ID APOB_HUMAN Reviewed; 4563 AA. AC P04114; O00502; P78479; P78480; P78481; Q13779; Q13785; Q13786; AC Q13787; Q13788; Q7Z600; Q9UMN0; DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1986, sequence version 1. DT 07-JUL-2009, entry version 124. DE RecName: Full=Apolipoprotein B-100; DE Short=Apo B-100; DE Contains: DE RecName: Full=Apolipoprotein B-48; DE Short=Apo B-48; DE Flags: Precursor; GN Name=APOB; 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 [MRNA]. RX MEDLINE=87016385; PubMed=3763409; DOI=10.1093/nar/14.18.7501; RA Knott T.C., Wallis S.C., Powell L.M., Pease R.J., Lusis A.J., RA Blackhart B., McCarthy B.J., Mahley R.W., Levy-Wilson B., Scott J.; RT "Complete cDNA and derived protein sequence of human apolipoprotein B- RT 100."; RL Nucleic Acids Res. 14:7501-7503(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-273; GLN-1218; RP LEU-2092; ALA-2365; LEU-2680; ILE-3732; PHE-3949; TYR-3964 AND RP GLU-4181. RX MEDLINE=88003974; PubMed=3652907; RA Ludwig E.H., Blackhart B.D., Pierotti V.R., Caiati L., Fortier C., RA Knott T., Scott J., Mahley R.W., Levy-Wilson B., McCarthy B.J.; RT "DNA sequence of the human apolipoprotein B gene."; RL DNA 6:363-372(1987). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ILE-98; LYS-273; VAL-618; RP GLN-1218; LEU-2092; ALA-2365; LEU-2680; ILE-3732; PHE-3949; TYR-3964 RP AND GLU-4181. RX MEDLINE=87008488; PubMed=3759943; RA Chen S.-H., Yang C.-Y., Chen P.-F., Setzer D., Tanimura M., Li W.-H., RA Gotto A.M. Jr., Chan L.; RT "The complete cDNA and amino acid sequence of human apolipoprotein B- RT 100."; RL J. Biol. Chem. 261:12918-12921(1986). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS LYS-273; GLN-1218; LEU-2092; RP ALA-2365; LEU-2680; ILE-3732 AND TYR-3964. RX MEDLINE=87041416; PubMed=3464946; DOI=10.1073/pnas.83.21.8142; RA Law S.W., Grant S.M., Higuchi K., Hospattankar A.V., Lackner K.J., RA Lee N., Brewer H.B. Jr.; RT "Human liver apolipoprotein B-100 cDNA: complete nucleic acid and RT derived amino acid sequence."; RL Proc. Natl. Acad. Sci. U.S.A. 83:8142-8146(1986). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-273; VAL-618; RP GLN-1218; LEU-2092; ALA-2365 AND LEU-2680. RX MEDLINE=87161758; PubMed=3030729; RA Cladaras C., Hadzopoulou-Cladaras M., Nolte R.T., Atkinson D., RA Zannis V.I.; RT "The complete sequence and structural analysis of human apolipoprotein RT B-100: relationship between apoB-100 and apoB-48 forms."; RL EMBO J. 5:3495-3507(1986). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-273; GLN-1218; RP LEU-2092; ALA-2365; LEU-2680; ASP-3319; THR-3427; GLN-3432; ILE-3732; RP PHE-3949; TYR-3964 AND GLU-4181. RG SeattleSNPs variation discovery resource; RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1670, AND VARIANTS ILE-98; LYS-273 AND RP GLN-1218. RX MEDLINE=86287319; PubMed=3461454; DOI=10.1073/pnas.83.15.5678; RA Protter A.A., Hardman D.A., Sato K.Y., Schilling J.W., Yamanaka M., RA Hort Y.J., Hjerrild K.A., Chen G.C., Kane J.P.; RT "Analysis of cDNA clones encoding the entire B-26 region of human RT apolipoprotein B."; RL Proc. Natl. Acad. Sci. U.S.A. 83:5678-5682(1986). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-291, AND VARIANT LYS-273. RX MEDLINE=86149325; PubMed=3513177; DOI=10.1073/pnas.83.5.1467; RA Protter A.A., Hardman D.A., Schilling J.W., Miller J., Appleby V., RA Chen G.C., Kirsher S.W., McEnroe G., Kane J.P.; RT "Isolation of a cDNA clone encoding the amino-terminal region of human RT apolipoprotein B."; RL Proc. Natl. Acad. Sci. U.S.A. 83:1467-1471(1986). RN [9] RP PARTIAL PROTEIN SEQUENCE, DISULFIDE BONDS, AND VARIANT ILE-98. RX MEDLINE=90319144; PubMed=2115173; DOI=10.1073/pnas.87.14.5523; RA Yang C.Y., Kim T.W., Weng S.A., Lee B.R., Yang M.L., Gotto A.M. Jr.; RT "Isolation and characterization of sulfhydryl and disulfide peptides RT of human apolipoprotein B-100."; RL Proc. Natl. Acad. Sci. U.S.A. 87:5523-5527(1990). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 485-1044. RC TISSUE=Liver; RX MEDLINE=86094221; PubMed=3001697; DOI=10.1073/pnas.82.24.8340; RA Law S.W., Lackner K.J., Hospattankar A.V., Anchors J.M., RA Sakaguchi A.Y., Naylor S.L., Brewer H.B. Jr.; RT "Human apolipoprotein B-100: cloning, analysis of liver mRNA, and RT assignment of the gene to chromosome 2."; RL Proc. Natl. Acad. Sci. U.S.A. 82:8340-8344(1985). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 709-906. RX MEDLINE=85270450; PubMed=3860836; DOI=10.1073/pnas.82.15.4983; RA Deeb S.S., Motulsky A.G., Albers J.J.; RT "A partial cDNA clone for human apolipoprotein B."; RL Proc. Natl. Acad. Sci. U.S.A. 82:4983-4986(1985). RN [12] RP PROTEIN SEQUENCE OF 873-896 AND 3113-3137. RX MEDLINE=84208786; PubMed=6373369; DOI=10.1016/0014-5793(84)81378-2; RA LeBoeuf R.C., Miller C., Shively J.E., Schumaker V.N., Balla M.A., RA Lusis A.J.; RT "Human apolipoprotein B: partial amino acid sequence."; RL FEBS Lett. 170:105-108(1984). RN [13] RP NUCLEOTIDE SEQUENCE OF 1042-1232, AND VARIANT GLN-1218. RX MEDLINE=89291895; PubMed=2567736; RA Huang L.S., Ripps M.E., Korman S.H., Deckelbaum R.J., Breslow J.L.; RT "Hypobetalipoproteinemia due to an apolipoprotein B gene exon 21 RT deletion derived by Alu-Alu recombination."; RL J. Biol. Chem. 264:11394-11400(1989). RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1282-4503, AND VARIANTS LEU-2092; RP ALA-2365; LEU-2680; PHE-3949; TYR-3964 AND GLU-4181. RX MEDLINE=87191999; PubMed=2883086; DOI=10.1016/0378-1119(86)90383-5; RA Carlsson P., Darnfors C., Olofsson S.O., Bjursell G.; RT "Analysis of the human apolipoprotein B gene; complete structure of RT the B-74 region."; RL Gene 49:29-51(1986). RN [15] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1671-2398, AND VARIANTS LEU-2092 AND RP ALA-2365. RX MEDLINE=88050832; PubMed=3676265; DOI=10.1021/bi00391a040; RA Hardman D.A., Protter A.A., Chen G.C., Schilling J.W., Sato K.Y., RA Lau K., Yamanaka M., Mikita T., Miller J., Crisp T., McEnroe G., RA Scarborough R.M., Kane J.P.; RT "Structural comparison of human apolipoproteins B-48 and B-100."; RL Biochemistry 26:5478-5486(1987). RN [16] RP NUCLEOTIDE SEQUENCE OF 1937-2018 AND 3811-4334, AND VARIANTS PHE-3949; RP TYR-3964 AND GLU-4181. RX MEDLINE=86093680; PubMed=3841204; DOI=10.1093/nar/13.24.8813; RA Carlsson P., Olofsson S.O., Bondjers G., Darnfors C., Wiklund O., RA Bjursell G.; RT "Molecular cloning of human apolipoprotein B cDNA."; RL Nucleic Acids Res. 13:8813-8826(1985). RN [17] RP NUCLEOTIDE SEQUENCE [MRNA] OF 2115-2179. RC TISSUE=Small intestine; RX MEDLINE=87301727; PubMed=3621347; DOI=10.1016/0092-8674(87)90510-1; RA Powell L.M., Wallis S.C., Pease R.J., Edwards Y.H., Knott T.J., RA Scott J.; RT "A novel form of tissue-specific RNA processing produces RT apolipoprotein-B48 in intestine."; RL Cell 50:831-840(1987). RN [18] RP NUCLEOTIDE SEQUENCE [MRNA] OF 2127-2179. RX MEDLINE=88158075; PubMed=2450346; DOI=10.1073/pnas.85.6.1772; RA Higuchi K., Hospattankar A.V., Law S.W., Meglin N., Cortright J., RA Brewer H.B. Jr.; RT "Human apolipoprotein B (apoB) mRNA: identification of two distinct RT apoB mRNAs, an mRNA with the apoB-100 sequence and an apoB mRNA RT containing a premature in-frame translational stop codon, in both RT liver and intestine."; RL Proc. Natl. Acad. Sci. U.S.A. 85:1772-1776(1988). RN [19] RP NUCLEOTIDE SEQUENCE [MRNA] OF 2129-2235. RX MEDLINE=88106542; PubMed=3426612; DOI=10.1016/0006-291X(87)90537-7; RA Hardman D.A., Protter A.A., Schilling J.W., Kane J.P.; RT "Carboxyl terminal analysis of human B-48 protein confirms the novel RT mechanism proposed for chain termination."; RL Biochem. Biophys. Res. Commun. 149:1214-1219(1987). RN [20] RP PROTEIN SEQUENCE OF 2169-2179. RX MEDLINE=88049670; PubMed=2445342; DOI=10.1016/0006-291X(87)91107-7; RA Hospattankar A.V., Higuchi K., Law S.W., Meglin N., Brewer H.B. Jr.; RT "Identification of a novel in-frame translational stop codon in human RT intestine apoB mRNA."; RL Biochem. Biophys. Res. Commun. 148:279-285(1987). RN [21] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3056-3159. RX MEDLINE=86041888; PubMed=3903660; DOI=10.1093/nar/13.19.6937; RA Mehrabian M., Schumaker V.N., Fareed G.C., West R., Johnson D.F., RA Kirchgessner T.G., Lin H.-C., Wang X., Ma Y., Mendiaz E., Lusis A.J.; RT "Human apolipoprotein B: identification of cDNA clones and RT characterization of mRNA."; RL Nucleic Acids Res. 13:6937-6953(1985). RN [22] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3109-4563. RX MEDLINE=85300528; PubMed=2994225; DOI=10.1126/science.2994225; RA Knott T.J., Rall S.C. Jr., Innerarity T.L., Jacobson S.F., Urdea M.S., RA Levy-Wilson B., Powell L.M., Pease R.J., Eddy R., Nakai H., Byers M., RA Priestley L.M., Robertson E., Rall L.B., Betsholtz C., Shows T.B., RA Mahley R.W., Scott J.; RT "Human apolipoprotein B: structure of carboxyl-terminal domains, sites RT of gene expression, and chromosomal localization."; RL Science 230:37-43(1985). RN [23] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3728-4563, AND VARIANTS ILE-3732; RP PHE-3949; TYR-3964 AND GLU-4181. RX MEDLINE=86042646; PubMed=2932736; DOI=10.1073/pnas.82.21.7265; RA Wei C.F., Chen S.H., Yang C.Y., Marcel Y.L., Milne R.W., Li W.H., RA Sparrow J.T., Gotto A.M. Jr., Chan L.; RT "Molecular cloning and expression of partial cDNAs and deduced amino RT acid sequence of a carboxyl-terminal fragment of human apolipoprotein