that are known to be involved in the pathway triacylglycerol degradation and in Glycerolipid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei725PROSITE-ProRule annotationBy similarity1
Active sitei994By similarity1
Active sitei1024By similarity1

GO - Molecular functioni

GO - Biological processi

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.
ZFISH:HS01328-MONOMER.
BRENDAi3.1.1.79. 2681.
ReactomeiR-HSA-163560. Hormone-sensitive lipase (HSL)-mediated triacylglycerol hydrolysis.
SABIO-RKQ05469.
SIGNORiQ05469.
UniPathwayiUPA00256.

Protein family/group databases

ESTHERihuman-LIPE. Hormone-sensitive_lipase_like_1.
MEROPSiS09.993.

Chemistry databases

SwissLipidsiSLP:000000316.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:6621. LIPE.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Lipodystrophy, familial partial, 6 (FPLD6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of lipodystrophy characterized by abnormal subcutaneous fat distribution. Affected individuals have increased visceral fat, impaired lipolysis, dyslipidemia, hepatic steatosis, systemic insulin resistance, and diabetes. Some patients manifest muscular dystrophy.
See also OMIM:615980

Keywords - Diseasei

Diabetes mellitus, Obesity

Organism-specific databases

DisGeNETi3991.
MalaCardsiLIPE.
MIMi615980. phenotype.
OpenTargetsiENSG00000079435.
PharmGKBiPA30393.

Chemistry databases

ChEMBLiCHEMBL3590.
GuidetoPHARMACOLOGYi2593.

Polymorphism and mutation databases

BioMutaiLIPE.
DMDMi145559491.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000715471 – 1076Hormone-sensitive lipaseAdd BLAST1076

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei853PhosphoserineBy similarity1
Modified residuei855Phosphoserine; by AMPKBy similarity1
Modified residuei897PhosphoserineBy similarity1
Modified residuei929PhosphoserineBy similarity1
Modified residuei950PhosphoserineBy similarity1
Modified residuei951PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ05469.
MaxQBiQ05469.
PaxDbiQ05469.
PeptideAtlasiQ05469.
PRIDEiQ05469.

PTM databases

iPTMnetiQ05469.
PhosphoSitePlusiQ05469.

Expressioni

Gene expression databases

BgeeiENSG00000079435.
CleanExiHS_LIPE.
ExpressionAtlasiQ05469. baseline and differential.
GenevisibleiQ05469. HS.

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. 3 interactors.
IntActiQ05469. 2 interactors.
MINTiMINT-1370154.
STRINGi9606.ENSP00000244289.

Chemistry databases

BindingDBiQ05469.

Structurei

3D structure databases

ProteinModelPortaliQ05469.
SMRiQ05469.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi651 – 653Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion holeBy similarity3

Sequence similaritiesi

Belongs to the 'GDXG' lipolytic enzyme family.Curated

Phylogenomic databases

eggNOGiKOG4388. Eukaryota.
COG0657. LUCA.
GeneTreeiENSGT00730000111056.
HOGENOMiHOG000047722.
HOVERGENiHBG000187.
InParanoidiQ05469.
KOiK07188.
OMAiFLNFTML.
OrthoDBiEOG091G0AZN.
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_HIS_AS.
IPR033140. Lipase_GDXG_put_SER_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 17, 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)DescriptionActionsGraphical viewLength
Sequence conflicti230T → A in AAA69810 (PubMed:8506334).Curated1
Sequence conflicti230T → A in AAC50666 (PubMed:8812477).Curated1
Sequence conflicti230T → A in ABA03168 (Ref. 3) Curated1
Sequence conflicti486S → Y in AAH70041 (PubMed:15489334).Curated1
Sequence conflicti608Y → C in AAH70041 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025108100Y → H.1 PublicationCorresponds to variant rs16975750dbSNPEnsembl.1
Natural variantiVAR_025109127Q → H.1 PublicationCorresponds to variant rs34080774dbSNPEnsembl.1
Natural variantiVAR_036539146P → Q in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_025110146P → S.1 PublicationCorresponds to variant rs34348028dbSNPEnsembl.1
Natural variantiVAR_025111177S → T.1 PublicationCorresponds to variant rs16975748dbSNPEnsembl.1
Natural variantiVAR_025112194A → V.1 PublicationCorresponds to variant rs34996020dbSNPEnsembl.1
Natural variantiVAR_025113217R → Q.1 PublicationCorresponds to variant rs3745238dbSNPEnsembl.1
Natural variantiVAR_025114497K → N.1 PublicationCorresponds to variant rs35938529dbSNPEnsembl.1
Natural variantiVAR_025115499N → H.1 PublicationCorresponds to variant rs33921216dbSNPEnsembl.1
Natural variantiVAR_025116938R → S.1 PublicationCorresponds to variant rs7246232dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0171161 – 301Missing in isoform 2. CuratedAdd BLAST301

