LOCUS       HUMAPOE4                5515 bp    DNA     linear   PRI 09-NOV-1994
DEFINITION  Human apolipoprotein E (epsilon-4 allele) gene, complete cds.
ACCESSION   M10065 J03053 J03054
VERSION     M10065.1  GI:178852
KEYWORDS    Alu repeat; allelic variation; apolipoprotein; apolipoprotein E;
            lipoprotein; repeat region; very low density lipoprotein.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 5515)
  AUTHORS   Das,H.K., McPherson,J., Bruns,G.A., Karathanasis,S.K. and
            Breslow,J.L.
  TITLE     Isolation, characterization, and mapping to chromosome 19 of the
            human apolipoprotein E gene
  JOURNAL   J. Biol. Chem. 260 (10), 6240-6247 (1985)
  MEDLINE   85207610
   PUBMED   3922972
REFERENCE   2  (bases 196 to 5269)
  AUTHORS   Paik,Y.K., Chang,D.J., Reardon,C.A., Davies,G.E., Mahley,R.W. and
            Taylor,J.M.
  TITLE     Nucleotide sequence and structure of the human apolipoprotein E
            gene
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 82 (10), 3445-3449 (1985)
  MEDLINE   85216517
   PUBMED   2987927
REFERENCE   3  (bases 1 to 5515)
  AUTHORS   Emi,M., Wu,L.L., Robertson,M.A., Myers,R.L., Hegele,R.A.,
            Williams,R.R., White,R. and Lalouel,J.M.
  TITLE     Genotyping and sequence analysis of apolipoprotein E isoforms
  JOURNAL   Genomics 3 (4), 373-379 (1988)
  MEDLINE   89212602
   PUBMED   3243553
COMMENT     Original source text: Human DNA [2], [1].
            [3]  two allelic variations.
Draft entry and computer-readable sequence for [3] kindly provided by M.Emi, 19-AUG-1988. Apolipoprotein E is a constituent of the human very low density lipoprotein in the plasma. There are at least six distinct phenotypes derived from the single E gene on chromosome 19; next to the epsilon-3 allele (see separate entry), the epsilon-4 allele, represented by the sequence below, is most common, the product difference being arginine in place of cysteine at residue 112 [2]. The gene structure of apo E is similar to that of other apo genes: presence of the 66-bp repeats in the fourth exon (starting at base 3782 below) makes the E gene highly similar to the A-I gene (see separate entry) as argued by [1]. A potential TATA box is found at positions 1014-1018, and a potential polyadenylation signal at 4616-4621. [2] and [1] had slight differences in the boundary positions for the Alu repeats and their flanks; the boundary positions indicated in [1] have been used in the FEATURES table below. Draft entries and clean copies were kindly supplied by J.M. Taylor, Gladstone Laboratories, San Francisco, and by J.P. Levine, Rockefeller University, New York.

FEATURES             Location/Qualifiers
     source          1..5515
                     /organism="Homo sapiens"
                     /mol_type="genomic DNA"
                     /db_xref="taxon:9606"
                     /map="19q13.2"
     exon            1047..1090
                     /note="apo E mRNA [2],[1]"
                     /number=1
     intron          1091..1847
                     /note="apo E mRNA intron 1 [2],[1]"
     CDS             join(1871..1913,3007..3199,3781..4498)
                     /note="precursor"
                     /codon_start=1
                     /product="apolipoprotein E"
                     /protein_id="AAB59397.1"
                     /db_xref="GI:178853"
                     /translation="MKVLWAALLVTFLAGCQAKVEQAVETEPEPELRQQTEWQSGQRWELALGRFWDYLRWVQ TLSEQVQEELLSSQVTQELRALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQARLGADMEDVRGRLVQYRGEVQAMLGQSTEELRVRLASHLRKLRKRLLRDADDLQKRLAVYQAGAREGAERGLSAIRERLGPLVEQGRVRAATVGSLAGQPLQERAQAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGTSAAPVPSDNH"
     gene            1871..1913
                     /gene="APOE"
     exon            1871..1913
                     /gene="APOE"
                     /note="preapolipoprotein E; G00-119-691"
                     /number=2
     intron          1914..3006
                     /note="apo E cds intron 2 [2],[1]"
     exon            3007..3199
                     /number=2
     intron          3200..3780
                     /note="apo E cds intron 3 [2],[1]"
     exon            3781..4640
                     /note="preapolipoprotein E"
                     /number=3

ORIGIN      201 bp upstream of BanII site on chromosome 19q12-q13.2.

       1 ggaacttgatgctcagagaggacaagtcatttgcccaaggtcacacagctggcaactggc
         ccttgaactacgagtctctcctgttcagtaaacgggttccagtgtgtcgaccgttgaccg

      61 agacgagattcacgccctggcaatttgactccagaatcctaaccttaacccagaagcacg
         tctgctctaagtgcgggaccgttaaactgaggtcttaggattggaattgggtcttcgtgc

     121 gcttcaagccctggaaaccacaatacctgtggcagccagggggaggtgctggaatctcat
         cgaagttcgggacctttggtgttatggacaccgtcggtccccctccacgaccttagagta

     181 ttcacatgtggggagggggctcctgtgctcaaggtcacaaccaaagaggaagctgtgatt
         aagtgtacacccctcccccgaggacacgagttccagtgttggtttctccttcgacactaa

     241 aaaacccaggtcccatttgcaaagcctcgacttttagcaggtgcatcatactgttcccac
         ttttgggtccagggtaaacgtttcggagctgaaaatcgtccacgtagtatgacaagggtg

     301 ccctcccatcccacttctgtccagccgcctagccccactttcttttttttctttttttga
         gggagggtagggtgaagacaggtcggcggatcggggtgaaagaaaaaaaagaaaaaaact

     361 gacagtctccctcttgctgaggctggagtgcagtggcgagatctcggctcactgtaacct
         ctgtcagagggagaacgactccgacctcacgtcaccgctctagagccgagtgacattgga

     421 ccgcctcccgggttcaagcgattctcctgcctcagcctcccaagtagctaggattacagg
         ggcggagggcccaagttcgctaagaggacggagtcggagggttcatcgatcctaatgtcc

     481 cgcccgccaccacgcctggctaacttttgtatttttagtagagatggggtttcaccatgt
         gcgggcggtggtgcggaccgattgaaaacataaaaatcatctctaccccaaagtggtaca

     541 tggccaggctggtctcaaactcctgaccttaagtgattcgcccactgtggcctcccaaag
         accggtccgaccagagtttgaggactggaattcactaagcgggtgacaccggagggtttc

     601 tgctgggattacaggcgtgagctaccgcccccagcccctcccatcccacttctgtccagc
         acgaccctaatgtccgcactcgatggcgggggtcggggagggtagggtgaagacaggtcg

     661 cccctagccctactttctttctgggatccaggagtccagatccccagccccctctccaga
         ggggatcgggatgaaagaaagaccctaggtcctcaggtctaggggtcgggggagaggtct

     721 ttacattcatccaggcacaggaaaggacagggtcaggaaaggaggactctgggcggcagc
         aatgtaagtaggtccgtgtcctttcctgtcccagtcctttcctcctgagacccgccgtcg

     781 ctccacattccccttccacgcttggcccccagaatggaggagggtgtctgtattactggg
         gaggtgtaaggggaaggtgcgaaccgggggtcttacctcctcccacagacataatgaccc

     841 cgaggtgtcctcccttcctggggactgtggggggtggtcaaaagacctctatgccccacc
         gctccacaggagggaaggacccctgacaccccccaccagttttctggagatacggggtgg

     901 tccttcctccctctgccctgctgtgcctggggcagggggagaacagcccacctcgtgact
         aggaaggagggagacgggacgacacggaccccgtccccctcttgtcgggtggagcactga

     961 gggctgcccagcccgccctatccctgggggagggggcgggacagggggagccctataatt
         cccgacgggtcgggcgggatagggaccccctcccccgccctgtccccctcgggatattaa

    1021 ggacaagtctgggatccttgagtcctactcagccccagcggaggtgaaggacgtccttcc
         cctgttcagaccctaggaactcaggatgagtcggggtcgcctccacttcctgcaggaagg

    1081 ccaggagccggtgagaagcgcagtcgggggcacggggatgagctcaggggcctctagaaa
         ggtcctcggccactcttcgcgtcagcccccgtgcccctactcgagtccccggagatcttt

    1141 gagctgggaccctgggaagccctggcctccaggtagtctcaggagagctactcggggtcg
         ctcgaccctgggacccttcgggaccggaggtccatcagagtcctctcgatgagccccagc

    1201 ggcttggggagaggaggagcgggggtgaggcaagcagcaggggactggacctgggaaggg
         ccgaacccctctcctcctcgcccccactccgttcgtcgtcccctgacctggacccttccc

    1261 ctgggcagcagagacgacccgacccgctagaaggtggggtggggagagcagctggactgg
         gacccgtcgtctctgctgggctgggcgatcttccaccccacccctctcgtcgacctgacc

    1321 gatgtaagccatagcaggactccacgagttgtcactatcattatcgagcacctactgggt
         ctacattcggtatcgtcctgaggtgctcaacagtgatagtaatagctcgtggatgaccca

    1381 gtccccagtgtcctcagatctccataactggggagccaggggcagcgacacggtagctag
         caggggtcacaggagtctagaggtattgacccctcggtccccgtcgctgtgccatcgatc

    1441 ccgtcgattggagaactttaaaatgaggactgaattagctcataaatggaacacggcgct
         ggcagctaacctcttgaaattttactcctgacttaatcgagtatttaccttgtgccgcga

    1501 taactgtgaggttggagcttagaatgtgaagggagaatgaggaatgcgagactgggactg
         attgacactccaacctcgaatcttacacttccctcttactccttacgctctgaccctgac

    1561 agatggaaccggcggtggggagggggtggggggatggaatttgaaccccgggagaggaag
         tctaccttggccgccacccctcccccacccccctaccttaaacttggggccctctccttc

    1621 atggaattttctatggaggccgacctggggatggggagataagagaagaccaggagggag
         taccttaaaagatacctccggctggacccctacccctctattctcttctggtcctccctc

    1681 ttaaatagggaatgggttgggggcggcttggtaaatgtgctgggattaggctgttgcaga
         aatttatcccttacccaacccccgccgaaccatttacacgaccctaatccgacaacgtct

    1741 taatgcaacaaggcttggaaggctaacctggggtgaggccgggttgggggcgctgggggt
         attacgttgttccgaaccttccgattggaccccactccggcccaacccccgcgaccccca

    1801 gggaggagtcctcactggcggttgattgacagtttctccttccccagactggccaatcac
         ccctcctcaggagtgaccgccaactaactgtcaaagaggaaggggtctgaccggttagtg

       1           M  K  V  L  W  A  A  L  L  V  T  F  L  A  G          >EXON1
    1861 aggcaggaagATGAAGGTTCTGTGGGCTGCGTTGCTGGTCACATTCCTGGCAGgtatggg
         tccgtccttcTACTTCCAAGACACCCGACGCAACGACCAGTGTAAGGACCGTCcataccc

    1921 ggcggggcttgctcggttccccccgctcctccccctctcatcctcacctcaacctcctgg
         ccgccccgaacgagccaaggggggcgaggagggggagagtaggagtggagttggaggacc

    1981 ccccattcagacagaccctgggccccctcttctgaggcttctgtgctgcttcctggctct
         ggggtaagtctgtctgggacccgggggagaagactccgaagacacgacgaaggaccgaga

    2041 gaacagcgatttgacgctctctgggcctcggtttcccccatccttgagataggagttaga
         cttgtcgctaaactgcgagagacccggagccaaagggggtaggaactctatcctcaatct

    2101 agttgttttgttgttgttgtttgttgttgttgttttgtttttttgagatgaagtctcgct
         tcaacaaaacaacaacaacaaacaacaacaacaaaacaaaaaaactctacttcagagcga

