P54310 (LIPS_MOUSE) 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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Mus › Mus

Protein attributes

Sequence length	759 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 By similarity.
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.
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
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 diacylglycerol catabolic process Inferred from direct assay PubMed 16804080. Source: MGI long-chain fatty acid catabolic process Inferred from direct assay PubMed 16804080. Source: MGI 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 16804080. Source: MGI
Cellular_component	caveola Inferred from sequence or structural similarity PubMed 17026959. Source: UniProtKB cytosol Inferred from direct assay PubMed 16804080PubMed 17074755. Source: MGI lipid particle Inferred from direct assay Ref.5. 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	hormone-sensitive lipase activity Inferred from electronic annotation. Source: EC rRNA primary transcript binding Inferred from sequence or structural similarity PubMed 9582279. Source: UniProtKB triglyceride lipase activity Inferred from mutant phenotype PubMed 17074755. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 759	759	Hormone-sensitive lipase		PRO_0000071548
Sites
	Active site	349	1	Potential
	Active site	423	1	Potential
Amino acid modifications
	Modified residue	557	1	Phosphoserine By similarity
	Modified residue	559	1	Phosphoserine; by AMPK Probable
	Modified residue	650	1	Phosphoserine By similarity
	Modified residue	651	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	113	1	A → T in BAE41414. Ref.3
	Sequence conflict	311	1	E → D in BAE41414. Ref.3
	Sequence conflict	330 – 331	2	EL → DV in AAC52163. Ref.1
	Sequence conflict	530	1	L → P in AAC52163. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P54310 [UniParc]. Last modified January 24, 2006. Version 2. Checksum: 3419AF52F6C85FF4	FASTA	759	83,348
	10 20 30 40 50 60 MDLRTMTQSL VTLAEDNMAF FSSQGPGETA RRLSNVFAGV REQALGLEPT LGQLLGVAHH 70 80 90 100 110 120 FDLDTETPAN GYRSLVHTAR CCLAHLLHKS RYVASNRKSI FFRASHNLAE LEAYLAALTQ 130 140 150 160 170 180 LRAMAYYAQR LLTINRPGVL FFEGDEGLTA DFLQEYVTLH KGCFYGRCLG FQFTPAIRPF 190 200 210 220 230 240 LQTLSIGLVS FGEHYKRNET GLSVTASSLF TGGRFAIDPE LRGAEFERII QNLDVHFWKA 250 260 270 280 290 300 FWNITEIEVL SSLANMASTT VRVSRLLSLP PEAFEMPLTS DPRLTVTISP PLAHTGPAPV 310 320 330 340 350 360 LARLISYDLR EGQDSKVLNS LAKSEGPRLE LRPRPHQAPR SRALVVHIHG GGFVAQTSKS 370 380 390 400 410 420 HEPYLKNWAQ ELGVPIFSID YSLAPEAPFP RALEECFFAY CWAVKHCDLL GSTGERICLA 430 440 450 460 470 480 GDSAGGNLCI TVSLRAAAYG VRVPDGIMAA YPVTTLQSSA SPSRLLSLMD PLLPLSVLSK 490 500 510 520 530 540 CVSAYSGTEA EDHFDSDQKA LGVMGLVQRD TSLFLRDLRL GASSWLNSFL ELSGRKPQKT 550 560 570 580 590 600 TSPTAESVRP TESMRRSVSE AALAQPEGLL GTDTLKKLTI KDLSNSEPSD SPEMSQSMET 610 620 630 640 650 660 LGPSTPSDVN FFLRPGNSQE EAEAKDEVRP MDGVPRVRAA FPEGFHPRRS SQGVLHMPLY 670 680 690 700 710 720 TSPIVKNPFM SPLLAPDSML KTLPPVHLVA CALDPMLDDS VMFARRLRDL GQPVTLKVVE 730 740 750 DLPHGFLSLA ALCRETRQAT EFCVQRIRLI LTPPAAPLN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of the gene for mouse hormone-sensitive lipase." Li Z., Sumida M., Birchbauer A., Schotz M.C., Reue K. Genomics 24:259-265(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Hormone-sensitive lipase (Lipe): sequence analysis of the 129Sv mouse Lipe gene." Sztrolovics R., Wang S.P., Lapierre P., Chen H.S., Robert M.-F., Mitchell G.A. Mamm. Genome 8:86-89(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 129/Sv.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: NOD.
[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]. Strain: FVB/N. Tissue: Salivary gland.
[5]	"Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes." Daval M., Diot-Dupuy F., Bazin R., Hainault I., Viollet B., Vaulont S., Hajduch E., Ferre P., Foufelle F. J. Biol. Chem. 280:25250-25257(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY AMPK.
[6]	"The stoichiometry of protein phosphorylation in adipocyte lipid droplets: analysis by N-terminal isotope tagging and enzymatic dephosphorylation." Kanshin E., Wang S., Ashmarina L., Fedjaev M., Nifant'ev I., Mitchell G.A., Pshezhetsky A.V. Proteomics 9:5067-5077(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-559.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U08188 mRNA. Translation: AAC52163.1. AF179427 Genomic DNA. Translation: AAC53069.1. AK169858 mRNA. Translation: BAE41414.1. BC021642 mRNA. Translation: AAH21642.1.
IPI	IPI00469416.
PIR	I49007.
RefSeq	NP_001034596.1. NM_001039507.2.
UniGene	Mm.158548. Mm.333679.
3D structure databases
ProteinModelPortal	P54310.
SMR	P54310. Positions 337-524.
ModBase	Search...
Protein family/group databases
MEROPS	S09.993.
PTM databases
PhosphoSite	P54310.
Proteomic databases
PaxDb	P54310.
PRIDE	P54310.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000054301; ENSMUSP00000050935; ENSMUSG00000003123.
GeneID	16890.
KEGG	mmu:16890.
Organism-specific databases
CTD	3991.
MGI	MGI:96790. Lipe.
Phylogenomic databases
eggNOG	COG0657.
GeneTree	ENSGT00550000074556.
HOGENOM	HOG000047722.
HOVERGEN	HBG000187.
InParanoid	P54310.
KO	K07188.
OrthoDB	EOG4DV5KG.
Enzyme and pathway databases
BRENDA	3.1.1.79. 3474.
UniPathway	UPA00256.
Gene expression databases
ArrayExpress	P54310.
Bgee	P54310.
CleanEx	MM_LIPE.
Genevestigator	P54310.
GermOnline	ENSMUSG00000003123. Mus musculus.
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
ChEMBL	CHEMBL5935.
NextBio	290908.
SOURCE	Search...

Entry information

Entry name

LIPS_MOUSE

Accession

Primary (citable) accession number: P54310
Secondary accession number(s): P97866, Q3TE34, Q6GU16

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 24, 2006
Last modified:	May 1, 2013
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program