P11150 (LIPC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hepatic triacylglycerol lipase
Short name=HL
Short name=Hepatic lipase
EC=3.1.1.3

Alternative name(s):
Lipase member C

Gene names

Name:	LIPC
Synonyms:	HTGL

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	499 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	Hepatic lipase has the capacity to catalyze hydrolysis of phospholipids, mono-, di-, and triglycerides, and acyl-CoA thioesters. It is an important enzyme in HDL metabolism. Hepatic lipase binds heparin.
Catalytic activity	Triacylglycerol + H2O = diacylglycerol + a carboxylate.
Subcellular location	Secreted.
Polymorphism	Genetic variations in LIPC define the high density lipoprotein cholesterol level quantitative trait locus 12 (HDLCQ12) [MIM:612797]. Genetic variations in LIPC are associated with non-insulin-dependent diabetes mellitus susceptibility (NIDDM susceptibility) [MIM:125853].
Involvement in disease	Hepatic lipase deficiency (HL deficiency) [MIM:614025]: A disorder characterized by elevated levels of beta-migrating very low density lipoproteins, and abnormally triglyceride-rich low and high density lipoproteins. Note: The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarities	Belongs to the AB hydrolase superfamily. Lipase family. Contains 1 PLAT domain.

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism
Cellular component	HDL Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Ligand	Heparin-binding
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol homeostasis Inferred from mutant phenotype PubMed 1883393. Source: BHF-UCL cholesterol metabolic process Inferred from electronic annotation. Source: Compara chylomicron remnant clearance Traceable author statement PubMed 9685400. Source: BHF-UCL fatty acid biosynthetic process Inferred from direct assay PubMed 182536. Source: BHF-UCL high-density lipoprotein particle remodeling Inferred from mutant phenotype PubMed 3244012. Source: BHF-UCL intermediate-density lipoprotein particle remodeling Traceable author statement Ref.3. Source: BHF-UCL low-density lipoprotein particle remodeling Inferred from mutant phenotype PubMed 3244012. Source: BHF-UCL phosphatidylcholine catabolic process Traceable author statement Ref.3. Source: BHF-UCL reverse cholesterol transport Inferred by curator PubMed 14531818. Source: BHF-UCL triglyceride catabolic process Inferred from direct assay PubMed 182536Ref.3PubMed 8640403. Source: BHF-UCL triglyceride homeostasis Inferred from mutant phenotype PubMed 1883393. Source: BHF-UCL very-low-density lipoprotein particle remodeling Inferred from direct assay PubMed 8640403. Source: BHF-UCL
Cellular_component	extracellular space Inferred from direct assay Ref.3. Source: BHF-UCL high-density lipoprotein particle Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	apolipoprotein binding Inferred from sequence or structural similarity. Source: BHF-UCL heparin binding Inferred from electronic annotation. Source: UniProtKB-KW low-density lipoprotein particle binding Inferred from sequence or structural similarity. Source: BHF-UCL phospholipase activity Traceable author statement PubMed 3244012. Source: BHF-UCL retinyl-palmitate esterase activity Inferred from electronic annotation. Source: EC triglyceride lipase activity Inferred from direct assay PubMed 182536Ref.3. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22
	Chain	23 – 499	477	Hepatic triacylglycerol lipase		PRO_0000017769
Regions
	Domain	352 – 486	135	PLAT
	Region	181 – 193	13	Heparin-binding Potential
Sites
	Active site	168	1	Nucleophile By similarity
	Active site	194	1	Charge relay system By similarity
	Active site	279	1	Charge relay system By similarity
Amino acid modifications
	Glycosylation	42	1	N-linked (GlcNAc...) Potential
	Glycosylation	78	1	N-linked (GlcNAc...) Potential
	Glycosylation	362	1	N-linked (GlcNAc...) Potential
	Glycosylation	397	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	95	1	V → M. Ref.15 Ref.17 Corresponds to variant rs6078 [ dbSNP | Ensembl ].		VAR_004206
	Natural variant	134	1	V → VHYTVAV in HL deficiency.		VAR_004207
	Natural variant	215	1	N → S. Ref.1 Ref.2 Ref.5 Ref.6 Ref.15 Ref.17 Corresponds to variant rs6083 [ dbSNP | Ensembl ].		VAR_004208
	Natural variant	289	1	S → F in HL deficiency. Ref.13 Ref.17		VAR_004209
	Natural variant	342	1	V → I. Ref.17		VAR_017024
	Natural variant	356	1	F → L. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.8 Ref.17 Corresponds to variant rs3829462 [ dbSNP | Ensembl ].		VAR_017025
	Natural variant	405	1	T → M in HL deficiency. Ref.13 Ref.17 Corresponds to variant rs28933094 [ dbSNP | Ensembl ].		VAR_004210
	Natural variant	409	1	D → A. Ref.17		VAR_017026
	Natural variant	440	1	S → N. Ref.15 Corresponds to variant rs6079 [ dbSNP | Ensembl ].		VAR_014179
Experimental info