    2161 ctgtcgcccaggctggagtgcagtggcgggatctcggctcactgcaagctccgcctccca
         gacagcgggtccgacctcacgtcaccgccctagagccgagtgacgttcgaggcggagggt

    2221 ggtccacgccattctcctgcctcagcctcccaagtagctgggactacaggcacatgccac
         ccaggtgcggtaagaggacggagtcggagggttcatcgaccctgatgtccgtgtacggtg

    2281 cacacccgactaacttttttgtattttcagtagagacggggtttcaccatgttggccagg
         gtgtgggctgattgaaaaaacataaaagtcatctctgccccaaagtggtacaaccggtcc

    2341 ctggtctggaactcctgacctcaggtgatctgcccgtttcgatctcccaaagtgctggga
         gaccagaccttgaggactggagtccactagacgggcaaagctagagggtttcacgaccct

    2401 ttacaggcgtgagccaccgcacctggctgggagttagaggtttctaatgcattgcaggca
         aatgtccgcactcggtggcgtggaccgaccctcaatctccaaagattacgtaacgtccgt

    2461 gatagtgaataccagacacggggcagctgtgatctttattctccatcacccccacacagc
         ctatcacttatggtctgtgccccgtcgacactagaaataagaggtagtgggggtgtgtcg

    2521 cctgcctggggcacacaaggacactcaatacatgcttttccgctgggccggtggctcacc
         ggacggaccccgtgtgttcctgtgagttatgtacgaaaaggcgacccggccaccgagtgg

    2581 cctgtaatcccagcactttgggaggccaaggtgggaggatcacttgagcccaggagttca
         ggacattagggtcgtgaaaccctccggttccaccctcctagtgaactcgggtcctcaagt

    2641 acaccagcctgggcaacatagtgagaccctgtctctactaaaaatacaaaaattagccag
         tgtggtcggacccgttgtatcactctgggacagagatgatttttatgtttttaatcggtc

    2701 gcatggtgccacacacctgtgctctcagctactcaggaggctgaggcaggaggatcgctt
         cgtaccacggtgtgtggacacgagagtcgatgagtcctccgactccgtcctcctagcgaa

    2761 gagcccagaaggtcaaggttgcagtgaaccatgttcaggccgctgcactccagcctgggt
         ctcgggtcttccagttccaacgtcacttggtacaagtccggcgacgtgaggtcggaccca

    2821 gacagagcaagaccctgtttataaatacataatgctttccaagtgattaaaccgactccc
         ctgtctcgttctgggacaaatatttatgtattacgaaaggttcactaatttggctgaggg

    2881 ccctcaccctgcccaccatggctccaaagaagcatttgtggagcaccttctgtgtgcccc
         gggagtgggacgggtggtaccgaggtttcttcgtaaacacctcgtggaagacacacgggg

    2941 taggtagctagatgcctggacggggtcagaaggaccctgacccgaccttgaacttgttcc
         atccatcgatctacggacctgccccagtcttcctgggactgggctggaacttgaacaagg

      16         C  Q  A  K  V  E  Q  A  V  E  T  E  P  E  P  E  L  R >EXON2
    3001 acacagGATGCCAGGCCAAGGTGGAGCAAGCGGTGGAGACAGAGCCGGAGCCCGAGCTGC
         tgtgtcCTACGGTCCGGTTCCACCTCGTTCGCCACCTCTGTCTCGGCCTCGGGCTCGACG

      34   Q  Q  T  E  W  Q  S  G  Q  R  W  E  L  A  L  G  R  F  W  D
    3061 GCCAGCAGACCGAGTGGCAGAGCGGCCAGCGCTGGGAACTGGCACTGGGTCGCTTTTGGG
         CGGTCGTCTGGCTCACCGTCTCGCCGGTCGCGACCCTTGACCGTGACCCAGCGAAAACCC

      54   Y  L  R  W  V  Q  T  L  S  E  Q  V  Q  E  E  L  L  S  S  Q
    3121 ATTACCTGCGCTGGGTGCAGACACTGTCTGAGCAGGTGCAGGAGGAGCTGCTCAGCTCCC
         TAATGGACGCGACCCACGTCTGTGACAGACTCGTCCACGTCCTCCTCGACGAGTCGAGGG

      74   V  T  Q  E  L  R                                          
    3181 AGGTCACCCAGGAACTGAGgtgagtgtccccatcctggcccttgaccctcctggtgggcg
         TCCAGTGGGTCCTTGACTCcactcacaggggtaggaccgggaactgggaggaccacccgc

    3241 gctatacctccccaggtccaggtttcattctgcccctgtcgctaagtcttggggggcctg
         cgatatggaggggtccaggtccaaagtaagacggggacagcgattcagaaccccccggac

    3301 ggtctctgctggttctagcttcctcttcccatttctgactcctggctttagctctctgga
         ccagagacgaccaagatcgaaggagaagggtaaagactgaggaccgaaatcgagagacct

    3361 attctctctctcagctttgtctctctctcttcccttctgactcagtctctcacactcgtc
         taagagagagagtcgaaacagagagagagaagggaagactgagtcagagagtgtgagcag

    3421 ctggctctgtctctgtccttccctagctcttttatatagagacagagagatggggtctca
         gaccgagacagagacaggaagggatcgagaaaatatatctctgtctctctaccccagagt

    3481 ctgtgttgcccaggctggtcttgaacttctgggctcaagcgatcctcccgcctcggcctc
         gacacaacgggtccgaccagaacttgaagacccgagttcgctaggagggcggagccggag

    3541 ccaaagtgctgggattagaggcatgagcaccttgcccggcctcctagctccttcttcgtc
         ggtttcacgaccctaatctccgtactcgtggaacgggccggaggatcgaggaagaagcag

    3601 tctgcctctgccctctgcatctgctctctgcatctgtctctgtctccttctctcggcctc
         agacggagacgggagacgtagacgagagacgtagacagagacagaggaagagagccggag

    3661 tgccccgttccttctctccctcttgggtctctctggctcatccccatctcgcccgcccca
         acggggcaaggaagagagggagaacccagagagaccgagtaggggtagagcgggcggggt

    3721 tcccagcccttctcccccgcctccccactgtgcgacaccctcccgccctctcggccgcag
         agggtcgggaagagggggcggaggggtgacacgctgtgggagggcgggagagccggcgtc

      80  A  L  M  D  E  T  M  K  E  L  K  A  Y  K  S  E  L  E  E  Q  >EXON3
    3781 GGCGCTGATGGACGAGACCATGAAGGAGTTGAAGGCCTACAAATCGGAACTGGAGGAACA
         CCGCGACTACCTGCTCTGGTACTTCCTCAACTTCCGGATGTTTAGCCTTGACCTCCTTGT

     100  L  T  P  V  A  E  E  T  R  A  R  L  S  K  E  L  Q  A  A  Q 
    3841 ACTGACCCCGGTGGCGGAGGAGACGCGGGCACGGCTGTCCAAGGAGCTGCAGGCGGCGCA
         TGACTGGGGCCACCGCCTCCTCTGCGCCCGTGCCGACAGGTTCCTCGACGTCCGCCGCGT
                    Primer: APO1->

HhaI
5’-G C G C
3’-C G C G

     120  A  R  L  G  A  D  M  E  D  V  R  G  R  L  V  Q  Y  R  G  E 
    3901 GGCCCGGCTGGGCGCGGACATGGAGGACGTGCGCGGCCGCCTGGTGCAGTACCGCGGCGA
         CCGGGCCGACCCGCGCCTGTACCTCCTGCACGCGCCGGCGGACCACGTCATGGCGCCGCT

