Q05469 (LIPS_HUMAN) 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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1076 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. Ref.5
Subcellular location	Cell membrane. Membrane › caveola. Cytoplasm › cytosol. 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 process	Cholesterol metabolism Lipid degradation Lipid metabolism Steroid metabolism Sterol metabolism
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
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 electronic annotation. Source: Compara 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_component	caveola 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_function	hormone-sensitive lipase activity Inferred from electronic annotation. Source: EC triglyceride lipase activity Inferred from electronic annotation. Source: Compara
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1076	1076	Hormone-sensitive lipase		PRO_0000071547
Sites
	Active site	651	1	Potential
	Active site	725	1	Potential
Amino acid modifications
	Modified residue	853	1	Phosphoserine By similarity
	Modified residue	855	1	Phosphoserine; by AMPK By similarity
	Modified residue	950	1	Phosphoserine By similarity
	Modified residue	951	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 301	301	Missing in isoform 2.		VSP_017116
	Natural variant	100	1	Y → H. Ref.3 Corresponds to variant rs16975750 [ dbSNP | Ensembl ].		VAR_025108
	Natural variant	127	1	Q → H. Ref.3 Corresponds to variant rs34080774 [ dbSNP | Ensembl ].		VAR_025109
	Natural variant	146	1	P → Q in a breast cancer sample; somatic mutation. Ref.8		VAR_036539
	Natural variant	146	1	P → S. Ref.3 Corresponds to variant rs34348028 [ dbSNP | Ensembl ].		VAR_025110
	Natural variant	177	1	S → T. Ref.3 Corresponds to variant rs16975748 [ dbSNP | Ensembl ].		VAR_025111
	Natural variant	194	1	A → V. Ref.3 Corresponds to variant rs34996020 [ dbSNP | Ensembl ].		VAR_025112
	Natural variant	217	1	R → Q. Ref.3 Corresponds to variant rs3745238 [ dbSNP | Ensembl ].		VAR_025113
	Natural variant	497	1	K → N. Ref.3 Corresponds to variant rs35938529 [ dbSNP | Ensembl ].		VAR_025114
	Natural variant	499	1	N → H. Ref.3 Corresponds to variant rs33921216 [ dbSNP | Ensembl ].		VAR_025115
	Natural variant	938	1	R → S. Ref.3 Corresponds to variant rs7246232 [ dbSNP | Ensembl ].		VAR_025116
Experimental info
	Sequence conflict	230	1	T → A in AAA69810. Ref.1
	Sequence conflict	230	1	T → A in AAC50666. Ref.2
	Sequence conflict	230	1	T → A in ABA03168. Ref.3
	Sequence conflict	486	1	S → Y in AAH70041. Ref.4
	Sequence conflict	608	1	Y → C in AAH70041. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Testicular) [UniParc]. Last modified April 17, 2007. Version 4. Checksum: 1CC0E3880FF64D74	FASTA	1,076	116,598
	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
	Isoform 2 [UniParc]. Checksum: 3462D4A99945661B	FASTA	775	84,128
	10 20 30 40 50 60 MDLRTMTQSL VTLAEDNIAF FSSQGPGETA QRLSGVFAGV REQALGLEPA LGRLLGVAHL 70 80 90 100 110 120 FDLDPETPAN GYRSLVHTAR CCLAHLLHKS RYVASNRRSI FFRTSHNLAE LEAYLAALTQ 130 140 150 160 170 180 LRALVYYAQR LLVTNRPGVL FFEGDEGLTA DFLREYVTLH KGCFYGRCLG FQFTPAIRPF 190 200 210 220 230 240 LQTISIGLVS FGEHYKRNET GLSVAASSLF TSGRFAIDPE LRGAEFERIT QNLDVHFWKA 250 260 270 280 290 300 FWNITEMEVL SSLANMASAT VRVSRLLSLP PEAFEMPLTA DPTLTVTISP PLAHTGPGPV 310 320 330 340 350 360 LVRLISYDLR EGQDSEELSS LIKSNGQRSL ELWPRPQQAP RSRSLIVHFH GGGFVAQTSR 370 380 390 400 410 420 SHEPYLKSWA QELGAPIISI DYSLAPEAPF PRALEECFFA YCWAIKHCAL LGSTGERICL 430 440 450 460 470 480 AGDSAGGNLC FTVALRAAAY GVRVPDGIMA AYPATMLQPA ASPSRLLSLM DPLLPLSVLS 490 500 510 520 530 540 KCVSAYAGAK TEDHSNSDQK ALGMMGLVRR DTALLLRDFR LGASSWLNSF LELSGRKSQK 550 560 570 580 590 600 MSEPIAEPMR RSVSEAALAQ PQGPLGTDSL KNLTLRDLSL RGNSETSSDT PEMSLSAETL 610 620 630 640 650 660 SPSTPSDVNF LLPPEDAGEE AEAKNELSPM DRGLGVRAAF PEGFHPRRSS QGATQMPLYS 670 680 690 700 710 720 SPIVKNPFMS PLLAPDSMLK SLPPVHIVAC ALDPMLDDSV MLARRLRNLG QPVTLRVVED 730 740 750 760 770 LPHGFLTLAA LCRETRQAAE LCVERIRLVL TPPAGAGPSG ETGAAGVDGG CGGRH

References

	« Hide 'large scale' referencesShow '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. , 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

SeattleSNPs

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.
IPI	IPI00419542. IPI00643204.
RefSeq	NP_005348.2. NM_005357.2.
UniGene	Hs.656980.
3D structure databases
ProteinModelPortal	Q05469.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q05469. 1 interaction.
MINT	MINT-1370154.
STRING	9606.ENSP00000244289.
Protein family/group databases
MEROPS	S09.993.
PTM databases
PhosphoSite	Q05469.
Polymorphism databases
DMDM	145559491.
Proteomic databases
PaxDb	Q05469.
PRIDE	Q05469.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000244289; ENSP00000244289; ENSG00000079435.
GeneID	3991.
KEGG	hsa:3991.
UCSC	uc002otr.3. human.
Organism-specific databases
CTD	3991.
GeneCards	GC19M042906.
H-InvDB	HIX0040096.
HGNC	HGNC:6621. LIPE.
HPA	CAB017700.
MIM	151750. gene.
neXtProt	NX_Q05469.
PharmGKB	PA30393.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0657.
HOGENOM	HOG000047722.
HOVERGEN	HBG000187.
InParanoid	Q05469.
KO	K07188.
OMA	LVVHIHG.
OrthoDB	EOG4DV5KG.
PhylomeDB	Q05469.
Enzyme and pathway databases
BioCyc	MetaCyc:HS01328-MONOMER.
BRENDA	3.1.1.79. 2681.
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00256.
Gene expression databases
Bgee	Q05469.
CleanEx	HS_LIPE.
Genevestigator	Q05469.
GermOnline	ENSG00000079435. Homo sapiens.
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	Q05469.
ChEMBL	CHEMBL3590.
GenomeRNAi	3991.
NextBio	15656.
SOURCE	Search...

Entry information

Entry name

LIPS_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 121 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.