Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P15304 (LIPS_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1068 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 By similarity.

Subcellular location

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

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
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcholesterol metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

female pregnancy

Inferred from expression pattern PubMed 16328496. Source: RGD

lipid catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

response to drug

Inferred from expression pattern PubMed 11016888PubMed 16906479. Source: RGD

termination of RNA polymerase I transcription

Inferred from sequence or structural similarity PubMed 9582279. Source: UniProtKB

transcription initiation from RNA polymerase I promoter

Inferred from sequence or structural similarity PubMed 9582279. Source: UniProtKB

triglyceride catabolic process

Inferred from direct assay PubMed 14739077. Source: RGD

   Cellular_componentcaveola

Inferred from sequence or structural similarity PubMed 17026959. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity PubMed 17026959. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 15654127. Source: RGD

lipid particle

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrion

Inferred from sequence or structural similarity PubMed 15242332. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity PubMed 15242332. Source: UniProtKB

   Molecular_functionacylglycerol lipase activity

Inferred from direct assay PubMed 15627655. Source: RGD

hormone-sensitive lipase activity

Inferred from electronic annotation. Source: UniProtKB-EC

hydrolase activity, acting on ester bonds

Inferred from direct assay PubMed 15697220. Source: RGD

rRNA primary transcript binding

Inferred from sequence or structural similarity PubMed 9582279. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P15304-1)

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: P15304-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-300: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10681068Hormone-sensitive lipase
PRO_0000071550

Regions

Motif649 – 6513Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion hole By similarity

Sites

Active site6491 Potential
Active site7231 Potential

Amino acid modifications

Modified residue8631Phosphoserine; by PKA Ref.5
Modified residue8651Phosphoserine; by AMPK By similarity
Modified residue9591Phosphoserine; by PKA Ref.5
Modified residue9601Phosphoserine; by PKA Ref.5

Natural variations

Alternative sequence1 – 300300Missing in isoform 2.
VSP_017117

Experimental info

Mutagenesis8631S → A or E: No effect on activation by PKA. Ref.5
Mutagenesis8651S → A: Increases activation by PKA. Ref.5
Mutagenesis8651S → E: No effect on activation by PKA. Ref.5
Mutagenesis9591S → A: Slightly decreases activation by PKA. Abolishes activation by PKA; when associated with A-960. Ref.5
Mutagenesis9601S → A: No effect on activation by PKA. Abolishes activation by PKA; when associated with A-959. Ref.5

Sequences

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

Last modified January 24, 2006. Version 3.
Checksum: 13B10C9315AC87F1

FASTA1,068116,812
        10         20         30         40         50         60 
MKPRRPISFT REITAMEPSS TSVSRPEWRP EAQQTLTDYP GSRELQEFGI PQKQSLPNEA 

        70         80         90        100        110        120 
TAQQGAEFQQ EQGVQQSTLL QKLLTPLAFP VPQQSFPSHK VHSDQQEATS QNGPGAGKVH 

       130        140        150        160        170        180 
TTQKELEHRD EHVGTAESGP AEPPPATEVE ATSIAQAVSG PDKKLPTQTD LVSQERAEQS 

       190        200        210        220        230        240 
DPTAQQTPLV QGVKSDQGSL IESGILARLQ KLAIQQPSQE WKTFLDCVTE SDMEKYLNSS 

       250        260        270        280        290        300 
SKSNPPEPSG GTVIPGTLPS KQKPDCGKMS GYGGKLPHGK KGILQKHKHY WDTASAFSHS 

       310        320        330        340        350        360 
MDLRTMTQSL VALAEDNMAF FSSQGPGETA RRLSNVFAGV REQALGLEPT LGQLLGVAHH 

       370        380        390        400        410        420 
FDLDTETPAN GYRSLVHTAR CCLAHLLHKS RYVASNRRSI FFRASHNLAE LEAYLAALTQ 

       430        440        450        460        470        480 
LRALAYYAQR LLTINRPGVL FFEGDEGLSA DFLQDYVTLH KGCFYGRCLG FQFTPAIRPF 

       490        500        510        520        530        540 
LQTLSIGLVS FGEHYKRNET GLSVTASSLF TGGRFAIDPE LRGAEFERII QNLDVHFWKA 

       550        560        570        580        590        600 
FWNITEIEVL SSLANMASTT VRVSRLLSLP PEAFEMPLTS DPKLTVTISP PLAHTGPGPV 

       610        620        630        640        650        660 
LARLISYDLR EGQDSKMLNS LAKSEGPRLE LRPRPQQAPR SRALVVHIHG GGFVAQTSKS 

