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P02656

- APOC3_HUMAN

UniProt

P02656 - APOC3_HUMAN

Protein

Apolipoprotein C-III

Gene

APOC3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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. cellular response to glucose stimulus Source: Ensembl
    2. cholesterol efflux Source: BHF-UCL
    3. cholesterol homeostasis Source: BHF-UCL
    4. cholesterol metabolic process Source: Ensembl
    5. chylomicron remnant clearance Source: BHF-UCL
    6. G-protein coupled receptor signaling pathway 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

    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

    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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 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

    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

    1
    99
    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.
    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.
    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

    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:
    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

    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: October 1, 2014
    This is version 148 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