ID APOC3_HUMAN Reviewed; 99 AA. AC P02656; Q08E83; Q6Q786; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 09-DEC-2015, entry version 160. DE RecName: Full=Apolipoprotein C-III; DE Short=Apo-CIII; DE Short=ApoC-III; DE AltName: Full=Apolipoprotein C3; DE Flags: Precursor; GN Name=APOC3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX PubMed=6439535; DOI=10.1089/dna.1.1984.3.449; RA Protter A.A., Levy-Wilson B., Miller J., Bencen G., White T., RA Seilhamer J.J.; RT "Isolation and sequence analysis of the human apolipoprotein CIII gene RT and the intergenic region between the apo AI and apo CIII genes."; RL DNA 3:449-456(1984). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=6548954; DOI=10.1089/dna.1984.3.359; RA Levy-Wilson B., Appleby V., Protter A.A., Auperin D., Seilhamer J.J.; RT "Isolation and DNA sequence of full-length cDNA for human RT preapolipoprotein CIII."; RL DNA 3:359-364(1984). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX PubMed=2989400; RA Karathanasis S.K., Zannis V.I., Breslow J.L.; RT "Isolation and characterization of cDNA clones corresponding to two RT different human apoC-III alleles."; RL J. Lipid Res. 26:451-456(1985). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY. RX PubMed=6328445; DOI=10.1093/nar/12.9.3917; RA Sharpe C.R., Sidoli A., Shelley C.S., Lucero M.A., Shoulders C.C., RA Baralle F.E.; RT "Human apolipoproteins AI, AII, CII and CIII. cDNA sequences and mRNA RT abundance."; RL Nucleic Acids Res. 12:3917-3932(1984). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=15108119; DOI=10.1007/s00439-004-1106-x; RA Fullerton S.M., Buchanan A.V., Sonpar V.A., Taylor S.L., Smith J.D., RA Carlson C.S., Salomaa V., Stengaard J.H., Boerwinkle E., Clark A.G., RA Nickerson D.A., Weiss K.M.; RT "The effects of scale: variation in the APOA1/C3/A4/A5 gene cluster."; RL Hum. Genet. 115:36-56(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pancreas, and Spleen; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 21-99. RX PubMed=3949020; DOI=10.1016/0014-5793(86)80300-3; RA Hospattankar A.V., Brewer H.B. Jr., Ronan R., Fairwell T.; RT "Amino acid sequence of human plasma apolipoprotein C-III from RT normolipidemic subjects."; RL FEBS Lett. 197:67-73(1986). RN [8] RP PROTEIN SEQUENCE OF 21-99. RX PubMed=4846755; RA Brewer H.B. Jr., Shulman R., Herbert P., Ronan R., Wehrly K.; RT "The complete amino acid sequence of alanine apolipoprotein (apoC-3), RT and apolipoprotein from human plasma very low density lipoproteins."; RL J. Biol. Chem. 249:4975-4984(1974). RN [9] RP REVIEW. RX PubMed=18201179; DOI=10.1111/j.1742-1241.2007.01678.x; RA Chan D.C., Chen M.M., Ooi E.M., Watts G.F.; RT "An ABC of apolipoprotein C-III: a clinically useful new RT cardiovascular risk factor?"; RL Int. J. Clin. Pract. 62:799-809(2008). RN [10] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT THR-94, AND STRUCTURE OF RP CARBOHYDRATES. RC TISSUE=Cerebrospinal fluid; RX PubMed=19838169; DOI=10.1038/nmeth.1392; RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., RA Brinkmalm G., Larson G.; RT "Enrichment of glycopeptides for glycan structure and attachment site RT identification."; RL Nat. Methods 6:809-811(2009). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP REVIEW. RX PubMed=22510806; DOI=10.1097/MOL.0b013e328352dc70; RA Yao Z., Wang Y.; RT "Apolipoprotein C-III and hepatic triglyceride-rich lipoprotein RT production."; RL Curr. Opin. Lipidol. 23:206-212(2012). RN [13] RP GLYCOSYLATION AT THR-94, STRUCTURE OF CARBOHYDRATES, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=23527852; DOI=10.1021/pr400136p; RA Nicolardi S., van der Burgt Y.E., Dragan I., Hensbergen P.J., RA Deelder A.M.; RT "Identification of new apolipoprotein-CIII glycoforms with ultrahigh RT resolution MALDI-FTICR mass spectrometry of human sera."; RL J. Proteome Res. 12:2260-2268(2013). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [15] RP VARIANT C-III-0 ALA-94, AND GLYCOSYLATION AT THR-94. RX PubMed=3123586; RA Maeda H., Hashimoto R.K., Oguro T., Hiraga S., Uzawa H.; RT "Molecular cloning of a human apoC-III variant: Thr 74-->Ala 74 RT mutation prevents O-glycosylation."; RL J. Lipid Res. 28:1405-1409(1987). RN [16] RP VARIANT HALP2 GLU-78. RX PubMed=2022742; DOI=10.1172/JCI115190; RA von Eckardstein A., Holz H., Sandkamp M., Weng W., Funke H., RA Assmann G.; RT "Apolipoprotein C-III(Lys-58-->Glu). Identification of an RT apolipoprotein C-III variant in a family with RT hyperalphalipoproteinemia."; RL J. Clin. Invest. 87:1724-1731(1991). CC -!- FUNCTION: Component of triglyceride-rich very low density CC lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma. CC Plays a multifaceted role in triglyceride homeostasis. CC Intracellularly, promotes hepatic very low density lipoprotein 1 CC (VLDL1) assembly and secretion; extracellularly, attenuates CC hydrolysis and clearance of triglyceride-rich lipoproteins (TRLs). CC Impairs the lipolysis of TRLs by inhibiting lipoprotein lipase and CC the hepatic uptake of TRLs by remnant receptors. CC {ECO:0000303|PubMed:18201179, ECO:0000303|PubMed:22510806}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000303|PubMed:18201179, CC ECO:0000303|PubMed:22510806}. CC -!- TISSUE SPECIFICITY: Liver. {ECO:0000269|PubMed:6328445}. CC -!- PTM: The most abundant glycoforms are characterized by an O-linked CC disaccharide galactose linked to N-acetylgalactosamine (Gal- CC GalNAc), further modified with up to 3 sialic acid residues. Less CC abundant glycoforms are characterized by more complex and CC fucosylated glycan moieties. O-glycosylated on Thr-94 with a core CC 1 or possibly core 8 glycan. {ECO:0000269|PubMed:19838169, CC ECO:0000269|PubMed:23527852, ECO:0000269|PubMed:3123586}. CC -!- DISEASE: Hyperalphalipoproteinemia 2 (HALP2) [MIM:614028]: A CC condition characterized by high levels of high density lipoprotein CC (HDL) and increased HDL cholesterol levels. CC {ECO:0000269|PubMed:2022742}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the apolipoprotein C3 family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J00098; AAB59515.1; -; Genomic_DNA. DR EMBL; M33043; AAB59372.1; -; Genomic_DNA. DR EMBL; M33041; AAB59372.1; JOINED; Genomic_DNA. DR EMBL; M33042; AAB59372.1; JOINED; Genomic_DNA. DR EMBL; X01392; CAA25648.1; -; Genomic_DNA. DR EMBL; X01388; CAA25644.1; -; mRNA. DR EMBL; X03120; CAA26895.1; -; Genomic_DNA. DR