P02656 (APOC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Apolipoprotein C-III
Short name=Apo-CIII
Short name=ApoC-III

Alternative name(s):
Apolipoprotein C3

Gene names

Name:

APOC3

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	99 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	Inhibits lipoprotein lipase and hepatic lipase and decreases the uptake of lymph chylomicrons by hepatic cells. This suggests that it delays the catabolism of triglyceride-rich particles.
Subcellular location	Secreted.
Tissue specificity	Constitutes 50% of the protein fraction of VLDL and 2% of that of HDL. Synthesized predominantly in liver and to a lesser degree in intestine.
Post-translational modification	The most abundant glycoforms are characterized by an O-linked disaccharide galactose linked to N-acetylgalactosamine (Gal-GalNAc), further modified with up to 3 sialic acid residues. Less abundant glycoforms are characterized by more complex and fucosylated glycan moieties. O-glycosylated on Thr-94 with a core 1 or possibly core 8 glycan. Ref.11 Ref.12
Involvement in disease	Hyperalphalipoproteinemia 2 (HALP2) [MIM:614028]: A condition characterized by high levels of high density lipoprotein (HDL) and increased HDL cholesterol levels. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13
Sequence similarities	Belongs to the apolipoprotein C3 family.

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism Lipid transport Transport
Cellular component	Chylomicron Secreted VLDL
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Ligand	Sialic acid
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Inferred from direct assay PubMed 16443932. Source: BHF-UCL cellular response to glucose stimulus Inferred from electronic annotation. Source: Ensembl cholesterol efflux Inferred from direct assay PubMed 11162594PubMed 16443932. Source: BHF-UCL cholesterol homeostasis Inferred from mutant phenotype PubMed 18767813. Source: BHF-UCL cholesterol metabolic process Inferred from electronic annotation. Source: Ensembl chylomicron remnant clearance Inferred from direct assay PubMed 4020294. Source: BHF-UCL high-density lipoprotein particle remodeling Inferred from mutant phenotype PubMed 17438339. Source: BHF-UCL inflammatory response Inferred from electronic annotation. Source: Ensembl lipoprotein metabolic process Traceable author statement. Source: Reactome lipoprotein transport Inferred from electronic annotation. Source: Ensembl negative regulation of cholesterol import Inferred from mutant phenotype PubMed 15778093. Source: BHF-UCL negative regulation of fatty acid biosynthetic process Inferred from direct assay PubMed 11060345PubMed 18635818. Source: BHF-UCL negative regulation of high-density lipoprotein particle clearance Inferred from mutant phenotype PubMed 15778093. Source: BHF-UCL negative regulation of lipid catabolic process Inferred from direct assay PubMed 15576844. Source: BHF-UCL negative regulation of lipid metabolic process Inferred from direct assay PubMed 182536. Source: BHF-UCL negative regulation of lipoprotein lipase activity Inferred from direct assay PubMed 11060345PubMed 18635818PubMed 3973011. Source: BHF-UCL negative regulation of low-density lipoprotein particle clearance Inferred from mutant phenotype PubMed 15778093. Source: BHF-UCL negative regulation of receptor-mediated endocytosis Inferred from direct assay PubMed 1917954. Source: BHF-UCL negative regulation of triglyceride catabolic process Inferred from direct assay PubMed 18635818PubMed 3973011. Source: BHF-UCL negative regulation of very-low-density lipoprotein particle clearance Inferred from direct assay PubMed 1917954. Source: BHF-UCL negative regulation of very-low-density lipoprotein particle remodeling Inferred from direct assay PubMed 3973011. Source: BHF-UCL phospholipid efflux Inferred from direct assay PubMed 11162594. Source: BHF-UCL phototransduction, visible light Traceable author statement. Source: Reactome regulation of Cdc42 protein signal transduction Inferred from direct assay PubMed 16443932. Source: BHF-UCL response to drug Inferred from electronic annotation. Source: Ensembl response to nutrient Inferred from electronic annotation. Source: Ensembl response to peptide hormone Inferred from electronic annotation. Source: Ensembl retinoid metabolic process Traceable author statement. Source: Reactome reverse cholesterol transport Inferred by curator PubMed 15778093. Source: BHF-UCL small molecule metabolic process Traceable author statement. Source: Reactome triglyceride catabolic process Inferred from direct assay PubMed 11060345. Source: BHF-UCL triglyceride homeostasis Inferred from mutant phenotype PubMed 18767813. Source: BHF-UCL triglyceride metabolic process Inferred from mutant phenotype PubMed 17142127. Source: HGNC triglyceride mobilization Inferred from electronic annotation. Source: Ensembl very-low-density lipoprotein particle assembly Traceable author statement PubMed 18399797. Source: BHF-UCL
Cellular_component	chylomicron Inferred from direct assay PubMed 8245722. Source: BHF-UCL early endosome Traceable author statement. Source: Reactome extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from direct assay PubMed 11060345. Source: BHF-UCL intermediate-density lipoprotein particle Inferred from direct assay PubMed 17336988. Source: BHF-UCL spherical high-density lipoprotein particle Inferred from direct assay PubMed 17438339. Source: BHF-UCL very-low-density lipoprotein particle Inferred from direct assay PubMed 16935699PubMed 17154273PubMed 3973011. Source: BHF-UCL
Molecular_function	cholesterol binding Inferred by curator PubMed 11162594. Source: BHF-UCL enzyme regulator activity Inferred from direct assay PubMed 11060345. Source: BHF-UCL high-density lipoprotein particle receptor binding Inferred from physical interaction PubMed 9254056. Source: BHF-UCL lipase inhibitor activity Inferred from direct assay PubMed 15576844PubMed 182536PubMed 18635818PubMed 3973011. Source: BHF-UCL phospholipid binding Inferred from direct assay PubMed 11060345PubMed 4066713. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Ref.7 Ref.8