RT B-100."; RL Proc. Natl. Acad. Sci. U.S.A. 82:7265-7269(1985). RN [24] RP NUCLEOTIDE SEQUENCE OF 3846-4298. RC TISSUE=Liver; RX MEDLINE=86130855; PubMed=3841481; DOI=10.1016/0021-9150(85)90073-5; RA Shoulders C.C., Myant N.B., Sidoli A., Rodriguez J.C., Cortese C., RA Baralle F.E., Cortese R.; RT "Molecular cloning of human LDL apolipoprotein B cDNA. Evidence for RT more than one gene per haploid genome."; RL Atherosclerosis 58:277-289(1985). RN [25] RP NUCLEOTIDE SEQUENCE OF 4217-4563, AND VARIANT SER-4338. RX MEDLINE=87076044; PubMed=3024665; RA Pfitzner R., Wagener R., Stoffel W.; RT "Isolation, expression and characterization of a human apolipoprotein RT B 100-specific cDNA clone."; RL Biol. Chem. Hoppe-Seyler 367:1077-1083(1986). RN [26] RP PARTIAL PROTEIN SEQUENCE, AND IDENTIFICATION OF APO-B48. RX MEDLINE=88018019; PubMed=3659919; DOI=10.1126/science.3659919; RA Chen S.-H., Habib G., Yang C.-H., Gu Z.-W., Lee B.R., Weng S.-H., RA Silberman S.R., Cai S.-J., Deslypere J.P., Rosseneu M., RA Gotto A.M. Jr., Li W.-H., Chan L.; RT "Apolipoprotein B-48 is the product of a messenger RNA with an organ- RT specific in-frame stop codon."; RL Science 238:363-366(1987). RN [27] RP DOMAINS. RX MEDLINE=87039351; PubMed=3773997; DOI=10.1038/323734a0; RA Knott T.C., Pease R.J., Powell L.M., Wallis S.C., Rall S.C. Jr., RA Innerarity T.L., Blackhart B., Taylor W.R., Marcel Y., Milne R., RA Johnson D., Fuller M., Lusis A.J., McCarthy B.J., Mahley R.W., RA Levy-Wilson B., Scott J.; RT "Complete protein sequence and identification of structural domains of RT human apolipoprotein B."; RL Nature 323:734-738(1986). RN [28] RP DOMAINS. RX PubMed=3095664; DOI=10.1038/323738a0; RA Yang C.-Y., Chen S.-H., Gianturco S.H., Bradley W.A., Sparrow J.T., RA Tanimura M., Li W.-H., Sparrow D.A., Deloof H., Rosseneu M., RA Lee F.-S., Gu Z.-W., Gotto A.M. Jr., Chan L.; RT "Sequence, structure, receptor-binding domains and internal repeats of RT human apolipoprotein B-100."; RL Nature 323:738-742(1986). RN [29] RP CALCIUM-BINDING DATA. RX MEDLINE=86242245; PubMed=3087360; DOI=10.1016/0006-291X(86)91237-4; RA Dashti N., Lee D.M., Mok T.; RT "Apolipoprotein B is a calcium binding protein."; RL Biochem. Biophys. Res. Commun. 137:493-499(1986). RN [30] RP PALMITOYLATION AT CYS-1112. RX MEDLINE=20143590; PubMed=10679026; RA Zhao Y., McCabe J.B., Vance J., Berthiaume L.G.; RT "Palmitoylation of apolipoprotein B is required for proper RT intracellular sorting and transport of cholesteroyl esters and RT triglycerides."; RL Mol. Biol. Cell 11:721-734(2000). RN [31] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-3358, AND MASS RP SPECTROMETRY. RC TISSUE=Plasma; RX PubMed=14760718; DOI=10.1002/pmic.200300556; RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.; RT "Screening for N-glycosylated proteins by liquid chromatography mass RT spectrometry."; RL Proteomics 4:454-465(2004). RN [32] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-1523; ASN-2982; ASN-3465 RP AND ASN-3895, AND MASS SPECTROMETRY. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., RA Moore R.J., Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4507, AND MASS RP SPECTROMETRY. RC TISSUE=Epithelium; RX PubMed=17924679; DOI=10.1021/pr070152u; RA Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa RT cells and high confident phosphopeptide identification by cross- RT validation of MS/MS and MS/MS/MS spectra."; RL J. Proteome Res. 6:4150-4162(2007). RN [34] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-928, AND MASS RP SPECTROMETRY. RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [35] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-185; ASN-1523; ASN-2239; RP ASN-2779; ASN-2982; ASN-3101; ASN-3224; ASN-3411; ASN-3465 AND RP ASN-3895, AND MASS SPECTROMETRY. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [36] RP VARIANT SER-4338. RX MEDLINE=91071750; PubMed=1979313; DOI=10.1007/BF00205183; RA Navajas M., Laurent A.-M., Moreel J.-F., Ragab A., Cambou J.-P., RA Cunny G., Cambien F., Roizes G.; RT "Detection by denaturing gradient gel electrophoresis of a new RT polymorphism in the apolipoprotein B gene."; RL Hum. Genet. 86:91-93(1990). RN [37] RP VARIANT FDB GLN-3527. RX MEDLINE=89098975; PubMed=2563166; DOI=10.1073/pnas.86.2.587; RA Soria L.F., Ludwig E.H., Clarke H.R.G., Vega G.L., Grundy S.M., RA McCarthy B.J.; RT "Association between a specific apolipoprotein B mutation and familial RT defective apolipoprotein B-100."; RL Proc. Natl. Acad. Sci. U.S.A. 86:587-591(1989). RN [38] RP VARIANT LEU-2739. RX MEDLINE=91016974; PubMed=2216805; DOI=10.1093/nar/18.19.5922-a; RA Huang L.-S., Gavish D., Breslow J.L.; RT "Sequence polymorphism in the human apoB gene at position 8344."; RL Nucleic Acids Res. 18:5922-5922(1990). RN [39] RP VARIANT FDB CYS-3558. RX MEDLINE=95190020; PubMed=7883971; RA Pullinger C.R., Hennessy L.K., Chatterton J.E., Liu W., Love J.A., RA Mendel C.M., Frost P.H., Malloy M.J., Schumaker V.N., Kane J.P.; RT "Familial ligand-defective apolipoprotein B. Identification of a new RT mutation that decreases LDL receptor binding affinity."; RL J. Clin. Invest. 95:1225-1234(1995). RN [40] RP VARIANTS LEU-1437; SER-1914; LYS-2566; THR-3121; ALA-3945; MET-4128 RP AND THR-4481. RX MEDLINE=97044521; PubMed=8889592; RX DOI=10.1002/(SICI)1098-1004(1996)8:3<282::AID-HUMU16>3.3.CO;2-Y; RA Poirier O., Ricard S., Behague I., Souriau C., Evans A.E., RA Arveiler D., Marques-Vidal P., Luc G., Roizes G., Cambien F.; RT "Detection of new variants in the apolipoprotein B (Apo B) gene by RT PCR-SSCP."; RL Hum. Mutat. 8:282-285(1996). RN [41] RP VARIANTS FDB GLN-3527 AND CYS-3558. RX MEDLINE=97403938; PubMed=9259199; RX DOI=10.1002/(SICI)1098-1004(1997)10:2<160::AID-HUMU8>3.3.CO;2-F; RA Rabes J.P., Varret M., Saint-Jore B., Erlich D., Jondeau G., RA Krempf M., Giraudet P., Junien C., Boileau C.; RT "Familial ligand-defective apolipoprotein B-100: simultaneous RT detection of the Arg3500-->Gln and Arg3531-->Cys mutations in a French RT population."; RL Hum. Mutat. 10:160-163(1997). RN [42] RP VARIANTS SER-1914; ARG-1923; LEU-2739; ASP-3319; THR-3427; GLN-3432 RP AND ILE-3921. RX MEDLINE=98141125; PubMed=9490296; DOI=10.1007/s004390050651; RA Leren T.P., Bakken K.S., Hoel V., Hjermann I., Berg K.; RT "Screening for mutations of the apolipoprotein B gene causing RT hypocholesterolemia."; RL Hum. Genet. 102:44-49(1998). RN [43] RP VARIANT FHBL TRP-490, VARIANT ILE-98, CHARACTERIZATION OF VARIANT RP TRP-490, AND MUTAGENESIS OF ASP-483 AND ARG-490. RX MEDLINE=22565988; PubMed=12551903; DOI=10.1074/jbc.M300235200; RA Burnett J.R., Shan J., Miskie B.A., Whitfield A.J., Yuan J., Tran K., RA McKnight C.J., Hegele R.A., Yao Z.; RT "A novel nontruncating APOB gene mutation, R463W, causes familial RT hypobetalipoproteinemia."; RL J. Biol. Chem. 278:13442-13452(2003). RN [44] RP VARIANT HIS-1128. RX PubMed=14732481; RA Lancellotti S., Di Leo E., Penacchioni J.Y., Balli F., Viola L., RA Bertolini S., Calandra S., Tarugi P.; RT "Hypobetalipoproteinemia with an apparently recessive inheritance due RT to a 'de novo' mutation of apolipoprotein B."; RL Biochim. Biophys. Acta 1688:61-67(2004). RN [45] RP VARIANT [LARGE SCALE ANALYSIS] CYS-2564. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Apolipoprotein B is a major protein constituent of CC chylomicrons (apo B-48), LDL (apo B-100) and VLDL (apo B-100). Apo CC B-100 functions as a recognition signal for the cellular binding CC and internalization of LDL particles by the apoB/E receptor. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- PTM: Palmitoylated; structural requirement for proper assembly of CC the hydrophobic core of the lipoprotein particle. CC -!- RNA EDITING: Modified_positions=2180; Note=The stop codon (UAA) at CC position 2180 is created by RNA editing. Apo B-48, derived from CC the fully edited RNA, is produced only in the intestine and is CC found in chylomicrons. Apo B-48 is a shortened form of apo B-100 CC which lacks the LDL-receptor region. The unedited version (apo B- CC 100) is produced by the liver and is found in the VLDL and LDL. CC -!- DISEASE: Defects in APOB are a cause of familial CC hypobetalipoproteinemia (FHBL) [MIM:107730]. FHBL is a genetically CC heterogeneous autosomal co-dominant disorder, associated with CC reduced plasma concentrations of apoB, LDL and VLDL. Heterozygotes CC for FHBL are usually asymptomatic with LDL cholesterol and apoB- CC 100 concentrations less than 50% of those in normal plasma. CC Homozygotes have extremely low plasma LDL cholesterol and apoB-100 CC concentrations, and clinical presentation may vary from no CC symptoms to severe gastrointestinal and neurological dysfunction CC similar to abetalipoproteinemia [MIM:200100]. CC -!- DISEASE: Defects in APOB are a cause of familial ligand-defective CC apolipoprotein B-100 (FDB) [MIM:144010]. FDB is a dominantly CC inherited disorder of lipoprotein metabolism leading to CC hypercholesterolemia and increased proneness to coronary artery CC disease (CAD). The plasma cholesterol levels are dramatically CC elevated due to impaired clearance of LDL particles by defective CC APOB/E receptors. CC -!- DISEASE: Defects in APOB associated with defects in other genes CC (polygenic) can contribute to hypocholesterolemia. CC -!- SIMILARITY: Contains 1 vitellogenin domain. CC -!