LOCUS       HUMAPOE3                1156 bp    mRNA    linear   HUM 21-OCT-2002
DEFINITION  Homo sapiens preapolipoprotein E (APOE) mRNA, complete cds.
ACCESSION   K00396
VERSION     K00396.1
KEYWORDS    apolipoprotein; apolipoprotein E; lipoprotein; polymorphism; very
            low density lipoprotein.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 355 to 1156)
  AUTHORS   Breslow,J.L., McPherson,J., Nussbaum,A.L., Williams,H.W.,
            Lofquist-Kahl,F., Karathanasis,S.K. and Zannis,V.I.
  TITLE     Identification and DNA sequence of a human apolipoprotein E cDNA
            clone
  JOURNAL   J. Biol. Chem. 257 (24), 14639-14641 (1982)
   PUBMED   6897404
REFERENCE   2  (bases 250 to 777)
  AUTHORS   Wallis,S.C., Rogne,S., Gill,L., Markham,A., Edge,M., Woods,D.,
            Williamson,R. and Humphries,S.
  TITLE     The isolation of cDNA clones for human apolipoprotein E and the
            detection of apoE RNA in hepatic and extra-hepatic tissues
  JOURNAL   EMBO J. 2 (12), 2369-2373 (1983)
   PUBMED   6199196
REFERENCE   3  (bases 1 to 1156)
  AUTHORS   Zannis,V.I., McPherson,J., Goldberger,G., Karathanasis,S.K. and
            Breslow,J.L.
  TITLE     Synthesis, intracellular processing, and signal peptide of human
            apolipoprotein E
  JOURNAL   J. Biol. Chem. 259 (9), 5495-5499 (1984)
   PUBMED   6325438
REFERENCE   4  (bases 88 to 1156)
  AUTHORS   McLean,J.W., Elshourbagy,N.A., Chang,D.J., Mahley,R.W. and
            Taylor,J.M.
  TITLE     Human apolipoprotein E mRNA. cDNA cloning and nucleotide sequencing
            of a new variant
  JOURNAL   J. Biol. Chem. 259 (10), 6498-6504 (1984)
   PUBMED   6327682
REFERENCE   5  (bases 577 to 624)
  AUTHORS   Gill,L.L., Peoples,O.P., Pearston,D.H., Robertson,F.W.,
            Humphries,S.E., Cumming,A.M. and Hardman,N.
  TITLE     Isolation and characterisation of a variant allele of the gene for
            human apolipoprotein E
  JOURNAL   Biochem. Biophys. Res. Commun. 130 (3), 1261-1266 (1985)
   PUBMED   2992507
REFERENCE   6  (sites)
  AUTHORS   Rall,S.C. Jr., Newhouse,Y.M., Clarke,H.R., Weisgraber,K.H.,
            McCarthy,B.J., Mahley,R.W. and Bersot,T.P.
  TITLE     Type III hyperlipoproteinemia associated with apolipoprotein E
            phenotype E3/3. Structure and genetics of an apolipoprotein E3
            variant
  JOURNAL   J. Clin. Invest. 83 (4), 1095-1101 (1989)
   PUBMED   2539388
COMMENT     [1]  corrected in [J. Biol. Chem. 258, 11422-11422 (1983)]. [J.
            Biol. Chem. 258, 11422-11422 (1983)]  correction of [1]. [4]
            epsilon-3 and variant.
            [5]  epsilon-2 allele.
            [6]  sites; mutations resulting in type III hyperlipoproteinemia.
            Apo E is a component of normal human very low density lipoprotein.
            There are six human apo E phenotypes known to result from a single
            structural gene, three of the common alleles being epsilon-4,
            epsilon-3 and epsilon-2. This sequence appears to be of the
            epsilon-3 allele. [1] argues that the apo E polymorphism involves
            mutations in the structural coding region; for example the
            epsilon-2 phenotype which is characterized by hyperlipoproteinemia
            is thought to result from a c to t change (arg to cys) at base 586
            below [3],[5]. The sequence shown is 57% homologous with human apo
            A-I and 81% homologous with rat apo E. For the epsilon-4 sequence,
            see the separate entry.
            [J. Biol. Chem. 258, 11422-11422 (1983)] is too extensively revised
            relative to [1] to record the
            revisions in the FEATURES table. The sequence below is that of [J.
            Biol. Chem. 258, 11422-11422 (1983)]
            and [3].
            Apo E  is located on chromosome 19 --Jackson, Bruns and Breslow ,
            PNAS USA 81, 2945-2949 (1984) -- and is believed to be linked to
            the Apo C-II gene (see separate entry).
            The two mutations causing type III hyperlipoproteinemia
            (apolipoprotein E phenotype E3/3) produces substitutions of Arg for
            Cys at amino acid 112 and Cys for Arg at amino acid position 142.
            Draft entry and printed copy of sequence for [1] kindly provided by
            L.L. Gill, University of Aberdeen.
            Complete source information:
            Human liver [1],[J. Biol. Chem. 258, 11422-11422 (1983)],[2],[3],
            [4] and blood [5], cDNA to mRNA.
FEATURES             Location/Qualifiers
     source          1..1156
                     /db_xref="H-InvDB:HIT000191348"
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /map="19q13.2"
                     /tissue_type="liver and blood"
     gene            1..1156
                     /gene="APOE"
     CDS             61..1014
                     /gene="APOE"
                     /codon_start=1
                     /product="preapolipoprotein E"
                     /protein_id="AAB59546.1"
                     /db_xref="GI:178851"
                     /db_xref="GDB:G00-119-691"
                     /translation="MKVLWAALLVTFLAGCQAKVEQAVETEPEPELRQQTEWQSGQRW
                     ELALGRFWDYLRWVQTLSEQVQEELLSSQVTQELRALMDETMKELKAYKSELEEQLTP
                     VAEETRARLSKELQAAQARLGADMEDVCGRLVQYRGEVQAMLGQSTEELRVRLASHLR
                     KLRKRLLRDADDLQKRLAVYQAGAREGAERGLSAIRERLGPLVEQGRVRAATVGSLAG
                     QPLQERAQAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQQIRLQAEAFQ
                     ARLKSWFEPLVEDMQRQWAGLVEKVQAAVGTSAAPVPSDNH"
     sig_peptide     61..114
                     /gene="APOE"
                     /note="apolipoprotein E"
     mat_peptide     115..1011
                     /gene="APOE"
                     /product="apolipoprotein E mature peptide"
     variation       267
                     /gene="APOE"
                     /note="g in [J. Biol. Chem. 258, 11422-11422 (1983)]"
                     /citation=[2]
                     /citation=[3]
                     /citation=[4]
                     /replace="c"
     variation       279
                     /gene="APOE"
                     /note="g in [J. Biol. Chem. 258, 11422-11422 (1983)]"
                     /citation=[3]
                     /citation=[4]
                     /replace="a"
     variation       288
                     /gene="APOE"
                     /note="g in [J. Biol. Chem. 258, 11422-11422 (1983)]"
                     /citation=[3]
                     /citation=[4]
                     /replace="a"
     variation       369
                     /gene="APOE"
                     /note="in variant"
                     /citation=[4]
                     /replace="a"
     variation       409
                     /gene="APOE"
                     /note="in variant"
                     /citation=[4]
                     /replace="a"
     variation       448
                     /gene="APOE"
                     /note="in type III hyperlipoproteinemia"
                     /replace="c"
     variation       538
                     /gene="APOE"
                     /note="in type III hyperlipoproteinemia"
                     /replace="t"
     variation       568
                     /gene="APOE"
                     /note="in variant"
                     /citation=[4]
                     /replace="c"
     variation       586
                     /gene="APOE"
                     /note="in epsilon-2 allele"
                     /citation=[3]
                     /citation=[5]
                     /replace="t"
     variation       702
                     /gene="APOE"
                     /note="c in [J. Biol. Chem. 258, 11422-11422 (1983)]"
                     /citation=[2]
                     /citation=[3]
                     /citation=[4]
                     /replace="g"
     variation       783
                     /gene="APOE"
                     /note="in variant"
                     /citation=[4]
                     /replace="t"
     variation       858
                     /gene="APOE"
                     /note="g in [J. Biol. Chem. 258, 11422-11422 (1983)],[3]
                     and [4] variant; a in [4]'normal'"
                     /citation=[4]
                     /replace="a"
BASE COUNT          208 a          368 c          432 g          148 t
ORIGIN      
        1 cgcagcggag gtgaaggacg tccttcccca ggagccgact ggccaatcac aggcaggaag
       61 atgaaggttc tgtgggctgc gttgctggtc acattcctgg caggatgcca ggccaaggtg
      121 gagcaagcgg tggagacaga gccggagccc gagctgcgcc agcagaccga gtggcagagc
      181 ggccagcgct gggaactggc actgggtcgc ttttgggatt acctgcgctg ggtgcagaca
      241 ctgtctgagc aggtgcagga ggagctgctc agctcccagg tcacccagga actgagggcg
      301 ctgatggacg agaccatgaa ggagttgaag gcctacaaat cggaactgga ggaacaactg
      361 accccggtgg cggaggagac gcgggcacgg ctgtccaagg agctgcaggc ggcgcaggcc
      421 cggctgggcg cggacatgga ggacgtgtgc ggccgcctgg tgcagtaccg cggcgaggtg
      481 caggccatgc tcggccagag caccgaggag ctgcgggtgc gcctcgcctc ccacctgcgc
      541 aagctgcgta agcggctcct ccgcgatgcc gatgacctgc agaagcgcct ggcagtgtac
      601 caggccgggg cccgcgaggg cgccgagcgc ggcctcagcg ccatccgcga gcgcctgggg
      661 cccctggtgg aacagggccg cgtgcgggcc gccactgtgg gctccctggc cggccagccg
      721 ctacaggagc gggcccaggc ctggggcgag cggctgcgcg cgcggatgga ggagatgggc
      781 agccggaccc gcgaccgcct ggacgaggtg aaggagcagg tggcggaggt gcgcgccaag
      841 ctggaggagc aggcccagca gatacgcctg caggccgagg ccttccaggc ccgcctcaag
      901 agctggttcg agcccctggt ggaagacatg cagcgccagt gggccgggct ggtggagaag
      961 gtgcaggctg ccgtgggcac cagcgccgcc cctgtgccca gcgacaatca ctgaacgccg
     1021 aagcctgcag ccatgcgacc ccacgccacc ccgtgcctcc tgcctccgcg cagcctgcag
     1081 cgggagaccc tgtccccgcc ccagccgtcc tcctggggtg gaccctagtt taataaagat
     1141 tcaccaagtt tcacgc
//