Chain

21 – 99

79

Apolipoprotein C-III Ref.7

PRO_0000002031

Regions

Region

68 – 99

32

Lipid-binding

Amino acid modifications

Glycosylation

94

1

O-linked (GalNAc...) Ref.9 Ref.11 Ref.12

CAR_000168

Natural variations

Natural variant

78

1

K → E in HALP2. Ref.13

VAR_000643

Natural variant

94

1

T → A in C-III-0; unglycosylated. Ref.12

VAR_000644

Experimental info

Sequence conflict

52 – 53

2

ES → SQ AA sequence Ref.8

Sequence conflict

57 – 59

3

QQA → AQQ AA sequence Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

99

Helix Strand Turn

Details...

Helix

29 – 39

11

Helix

40 – 42

3

Helix

43 – 48

6

Helix

49 – 55

7

Helix

56 – 62

7

Turn

63 – 68

6

Helix

69 – 80

12

Helix

83 – 85

3

Helix

93 – 98

6

Sequences

	Sequence		Length	Mass (Da)
	P02656 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: D4E806339FAE4DA7	FASTA	99	10,852
	10 20 30 40 50 60 MQPRVLLVVA LLALLASARA SEAEDASLLS FMQGYMKHAT KTAKDALSSV QESQVAQQAR 70 80 90 GWVTDGFSSL KDYWSTVKDK FSEFWDLDPE VRPTSAVAA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and sequence analysis of the human apolipoprotein CIII gene and the intergenic region between the apo AI and apo CIII genes." Protter A.A., Levy-Wilson B., Miller J., Bencen G., White T., Seilhamer J.J. DNA 3:449-456(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"Isolation and DNA sequence of full-length cDNA for human preapolipoprotein CIII." Levy-Wilson B., Appleby V., Protter A.A., Auperin D., Seilhamer J.J. DNA 3:359-364(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Isolation and characterization of cDNA clones corresponding to two different human apoC-III alleles." Karathanasis S.K., Zannis V.I., Breslow J.L. J. Lipid Res. 26:451-456(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[4]	"Human apolipoproteins AI, AII, CII and CIII. cDNA sequences and mRNA abundance." Sharpe C.R., Sidoli A., Shelley C.S., Lucero M.A., Shoulders C.C., Baralle F.E. Nucleic Acids Res. 12:3917-3932(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The effects of scale: variation in the APOA1/C3/A4/A5 gene cluster." Fullerton S.M., Buchanan A.V., Sonpar V.A., Taylor S.L., Smith J.D., Carlson C.S., Salomaa V., Stengaard J.H., Boerwinkle E., Clark A.G., Nickerson D.A., Weiss K.M. Hum. Genet. 115:36-56(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [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]. Tissue: Pancreas and Spleen.
[7]	"Amino acid sequence of human plasma apolipoprotein C-III from normolipidemic subjects." Hospattankar A.V., Brewer H.B. Jr., Ronan R., Fairwell T. FEBS Lett. 197:67-73(1986) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-99.
[8]	"The complete amino acid sequence of alanine apolipoprotein (apoC-3), and apolipoprotein from human plasma very low density lipoproteins." Brewer H.B. Jr., Shulman R., Herbert P., Ronan R., Wehrly K. J. Biol. Chem. 249:4975-4984(1974) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-99.
[9]	"Enrichment of glycopeptides for glycan structure and attachment site identification." Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G. Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT THR-94, STRUCTURE OF CARBOHYDRATES. Tissue: Cerebrospinal fluid.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"Identification of new apolipoprotein-CIII glycoforms with ultrahigh resolution MALDI-FTICR mass spectrometry of human sera." Nicolardi S., van der Burgt Y.E., Dragan I., Hensbergen P.J., Deelder A.M. J. Proteome Res. 12:2260-2268(2013) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-94, STRUCTURE OF CARBOHYDRATES, IDENTIFICATION BY MASS SPECTROMETRY.
[12]	"Molecular cloning of a human apoC-III variant: Thr 74-->Ala 74 mutation prevents O-glycosylation." Maeda H., Hashimoto R.K., Oguro T., Hiraga S., Uzawa H. J. Lipid Res. 28:1405-1409(1987) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT C-III-0 ALA-94, GLYCOSYLATION AT THR-94.
[13]	"Apolipoprotein C-III(Lys-58-->Glu). Identification of an apolipoprotein C-III variant in a family with hyperalphalipoproteinemia." von Eckardstein A., Holz H., Sandkamp M., Weng W., Funke H., Assmann G. J. Clin. Invest. 87:1724-1731(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HALP2 GLU-78.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J00098 Genomic DNA. Translation: AAB59515.1.
M33043, M33041, M33042 Genomic DNA. Translation: AAB59372.1.
X01392 Genomic DNA. Translation: CAA25648.1.
X01388 mRNA. Translation: CAA25644.1.
X03120 Genomic DNA. Translation: CAA26895.1.
V01513 mRNA. Translation: CAA24757.1.
M28613 mRNA. Translation: AAA51760.1.
M28614 mRNA. Translation: AAA51761.1.
X00567 mRNA. Translation: CAA25233.1.
AY422951 Genomic DNA. Translation: AAQ91810.1.
AY555191 Genomic DNA. Translation: AAS68230.1.
BC027977 mRNA. Translation: AAH27977.1.
BC121081 mRNA. Translation: AAI21082.1.

