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Protein

Apolipoprotein C-III

Gene

APOC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of triglyceride-rich very low density lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma. Plays a multifaceted role in triglyceride homeostasis. Intracellularly, promotes hepatic very low density lipoprotein 1 (VLDL1) assembly and secretion; extracellularly, attenuates hydrolysis and clearance of triglyceride-rich lipoproteins (TRLs). Impairs the lipolysis of TRLs by inhibiting lipoprotein lipase and the hepatic uptake of TRLs by remnant receptors.2 Publications

GO - Molecular functioni

  • cholesterol binding Source: BHF-UCL
  • enzyme regulator activity Source: BHF-UCL
  • high-density lipoprotein particle receptor binding Source: BHF-UCL
  • lipase inhibitor activity Source: BHF-UCL
  • phospholipid binding Source: BHF-UCL

GO - Biological processi

  • cellular response to glucose stimulus Source: Ensembl
  • cholesterol efflux Source: BHF-UCL
  • cholesterol homeostasis Source: BHF-UCL
  • cholesterol metabolic process Source: Ensembl
  • chylomicron remnant clearance Source: BHF-UCL
  • G-protein coupled receptor signaling pathway Source: BHF-UCL
  • high-density lipoprotein particle remodeling Source: BHF-UCL
  • inflammatory response Source: Ensembl
  • lipoprotein metabolic process Source: Reactome
  • lipoprotein transport Source: Ensembl
  • negative regulation of cholesterol import Source: BHF-UCL
  • negative regulation of fatty acid biosynthetic process Source: BHF-UCL
  • negative regulation of high-density lipoprotein particle clearance Source: BHF-UCL
  • negative regulation of lipid catabolic process Source: BHF-UCL
  • negative regulation of lipid metabolic process Source: BHF-UCL
  • negative regulation of lipoprotein lipase activity Source: BHF-UCL
  • negative regulation of low-density lipoprotein particle clearance Source: BHF-UCL
  • negative regulation of receptor-mediated endocytosis Source: BHF-UCL
  • negative regulation of triglyceride catabolic process Source: BHF-UCL
  • negative regulation of very-low-density lipoprotein particle clearance Source: BHF-UCL
  • negative regulation of very-low-density lipoprotein particle remodeling Source: BHF-UCL
  • phospholipid efflux Source: BHF-UCL
  • phototransduction, visible light Source: Reactome
  • regulation of Cdc42 protein signal transduction Source: BHF-UCL
  • response to drug Source: Ensembl
  • response to nutrient Source: Ensembl
  • response to peptide hormone Source: Ensembl
  • retinoid metabolic process Source: Reactome
  • reverse cholesterol transport Source: BHF-UCL
  • small molecule metabolic process Source: Reactome
  • triglyceride catabolic process Source: BHF-UCL
  • triglyceride homeostasis Source: BHF-UCL
  • triglyceride metabolic process Source: HGNC
  • triglyceride mobilization Source: Ensembl
  • very-low-density lipoprotein particle assembly Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Lipid degradation, Lipid metabolism, Lipid transport, Transport

Keywords - Ligandi

Sialic acid

Enzyme and pathway databases

ReactomeiREACT_13621. HDL-mediated lipid transport.
REACT_24968. Retinoid metabolism and transport.
REACT_6841. Chylomicron-mediated lipid transport.

Names & Taxonomyi

Protein namesi
Recommended name:
Apolipoprotein C-III
Short name:
Apo-CIII
Short name:
ApoC-III
Alternative name(s):
Apolipoprotein C3
Gene namesi
Name:APOC3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:610. APOC3.

Subcellular locationi

GO - Cellular componenti

  • chylomicron Source: BHF-UCL
  • early endosome Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: BHF-UCL
  • intermediate-density lipoprotein particle Source: BHF-UCL
  • spherical high-density lipoprotein particle Source: BHF-UCL
  • very-low-density lipoprotein particle Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Chylomicron, Secreted, VLDL

Pathology & Biotechi

Involvement in diseasei

Hyperalphalipoproteinemia 2 (HALP2)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA condition characterized by high levels of high density lipoprotein (HDL) and increased HDL cholesterol levels.

See also OMIM:614028
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti78 – 781K → E in HALP2. 1 Publication
VAR_000643

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi614028. phenotype.
Orphaneti79506. Cholesterol-ester transfer protein deficiency.
33271. Non-alcoholic fatty liver disease.
PharmGKBiPA53.

Polymorphism and mutation databases

BioMutaiAPOC3.
DMDMi114026.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 20202 PublicationsAdd
BLAST
Chaini21 – 9979Apolipoprotein C-III1 PublicationPRO_0000002031Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi94 – 941O-linked (GalNAc...)3 PublicationsCAR_000168

Post-translational modificationi

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.3 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiP02656.
PaxDbiP02656.
PRIDEiP02656.

2D gel databases

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

PTM databases

PhosphoSiteiP02656.
UniCarbKBiP02656.

Expressioni

Tissue specificityi

Liver.1 Publication

Gene expression databases

BgeeiP02656.
CleanExiHS_APOC3.
ExpressionAtlasiP02656. baseline and differential.
GenevestigatoriP02656.

Interactioni

Protein-protein interaction databases

BioGridi106842. 5 interactions.
IntActiP02656. 3 interactions.
MINTiMINT-5000873.
STRINGi9606.ENSP00000227667.

Structurei

Secondary structure

1
99
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi29 – 3911Combined sources
Helixi40 – 423Combined sources
Helixi43 – 486Combined sources
Helixi49 – 557Combined sources
Helixi56 – 627Combined sources
Turni63 – 686Combined sources
Helixi69 – 8012Combined sources
Helixi83 – 853Combined sources
Helixi93 – 986Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JQ3NMR-A21-99[»]
ProteinModelPortaliP02656.
SMRiP02656. Positions 21-99.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP02656.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni68 – 9932Lipid-bindingAdd
BLAST

Sequence similaritiesi

Belongs to the apolipoprotein C3 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG39866.
GeneTreeiENSGT00390000015395.
HOGENOMiHOG000247042.
HOVERGENiHBG050549.
InParanoidiP02656.
KOiK08759.
PhylomeDBiP02656.
TreeFamiTF338209.

Family and domain databases

InterProiIPR008403. Apo-CIII.
[Graphical view]
PANTHERiPTHR14225. PTHR14225. 1 hit.
PfamiPF05778. Apo-CIII. 1 hit.
[Graphical view]
ProDomiPD010414. Apo-CIII. 1 hit.
[Graphical view] [Entries sharing at least one domain]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P02656-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQPRVLLVVA LLALLASARA SEAEDASLLS FMQGYMKHAT KTAKDALSSV
60 70 80 90
QESQVAQQAR GWVTDGFSSL KDYWSTVKDK FSEFWDLDPE VRPTSAVAA
Length:99
Mass (Da):10,852
Last modified:July 21, 1986 - v1
Checksum:iD4E806339FAE4DA7
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti52 – 532ES → SQ AA sequence (PubMed:4846755).Curated
Sequence conflicti57 – 593QQA → AQQ AA sequence (PubMed:4846755).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti78 – 781K → E in HALP2. 1 Publication
VAR_000643
Natural varianti94 – 941T → A in C-III-0; unglycosylated. 1 Publication
VAR_000644

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS8377.1.
PIRiA90950. LPHUC3.
RefSeqiNP_000031.1. NM_000040.1.
UniGeneiHs.73849.

Genome annotation databases

EnsembliENST00000227667; ENSP00000227667; ENSG00000110245.
GeneIDi345.
KEGGihsa:345.
UCSCiuc001ppt.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS8377.1.
PIRiA90950. LPHUC3.
RefSeqiNP_000031.1. NM_000040.1.
UniGeneiHs.73849.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JQ3NMR-A21-99[»]
ProteinModelPortaliP02656.
SMRiP02656. Positions 21-99.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106842. 5 interactions.
IntActiP02656. 3 interactions.
MINTiMINT-5000873.
STRINGi9606.ENSP00000227667.

PTM databases

PhosphoSiteiP02656.
UniCarbKBiP02656.

Polymorphism and mutation databases

BioMutaiAPOC3.
DMDMi114026.

2D gel databases

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

Proteomic databases

MaxQBiP02656.
PaxDbiP02656.
PRIDEiP02656.

Protocols and materials databases

DNASUi345.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000227667; ENSP00000227667; ENSG00000110245.
GeneIDi345.
KEGGihsa:345.
UCSCiuc001ppt.1. human.

Organism-specific databases

CTDi345.
GeneCardsiGC11P116700.
HGNCiHGNC:610. APOC3.
MIMi107720. gene.
614028. phenotype.
neXtProtiNX_P02656.
Orphaneti79506. Cholesterol-ester transfer protein deficiency.
33271. Non-alcoholic fatty liver disease.
PharmGKBiPA53.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG39866.
GeneTreeiENSGT00390000015395.
HOGENOMiHOG000247042.
HOVERGENiHBG050549.
InParanoidiP02656.
KOiK08759.
PhylomeDBiP02656.
TreeFamiTF338209.

Enzyme and pathway databases

ReactomeiREACT_13621. HDL-mediated lipid transport.
REACT_24968. Retinoid metabolism and transport.
REACT_6841. Chylomicron-mediated lipid transport.

Miscellaneous databases

EvolutionaryTraceiP02656.
GeneWikiiApolipoprotein_C3.
GenomeRNAii345.
NextBioi1423.
PROiP02656.
SOURCEiSearch...

Gene expression databases

BgeeiP02656.
CleanExiHS_APOC3.
ExpressionAtlasiP02656. baseline and differential.
GenevestigatoriP02656.

Family and domain databases

InterProiIPR008403. Apo-CIII.
[Graphical view]
PANTHERiPTHR14225. PTHR14225. 1 hit.
PfamiPF05778. Apo-CIII. 1 hit.
[Graphical view]
ProDomiPD010414. Apo-CIII. 1 hit.
[Graphical view] [Entries sharing at least one domain]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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], TISSUE SPECIFICITY.
  5. 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. "An ABC of apolipoprotein C-III: a clinically useful new cardiovascular risk factor?"
    Chan D.C., Chen M.M., Ooi E.M., Watts G.F.
    Int. J. Clin. Pract. 62:799-809(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  10. "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.
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. "Apolipoprotein C-III and hepatic triglyceride-rich lipoprotein production."
    Yao Z., Wang Y.
    Curr. Opin. Lipidol. 23:206-212(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  13. "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.
  14. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  15. "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.
  16. "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.

Entry informationi

Entry nameiAPOC3_HUMAN
AccessioniPrimary (citable) accession number: P02656
Secondary accession number(s): Q08E83, Q6Q786
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: May 27, 2015
This is version 154 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.