     140  V  Q  A  M  L  G  Q  S  T  E  E  L  R  V  R  L  A  S  H  L 

C
TGC

R
CGC

    3961 GGTGCAGGCCATGCTCGGCCAGAGCACCGAGGAGCTGCGGGTGCGCCTCGCCTCCCACCT

         CCACGTCCGGTACGAGCCGGTCTCGTGGCTCCTCGACGCCCACGCGGAGCGGAGGGTGGA

     160  R  K  L  R  K  R  L  L  R  D  A  D  D  L  Q  K  R  L  A  V 
    4021 GCGCAAGCTGCGTAAGCGGCTCCTCCGCGATGCCGATGACCTGCAGAAGCGCCTGGCAGT
         CGCGTTCGACGCATTCGCCGAGGAGGCGCTACGGCTACTGGACGTCTTCGCGGACCGTCA

     180  Y  Q  A  G  A  R  E  G  A  E  R  G  L  S  A  I  R  E  R  L 
    4081 GTACCAGGCCGGGGCCCGCGAGGGCGCCGAGCGCGGCCTCAGCGCCATCCGCGAGCGCCT
         CATGGTCCGGCCCCGGGCGCTCCCGCGGCTCGCGCCGGAGTCGCGGTAGGCGCTCGCGGA
     Primer: APO2<-

     200  G  P  L  V  E  Q  G  R  V  R  A  A  T  V  G  S  L  A  G  Q 
    4141 GGGGCCCCTGGTGGAACAGGGCCGCGTGCGGGCCGCCACTGTGGGCTCCCTGGCCGGCCA
         CCCCGGGGACCACCTTGTCCCGGCGCACGCCCGGCGGTGACACCCGAGGGACCGGCCGGT

     220  P  L  Q  E  R  A  Q  A  W  G  E  R  L  R  A  R  M  E  E  M 
    4201 GCCGCTACAGGAGCGGGCCCAGGCCTGGGGCGAGCGGCTGCGCGCGCGGATGGAGGAGAT
         CGGCGATGTCCTCGCCCGGGTCCGGACCCCGCTCGCCGACGCGCGCGCCTACCTCCTCTA

     240  G  S  R  T  R  D  R  L  D  E  V  K  E  Q  V  A  E  V  R  A 
    4261 GGGCAGCCGGACCCGCGACCGCCTGGACGAGGTGAAGGAGCAGGTGGCGGAGGTGCGCGC
         CCCGTCGGCCTGGGCGCTGGCGGACCTGCTCCACTTCCTCGTCCACCGCCTCCACGCGCG

     260  K  L  E  E  Q  A  Q  Q  I  R  L  Q  A  E  A  F  Q  A  R  L 
    4321 CAAGCTGGAGGAGCAGGCCCAGCAGATACGCCTGCAGGCCGAGGCCTTCCAGGCCCGCCT
         GTTCGACCTCCTCGTCCGGGTCGTCTATGCGGACGTCCGGCTCCGGAAGGTCCGGGCGGA

     280  K  S  W  F  E  P  L  V  E  D  M  Q  R  Q  W  A  G  L  V  E 
    4381 CAAGAGCTGGTTCGAGCCCCTGGTGGAAGACATGCAGCGCCAGTGGGCCGGGCTGGTGGA
         GTTCTCGACCAAGCTCGGGGACCACCTTCTGTACGTCGCGGTCACCCGGCCCGACCACCT

     300  K  V  Q  A  A  V  G  T  S  A  A  P  V  P  S  D  N  H  *    
    4441 GAAGGTGCAGGCTGCCGTGGGCACCAGCGCCGCCCCTGTGCCCAGCGACAATCACTGAac
         CTTCCACGTCCGACGGCACCCGTGGTCGCGGCGGGGACACGGGTCGCTGTTAGTGACTtg

    4501 gccgaagcctgcagccatgcgaccccacgccaccccgtgcctcctgcctccgcgcagcct
         cggcttcggacgtcggtacgctggggtgcggtggggcacggaggacggaggcgcgtcgga

    4561 gcagcgggagaccctgtccccgccccagccgtcctcctggggtggaccctagtttaataa
         cgtcgccctctgggacaggggcggggtcggcaggaggaccccacctgggatcaaattatt

    4621 agattcaccaagtttcacgcatctgctggcctccccctgtgatttcctctaagccccagc
         tctaagtggttcaaagtgcgtagacgaccggagggggacactaaaggagattcggggtcg

    4681 ctcagtttctctttctgcccacatactgccacacaattctcagccccctcctctccatct
         gagtcaaagagaaagacgggtgtatgacggtgtgttaagagtcgggggaggagaggtaga

    4741 gtgtctgtgtgtatctttctctctgccctttttttttttttagacggagtctggctctgt
         cacagacacacatagaaagagagacgggaaaaaaaaaaaaatctgcctcagaccgagaca

    4801 cacccaggctagagtgcagtggcacgatcttggctcactgcaacctctgcctcttgggtt
         gtgggtccgatctcacgtcaccgtgctagaaccgagtgacgttggagacggagaacccaa

    4861 caagcgattctgctgcctcagtagctgggattacaggctcacaccaccacacccggctaa
         gttcgctaagacgacggagtcatcgaccctaatgtccgagtgtggtggtgtgggccgatt

    4921 tttttgtatttttagtagagacgagctttcaccatgttggccaggcaggtctcaaactcc
         aaaaacataaaaatcatctctgctcgaaagtggtacaaccggtccgtccagagtttgagg

    4981 tgaccaagtgatccacccgccggcctcccaaagtgctgagattacaggcctgagccacca
         actggttcactaggtgggcggccggagggtttcacgactctaatgtccggactcggtggt

    5041 tgcccggcctctgcccctctttcttttttagggggcagggaaaggtctcaccctgtcacc
         acgggccggagacggggagaaagaaaaaatcccccgtccctttccagagtgggacagtgg

    5101 cgccatcacagctcactgcagcctccacctcctggactcaagtgataagtgatcctcccg
         gcggtagtgtcgagtgacgtcggaggtggaggacctgagttcactattcactaggagggc

    5161 cctcagcctttccagtagctgagactacaggcgcataccactaggattaatttggggggg
         ggagtcggaaaggtcatcgactctgatgtccgcgtatggtgatcctaattaaaccccccc

    5221 ggtggtgtgtgtggagatggggtctggctttgttggccaggctgatgtggaattcctggg
         ccaccacacacacctctaccccagaccgaaacaaccggtccgactacaccttaaggaccc

    5281 ctcaagcgatactcccaccttggcctcctgagtagctgagactactggctagcaccacca
         gagttcgctatgagggtggaaccggaggactcatcgactctgatgaccgatcgtggtggt

    5341 cacccagctttttattattatttgtagagacaaggtctcaatatgttgcccaggctagtc
         gtgggtcgaaaaataataataaacatctctgttccagagttatacaacgggtccgatcag

    5401 tcaaacccctggctcaagagatcctccgccatcggcctcccaaagtgctgggattccagg
         agtttggggaccgagttctctaggaggcggtagccggagggtttcacgaccctaaggtcc

    5461 catgggctccgagcggcctgcccaacttaataatattgttcctagagttgcactc
         gtacccgaggctcgccggacgggttgaattattataacaaggatctcaacgtgag//

Molecular Basis of Polymorphism (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107741)
The 3 major isoforms of human apolipoprotein E (apoE2, -E3, and -E4), as identified by isoelectric focusing, are coded for by 3 alleles (epsilon 2, 3, and 4). The E2, E3, and E4 isoforms differ in amino acid sequence at 2 sites, residue 112 (called site A) and residue 158 (called site B). At sites A/B, apoE2, -E3, and -E4 contain cysteine/cysteine, cysteine/arginine, and arginine/arginine, respectively (Weisgraber et al., 1981; Rall et al., 1982). The 3 forms have 0, 1+, and 2+ charges to account for electrophoretic differences (Margolis, 1982). (The nomenclature of the apolipoprotein E isoforms, defined by isoelectric focusing, has gone through an evolution.) E3 is the most frequent ('wildtype') isoform. As reviewed by Smit et al. (1990), E4 differs from E3 by a cys-to-arg change at position 112 and is designated E4(cys112-to-arg).