	Sequence conflict	256	1	F → S in AAA61165. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P11150 [UniParc]. Last modified January 11, 2011. Version 3. Checksum: 1FC7567CAE3E514B	FASTA	499	55,914
	10 20 30 40 50 60 MDTSPLCFSI LLVLCIFIQS SALGQSLKPE PFGRRAQAVE TNKTLHEMKT RFLLFGETNQ 70 80 90 100 110 120 GCQIRINHPD TLQECGFNSS LPLVMIIHGW SVDGVLENWI WQMVAALKSQ PAQPVNVGLV 130 140 150 160 170 180 DWITLAHDHY TIAVRNTRLV GKEVAALLRW LEESVQLSRS HVHLIGYSLG AHVSGFAGSS 190 200 210 220 230 240 IGGTHKIGRI TGLDAAGPLF EGSAPSNRLS PDDANFVDAI HTFTREHMGL SVGIKQPIGH 250 260 270 280 290 300 YDFYPNGGSF QPGCHFLELY RHIAQHGFNA ITQTIKCSHE RSVHLFIDSL LHAGTQSMAY 310 320 330 340 350 360 PCGDMNSFSQ GLCLSCKKGR CNTLGYHVRQ EPRSKSKRLF LVTRAQSPFK VYHYQFKIQF 370 380 390 400 410 420 INQTETPIQT TFTMSLLGTK EKMQKIPITL GKGIASNKTY SFLITLDVDI GELIMIKFKW 430 440 450 460 470 480 ENSAVWANVW DTVQTIIPWS TGPRHSGLVL KTIRVKAGET QQRMTFCSEN TDDLLLRPTQ 490 EKIFVKCEIK SKTSKRKIR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human hepatic triglyceride lipase: cDNA cloning, amino acid sequence and expression in a cultured cell line." Stahnke G., Sprengel R., Augustin J., Will H. Differentiation 35:45-52(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SER-215 AND LEU-356. Tissue: Liver.
[2]	"Human hepatic lipase. Cloned cDNA sequence, restriction fragment length polymorphisms, chromosomal localization, and evolutionary relationships with lipoprotein lipase and pancreatic lipase." Datta S., Luo C.C., Li W.H., VanTuinen P., Ledbetter D.H., Brown M.A., Chen S.H., Liu S., Chan L. J. Biol. Chem. 263:1107-1110(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SER-215 AND LEU-356. Tissue: Liver.
[3]	"Isolation and cDNA sequence of human postheparin plasma hepatic triglyceride lipase." Martin G.A., Busch S.J., Meredith G.D., Cardin A.D., Blankenship D.T., Mao S.J.T., Rechtin A.E., Woods C.W., Racke M.M., Schafer M.P., Fitzgerald M.C., Burke D.M., Flanagan M.A., Jackson R.L. J. Biol. Chem. 263:10907-10914(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANT LEU-356. Tissue: Liver.
[4]	"Structure of the human hepatic triglyceride lipase gene." Cai S.J., Wong D.M., Chen S.H., Chan L. Biochemistry 28:8966-8971(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-356.
[5]	"Isolation and characterization of the human hepatic lipase gene." Ameis D., Stahnke G., Kobayashi J., McLean J., Lee G., Buscher M., Schotz M.C., Will H. J. Biol. Chem. 265:6552-6555(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-215 AND LEU-356.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS SER-215 AND LEU-356. Tissue: Kidney and Thymus.
[7]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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], VARIANT LEU-356.
[9]	"18 bp insertion/duplication with internal missense mutation in human hepatic lipase gene exon 3." Tiebel O., Gehrisch S., Pietzsch J., Gromeier S., Jaross W. Hum. Mutat. 12:216-216(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 92-152, VARIANT HL DEFICIENCY HIS-TYR-THR-VAL-ALA-VAL-134 INS.
[10]	"Identification of a BstNI polymorphism in exon 9 of the human hepatic triglyceride lipase gene." Takagi A., Ikeda Y., Mori A., Ashida Y., Yamamoto A. Mol. Cell. Probes 10:313-314(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 464-499.
[11]	"The G-250A promoter polymorphism of the hepatic lipase gene predicts the conversion from impaired glucose tolerance to type 2 diabetes mellitus: the Finnish diabetes prevention study." Todorova B., Kubaszek A., Pihlajamaki J., Lindstrom J., Eriksson J., Valle T.T., Hamalainen H., Ilanne-Parikka P., Keinanen-Kiukaanniemi S., Tuomilehto J., Uusitupa M., Laakso M. J. Clin. Endocrinol. Metab. 89:2019-2023(2004) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION WITH NIDDM SUSCEPTIBILITY.
[12]	"The -250G>A promoter variant in hepatic lipase associates with elevated fasting serum high-density lipoprotein cholesterol modulated by interaction with physical activity in a study of 16,156 Danish subjects." Grarup N., Andreasen C.H., Andersen M.K., Albrechtsen A., Sandbaek A., Lauritzen T., Borch-Johnsen K., Jorgensen T., Schmitz O., Hansen T., Pedersen O. J. Clin. Endocrinol. Metab. 93:2294-2299(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN HDLCQ12.
[13]	"Human hepatic lipase mutations and polymorphisms." Hegele R.A., Tu L., Connelly P.W. Hum. Mutat. 1:320-324(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HL DEFICIENCY PHE-289 AND MET-405.
[14]	"Genetic variants affecting human lipoprotein and hepatic lipases." Hayden M.R., Ma Y., Brunzell J., Henderson H.E. Curr. Opin. Lipidol. 2:104-109(1991) Cited for: REVIEW ON POLYMORPHISM.
[15]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MET-95; SER-215 AND ASN-440.
[16]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
[17]	"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 MET-95; SER-215; PHE-289; ILE-342; LEU-356; MET-405 AND ALA-409.
+	Additional computationally mapped references.

