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P02656 (APOC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Apolipoprotein C-III

Short name=Apo-CIII
Short name=ApoC-III
Alternative name(s):
Apolipoprotein C3
Gene names
Name:APOC3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length99 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processLipid degradation
Lipid metabolism
Lipid transport
Transport
   Cellular componentChylomicron
Secreted
VLDL
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainSignal
   LigandSialic acid
   PTMGlycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processG-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_componentchylomicron

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_functioncholesterol 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Ref.7 Ref.8
Chain21 – 9979Apolipoprotein C-III Ref.7
PRO_0000002031

Regions

Region68 – 9932Lipid-binding

Amino acid modifications

Glycosylation941O-linked (GalNAc...) Ref.9 Ref.11 Ref.12
CAR_000168

Natural variations

Natural variant781K → E in HALP2. Ref.13
VAR_000643
Natural variant941T → A in C-III-0; unglycosylated. Ref.12
VAR_000644

Experimental info

Sequence conflict52 – 532ES → SQ AA sequence Ref.8
Sequence conflict57 – 593QQA → AQQ AA sequence Ref.8

Secondary structure

............. 99
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P02656 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: D4E806339FAE4DA7

FASTA9910,852
        10         20         30         40         50         60 
MQPRVLLVVA LLALLASARA SEAEDASLLS FMQGYMKHAT KTAKDALSSV QESQVAQQAR 

        70         80         90 
GWVTDGFSSL KDYWSTVKDK FSEFWDLDPE VRPTSAVAA 

« Hide

References

« Hide '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.
CCDSCCDS8377.1.
PIRLPHUC3. A90950.
RefSeqNP_000031.1. NM_000040.1.
UniGeneHs.73849.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2JQ3NMR-A21-99[»]
ProteinModelPortalP02656.
SMRP02656. Positions 21-99.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106842. 5 interactions.
IntActP02656. 3 interactions.
MINTMINT-5000873.
STRING9606.ENSP00000227667.

PTM databases

PhosphoSiteP02656.
UniCarbKBP02656.

Polymorphism databases

DMDM114026.

2D gel databases

DOSAC-COBS-2DPAGEP02656.
SWISS-2DPAGEP02656.

Proteomic databases

MaxQBP02656.
PaxDbP02656.
PRIDEP02656.

Protocols and materials databases

DNASU345.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000227667; ENSP00000227667; ENSG00000110245.
GeneID345.
KEGGhsa:345.
UCSCuc001ppt.1. human.

Organism-specific databases

CTD345.
GeneCardsGC11P116700.
HGNCHGNC:610. APOC3.
MIM107720. gene.
614028. phenotype.
neXtProtNX_P02656.
Orphanet79506. Cholesterol-ester transfer protein deficiency.
33271. Non-alcoholic fatty liver disease.
PharmGKBPA53.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39866.
HOGENOMHOG000247042.
HOVERGENHBG050549.
InParanoidP02656.
KOK08759.
PhylomeDBP02656.
TreeFamTF338209.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_116125. Disease.

Gene expression databases

ArrayExpressP02656.
BgeeP02656.
CleanExHS_APOC3.
GenevestigatorP02656.

Family and domain databases

InterProIPR008403. Apo-CIII.
[Graphical view]
PANTHERPTHR14225. PTHR14225. 1 hit.
PfamPF05778. Apo-CIII. 1 hit.
[Graphical view]
ProDomPD010414. Apo-CIII. 1 hit.
[Graphical view] [Entries sharing at least one domain]
ProtoNetSearch...

Other

EvolutionaryTraceP02656.
GeneWikiApolipoprotein_C3.
GenomeRNAi345.
NextBio1423.
PROP02656.
SOURCESearch...

Entry information

Entry nameAPOC3_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM