UniProtKB - P02656 (APOC3_HUMAN)
Protein
Apolipoprotein C-III
Gene
APOC3
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 37 | May interact with the LDL receptor1 Publication | 1 | |
Sitei | 41 | May interact with the LDL receptor1 Publication | 1 | |
Sitei | 44 | May interact with the LDL receptor1 Publication | 1 |
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-UCL
- very-low-density lipoprotein particle assembly Source: BHF-UCL
Keywordsi
Biological process | Lipid degradation, Lipid metabolism, Lipid transport, Transport |
Ligand | Sialic acid |
Enzyme and pathway databases
PathwayCommonsi | P02656 |
Reactomei | R-HSA-8963888, Chylomicron assembly R-HSA-8963901, Chylomicron remodeling R-HSA-8964058, HDL remodeling R-HSA-975634, Retinoid metabolism and transport |
SIGNORi | P02656 |
Names & Taxonomyi
Protein namesi | Recommended name: Apolipoprotein C-IIIShort name: Apo-CIII Short name: ApoC-III Alternative name(s): Apolipoprotein C3 |
Gene namesi | Name:APOC3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000110245.11 |
HGNCi | HGNC:610, APOC3 |
MIMi | 107720, gene |
neXtProti | NX_P02656 |
Subcellular locationi
Extracellular region or secreted
- Secreted 2 Publications
Endosome
- early endosome Source: Reactome
Extracellular region or secreted
- chylomicron Source: BHF-UCL
- collagen-containing extracellular matrix Source: BHF-UCL
- 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
Keywords - Cellular componenti
Chylomicron, Secreted, VLDLPathology & 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_000643 | 78 | K → E in HALP2. 1 PublicationCorresponds to variant dbSNP:rs121918382EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 345 |
MalaCardsi | APOC3 |
MIMi | 614028, phenotype |
OpenTargetsi | ENSG00000110245 |
Orphaneti | 79506, Cholesterol-ester transfer protein deficiency 426, NON RARE IN EUROPE: Familial hypobetalipoproteinemia 33271, NON RARE IN EUROPE: Non-alcoholic fatty liver disease |
PharmGKBi | PA53 |
Miscellaneous databases
Pharosi | P02656, Tbio |
Chemistry databases
DrugBanki | DB09130, Copper |
Polymorphism and mutation databases
BioMutai | APOC3 |
DMDMi | 114026 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | 2 PublicationsAdd BLAST | 20 | |
ChainiPRO_0000002031 | 21 – 99 | Apolipoprotein C-III1 PublicationAdd BLAST | 79 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
GlycosylationiCAR_000168 | 94 | O-linked (GalNAc...) threonine3 Publications | 1 |
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
GlycoproteinProteomic databases
CPTACi | non-CPTAC-1083 |
EPDi | P02656 |
jPOSTi | P02656 |
MassIVEi | P02656 |
MaxQBi | P02656 |
PaxDbi | P02656 |
PeptideAtlasi | P02656 |
PRIDEi | P02656 |
ProteomicsDBi | 51541 |
2D gel databases
DOSAC-COBS-2DPAGEi | P02656 |
SWISS-2DPAGEi | P02656 |
PTM databases
CarbonylDBi | P02656 |
GlyConnecti | 58, 4 O-Linked glycans (1 site) |
GlyGeni | P02656, 1 site, 5 O-linked glycans (1 site) |
iPTMneti | P02656 |
PhosphoSitePlusi | P02656 |
UniCarbKBi | P02656 |
Expressioni
Tissue specificityi
Liver.1 Publication
Gene expression databases
Bgeei | ENSG00000110245, Expressed in liver and 109 other tissues |
ExpressionAtlasi | P02656, baseline and differential |
Genevisiblei | P02656, HS |
Organism-specific databases
HPAi | ENSG00000110245, Tissue enriched (liver) |
Interactioni
Binary interactionsi
Hide detailsP02656
With | #Exp. | IntAct |
---|---|---|
ERGIC3 [Q9Y282] | 3 | EBI-1220113,EBI-781551 |
FAM209A [Q5JX71] | 3 | EBI-1220113,EBI-18304435 |
GPX8 [Q8TED1] | 3 | EBI-1220113,EBI-11721746 |
GO - Molecular functioni
- high-density lipoprotein particle receptor binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 106842, 28 interactors |
IntActi | P02656, 8 interactors |
STRINGi | 9606.ENSP00000227667 |
Miscellaneous databases
RNActi | P02656, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | P02656 |
SMRi | P02656 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P02656 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 68 – 99 | Lipid-bindingAdd BLAST | 32 |
Sequence similaritiesi
Belongs to the apolipoprotein C3 family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502SZ00, Eukaryota |
GeneTreei | ENSGT00390000015395 |
HOGENOMi | CLU_154694_0_0_1 |
InParanoidi | P02656 |
OrthoDBi | 1613530at2759 |
PhylomeDBi | P02656 |
TreeFami | TF338209 |
Family and domain databases
Gene3Di | 1.10.225.30, 1 hit |
InterProi | View protein in InterPro IPR008403, Apo-CIII IPR038195, Apo_CIII_sf |
