P15304 (LIPS_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hormone-sensitive lipase
Short name=HSL
EC=3.1.1.79

Gene names

Name:

Lipe

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1068 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Membrane › caveola By similarity. Cytoplasm › cytosol 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 process	Cholesterol metabolism Lipid degradation Lipid metabolism Steroid metabolism Sterol metabolism
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol metabolic process Inferred from electronic annotation. Source: UniProtKB-KW female pregnancy Inferred from expression pattern PubMed 16328496. Source: RGD 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_component	caveola 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_function	acylglycerol lipase activity Inferred from direct assay PubMed 15627655. Source: RGD hormone-sensitive lipase activity Inferred from electronic annotation. Source: EC 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1068	1068	Hormone-sensitive lipase		PRO_0000071550
Sites
	Active site	649	1	Potential
	Active site	723	1	Potential
Amino acid modifications
	Modified residue	863	1	Phosphoserine; by PKA Ref.5
	Modified residue	865	1	Phosphoserine; by AMPK By similarity
	Modified residue	959	1	Phosphoserine; by PKA Ref.5
	Modified residue	960	1	Phosphoserine; by PKA Ref.5
Natural variations
	Alternative sequence	1 – 300	300	Missing in isoform 2.		VSP_017117
Experimental info
	Mutagenesis	863	1	S → A or E: No effect on activation by PKA. Ref.5
	Mutagenesis	865	1	S → A: Increases activation by PKA. Ref.5
	Mutagenesis	865	1	S → E: No effect on activation by PKA. Ref.5
	Mutagenesis	959	1	S → A: Slightly decreases activation by PKA. Abolishes activation by PKA; when associated with A-960. Ref.5
	Mutagenesis	960	1	S → A: No effect on activation by PKA. Abolishes activation by PKA; when associated with A-959. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Testicular) [UniParc]. Last modified January 24, 2006. Version 3. Checksum: 13B10C9315AC87F1	FASTA	1,068	116,812
	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
	Isoform 2 [UniParc]. Checksum: 90A1F0432DAC8B4C	FASTA	768	84,170
	10 20 30 40 50 60 MDLRTMTQSL VALAEDNMAF FSSQGPGETA RRLSNVFAGV REQALGLEPT LGQLLGVAHH 70 80 90 100 110 120 FDLDTETPAN GYRSLVHTAR CCLAHLLHKS RYVASNRRSI FFRASHNLAE LEAYLAALTQ 130 140 150 160 170 180 LRALAYYAQR LLTINRPGVL FFEGDEGLSA DFLQDYVTLH KGCFYGRCLG FQFTPAIRPF 190 200 210 220 230 240 LQTLSIGLVS FGEHYKRNET GLSVTASSLF TGGRFAIDPE LRGAEFERII QNLDVHFWKA 250 260 270 280 290 300 FWNITEIEVL SSLANMASTT VRVSRLLSLP PEAFEMPLTS DPKLTVTISP PLAHTGPGPV 310 320 330 340 350 360 LARLISYDLR EGQDSKMLNS LAKSEGPRLE LRPRPQQAPR SRALVVHIHG GGFVAQTSKS 370 380 390 400 410 420 HEPYLKNWAQ ELGVPIISID YSLAPEAPFP RALEECFFAY CWAVKHCELL GSTGERICLA 430 440 450 460 470 480 GDSAGGNLCI TVSLRAAAYG VRVPDGIMAA YPVTTLQSSA SPSRLLSLMD PLLPLSVLSK 490 500 510 520 530 540 CVSAYSGTET EDHFDSDQKA LGVMGLVQRD TSLFLRDLRL GASSWLNSFL ELSGRKPHKT 550 560 570 580 590 600 PLPATETLRP TDSGRLTESM RRSVSEAALA QPEGLLGTDS LKKLTIKDLS FKGNSEPSDS 610 620 630 640 650 660 PEMSQSMETL GPSTPSDVNF FLRSGNSQEE AETRDDISPM DGIPRVRAAF PDGFHPRRSS 670 680 690 700 710 720 QGVLHMPLYS SPIVKNPFMS PLLAPDVMLK TLPPVHLVAC ALDPMLDDSV MFARRLKDLG 730 740 750 760 QPVTLKVVED LPHGFLSLAA LCRETRQAAE LCVQRIRLIL TPPAAPLT

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.
IPI	IPI00362182. IPI00952030.
PIR	LIRTH. S03672.
RefSeq	NP_036991.1. NM_012859.1.
UniGene	Rn.10566.
3D structure databases
ProteinModelPortal	P15304.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4783535.
Protein family/group databases
MEROPS	S09.993.
PTM databases
PhosphoSite	P15304.
Proteomic databases
PaxDb	P15304.
PRIDE	P15304.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	25330.
KEGG	rno:25330.
UCSC	RGD:3010. rat.
Organism-specific databases
CTD	3991.
RGD	3010. Lipe.
Phylogenomic databases
eggNOG	COG0657.
HOGENOM	HOG000047722.
HOVERGEN	HBG000187.
InParanoid	P15304.
KO	K07188.
OrthoDB	EOG4DV5KG.
Enzyme and pathway databases
Reactome	REACT_113568. Metabolism.
UniPathway	UPA00256.
Gene expression databases
ArrayExpress	P15304.
Genevestigator	P15304.
GermOnline	ENSRNOG00000020546. Rattus norvegicus.
Family and domain databases
InterPro	IPR013094. AB_hydrolase_3. IPR010468. HSL_N. IPR002168. Lipase_GDXG_AS. [Graphical view]
Pfam	PF07859. Abhydrolase_3. 2 hits. PF06350. HSL_N. 1 hit. [Graphical view]
PROSITE	PS01173. LIPASE_GDXG_HIS. 1 hit. PS01174. LIPASE_GDXG_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P15304.
ChEMBL	CHEMBL5582.
NextBio	606207.

Entry information

Entry name

LIPS_RAT

Accession

Primary (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 3, 2013
This is version 113 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program