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_005258940.3. [Q05469-2]
XP_006723281.1. XM_006723218.2. [Q05469-2]
XP_016882299.1. XM_017026810.1. [Q05469-2]
UniGeneiHs.656980.

Genome annotation databases

EnsembliENST00000244289; ENSP00000244289; ENSG00000079435. [Q05469-1]
GeneIDi3991.
KEGGihsa:3991.
UCSCiuc002otr.4. human. [Q05469-1]

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_005258940.3. [Q05469-2]
XP_006723281.1. XM_006723218.2. [Q05469-2]
XP_016882299.1. XM_017026810.1. [Q05469-2]
UniGeneiHs.656980.

3D structure databases

ProteinModelPortaliQ05469.
SMRiQ05469.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110179. 3 interactors.
IntActiQ05469. 2 interactors.
MINTiMINT-1370154.
STRINGi9606.ENSP00000244289.

Chemistry databases

BindingDBiQ05469.
ChEMBLiCHEMBL3590.
GuidetoPHARMACOLOGYi2593.
SwissLipidsiSLP:000000316.

Protein family/group databases

ESTHERihuman-LIPE. Hormone-sensitive_lipase_like_1.
MEROPSiS09.993.

PTM databases

iPTMnetiQ05469.
PhosphoSitePlusiQ05469.

Polymorphism and mutation databases

BioMutaiLIPE.
DMDMi145559491.

Proteomic databases

EPDiQ05469.
MaxQBiQ05469.
PaxDbiQ05469.
PeptideAtlasiQ05469.
PRIDEiQ05469.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000244289; ENSP00000244289; ENSG00000079435. [Q05469-1]
GeneIDi3991.
KEGGihsa:3991.
UCSCiuc002otr.4. human. [Q05469-1]

Organism-specific databases

CTDi3991.
DisGeNETi3991.
GeneCardsiLIPE.
H-InvDBHIX0040096.
HGNCiHGNC:6621. LIPE.
HPAiCAB017700.
MalaCardsiLIPE.
MIMi151750. gene.
615980. phenotype.
neXtProtiNX_Q05469.
OpenTargetsiENSG00000079435.
PharmGKBiPA30393.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4388. Eukaryota.
COG0657. LUCA.
GeneTreeiENSGT00730000111056.
HOGENOMiHOG000047722.
HOVERGENiHBG000187.
InParanoidiQ05469.
KOiK07188.
OMAiFLNFTML.
OrthoDBiEOG091G0AZN.
PhylomeDBiQ05469.
TreeFamiTF314423.

Enzyme and pathway databases

UniPathwayiUPA00256.
BioCyciMetaCyc:HS01328-MONOMER.
ZFISH:HS01328-MONOMER.
BRENDAi3.1.1.79. 2681.
ReactomeiR-HSA-163560. Hormone-sensitive lipase (HSL)-mediated triacylglycerol hydrolysis.
SABIO-RKQ05469.
SIGNORiQ05469.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000079435.
CleanExiHS_LIPE.
ExpressionAtlasiQ05469. baseline and differential.
GenevisibleiQ05469. HS.

Family and domain databases

Gene3Di3.40.50.1820. 2 hits.
InterProiIPR029058. AB_hydrolase.
IPR013094. AB_hydrolase_3.
IPR010468. HSL_N.
IPR002168. Lipase_GDXG_HIS_AS.
IPR033140. Lipase_GDXG_put_SER_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...

Entry informationi

Entry nameiLIPS_HUMAN
AccessioniPrimary (citable) accession number: Q05469
Secondary accession number(s): Q3LRT2, Q6NSL7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: April 17, 2007
Last modified: November 2, 2016
This is version 155 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

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 one 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.