PANTHERi | PTHR14225, PTHR14225, 1 hit |
Pfami | View protein in Pfam PF05778, Apo-CIII, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
P02656-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MQPRVLLVVA LLALLASARA SEAEDASLLS FMQGYMKHAT KTAKDALSSV
60 70 80 90
QESQVAQQAR GWVTDGFSSL KDYWSTVKDK FSEFWDLDPE VRPTSAVAA
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketB0YIW2 | B0YIW2_HUMAN | Apolipoprotein C-III | APOC3 | 117 | Annotation score: | ||
C9J2Q0 | C9J2Q0_HUMAN | Apolipoprotein C-III | APOC3 | 55 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 52 – 53 | ES → SQ AA sequence (PubMed:4846755).Curated | 2 | |
Sequence conflicti | 57 – 59 | QQA → AQQ AA sequence (PubMed:4846755).Curated | 3 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_000643 | 78 | K → E in HALP2. 1 PublicationCorresponds to variant dbSNP:rs121918382EnsemblClinVar. | 1 | |
Natural variantiVAR_000644 | 94 | T → 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 |
CCDSi | CCDS8377.1 |
PIRi | A90950, LPHUC3 |
RefSeqi | NP_000031.1, NM_000040.1 |
Genome annotation databases
Ensembli | ENST00000227667; ENSP00000227667; ENSG00000110245 |
GeneIDi | 345 |
KEGGi | hsa:345 |
UCSCi | uc001ppt.2, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
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 |
CCDSi | CCDS8377.1 |
PIRi | A90950, LPHUC3 |
RefSeqi | NP_000031.1, NM_000040.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2JQ3 | NMR | - | A | 21-99 | [»] | |
BMRBi | P02656 | |||||
SMRi | P02656 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 106842, 28 interactors |
IntActi | P02656, 8 interactors |
STRINGi | 9606.ENSP00000227667 |
Chemistry databases
DrugBanki | DB09130, Copper |
PTM databases
CarbonylDBi | P02656 |
GlyConnecti | 58, 4 O-Linked glycans (1 site) |
GlyGeni | P02656, 1 site, 5 O-linked glycans (1 site) |
iPTMneti | P02656 |
PhosphoSitePlusi | P02656 |
UniCarbKBi | P02656 |
Polymorphism and mutation databases
BioMutai | APOC3 |
DMDMi | 114026 |
2D gel databases
DOSAC-COBS-2DPAGEi | P02656 |
SWISS-2DPAGEi | P02656 |
Proteomic databases
CPTACi | non-CPTAC-1083 |
EPDi | P02656 |
jPOSTi | P02656 |
MassIVEi | P02656 |
MaxQBi | P02656 |
PaxDbi | P02656 |
PeptideAtlasi | P02656 |
PRIDEi | P02656 |
ProteomicsDBi | 51541 |
Protocols and materials databases
Antibodypediai | 32278, 370 antibodies |
DNASUi | 345 |
Genome annotation databases
Ensembli | ENST00000227667; ENSP00000227667; ENSG00000110245 |
GeneIDi | 345 |
KEGGi | hsa:345 |
UCSCi | uc001ppt.2, human |
Organism-specific databases
CTDi | 345 |
DisGeNETi | 345 |
EuPathDBi | HostDB:ENSG00000110245.11 |
GeneCardsi | APOC3 |
HGNCi | HGNC:610, APOC3 |
HPAi | ENSG00000110245, Tissue enriched (liver) |
MalaCardsi | APOC3 |
MIMi | 107720, gene 614028, phenotype |
neXtProti | NX_P02656 |
OpenTargetsi | ENSG00000110245 |
Orphaneti | 79506, Cholesterol-ester transfer protein deficiency 426, NON RARE IN EUROPE: Familial hypobetalipoproteinemia 33271, NON RARE IN EUROPE: Non-alcoholic fatty liver disease |
PharmGKBi | PA53 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502SZ00, Eukaryota |
GeneTreei | ENSGT00390000015395 |
HOGENOMi | CLU_154694_0_0_1 |
InParanoidi | P02656 |
OrthoDBi | 1613530at2759 |
PhylomeDBi | P02656 |
TreeFami | TF338209 |
Enzyme and pathway databases
PathwayCommonsi | P02656 |
Reactomei | R-HSA-8963888, Chylomicron assembly R-HSA-8963901, Chylomicron remodeling R-HSA-8964058, HDL remodeling R-HSA-975634, Retinoid metabolism and transport |
SIGNORi | P02656 |
Miscellaneous databases
BioGRID-ORCSi | 345, 4 hits in 845 CRISPR screens |
ChiTaRSi | APOC3, human |
EvolutionaryTracei | P02656 |
GeneWikii | Apolipoprotein_C3 |
GenomeRNAii | 345 |
Pharosi | P02656, Tbio |
PROi | PR:P02656 |
RNActi | P02656, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000110245, Expressed in liver and 109 other tissues |
ExpressionAtlasi | P02656, baseline and differential |
Genevisiblei | P02656, HS |
Family and domain databases
Gene3Di | 1.10.225.30, 1 hit |
InterProi | View protein in InterPro IPR008403, Apo-CIII IPR038195, Apo_CIII_sf |
PANTHERi | PTHR14225, PTHR14225, 1 hit |
Pfami | View protein in Pfam PF05778, Apo-CIII, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | APOC3_HUMAN | |
Accessioni | P02656Primary (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: | December 2, 2020 | |
This is version 200 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations