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Q05469 (LIPS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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:
Hormone-sensitive lipase

Short name=HSL
EC=3.1.1.79
Gene names
Name:LIPE
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1076 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

Diacylglycerol + H2O = monoacylglycerol + a carboxylate.

Triacylglycerol + H2O = diacylglycerol + a carboxylate.

Monoacylglycerol + H2O = glycerol + a carboxylate.

Enzyme regulation

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

Pathway

Glycerolipid metabolism; triacylglycerol degradation.

Subunit structure

Interacts with PTRF in the adipocyte cytoplasm. Interacts with PLIN5 By similarity. Ref.5

Subcellular location

Cell membrane. Membranecaveola. Cytoplasmcytosol. Note: Found in the high-density caveolae. Translocates to the cytoplasm from the caveolae upon insulin stimulation. Ref.5 Ref.6

Post-translational modification

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

Sequence similarities

Belongs to the 'GDXG' lipolytic enzyme family.

Ontologies

Keywords
   Biological processCholesterol metabolism
Lipid degradation
Lipid metabolism
Steroid metabolism
Sterol metabolism
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcholesterol metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

diacylglycerol catabolic process

Inferred from electronic annotation. Source: Ensembl

lipid catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

long-chain fatty acid catabolic process

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Traceable author statement PubMed 3420405. Source: ProtInc

small molecule metabolic process

Traceable author statement. Source: Reactome

triglyceride catabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcaveola

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

lipid particle

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionhormone-sensitive lipase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein binding

Inferred from physical interaction Ref.5. Source: UniProtKB

triglyceride lipase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q05469-1)

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.
Isoform 2 (identifier: Q05469-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10761076Hormone-sensitive lipase
PRO_0000071547

Regions

Motif651 – 6533Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion hole By similarity

Sites

Active site6511 Potential
Active site7251 Potential

Amino acid modifications

Modified residue8531Phosphoserine By similarity
Modified residue8551Phosphoserine; by AMPK By similarity
Modified residue9501Phosphoserine By similarity
Modified residue9511Phosphoserine By similarity

Natural variations

Alternative sequence1 – 301301Missing in isoform 2.
VSP_017116
Natural variant1001Y → H. Ref.3
Corresponds to variant rs16975750 [ dbSNP | Ensembl ].
VAR_025108
Natural variant1271Q → H. Ref.3
Corresponds to variant rs34080774 [ dbSNP | Ensembl ].
VAR_025109
Natural variant1461P → Q in a breast cancer sample; somatic mutation. Ref.8
VAR_036539
Natural variant1461P → S. Ref.3
Corresponds to variant rs34348028 [ dbSNP | Ensembl ].
VAR_025110
Natural variant1771S → T. Ref.3
Corresponds to variant rs16975748 [ dbSNP | Ensembl ].
VAR_025111
Natural variant1941A → V. Ref.3
Corresponds to variant rs34996020 [ dbSNP | Ensembl ].
VAR_025112
Natural variant2171R → Q. Ref.3
Corresponds to variant rs3745238 [ dbSNP | Ensembl ].
VAR_025113
Natural variant4971K → N. Ref.3
Corresponds to variant rs35938529 [ dbSNP | Ensembl ].
VAR_025114
Natural variant4991N → H. Ref.3
Corresponds to variant rs33921216 [ dbSNP | Ensembl ].
VAR_025115
Natural variant9381R → S. Ref.3
Corresponds to variant rs7246232 [ dbSNP | Ensembl ].
VAR_025116

Experimental info

Sequence conflict2301T → A in AAA69810. Ref.1
Sequence conflict2301T → A in AAC50666. Ref.2
Sequence conflict2301T → A in ABA03168. Ref.3
Sequence conflict4861S → Y in AAH70041. Ref.4
Sequence conflict6081Y → C in AAH70041. Ref.4

Sequences

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

Last modified April 17, 2007. Version 4.
Checksum: 1CC0E3880FF64D74

FASTA1,076116,598
        10         20         30         40         50         60 
MEPGSKSVSR SDWQPEPHQR PITPLEPGPE KTPIAQPESK TLQGSNTQQK PASNQRPLTQ 

        70         80         90        100        110        120 
QETPAQHDAE SQKEPRAQQK SASQEEFLAP QKPAPQQSPY IQRVLLTQQE AASQQGPGLG 

       130        140        150        160        170        180 
KESITQQEPA LRQRHVAQPG PGPGEPPPAQ QEAESTPAAQ AKPGAKREPS APTESTSQET 

       190        200        210        220        230        240 
PEQSDKQTTP VQGAKSKQGS LTELGFLTKL QELSIQRSAL EWKALSEWVT DSESESDVGS 

       250        260        270        280        290        300 
SSDTDSPATM GGMVAQGVKL GFKGKSGYKV MSGYSGTSPH EKTSARNHRH YQDTASRLIH 

       310        320        330        340        350        360 
NMDLRTMTQS LVTLAEDNIA FFSSQGPGET AQRLSGVFAG VREQALGLEP ALGRLLGVAH 

       370        380        390        400        410        420 
LFDLDPETPA NGYRSLVHTA RCCLAHLLHK SRYVASNRRS IFFRTSHNLA ELEAYLAALT 

       430        440        450        460        470        480 
QLRALVYYAQ RLLVTNRPGV LFFEGDEGLT ADFLREYVTL HKGCFYGRCL GFQFTPAIRP 

       490        500        510        520        530        540 
FLQTISIGLV SFGEHYKRNE TGLSVAASSL FTSGRFAIDP ELRGAEFERI TQNLDVHFWK 

       550        560        570        580        590        600 
AFWNITEMEV LSSLANMASA TVRVSRLLSL PPEAFEMPLT ADPTLTVTIS PPLAHTGPGP 

       610        620        630        640        650        660 
VLVRLISYDL REGQDSEELS SLIKSNGQRS LELWPRPQQA PRSRSLIVHF HGGGFVAQTS 

       670        680        690        700        710        720 
RSHEPYLKSW AQELGAPIIS IDYSLAPEAP FPRALEECFF AYCWAIKHCA LLGSTGERIC 

       730        740        750        760        770        780 
LAGDSAGGNL CFTVALRAAA YGVRVPDGIM AAYPATMLQP AASPSRLLSL MDPLLPLSVL 

       790        800        810        820        830        840 
SKCVSAYAGA KTEDHSNSDQ KALGMMGLVR RDTALLLRDF RLGASSWLNS FLELSGRKSQ 

       850        860        870        880        890        900 
KMSEPIAEPM RRSVSEAALA QPQGPLGTDS LKNLTLRDLS LRGNSETSSD TPEMSLSAET 

       910        920        930        940        950        960 
LSPSTPSDVN FLLPPEDAGE EAEAKNELSP MDRGLGVRAA FPEGFHPRRS SQGATQMPLY 

       970        980        990       1000       1010       1020 
SSPIVKNPFM SPLLAPDSML KSLPPVHIVA CALDPMLDDS VMLARRLRNL GQPVTLRVVE 

      1030       1040       1050       1060       1070 
DLPHGFLTLA ALCRETRQAA ELCVERIRLV LTPPAGAGPS GETGAAGVDG GCGGRH 

« Hide

Isoform 2 [UniParc].

Checksum: 3462D4A99945661B
Show »

FASTA77584,128

References

« Hide 'large scale' references
[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(1993) [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(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Testis.
[3]SeattleSNPs variation discovery resource
Submitted (AUG-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(2004) [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(2006) [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(2006) [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(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[8]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-146.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L11706 Genomic DNA. Translation: AAA69810.1.
U40001 mRNA. Translation: AAC50666.1.
DQ188033 Genomic DNA. Translation: ABA03168.1.
BC070041 mRNA. Translation: AAH70041.1.
CCDSCCDS12607.1. [Q05469-1]
RefSeqNP_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]
UniGeneHs.656980.

3D structure databases

ProteinModelPortalQ05469.
SMRQ05469. Positions 636-826, 970-1059.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110179. 3 interactions.
IntActQ05469. 1 interaction.
MINTMINT-1370154.
STRING9606.ENSP00000244289.

Chemistry

BindingDBQ05469.
ChEMBLCHEMBL3590.
GuidetoPHARMACOLOGY2593.

Protein family/group databases

MEROPSS09.993.

PTM databases

PhosphoSiteQ05469.

Polymorphism databases

DMDM145559491.

Proteomic databases

MaxQBQ05469.
PaxDbQ05469.
PRIDEQ05469.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000244289; ENSP00000244289; ENSG00000079435. [Q05469-1]
GeneID3991.
KEGGhsa:3991.
UCSCuc002otr.3. human. [Q05469-1]

Organism-specific databases

CTD3991.
GeneCardsGC19M042906.
H-InvDBHIX0040096.
HGNCHGNC:6621. LIPE.
HPACAB017700.
MIM151750. gene.
neXtProtNX_Q05469.
PharmGKBPA30393.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0657.
HOGENOMHOG000047722.
HOVERGENHBG000187.
InParanoidQ05469.
KOK07188.
OMALVVHIHG.
OrthoDBEOG7KSX7S.
PhylomeDBQ05469.
TreeFamTF314423.

Enzyme and pathway databases

BioCycMetaCyc:HS01328-MONOMER.
BRENDA3.1.1.79. 2681.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00256.

Gene expression databases

ArrayExpressQ05469.
BgeeQ05469.
CleanExHS_LIPE.
GenevestigatorQ05469.

Family and domain databases

Gene3D3.40.50.1820. 2 hits.
InterProIPR029058. AB_hydrolase.
IPR013094. AB_hydrolase_3.
IPR010468. HSL_N.
IPR002168. Lipase_GDXG_AS.
[Graphical view]
PfamPF07859. Abhydrolase_3. 2 hits.
PF06350. HSL_N. 1 hit.
[Graphical view]
SUPFAMSSF53474. SSF53474. 2 hits.
PROSITEPS01173. LIPASE_GDXG_HIS. 1 hit.
PS01174. LIPASE_GDXG_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiHormone-sensitive_lipase.
GenomeRNAi3991.
NextBio15656.
PROQ05469.
SOURCESearch...

Entry information

Entry nameLIPS_HUMAN
AccessionPrimary (citable) accession number: Q05469
Secondary accession number(s): Q3LRT2, Q6NSL7
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: April 17, 2007
Last modified: July 9, 2014
This is version 133 of the entry and version 4 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

PATHWAY comments

Index of metabolic and biosynthesis pathways

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 19

Human chromosome 19: entries, gene names and cross-references to MIM