- SEQUENCE CAUTION: CC Sequence=AAA51752.1; Type=Frameshift; Positions=942, 951, 1139, 1165, 1164, 1371, 1385; CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.genetests.org/query?gene=APOB"; CC -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and CC polymorphism database; CC URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=APOB"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Apolipoprotein B entry; CC URL="http://en.wikipedia.org/wiki/Apolipoprotein_B"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X04506; CAA28191.1; -; mRNA. DR EMBL; M19828; AAB00481.1; -; Genomic_DNA. DR EMBL; M19808; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; M19809; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; M19810; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; M19811; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; M19812; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; M19813; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; M19815; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; M19816; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; M19818; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; M19820; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; M19821; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; M19823; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; M19824; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; M19825; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; M19827; AAB00481.1; JOINED; Genomic_DNA. DR EMBL; J02610; AAA35549.1; -; mRNA. DR EMBL; M14162; AAB04636.1; -; mRNA. DR EMBL; M15053; AAB60718.1; -; Genomic_DNA. DR EMBL; X04714; CAA28420.1; -; mRNA. DR EMBL; AY324608; AAP72970.1; -; Genomic_DNA. DR EMBL; M14081; AAA51752.1; ALT_FRAME; mRNA. DR EMBL; M12681; AAA51753.1; -; mRNA. DR EMBL; M12480; AAA51751.1; -; mRNA. DR EMBL; K03175; AAA51759.1; -; mRNA. DR EMBL; M15421; AAA51758.1; -; mRNA. DR EMBL; M17367; AAA51741.1; -; mRNA. DR EMBL; M31030; AAA51756.1; -; mRNA. DR EMBL; X03325; CAA27044.1; -; mRNA. DR EMBL; X03326; CAA27045.1; -; mRNA. DR EMBL; M17779; AAA51755.1; -; mRNA. DR EMBL; M19734; AAA35544.1; -; mRNA. DR EMBL; M18471; AAA35541.1; -; mRNA. DR EMBL; X03045; CAA26850.1; -; mRNA. DR EMBL; M10374; AAA51750.1; -; mRNA. DR EMBL; M12413; AAA51742.1; -; mRNA. DR EMBL; M36676; AAA35548.1; -; mRNA. DR IPI; IPI00022229; -. DR PIR; A27850; LPHUB. DR RefSeq; NP_000375.2; -. DR UniGene; Hs.120759; -. DR GlycoSuiteDB; P04114; -. DR PhosphoSite; P04114; -. DR Cornea-2DPAGE; P04114; -. DR PeptideAtlas; P04114; -. DR PRIDE; P04114; -. DR Ensembl; ENSG00000084674; Homo sapiens. DR GeneID; 338; -. DR KEGG; hsa:338; -. DR GeneCards; GC02M021135; -. DR H-InvDB; HIX0024005; -. DR HGNC; HGNC:603; APOB. DR HPA; CAB016070; -. DR MIM; 107730; gene+phenotype. DR MIM; 144010; phenotype. DR Orphanet; 89; Defective apolipoprotein B-100, familial. DR Orphanet; 406; Hypercholesterolemia, familial. DR PharmGKB; PA50; -. DR HOVERGEN; P04114; -. DR Pathway_Interaction_DB; amb2_neutrophils_pathway; amb2 Integrin signaling. DR Pathway_Interaction_DB; hnf3apathway; FOXA1 transcription factor network. DR Reactome; REACT_602; Metabolism of lipids and lipoproteins. DR Reactome; REACT_604; Hemostasis. DR Reactome; REACT_6900; Signaling in Immune system. DR DrugBank; DB01076; Atorvastatin. DR NextBio; 1399; -. DR ArrayExpress; P04114; -. DR Bgee; P04114; -. DR GermOnline; ENSG00000084674; Homo sapiens. DR GO; GO:0034360; C:chylomicron remnant; TAS:UniProtKB. DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; EXP:Reactome. DR GO; GO:0005788; C:endoplasmic reticulum lumen; EXP:Reactome. DR GO; GO:0031904; C:endosome lumen; EXP:Reactome. DR GO; GO:0010008; C:endosome membrane; EXP:Reactome. DR GO; GO:0034363; C:intermediate-density lipoprotein particle; IDA:UniProtKB. DR GO; GO:0034362; C:low-density lipoprotein particle; IDA:UniProtKB. DR GO; GO:0034359; C:mature chylomicron; IDA:UniProtKB. DR GO; GO:0005792; C:microsome; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; EXP:Reactome. DR GO; GO:0034361; C:very-low-density lipoprotein particle; IDA:UniProtKB. DR GO; GO:0017127; F:cholesterol transporter activity; IMP:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB. DR GO; GO:0050750; F:low-density lipoprotein receptor binding; IMP:UniProtKB. DR GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB. DR GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB. DR GO; GO:0008203; P:cholesterol metabolic process; IMP:UniProtKB. DR GO; GO:0030301; P:cholesterol transport; IMP:UniProtKB. DR GO; GO:0034383; P:low-density lipoprotein particle clearance; IMP:UniProtKB. DR GO; GO:0034374; P:low-density lipoprotein particle remodeling; IMP:UniProtKB. DR GO; GO:0010886; P:positive regulation of cholesterol storage; IDA:UniProtKB. DR GO; GO:0010744; P:positive regulation of foam cell differenti...; IDA:UniProtKB. DR GO; GO:0034379; P:very-low-density lipoprotein particle assembly; IC:UniProtKB. DR InterPro; IPR001747; Lipid_transpt_N. DR InterPro; IPR009454; Lipid_transpt_open_b-sht. DR InterPro; IPR015255; Vitellinogen_open_b-sht. DR InterPro; IPR011030; Vitellinogen_superhlx. DR Gene3D; G3DSA:1.25.10.20; Vitellinogen_superhlx; 1. DR Pfam; PF06448; DUF1081; 1. DR Pfam; PF09172; DUF1943; 1. DR Pfam; PF01347; Vitellogenin_N; 1. DR SMART; SM00638; LPD_N; 1. DR PROSITE; PS51211; VITELLOGENIN; 1. PE 1: Evidence at protein level; KW Atherosclerosis; Cholesterol metabolism; Chylomicron; KW Complete proteome; Direct protein sequencing; Disease mutation; KW Disulfide bond; Glycoprotein; Heparin-binding; LDL; Lipid metabolism; KW Lipid transport; Lipoprotein; Palmitate; Phosphoprotein; Polymorphism; KW RNA editing; Secreted; Signal; Steroid metabolism; Transport; VLDL. FT SIGNAL 1 27 FT CHAIN 28 4563 Apolipoprotein B-100. FT /FTId=PRO_0000020750. FT CHAIN 28 2179 Apolipoprotein B-48. FT /FTId=PRO_0000020751. FT DOMAIN 46 672 Vitellogenin. FT REGION 32 126 Heparin-binding. FT REGION 232 306 Heparin-binding. FT REGION 902 959 Heparin-binding. FT REGION 2043 2178 Heparin-binding. FT REGION 3161 3236 Heparin-binding. FT REGION 3174 3184 Basic (possible receptor binding region). FT REGION 3373 3393 LDL receptor binding. FT REGION 3383 3516 Heparin-binding. FT REGION 3386 3394 Basic (possible receptor binding region). FT MOD_RES 928 928 Phosphoserine. FT MOD_RES 4507 4507 Phosphoserine. FT LIPID 1112 1112 S-palmitoyl cysteine. FT CARBOHYD 34 34 N-linked (GlcNAc...) (Potential). FT CARBOHYD 185 185 N-linked (GlcNAc...). FT CARBOHYD 983 983 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1368 1368 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1377 1377 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1523 1523 N-linked (GlcNAc...). FT CARBOHYD 2239 2239 N-linked (GlcNAc...). FT CARBOHYD 2560 2560 N-linked (GlcNAc...) (Potential). FT CARBOHYD 2779 2779 N-linked (GlcNAc...). FT CARBOHYD 2982 2982 N-linked (GlcNAc...). FT CARBOHYD 3101 3101 N-linked (GlcNAc...). FT CARBOHYD 3224 3224 N-linked (GlcNAc...). FT CARBOHYD 3336 3336 N-linked (GlcNAc...) (Potential). FT CARBOHYD 3358 3358 N-linked (GlcNAc...). FT CARBOHYD 3411 3411 N-linked (GlcNAc...). FT CARBOHYD 3465 3465 N-linked (GlcNAc...). FT CARBOHYD 3895 3895 N-linked (GlcNAc...). FT CARBOHYD 4237 4237 N-linked (GlcNAc...) (Potential). FT CARBOHYD 4431 4431 N-linked (GlcNAc...) (Potential). FT DISULFID 39 88 FT DISULFID 78 97 FT DISULFID 186 212 FT DISULFID 245 261 FT DISULFID 385 390 FT DISULFID 478 513 FT DISULFID 966 976 FT DISULFID 3194 3324 FT VARIANT 98 98 T -> I (in dbSNP:rs1367117). FT /FTId=VAR_016184. FT VARIANT 103 103 Y -> H (in dbSNP:rs9282603). FT /FTId=VAR_022036. FT VARIANT 145 145 P -> S (in dbSNP:rs6752026). FT /FTId=VAR_022037. FT VARIANT 194 194 T -> M (in dbSNP:rs13306198). FT /FTId=VAR_056737. FT VARIANT 273 273 N -> K (in dbSNP:rs1126419). FT /FTId=VAR_019827. FT VARIANT 408 408 I -> T (in dbSNP:rs12714225). FT /FTId=VAR_029341. FT VARIANT 490 490 R -> W (in FHBL; reduced protein FT secretion). FT /FTId=VAR_022610. FT VARIANT 554 554 P -> L (in dbSNP:rs12714214). FT /FTId=VAR_020135. FT VARIANT 618 618 A -> V (in dbSNP:rs679899). FT /FTId=VAR_019828. FT VARIANT 730 730 V -> I (in dbSNP:rs12691202). FT /FTId=VAR_020136. FT VARIANT 733 733 V -> I (in dbSNP:rs1800476). FT /FTId=VAR_016185. FT VARIANT 741 741 T -> N (in dbSNP:rs12714192). FT /FTId=VAR_020137. FT VARIANT 877 877 P -> L (in dbSNP:rs12714097). FT /FTId=VAR_029342. FT VARIANT 955 955 P -> S (in dbSNP:rs13306206). FT /FTId=VAR_056738. FT VARIANT 1086 1086 G -> S (in dbSNP:rs12720801). FT /FTId=VAR_029343. FT VARIANT 1113 1113 D -> H (in dbSNP:rs12713844). FT /FTId=VAR_029344. FT VARIANT 1128 1128 R -> H (in dbSNP:rs12713843). FT /FTId=VAR_022611. FT VARIANT 1218 1218 E -> Q (in dbSNP:rs1041956). FT /FTId=VAR_019829. FT VARIANT 1388 1388 R -> H (in dbSNP:rs13306187). FT /FTId=VAR_029345. FT VARIANT 1437 1437 F -> L (in dbSNP:rs1801697). FT /FTId=VAR_005016. FT VARIANT 1914 1914 N -> S (in dbSNP:rs1801699). FT /FTId=VAR_005017. FT VARIANT 1923 1923 H -> R (in dbSNP:rs533617). FT /FTId=VAR_005018. FT VARIANT 2092 2092 V -> L (in dbSNP:rs1041960). FT /FTId=VAR_019830. FT VARIANT 2299 2299 D -> H (in dbSNP:rs12713681). FT /FTId=VAR_029346. FT VARIANT 2365 2365 T -> A (in dbSNP:rs1041971). FT /FTId=VAR_019831. FT VARIANT 2456 2456 A -> D (in dbSNP:rs12713675). FT /FTId=VAR_020138. FT VARIANT 2564 2564 F -> C (in a colorectal cancer sample; FT somatic mutation). FT /FTId=VAR_035795. FT VARIANT 2566 2566 E -> K (in dbSNP:rs1801696). FT /FTId=VAR_005019. FT VARIANT 2680 2680 Q -> L (in dbSNP:rs1042013). FT /FTId=VAR_019832. FT VARIANT 2739 2739 P -> L (in dbSNP:rs676210). FT /FTId=VAR_005020. FT VARIANT 2785 2785 N -> H (in dbSNP:rs2163204). FT /FTId=VAR_022038. FT VARIANT 3121 3121 A -> T (in dbSNP:rs1801694). FT /FTId=VAR_005021. FT VARIANT 3182 3182 H -> N (in dbSNP:rs12720848). FT /FTId=VAR_029347. FT VARIANT 3279 3279 S -> G (in dbSNP:rs12720854). FT /FTId=VAR_029348. FT VARIANT 3294 3294 S -> P (in dbSNP:rs12720855). FT /FTId=VAR_020139. FT VARIANT 3319 3319 H -> D. FT /FTId=VAR_005022. FT VARIANT 3427 3427 K -> T. FT /FTId=VAR_005023. FT VARIANT 3432 3432 E -> Q (in dbSNP:rs1042023). FT /FTId=VAR_005024. FT VARIANT 3527 3527 R -> Q (in FDB; dbSNP:rs5742904). FT /FTId=VAR_005025. FT VARIANT 3558 3558 R -> C (in FDB; dbSNP:rs12713559). FT /FTId=VAR_005026. FT VARIANT 3638 3638 R -> Q (in dbSNP:rs1801701). FT /FTId=VAR_016186. FT VARIANT 3732 3732 T -> I (in dbSNP:rs1042025). FT /FTId=VAR_019833. FT VARIANT 3801 3801 S -> T (in dbSNP:rs12713540). FT /FTId=VAR_029349. FT VARIANT 3921 3921 V -> I. FT /FTId=VAR_005027. FT VARIANT 3945 3945 T -> A (in dbSNP:rs1801698). FT /FTId=VAR_005028. FT VARIANT 3949 3949 L -> F (in dbSNP:rs1042027). FT /FTId=VAR_019834. FT VARIANT 3964 3964 F -> Y (in dbSNP:rs1126468). FT /FTId=VAR_019835. FT VARIANT 4128 4128 V -> M (in dbSNP:rs1801703). FT /FTId=VAR_005029. FT VARIANT 4181 4181 K -> E (in dbSNP:rs1042031). FT /FTId=VAR_016187. FT VARIANT 4270 4270 R -> T (in dbSNP:rs1801702). FT /FTId=VAR_016188. FT VARIANT 4338 4338 N -> S (in dbSNP:rs1042034). FT /FTId=VAR_005030. FT VARIANT 4394 4394 V -> A (in dbSNP:rs12720843). FT /FTId=VAR_029350. FT VARIANT 4481 4481 A -> T (in dbSNP:rs1801695). FT /FTId=VAR_005031. FT VARIANT 4484 4484 T -> M (in dbSNP:rs12713450). FT /FTId=VAR_020140. FT MUTAGEN 483 483 D->N: Impairs protein secretion. FT MUTAGEN 483 483 D->Q: Does not affect protein secretion. FT MUTAGEN 490 490 R->A: Impairs protein secretion. FT MUTAGEN 490 490 R->K: Does not affect protein secretion. FT CONFLICT 11 13 Missing (in Ref. 5). FT CONFLICT 329 329 L -> V (in Ref. 3). FT CONFLICT 645 645 L -> I (in Ref. 3). FT CONFLICT 704 704 L -> P (in Ref. 4). FT CONFLICT 792 809 LQLLGKLLLMGARTLQGI -> SSSWKAASHGCPHSAGD FT (in Ref. 11). FT CONFLICT 793 793 Q -> R (in Ref. 4). FT CONFLICT 893 893 D -> K (in Ref. 12; AA sequence). FT CONFLICT 919 919 A -> P (in Ref. 3). FT CONFLICT 1109 1109 H -> D (in Ref. 5). FT CONFLICT 1180 1180 T -> R (in Ref. 7). FT CONFLICT 1271 1271 F -> S (in Ref. 4). FT CONFLICT 1418 1418 F -> S (in Ref. 5). FT CONFLICT 1445 1445 N -> I (in Ref. 7). FT CONFLICT 1535 1535 G -> E (in Ref. 7). FT CONFLICT 1670 1670 E -> D (in Ref. 7). FT CONFLICT 1867 1867 R -> G (in Ref. 4). FT CONFLICT 2037 2037 I -> N (in Ref. 4). FT CONFLICT 2098 2098 N -> K (in Ref. 5). FT CONFLICT 2218 2218 I -> T (in Ref. 4). FT CONFLICT 2221 2221 N -> I (in Ref. 5). FT CONFLICT 2324 2326 LIG -> PYW (in Ref. 15). FT CONFLICT 2353 2353 Q -> H (in Ref. 15). FT CONFLICT 2540 2540 G -> S (in Ref. 5). FT CONFLICT 2718 2737 Missing (in Ref. 14). FT CONFLICT 2933 2933 C -> S (in Ref. 4). FT CONFLICT 3114 3114 H -> L (in Ref. 12; AA sequence). FT CONFLICT 3131 3131 T -> R (in Ref. 12; AA sequence). FT CONFLICT 3134 3134 E -> P (in Ref. 12; AA sequence). FT CONFLICT 3137 3137 L -> R (in Ref. 12; AA sequence). FT CONFLICT 3239 3239 H -> Q (in Ref. 5). FT CONFLICT 3286 3286 L -> I (in Ref. 4). FT CONFLICT 3291 3291 R -> L (in Ref. 14). FT CONFLICT 3337 3337 I -> N (in Ref. 14). FT CONFLICT 3431 3431 A -> P (in Ref. 4). FT CONFLICT 3728 3728 D -> N (in Ref. 23). FT CONFLICT 3782 3782 N -> T (in Ref. 4). FT CONFLICT 3824 3824 Q -> R (in Ref. 5 and 22). FT CONFLICT 3876 3876 V -> A (in Ref. 3 and 23). FT CONFLICT 3911 3911 T -> Y (in Ref. 9; AA sequence). FT CONFLICT 3983 3983 F -> S (in Ref. 23). FT CONFLICT 4002 4002 A -> P (in Ref. 23). FT CONFLICT 4110 4111 NN -> DH (in Ref. 3 and 23). FT CONFLICT 4122 4122 Q -> E (in Ref. 3 and 23). FT CONFLICT 4128 4128 V -> E (in Ref. 3 and 23). FT CONFLICT 4133 4133 A -> G (in Ref. 3 and 23). FT CONFLICT 4188 4188 H -> K (in Ref. 4). FT CONFLICT 4217 4218 CT -> FP (in Ref. 25). FT CONFLICT 4221 4221 I -> M (in Ref. 4). SQ SEQUENCE 4563 AA; 515563 MW; 2AD50594D3ADD22E CRC64; MDPPRPALLA LLALPALLLL LLAGARAEEE MLENVSLVCP KDATRFKHLR KYTYNYEAES SSGVPGTADS RSATRINCKV ELEVPQLCSF ILKTSQCTLK EVYGFNPEGK ALLKKTKNSE EFAAAMSRYE LKLAIPEGKQ VFLYPEKDEP TYILNIKRGI ISALLVPPET EEAKQVLFLD TVYGNCSTHF TVKTRKGNVA TEISTERDLG QCDRFKPIRT GISPLALIKG MTRPLSTLIS SSQSCQYTLD AKRKHVAEAI CKEQHLFLPF SYNNKYGMVA QVTQTLKLED TPKINSRFFG EGTKKMGLAF ESTKSTSPPK QAEAVLKTLQ ELKKLTISEQ NIQRANLFNK LVTELRGLSD EAVTSLLPQL IEVSSPITLQ ALVQCGQPQC STHILQWLKR VHANPLLIDV VTYLVALIPE PSAQQLREIF NMARDQRSRA TLYALSHAVN NYHKTNPTGT QELLDIANYL MEQIQDDCTG DEDYTYLILR VIGNMGQTME QLTPELKSSI LKCVQSTKPS LMIQKAAIQA LRKMEPKDKD QEVLLQTFLD DASPGDKRLA AYLMLMRSPS QADINKIVQI LPWEQNEQVK NFVASHIANI LNSEELDIQD LKKLVKEALK ESQLPTVMDF RKFSRNYQLY KSVSLPSLDP ASAKIEGNLI FDPNNYLPKE SMLKTTLTAF GFASADLIEI GLEGKGFEPT LEALFGKQGF FPDSVNKALY WVNGQVPDGV SKVLVDHFGY TKDDKHEQDM VNGIMLSVEK LIKDLKSKEV PEARAYLRIL GEELGFASLH DLQLLGKLLL MGARTLQGIP QMIGEVIRKG SKNDFFLHYI FMENAFELPT GAGLQLQISS SGVIAPGAKA GVKLEVANMQ AELVAKPSVS VEFVTNMGII IPDFARSGVQ MNTNFFHESG LEAHVALKAG KLKFIIPSPK RPVKLLSGGN TLHLVSTTKT EVIPPLIENR QSWSVCKQVF PGLNYCTSGA YSNASSTDSA SYYPLTGDTR LELELRPTGE IEQYSVSATY ELQREDRALV DTLKFVTQAE GAKQTEATMT FKYNRQSMTL SSEVQIPDFD VDLGTILRVN DESTEGKTSY RLTLDIQNKK ITEVALMGHL SCDTKEERKI KGVISIPRLQ AEARSEILAH WSPAKLLLQM DSSATAYGST VSKRVAWHYD EEKIEFEWNT GTNVDTKKMT SNFPVDLSDY PKSLHMYANR LLDHRVPETD MTFRHVGSKL IVAMSSWLQK ASGSLPYTQT LQDHLNSLKE FNLQNMGLPD FHIPENLFLK SDGRVKYTLN KNSLKIEIPL PFGGKSSRDL KMLETVRTPA LHFKSVGFHL PSREFQVPTF TIPKLYQLQV PLLGVLDLST NVYSNLYNWS ASYSGGNTST DHFSLRARYH MKADSVVDLL SYNVQGSGET TYDHKNTFTL SCDGSLRHKF LDSNIKFSHV EKLGNNPVSK GLLIFDASSS WGPQMSASVH LDSKKKQHLF VKEVKIDGQF RVSSFYAKGT YGLSCQRDPN TGRLNGESNL RFNSSYLQGT NQITGRYEDG TLSLTSTSDL QSGIIKNTAS LKYENYELTL KSDTNGKYKN FATSNKMDMT FSKQNALLRS EYQADYESLR FFSLLSGSLN SHGLELNADI LGTDKINSGA HKATLRIGQD GISTSATTNL KCSLLVLENE LNAELGLSGA SMKLTTNGRF REHNAKFSLD GKAALTELSL GSAYQAMILG VDSKNIFNFK VSQEGLKLSN DMMGSYAEMK FDHTNSLNIA GLSLDFSSKL DNIYSSDKFY KQTVNLQLQP YSLVTTLNSD LKYNALDLTN NGKLRLEPLK LHVAGNLKGA YQNNEIKHIY AISSAALSAS YKADTVAKVQ GVEFSHRLNT DIAGLASAID MSTNYNSDSL HFSNVFRSVM APFTMTIDAH TNGNGKLALW GEHTGQLYSK FLLKAEPLAF TFSHDYKGST SHHLVSRKSI SAALEHKVSA LLTPAEQTGT WKLKTQFNNN EYSQDLDAYN TKDKIGVELT GRTLADLTLL DSPIKVPLLL SEPINIIDAL EMRDAVEKPQ EFTIVAFVKY DKNQDVHSIN LPFFETLQEY FERNRQTIIV VVENVQRNLK HINIDQFVRK YRAALGKLPQ QANDYLNSFN WERQVSHAKE KLTALTKKYR ITENDIQIAL DDAKINFNEK LSQLQTYMIQ FDQYIKDSYD LHDLKIAIAN IIDEIIEKLK SLDEHYHIRV NLVKTIHDLH LFIENIDFNK SGSSTASWIQ NVDTKYQIRI QIQEKLQQLK RHIQNIDIQH LAGKLKQHIE AIDVRVLLDQ LGTTISFERI NDVLEHVKHF VINLIGDFEV AEKINAFRAK VHELIERYEV DQQIQVLMDK LVELTHQYKL KETIQKLSNV LQQVKIKDYF EKLVGFIDDA VKKLNELSFK TFIEDVNKFL DMLIKKLKSF DYHQFVDETN DKIREVTQRL NGEIQALELP QKAEALKLFL EETKATVAVY LESLQDTKIT LIINWLQEAL SSASLAHMKA KFRETLEDTR DRMYQMDIQQ ELQRYLSLVG QVYSTLVTYI SDWWTLAAKN LTDFAEQYSI QDWAKRMKAL VEQGFTVPEI KTILGTMPAF EVSLQALQKA TFQTPDFIVP LTDLRIPSVQ INFKDLKNIK IPSRFSTPEF TILNTFHIPS FTIDFVEMKV KIIRTIDQMQ NSELQWPVPD IYLRDLKVED IPLARITLPD FRLPEIAIPE FIIPTLNLND FQVPDLHIPE FQLPHISHTI EVPTFGKLYS ILKIQSPLFT LDANADIGNG TTSANEAGIA ASITAKGESK LEVLNFDFQA NAQLSNPKIN PLALKESVKF SSKYLRTEHG SEMLFFGNAI EGKSNTVASL HTEKNTLELS NGVIVKINNQ LTLDSNTKYF HKLNIPKLDF SSQADLRNEI KTLLKAGHIA WTSSGKGSWK WACPRFSDEG THESQISFTI EGPLTSFGLS NKINSKHLRV NQNLVYESGS LNFSKLEIQS QVDSQHVGHS VLTAKGMALF GEGKAEFTGR HDAHLNGKVI GTLKNSLFFS AQPFEITAST NNEGNLKVRF PLRLTGKIDF LNNYALFLSP SAQQASWQVS ARFNQYKYNQ NFSAGNNENI MEAHVGINGE ANLDFLNIPL TIPEMRLPYT IITTPPLKDF SLWEKTGLKE FLKTTKQSFD LSVKAQYKKN KHRHSITNPL AVLCEFISQS IKSFDRHFEK NRNNALDFVT KSYNETKIKF DKYKAEKSHD ELPRTFQIPG YTVPVVNVEV SPFTIEMSAF GYVFPKAVSM PSFSILGSDV RVPSYTLILP SLELPVLHVP RNLKLSLPHF KELCTISHIF IPAMGNITYD FSFKSSVITL NTNAELFNQS DIVAHLLSSS SSVIDALQYK LEGTTRLTRK RGLKLATALS LSNKFVEGSH NSTVSLTTKN MEVSVAKTTK AEIPILRMNF KQELNGNTKS KPTVSSSMEF KYDFNSSMLY STAKGAVDHK LSLESLTSYF SIESSTKGDV KGSVLSREYS GTIASEANTY LNSKSTRSSV KLQGTSKIDD IWNLEVKENF AGEATLQRIY SLWEHSTKNH LQLEGLFFTN GEHTSKATLE LSPWQMSALV QVHASQPSSF HDFPDLGQEV ALNANTKNQK IRWKNEVRIH SGSFQSQVEL SNDQEKAHLD IAGSLEGHLR FLKNIILPVY DKSLWDFLKL DVTTSIGRRQ HLRVSTAFVY TKNPNGYSFS IPVKVLADKF ITPGLKLNDL NSVLVMPTFH VPFTDLQVPS CKLDFREIQI YKKLRTSSFA LNLPTLPEVK FPEVDVLTKY SQPEDSLIPF FEITVPESQL TVSQFTLPKS VSDGIAALDL NAVANKIADF ELPTIIVPEQ TIEIPSIKFS VPAGIVIPSF QALTARFEVD SPVYNATWSA SLKNKADYVE TVLDSTCSST VQFLEYELNV LGTHKIEDGT LASKTKGTLA HRDFSAEYEE DGKFEGLQEW EGKAHLNIKS PAFTDLHLRY QKDKKGISTS AASPAVGTVG MDMDEDDDFS KWNFYYSPQS SPDKKLTIFK TELRVRESDE ETQIKVNWEE EAASGLLTSL KDNVPKATGV LYDYVNKYHW EHTGLTLREV SSKLRRNLQN NAEWVYQGAI RQIDDIDVRF QKAASGTTGT YQEWKDKAQN LYQELLTQEG QASFQGLKDN VFDGLVRVTQ KFHMKVKHLI DSLIDFLNFP RFQFPGKPGI YTREELCTMF IREVGTVLSQ VYSKVHNGSE ILFSYFQDLV ITLPFELRKH KLIDVISMYR ELLKDLSKEA QEVFKAIQSL KTTEVLRNLQ DLLQFIFQLI EDNIKQLKEM KFTYLINYIQ DEINTIFNDY IPYVFKLLKE NLCLNLHKFN EFIQNELQEA SQELQQIHQY IMALREEYFD PSIVGWTVKY YELEEKIVSL IKNLLVALKD FHSEYIVSAS NFTSQLSSQV EQFLHRNIQE YLSILTDPDG KGKEKIAELS ATAQEIIKSQ AIATKKIISD YHQQFRYKLQ DFSDQLSDYY EKFIAESKRL IDLSIQNYHT FLIYITELLK KLQSTTVMNP YMKLAPGELT IIL //