CCDS

CCDS8377.1.

PIR

LPHUC3. A90950.

RefSeq

NP_000031.1. NM_000040.1.

UniGene

Hs.73849.

3D structure databases

PDBe
RCSB-PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JQ3	NMR	-	A	21-99	[»]

ProteinModelPortal

P02656.

SMR

P02656. Positions 21-99.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

106842. 5 interactions.

IntAct

P02656. 3 interactions.

MINT

MINT-5000873.

STRING

9606.ENSP00000227667.

PTM databases

PhosphoSite

P02656.

UniCarbKB

P02656.

Polymorphism databases

DMDM

114026.

2D gel databases

DOSAC-COBS-2DPAGE

P02656.

SWISS-2DPAGE

P02656.

Proteomic databases

MaxQB

P02656.

PaxDb

P02656.

PRIDE

P02656.

Protocols and materials databases

DNASU

345.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000227667; ENSP00000227667; ENSG00000110245.

GeneID

345.

KEGG

hsa:345.

UCSC

uc001ppt.1. human.

Organism-specific databases

CTD

345.

GeneCards

GC11P116700.

HGNC

HGNC:610. APOC3.

MIM

107720. gene.
614028. phenotype.

neXtProt

NX_P02656.

Orphanet

79506. Cholesterol-ester transfer protein deficiency.
33271. Non-alcoholic fatty liver disease.

PharmGKB

PA53.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39866.

HOGENOM

HOG000247042.

HOVERGEN

HBG050549.

InParanoid

P02656.

KO

K08759.

PhylomeDB

P02656.

TreeFam

TF338209.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_116125. Disease.

Gene expression databases

ArrayExpress

P02656.

Bgee

P02656.

CleanEx

HS_APOC3.

Genevestigator

P02656.

Family and domain databases

InterPro

IPR008403. Apo-CIII.
[Graphical view]

PANTHER

PTHR14225. PTHR14225. 1 hit.

Pfam

PF05778. Apo-CIII. 1 hit.
[Graphical view]

ProDom

PD010414. Apo-CIII. 1 hit.
[Graphical view] [Entries sharing at least one domain]

ProtoNet

Search...

Other

EvolutionaryTrace

P02656.

GeneWiki

Apolipoprotein_C3.

GenomeRNAi

345.

NextBio

1423.

PRO

P02656.

SOURCE

Search...

Entry information

Entry name

APOC3_HUMAN

Accession

Primary (citable) accession number: P02656
Secondary accession number(s): Q08E83, Q6Q786

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	July 9, 2014
This is version 146 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.