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P02656

- APOC3_HUMAN

UniProt

P02656 - APOC3_HUMAN

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Protein
Apolipoprotein C-III
Gene
APOC3
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  1. cholesterol binding Source: BHF-UCL
  2. enzyme regulator activity Source: BHF-UCL
  3. high-density lipoprotein particle receptor binding Source: BHF-UCL
  4. lipase inhibitor activity Source: BHF-UCL
  5. phospholipid binding Source: BHF-UCL

GO - Biological processi

  1. G-protein coupled receptor signaling pathway Source: BHF-UCL
  2. cellular response to glucose stimulus Source: Ensembl
  3. cholesterol efflux Source: BHF-UCL
  4. cholesterol homeostasis Source: BHF-UCL
  5. cholesterol metabolic process Source: Ensembl
  6. chylomicron remnant clearance Source: BHF-UCL
  7. high-density lipoprotein particle remodeling Source: BHF-UCL
  8. inflammatory response Source: Ensembl
  9. lipoprotein metabolic process Source: Reactome
  10. lipoprotein transport Source: Ensembl
  11. negative regulation of cholesterol import Source: BHF-UCL
  12. negative regulation of fatty acid biosynthetic process Source: BHF-UCL
  13. negative regulation of high-density lipoprotein particle clearance Source: BHF-UCL
  14. negative regulation of lipid catabolic process Source: BHF-UCL
  15. negative regulation of lipid metabolic process Source: BHF-UCL
  16. negative regulation of lipoprotein lipase activity Source: BHF-UCL
  17. negative regulation of low-density lipoprotein particle clearance Source: BHF-UCL
  18. negative regulation of receptor-mediated endocytosis Source: BHF-UCL
  19. negative regulation of triglyceride catabolic process Source: BHF-UCL
  20. negative regulation of very-low-density lipoprotein particle clearance Source: BHF-UCL
  21. negative regulation of very-low-density lipoprotein particle remodeling Source: BHF-UCL
  22. phospholipid efflux Source: BHF-UCL
  23. phototransduction, visible light Source: Reactome
  24. regulation of Cdc42 protein signal transduction Source: BHF-UCL
  25. response to drug Source: Ensembl
  26. response to nutrient Source: Ensembl
  27. response to peptide hormone Source: Ensembl
  28. retinoid metabolic process Source: Reactome
  29. reverse cholesterol transport Source: BHF-UCL
  30. small molecule metabolic process Source: Reactome
  31. triglyceride catabolic process Source: BHF-UCL
  32. triglyceride homeostasis Source: BHF-UCL
  33. triglyceride metabolic process Source: HGNC
  34. triglyceride mobilization Source: Ensembl
  35. 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: Chromosome 11

Organism-specific databases

HGNCiHGNC:610. APOC3.

Subcellular locationi

GO - Cellular componenti

  1. chylomicron Source: BHF-UCL
  2. early endosome Source: Reactome
  3. extracellular region Source: Reactome
  4. extracellular space Source: BHF-UCL
  5. extracellular vesicular exosome Source: UniProt
  6. intermediate-density lipoprotein particle Source: BHF-UCL
  7. spherical high-density lipoprotein particle Source: BHF-UCL
  8. 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) [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.1 Publication
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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 20202 Publications
Add
BLAST
Chaini21 – 9979Apolipoprotein C-III1 Publication
PRO_0000002031Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi94 – 941O-linked (GalNAc...)3 Publications
CAR_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.2 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiP02656.
PaxDbiP02656.
PRIDEiP02656.

2D gel databases

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

PTM databases

PhosphoSiteiP02656.
UniCarbKBiP02656.

Expressioni

Tissue specificityi

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.

Gene expression databases

ArrayExpressiP02656.
BgeeiP02656.
CleanExiHS_APOC3.
GenevestigatoriP02656.

Interactioni

Protein-protein interaction databases

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

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JQ3NMR-A21-99[»]
ProteinModelPortaliP02656.
SMRiP02656. Positions 21-99.

Miscellaneous databases

EvolutionaryTraceiP02656.

Family & Domainsi

Region

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

Sequence similaritiesi

Belongs to the apolipoprotein C3 family.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG39866.
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

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

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 conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti52 – 532ES → SQ AA sequence 1 Publication
Sequence conflicti57 – 593QQA → AQQ AA sequence 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

Polymorphism databases

DMDMi114026.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UniGenei Hs.73849.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2JQ3 NMR - A 21-99 [» ]
ProteinModelPortali P02656.
SMRi P02656. Positions 21-99.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 106842. 5 interactions.
IntActi P02656. 3 interactions.
MINTi MINT-5000873.
STRINGi 9606.ENSP00000227667.

PTM databases

PhosphoSitei P02656.
UniCarbKBi P02656.

Polymorphism databases

DMDMi 114026.

2D gel databases

DOSAC-COBS-2DPAGE P02656.
SWISS-2DPAGE P02656.

Proteomic databases

MaxQBi P02656.
PaxDbi P02656.
PRIDEi P02656.

Protocols and materials databases

DNASUi 345.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000227667 ; ENSP00000227667 ; ENSG00000110245 .
GeneIDi 345.
KEGGi hsa:345.
UCSCi uc001ppt.1. human.

Organism-specific databases

CTDi 345.
GeneCardsi GC11P116700.
HGNCi HGNC:610. APOC3.
MIMi 107720. gene.
614028. phenotype.
neXtProti NX_P02656.
Orphaneti 79506. Cholesterol-ester transfer protein deficiency.
33271. Non-alcoholic fatty liver disease.
PharmGKBi PA53.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG39866.
HOGENOMi HOG000247042.
HOVERGENi HBG050549.
InParanoidi P02656.
KOi K08759.
PhylomeDBi P02656.
TreeFami TF338209.

Enzyme and pathway databases

Reactomei REACT_13621. HDL-mediated lipid transport.
REACT_24968. Retinoid metabolism and transport.
REACT_6841. Chylomicron-mediated lipid transport.

Miscellaneous databases

EvolutionaryTracei P02656.
GeneWikii Apolipoprotein_C3.
GenomeRNAii 345.
NextBioi 1423.
PROi P02656.
SOURCEi Search...

Gene expression databases

ArrayExpressi P02656.
Bgeei P02656.
CleanExi HS_APOC3.
Genevestigatori P02656.

Family and domain databases

InterProi IPR008403. Apo-CIII.
[Graphical view ]
PANTHERi PTHR14225. PTHR14225. 1 hit.
Pfami PF05778. Apo-CIII. 1 hit.
[Graphical view ]
ProDomi PD010414. Apo-CIII. 1 hit.
[Graphical view ] [Entries sharing at least one domain ]
ProtoNeti Search...

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].
  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. "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. 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.

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: September 3, 2014
This is version 147 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

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