Q9Y5X9 (LIPE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Endothelial lipase
EC=3.1.1.3

Alternative name(s):
Endothelial cell-derived lipase
Short name=EDL
Short name=EL

Gene names

Name:	LIPG
ORF Names:	UNQ387/PRO719

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	500 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Has phospholipase and triglyceride lipase activities. Hydrolyzes high density lipoproteins (HDL) more efficiently than other lipoproteins. Binds heparin.
Catalytic activity	Triacylglycerol + H2O = diacylglycerol + a carboxylate.
Enzyme regulation	Inhibited by serum.
Subunit structure	Head to tail homodimer. Ref.9
Subcellular location	Secreted.
Tissue specificity	High level of expression in the liver, placenta, lung, thyroid, kidney, testis and in the corpus luteum of the ovary. Expressed also in coronary artery endothelial cells, umbilical vein endothelial cells and in hepatocytes and osteosarcoma cell lines. Not detected in heart, brain and muscle.
Miscellaneous	It is termed endothelial lipase due to the fact that it is synthesized in endothelial cells, a characteristic that distinguishes it from other members of the family. However, this protein is also expressed in other cell types.
Sequence similarities	Belongs to the AB hydrolase superfamily. Lipase family. Contains 1 PLAT domain.

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Ligand	Heparin-binding
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell proliferation Inferred from electronic annotation. Source: Compara cholesterol homeostasis Inferred from mutant phenotype PubMed 19136670. Source: BHF-UCL high-density lipoprotein particle remodeling Inferred from mutant phenotype PubMed 19136670. Source: BHF-UCL phospholipid catabolic process Non-traceable author statement PubMed 19136670. Source: BHF-UCL phospholipid homeostasis Inferred from mutant phenotype PubMed 19136670. Source: BHF-UCL positive regulation of cholesterol transport Inferred from direct assay PubMed 19136670. Source: BHF-UCL positive regulation of high-density lipoprotein particle clearance Inferred from mutant phenotype PubMed 19136670. Source: BHF-UCL regulation of lipoprotein metabolic process Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara reverse cholesterol transport Inferred from mutant phenotype PubMed 19136670. Source: BHF-UCL
Cellular_component	extracellular space Inferred from direct assay Ref.2. Source: BHF-UCL
Molecular_function	heparin binding Inferred from electronic annotation. Source: UniProtKB-KW lipoprotein lipase activity Inferred from electronic annotation. Source: InterPro phosphatidylcholine 1-acylhydrolase activity Inferred from direct assay Ref.1. Source: MGI retinyl-palmitate esterase activity Inferred from electronic annotation. Source: EC triglyceride lipase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y5X9-1)