       670        680        690        700        710        720 
HEPYLKNWAQ ELGVPIISID YSLAPEAPFP RALEECFFAY CWAVKHCELL GSTGERICLA 

       730        740        750        760        770        780 
GDSAGGNLCI TVSLRAAAYG VRVPDGIMAA YPVTTLQSSA SPSRLLSLMD PLLPLSVLSK 

       790        800        810        820        830        840 
CVSAYSGTET EDHFDSDQKA LGVMGLVQRD TSLFLRDLRL GASSWLNSFL ELSGRKPHKT 

       850        860        870        880        890        900 
PLPATETLRP TDSGRLTESM RRSVSEAALA QPEGLLGTDS LKKLTIKDLS FKGNSEPSDS 

       910        920        930        940        950        960 
PEMSQSMETL GPSTPSDVNF FLRSGNSQEE AETRDDISPM DGIPRVRAAF PDGFHPRRSS 

       970        980        990       1000       1010       1020 
QGVLHMPLYS SPIVKNPFMS PLLAPDVMLK TLPPVHLVAC ALDPMLDDSV MFARRLKDLG 

      1030       1040       1050       1060 
QPVTLKVVED LPHGFLSLAA LCRETRQAAE LCVQRIRLIL TPPAAPLT 

« Hide

Isoform 2 [UniParc].

Checksum: 90A1F0432DAC8B4C
Show »

FASTA76884,170

References

[1]"Nucleotide sequence of rat adipose hormone sensitive lipase cDNA."
Holm C., Kirchgessner T.G., Svenson K.L., Lusis A.J., Belfrage P., Schotz M.C.
Nucleic Acids Res. 16:9879-9879(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Adipose tissue.
[2]"Hormone-sensitive lipase: sequence, expression, and chromosomal localization to 19 cent-q13.3."
Holm C., Kirchgessner T.G., Svenson K.L., Fredrikson G., Nilsson S., Miller C.G., Shively J.E., Heinzmann C., Sparkes R.S., Mohandas T., Lusis A.J., Belfrage P., Schotz M.C.
Science 241:1503-1506(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Adipose tissue.
[3]Holm C.
Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 842-855 AND 1046-1068.
[4]"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).
Strain: Sprague-Dawley.
Tissue: Testis.
[5]"Identification of novel phosphorylation sites in hormone-sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro."
Anthonsen M.W., Roennstrand L., Wernstedt C., Degerman E., Holm C.
J. Biol. Chem. 273:215-221(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-863; SER-959 AND SER-960, MUTAGENESIS OF SER-863; SER-865; SER-959 AND SER-960.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X51415 mRNA. Translation: CAA35777.1.
U40001 mRNA. Translation: AAC52771.1.
PIRLIRTH. S03672.
RefSeqNP_036991.1. NM_012859.1.
XP_006228456.1. XM_006228394.1.
UniGeneRn.10566.

3D structure databases

ProteinModelPortalP15304.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid247369. 2 interactions.
IntActP15304. 1 interaction.
MINTMINT-4783535.

Chemistry

BindingDBP15304.
ChEMBLCHEMBL5582.

Protein family/group databases

MEROPSS09.993.

PTM databases

PhosphoSiteP15304.

Proteomic databases

PaxDbP15304.
PRIDEP15304.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID25330.
KEGGrno:25330.
UCSCRGD:3010. rat. [P15304-1]

Organism-specific databases

CTD3991.
RGD3010. Lipe.

Phylogenomic databases

eggNOGCOG0657.
HOGENOMHOG000047722.
HOVERGENHBG000187.
InParanoidP15304.
KOK07188.
PhylomeDBP15304.

Enzyme and pathway databases

UniPathwayUPA00256.

Gene expression databases

GenevestigatorP15304.

Family and domain databases

InterProIPR013094. AB_hydrolase_3.
IPR010468. HSL_N.
IPR002168. Lipase_GDXG_AS.
[Graphical view]
PfamPF07859. Abhydrolase_3. 2 hits.
PF06350. HSL_N. 1 hit.
[Graphical view]
PROSITEPS01173. LIPASE_GDXG_HIS. 1 hit.
PS01174. LIPASE_GDXG_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio606207.
PROP15304.

Entry information

Entry nameLIPS_RAT
AccessionPrimary (citable) accession number: P15304
Secondary accession number(s): Q6LCQ2
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: January 24, 2006
Last modified: April 16, 2014
This is version 122 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways