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Protein

Apolipoprotein C-III

Gene

APOC3

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

Functioni

Component of triglyceride-rich very low density lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma (PubMed:18201179, PubMed:22510806). Plays a multifaceted role in triglyceride homeostasis (PubMed:18201179, PubMed:22510806). Intracellularly, promotes hepatic very low density lipoprotein 1 (VLDL1) assembly and secretion; extracellularly, attenuates hydrolysis and clearance of triglyceride-rich lipoproteins (TRLs) (PubMed:18201179, PubMed:22510806). Impairs the lipolysis of TRLs by inhibiting lipoprotein lipase and the hepatic uptake of TRLs by remnant receptors (PubMed:18201179, PubMed:22510806). Formed of several curved helices connected via semiflexible hinges, so that it can wrap tightly around the curved micelle surface and easily adapt to the different diameters of its natural binding partners (PubMed:18408013).2 Publications1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei37May interact with the LDL receptor1 Publication1
Sitei41May interact with the LDL receptor1 Publication1
Sitei44May interact with the LDL receptor1 Publication1

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

  • cholesterol efflux Source: BHF-UCL
  • cholesterol homeostasis Source: BHF-UCL
  • chylomicron assembly Source: Reactome
  • chylomicron remnant clearance Source: BHF-UCL
  • chylomicron remodeling Source: Reactome
  • G-protein coupled receptor signaling pathway Source: BHF-UCL
  • high-density lipoprotein particle remodeling Source: BHF-UCL
  • lipoprotein metabolic process Source: InterPro
  • 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
  • regulation of Cdc42 protein signal transduction Source: BHF-UCL
  • retinoid metabolic process Source: Reactome
  • reverse cholesterol transport Source: BHF-UCL
  • triglyceride catabolic process Source: BHF-UCL
  • triglyceride homeostasis Source: BHF-UCL
  • triglyceride metabolic process Source: HGNC
  • very-low-density lipoprotein particle assembly Source: BHF-UCL

Keywordsi

Biological processLipid degradation, Lipid metabolism, Lipid transport, Transport
LigandSialic acid

Enzyme and pathway databases

ReactomeiR-HSA-8963888 Chylomicron assembly
R-HSA-8963901 Chylomicron remodeling
R-HSA-8964058 HDL remodeling
R-HSA-975634 Retinoid metabolism and transport
SIGNORiP02656

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
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000110245.11
HGNCiHGNC:610 APOC3
MIMi107720 gene
neXtProtiNX_P02656

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_00064378K → E in HALP2. 1 PublicationCorresponds to variant dbSNP:rs121918382EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi345
MalaCardsiAPOC3
MIMi614028 phenotype
OpenTargetsiENSG00000110245
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)DescriptionActionsGraphical viewLength
Signal peptidei1 – 202 PublicationsAdd BLAST20
ChainiPRO_000000203121 – 99Apolipoprotein C-III1 PublicationAdd BLAST79

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
GlycosylationiCAR_00016894O-linked (GalNAc...) threonine3 Publications1

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
PeptideAtlasiP02656
PRIDEiP02656
ProteomicsDBi51541

2D gel databases

DOSAC-COBS-2DPAGEiP02656
SWISS-2DPAGEiP02656

PTM databases

CarbonylDBiP02656
GlyConnecti58
iPTMnetiP02656
PhosphoSitePlusiP02656
UniCarbKBiP02656

Expressioni

Tissue specificityi

Liver.1 Publication

Gene expression databases

BgeeiENSG00000110245
CleanExiHS_APOC3
ExpressionAtlasiP02656 baseline and differential
GenevisibleiP02656 HS

Organism-specific databases

HPAiHPA065365

Interactioni

GO - Molecular functioni

  • high-density lipoprotein particle receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi106842, 23 interactors
IntActiP02656, 3 interactors
STRINGi9606.ENSP00000227667

Structurei

Secondary structure

199
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi29 – 39Combined sources11
Helixi40 – 42Combined sources3
Helixi43 – 48Combined sources6
Helixi49 – 55Combined sources7
Helixi56 – 62Combined sources7
Turni63 – 68Combined sources6
Helixi69 – 80Combined sources12
Helixi83 – 85Combined sources3
Helixi93 – 98Combined sources6

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP02656

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni68 – 99Lipid-bindingAdd BLAST32

Sequence similaritiesi

Belongs to the apolipoprotein C3 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410JE3N Eukaryota
ENOG4111APE LUCA
GeneTreeiENSGT00390000015395
HOGENOMiHOG000247042
HOVERGENiHBG050549
InParanoidiP02656
KOiK08759
PhylomeDBiP02656
TreeFamiTF338209

Family and domain databases

Gene3Di1.10.225.30, 1 hit
InterProiView protein in InterPro
IPR008403 Apo-CIII
IPR038195 Apo_CIII_sf
PANTHERiPTHR14225 PTHR14225, 1 hit
PfamiView protein in Pfam
PF05778 Apo-CIII, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD010414 Apo-CIII, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti52 – 53ES → SQ AA sequence (PubMed:4846755).Curated2
Sequence conflicti57 – 59QQA → AQQ AA sequence (PubMed:4846755).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00064378K → E in HALP2. 1 PublicationCorresponds to variant dbSNP:rs121918382EnsemblClinVar.1
Natural variantiVAR_00064494T → A in C-III-0; unglycosylated. 1 PublicationCorresponds to variant dbSNP:rs121918381EnsemblClinVar.1

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.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAPOC3_HUMAN
AccessioniPrimary (citable) accession number: P02656
Secondary accession number(s): Q08E83, Q6Q786
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: June 20, 2018
This is version 183 of the entry and version 1 of the sequence. See 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

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