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: Q9Y5X9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     346-354: VYHYQMKIH → GNLQSLECP
     355-500: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 500	480	Endothelial lipase		PRO_0000017797
Regions
	Domain	347 – 482	136	PLAT
	Region	325 – 337	13	Heparin-binding By similarity
	Compositional bias	118 – 121	4	Poly-Val
Sites
	Active site	169	1	Nucleophile By similarity
	Active site	193	1	Charge relay system By similarity
	Active site	274	1	Charge relay system By similarity
Amino acid modifications
	Glycosylation	80	1	N-linked (GlcNAc...) Potential
	Glycosylation	136	1	N-linked (GlcNAc...) Potential
	Glycosylation	393	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	469	1	N-linked (GlcNAc...) Potential
	Glycosylation	491	1	N-linked (GlcNAc...) Potential
	Disulfide bond	64 ↔ 77		By similarity
	Disulfide bond	252 ↔ 272		By similarity
	Disulfide bond	297 ↔ 316		By similarity
	Disulfide bond	308 ↔ 311		By similarity
	Disulfide bond	463 ↔ 483		By similarity
Natural variations
	Alternative sequence	346 – 354	9	VYHYQMKIH → GNLQSLECP in isoform 2.		VSP_013302
	Alternative sequence	355 – 500	146	Missing in isoform 2.		VSP_013303
	Natural variant	26	1	G → S. Corresponds to variant rs9963243 [ dbSNP | Ensembl ].		VAR_034082
	Natural variant	96	1	G → S. Ref.10		VAR_017027
	Natural variant	111	1	T → I. Ref.10 Corresponds to variant rs2000813 [ dbSNP | Ensembl ].		VAR_017028
	Natural variant	312	1	R → H. Ref.10		VAR_017029
Experimental info
	Sequence conflict	476	1	R → Q in AAH60825. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 96EC95125CD2A3FD	FASTA	500	56,795
	10 20 30 40 50 60 MSNSVPLLCF WSLCYCFAAG SPVPFGPEGR LEDKLHKPKA TQTEVKPSVR FNLRTSKDPE 70 80 90 100 110 120 HEGCYLSVGH SQPLEDCSFN MTAKTFFIIH GWTMSGIFEN WLHKLVSALH TREKDANVVV 130 140 150 160 170 180 VDWLPLAHQL YTDAVNNTRV VGHSIARMLD WLQEKDDFSL GNVHLIGYSL GAHVAGYAGN 190 200 210 220 230 240 FVKGTVGRIT GLDPAGPMFE GADIHKRLSP DDADFVDVLH TYTRSFGLSI GIQMPVGHID 250 260 270 280 290 300 IYPNGGDFQP GCGLNDVLGS IAYGTITEVV KCEHERAVHL FVDSLVNQDK PSFAFQCTDS 310 320 330 340 350 360 NRFKKGICLS CRKNRCNSIG YNAKKMRNKR NSKMYLKTRA GMPFRVYHYQ MKIHVFSYKN 370 380 390 400 410 420 MGEIEPTFYV TLYGTNADSQ TLPLEIVERI EQNATNTFLV YTEEDLGDLL KIQLTWEGAS 430 440 450 460 470 480 QSWYNLWKEF RSYLSQPRNP GRELNIRRIR VKSGETQRKL TFCTEDPENT SISPGRELWF 490 500 RKCRDGWRMK NETSPTVELP
	Isoform 2 [UniParc]. Checksum: 939A47B18F97B7FA	FASTA	354	39,362
	10 20 30 40 50 60 MSNSVPLLCF WSLCYCFAAG SPVPFGPEGR LEDKLHKPKA TQTEVKPSVR FNLRTSKDPE 70 80 90 100 110 120 HEGCYLSVGH SQPLEDCSFN MTAKTFFIIH GWTMSGIFEN WLHKLVSALH TREKDANVVV 130 140 150 160 170 180 VDWLPLAHQL YTDAVNNTRV VGHSIARMLD WLQEKDDFSL GNVHLIGYSL GAHVAGYAGN 190 200 210 220 230 240 FVKGTVGRIT GLDPAGPMFE GADIHKRLSP DDADFVDVLH TYTRSFGLSI GIQMPVGHID 250 260 270 280 290 300 IYPNGGDFQP GCGLNDVLGS IAYGTITEVV KCEHERAVHL FVDSLVNQDK PSFAFQCTDS 310 320 330 340 350 NRFKKGICLS CRKNRCNSIG YNAKKMRNKR NSKMYLKTRA GMPFRGNLQS LECP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a unique lipase from endothelial cells extends the lipase gene family." Hirata K., Dichek H.L., Cioffi J.A., Choi S.Y., Leeper N.J., Quintana L., Kronmal G.S., Cooper A.D., Quertermous T. J. Biol. Chem. 274:14170-14175(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Endothelial cell.
[2]	"A novel endothelial-derived lipase that modulates HDL metabolism." Jaye M., Lynch K.J., Krawiec J., Marchadier D., Maugeais C., Doan K., South V., Amin D., Perrone M., Rader D.J. Nat. Genet. 21:424-428(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: Placenta.
[7]	"Characterization of the lipolytic activity of endothelial lipase." McCoy M.G., Sun G.-S., Marchadier D., Maugeais C., Glick J.M., Rader D.J. J. Lipid Res. 43:921-929(2002) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[8]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-393, MASS SPECTROMETRY. Tissue: Plasma.
[9]	"Identification of the active form of endothelial lipase, a homodimer in a head-to-tail conformation." Griffon N., Jin W., Petty T.J., Millar J., Badellino K.O., Saven J.G., Marchadier D.H., Kempner E.S., Billheimer J., Glick J.M., Rader D.J. J. Biol. Chem. 284:23322-23330(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[10]	"Association of extreme blood lipid profile phenotypic variation with 11 reverse cholesterol transport genes and 10 non-genetic cardiovascular disease risk factors." Morabia A., Cayanis E., Costanza M.C., Ross B.M., Flaherty M.S., Alvin G.B., Das K., Gilliam T.C. Hum. Mol. Genet. 12:2733-2743(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SER-96; ILE-111 AND HIS-312.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF118767 mRNA. Translation: AAD30434.1. AY358928 mRNA. Translation: AAQ89287.1. EU332856 Genomic DNA. Translation: ABY87545.1. CH471096 Genomic DNA. Translation: EAW62947.1. BC060825 mRNA. Translation: AAH60825.1.
IPI	IPI00005686. IPI00554544.
RefSeq	NP_006024.1. NM_006033.2.
UniGene	Hs.465102.
3D structure databases
ProteinModelPortal	Q9Y5X9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y5X9. 2 interactions.
STRING	9606.ENSP00000261292.
Polymorphism databases
DMDM	22001808.
Proteomic databases
PaxDb	Q9Y5X9.
PRIDE	Q9Y5X9.
Protocols and materials databases
DNASU	9388.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261292; ENSP00000261292; ENSG00000101670. ENST00000580036; ENSP00000462420; ENSG00000101670.
GeneID	9388.
KEGG	hsa:9388.
UCSC	uc002ldu.1. human. uc002ldv.3. human.
Organism-specific databases
CTD	9388.
GeneCards	GC18P047088.
HGNC	HGNC:6623. LIPG.
HPA	HPA016966.
MIM	603684. gene.
neXtProt	NX_Q9Y5X9.
PharmGKB	PA30395.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG40923.
HOGENOM	HOG000038553.
HOVERGEN	HBG002259.
InParanoid	Q9Y5X9.
KO	K01046.
OMA	KLTFCAE.
OrthoDB	EOG4320Z4.
PhylomeDB	Q9Y5X9.
Gene expression databases
ArrayExpress	Q9Y5X9.
Bgee	Q9Y5X9.
CleanEx	HS_LIPG.
Genevestigator	Q9Y5X9.
GermOnline	ENSG00000101670. Homo sapiens.
Family and domain databases
Gene3D	2.60.60.20. 1 hit.
InterPro	IPR000734. Lipase. IPR008976. Lipase_LipOase. IPR013818. Lipase_N. IPR002330. Lipo_Lipase. IPR001024. LipOase_LH2. IPR016272. Lipoprotein_lipase_LIPH. [Graphical view]
PANTHER	PTHR11610. PTHR11610. 1 hit.
Pfam	PF00151. Lipase. 1 hit. PF01477. PLAT. 1 hit. [Graphical view]
PIRSF	PIRSF000865. Lipoprotein_lipase_LIPH. 1 hit.
PRINTS	PR00822. LIPOLIPASE. PR00821. TAGLIPASE.
SUPFAM	SSF49723. Lipase_LipOase. 1 hit.
PROSITE	PS00120. LIPASE_SER. 1 hit. PS50095. PLAT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9Y5X9.
ChEMBL	CHEMBL5080.
ChiTaRS	LIPG. human.
GenomeRNAi	9388.
NextBio	35175.
PMAP-CutDB	Q9Y5X9.
SOURCE	Search...

Entry information

Entry name

LIPE_HUMAN

Accession

Primary (citable) accession number: Q9Y5X9
Secondary accession number(s): B0LPG6, Q6P9C8, Q6UW82

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 26, 2002
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 120 of the entry and version 1 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.