Web resources

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases
EMBL GenBank DDBJ	D83548 mRNA. Translation: BAA12014.1. X07228 mRNA. Translation: CAA30188.1. J03540 mRNA. Translation: AAA59520.1. J03895 mRNA. Translation: AAA61165.1. M29194 , M29186, M29187, M29188, M29189, M29190, M29191, M29192, M29193 Genomic DNA. Translation: AAB60702.1. D83062 Genomic DNA. Translation: BAA11760.1. M35433 , M35425, M35426, M35427, M35429, M35430, M35431, M35432 Genomic DNA. Translation: AAA59521.1. AK292631 mRNA. Translation: BAF85320.1. AK315306 mRNA. Translation: BAG37710.1. AC018904 Genomic DNA. No translation available. AC084781 Genomic DNA. No translation available. BC132825 mRNA. Translation: AAI32826.1. BC136495 mRNA. Translation: AAI36496.1. AF037404 Genomic DNA. Translation: AAC34206.1.
IPI	IPI00003882.
PIR	A28997.
RefSeq	NP_000227.2. NM_000236.2.
UniGene	Hs.654472.
3D structure databases
ProteinModelPortal	P11150.
SMR	P11150. Positions 47-425.
ModBase	Search...
Protein-protein interaction databases
IntAct	P11150. 1 interaction.
STRING	9606.ENSP00000299022.
PTM databases
PhosphoSite	P11150.
Polymorphism databases
DMDM	126308.
Proteomic databases
PaxDb	P11150.
PRIDE	P11150.
Protocols and materials databases
DNASU	3990.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000299022; ENSP00000299022; ENSG00000166035. ENST00000356113; ENSP00000348425; ENSG00000166035.
GeneID	3990.
KEGG	hsa:3990.
UCSC	uc002afa.2. human.
Organism-specific databases
CTD	3990.
GeneCards	GC15P058702.
H-InvDB	HIX0038150.
HGNC	HGNC:6619. LIPC.
HPA	CAB016141.
MIM	125853. phenotype. 151670. gene. 612797. phenotype. 614025. phenotype.
neXtProt	NX_P11150.
Orphanet	140905. Hyperlipidemia due to hepatic triglyceride lipase deficiency.
PharmGKB	PA230.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG81747.
HOGENOM	HOG000038553.
HOVERGEN	HBG002259.
InParanoid	P11150.
KO	K01046.
OrthoDB	EOG47D9G8.
PhylomeDB	P11150.
Gene expression databases
ArrayExpress	P11150.
Bgee	P11150.
CleanEx	HS_LIPC.
Genevestigator	P11150.
Family and domain databases
Gene3D	2.60.60.20. 1 hit.
InterPro	IPR000734. Lipase. IPR002333. Lipase_hep. IPR008976. Lipase_LipOase. IPR013818. Lipase_N. IPR001024. LipOase_LH2. IPR016272. Lipoprotein_lipase_LIPH. [Graphical view]
PANTHER	PTHR11610. PTHR11610. 1 hit. PTHR11610:SF2. PTHR11610:SF2. 1 hit.
Pfam	PF00151. Lipase. 1 hit. PF01477. PLAT. 1 hit. [Graphical view]
PIRSF	PIRSF000865. Lipoprotein_lipase_LIPH. 1 hit.
PRINTS	PR00824. HEPLIPASE. PR00821. TAGLIPASE.
SMART	SM00308. LH2. 1 hit. [Graphical view]
SUPFAM	SSF49723. Lipase_LipOase. 1 hit.
PROSITE	PS00120. LIPASE_SER. 1 hit. PS50095. PLAT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P11150.
ChEMBL	CHEMBL2127.
ChiTaRS	LIPC. human.
GenomeRNAi	3990.
NextBio	15652.
SOURCE	Search...

Entry information

Entry name

LIPC_HUMAN

Accession

Primary (citable) accession number: P11150
Secondary accession number(s): A2RUB4 , A8K9B6, O43571, P78529, Q99465

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	January 11, 2011
Last modified:	May 1, 2013
This is version 152 of the entry and version 3 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.