EMBL; V01513; CAA24757.1; -; mRNA. DR EMBL; M28613; AAA51760.1; -; mRNA. DR EMBL; M28614; AAA51761.1; -; mRNA. DR EMBL; X00567; CAA25233.1; -; mRNA. DR EMBL; AY422951; AAQ91810.1; -; Genomic_DNA. DR EMBL; AY555191; AAS68230.1; -; Genomic_DNA. DR EMBL; BC027977; AAH27977.1; -; mRNA. DR EMBL; BC121081; AAI21082.1; -; mRNA. DR CCDS; CCDS8377.1; -. DR PIR; A90950; LPHUC3. DR RefSeq; NP_000031.1; NM_000040.1. DR UniGene; Hs.73849; -. DR PDB; 2JQ3; NMR; -; A=21-99. DR PDBsum; 2JQ3; -. DR ProteinModelPortal; P02656; -. DR SMR; P02656; 21-99. DR BioGrid; 106842; 5. DR IntAct; P02656; 3. DR MINT; MINT-5000873; -. DR STRING; 9606.ENSP00000227667; -. DR PhosphoSite; P02656; -. DR UniCarbKB; P02656; -. DR BioMuta; APOC3; -. DR DMDM; 114026; -. DR DOSAC-COBS-2DPAGE; P02656; -. DR SWISS-2DPAGE; P02656; -. DR MaxQB; P02656; -. DR PaxDb; P02656; -. DR PRIDE; P02656; -. DR DNASU; 345; -. DR Ensembl; ENST00000227667; ENSP00000227667; ENSG00000110245. DR GeneID; 345; -. DR KEGG; hsa:345; -. DR UCSC; uc001ppt.1; human. DR CTD; 345; -. DR GeneCards; APOC3; -. DR HGNC; HGNC:610; APOC3. DR MalaCards; APOC3; -. DR MIM; 107720; gene. DR MIM; 614028; phenotype. DR neXtProt; NX_P02656; -. DR Orphanet; 79506; Cholesterol-ester transfer protein deficiency. DR Orphanet; 33271; Non-alcoholic fatty liver disease. DR PharmGKB; PA53; -. DR eggNOG; ENOG410JE3N; Eukaryota. DR eggNOG; ENOG4111APE; LUCA. DR GeneTree; ENSGT00390000015395; -. DR HOGENOM; HOG000247042; -. DR HOVERGEN; HBG050549; -. DR InParanoid; P02656; -. DR KO; K08759; -. DR PhylomeDB; P02656; -. DR TreeFam; TF338209; -. DR Reactome; R-HSA-174800; Chylomicron-mediated lipid transport. DR Reactome; R-HSA-194223; HDL-mediated lipid transport. DR Reactome; R-HSA-975634; Retinoid metabolism and transport. DR EvolutionaryTrace; P02656; -. DR GeneWiki; Apolipoprotein_C3; -. DR GenomeRNAi; 345; -. DR NextBio; 1423; -. DR PRO; PR:P02656; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; P02656; -. DR CleanEx; HS_APOC3; -. DR ExpressionAtlas; P02656; baseline and differential. DR Genevisible; P02656; HS. DR GO; GO:0042627; C:chylomicron; IDA:BHF-UCL. DR GO; GO:0005769; C:early endosome; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0034363; C:intermediate-density lipoprotein particle; IDA:BHF-UCL. DR GO; GO:0034366; C:spherical high-density lipoprotein particle; IDA:BHF-UCL. DR GO; GO:0034361; C:very-low-density lipoprotein particle; IDA:BHF-UCL. DR GO; GO:0015485; F:cholesterol binding; IC:BHF-UCL. DR GO; GO:0030234; F:enzyme regulator activity; IDA:BHF-UCL. DR GO; GO:0070653; F:high-density lipoprotein particle receptor binding; IPI:BHF-UCL. DR GO; GO:0055102; F:lipase inhibitor activity; IDA:BHF-UCL. DR GO; GO:0005543; F:phospholipid binding; IDA:BHF-UCL. DR GO; GO:0033344; P:cholesterol efflux; IDA:BHF-UCL. DR GO; GO:0042632; P:cholesterol homeostasis; IMP:BHF-UCL. DR GO; GO:0034382; P:chylomicron remnant clearance; IDA:BHF-UCL. DR GO; GO:0007186; P:G-protein coupled receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0034375; P:high-density lipoprotein particle remodeling; IMP:BHF-UCL. DR GO; GO:0042157; P:lipoprotein metabolic process; TAS:Reactome. DR GO; GO:0060621; P:negative regulation of cholesterol import; IMP:BHF-UCL. DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; IDA:BHF-UCL. DR GO; GO:0010987; P:negative regulation of high-density lipoprotein particle clearance; IMP:BHF-UCL. DR GO; GO:0050995; P:negative regulation of lipid catabolic process; IDA:BHF-UCL. DR GO; GO:0045833; P:negative regulation of lipid metabolic process; IDA:BHF-UCL. DR GO; GO:0051005; P:negative regulation of lipoprotein lipase activity; IDA:BHF-UCL. DR GO; GO:0010989; P:negative regulation of low-density lipoprotein particle clearance; IMP:BHF-UCL. DR GO; GO:0048261; P:negative regulation of receptor-mediated endocytosis; IDA:BHF-UCL. DR GO; GO:0010897; P:negative regulation of triglyceride catabolic process; IDA:BHF-UCL. DR GO; GO:0010916; P:negative regulation of very-low-density lipoprotein particle clearance; IDA:BHF-UCL. DR GO; GO:0010903; P:negative regulation of very-low-density lipoprotein particle remodeling; IDA:BHF-UCL. DR GO; GO:0033700; P:phospholipid efflux; IDA:BHF-UCL. DR GO; GO:0007603; P:phototransduction, visible light; TAS:Reactome. DR GO; GO:0032489; P:regulation of Cdc42 protein signal transduction; IDA:BHF-UCL. DR GO; GO:0001523; P:retinoid metabolic process; TAS:Reactome. DR GO; GO:0043691; P:reverse cholesterol transport; IC:BHF-UCL. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0019433; P:triglyceride catabolic process; IDA:BHF-UCL. DR GO; GO:0070328; P:triglyceride homeostasis; IMP:BHF-UCL. DR GO; GO:0006641; P:triglyceride metabolic process; IMP:HGNC. DR GO; GO:0034379; P:very-low-density lipoprotein particle assembly; TAS:BHF-UCL. DR InterPro; IPR008403; Apo-CIII. DR PANTHER; PTHR14225; PTHR14225; 1. DR Pfam; PF05778; Apo-CIII; 1. DR ProDom; PD010414; Apo-CIII; 1. PE 1: Evidence at protein level; KW 3D-structure; Chylomicron; Complete proteome; KW Direct protein sequencing; Disease mutation; Glycoprotein; KW Lipid degradation; Lipid metabolism; Lipid transport; Polymorphism; KW Reference proteome; Secreted; Sialic acid; Signal; Transport; VLDL. FT SIGNAL 1 20 {ECO:0000269|PubMed:3949020, FT ECO:0000269|PubMed:4846755}. FT CHAIN 21 99 Apolipoprotein C-III. FT {ECO:0000269|PubMed:3949020}. FT /FTId=PRO_0000002031. FT REGION 68 99 Lipid-binding. FT CARBOHYD 94 94 O-linked (GalNAc...). FT {ECO:0000269|PubMed:19838169, FT ECO:0000269|PubMed:23527852, FT ECO:0000269|PubMed:3123586}. FT /FTId=CAR_000168. FT VARIANT 78 78 K -> E (in HALP2). FT {ECO:0000269|PubMed:2022742}. FT /FTId=VAR_000643. FT VARIANT 94 94 T -> A (in C-III-0; unglycosylated). FT {ECO:0000269|PubMed:3123586}. FT /FTId=VAR_000644. FT CONFLICT 52 53 ES -> SQ (in Ref. 8; AA sequence). FT {ECO:0000305}. FT CONFLICT 57 59 QQA -> AQQ (in Ref. 8; AA sequence). FT {ECO:0000305}. FT HELIX 29 39 {ECO:0000244|PDB:2JQ3}. FT HELIX 40 42 {ECO:0000244|PDB:2JQ3}. FT HELIX 43 48 {ECO:0000244|PDB:2JQ3}. FT HELIX 49 55 {ECO:0000244|PDB:2JQ3}. FT HELIX 56 62 {ECO:0000244|PDB:2JQ3}. FT TURN 63 68 {ECO:0000244|PDB:2JQ3}. FT HELIX 69 80 {ECO:0000244|PDB:2JQ3}. FT HELIX 83 85 {ECO:0000244|PDB:2JQ3}. FT HELIX 93 98 {ECO:0000244|PDB:2JQ3}. SQ SEQUENCE 99 AA; 10852 MW; D4E806339FAE4DA7 CRC64; MQPRVLLVVA LLALLASARA SEAEDASLLS FMQGYMKHAT KTAKDALSSV QESQVAQQAR GWVTDGFSSL KDYWSTVKDK FSEFWDLDPE VRPTSAVAA //