LOCUS AAB59514.1 267 aa PRT HUM 30-OCT-2000
DEFINITION Homo sapiens APOA1 protein.
ACCESSION J00098-1
PROTEIN_ID AAB59514.1
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (bases 1743 to 1790)
AUTHORS Shoulders,C.C. and Baralle,F.E.
TITLE Isolation of the human HDL apoprotein A1 gene
JOURNAL Nucleic Acids Res. 10 (16), 4873-4882 (1982)
PUBMED 6290991
REFERENCE 2 (bases 1828 to 2334)
AUTHORS Breslow,J.L., Ross,D., McPherson,J., Williams,H., Kurnit,D.,
Nussbaum,A.L., Karathanasis,S.K. and Zannis,V.I.
TITLE Isolation and characterization of cDNA clones for human
apolipoprotein A-I
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 79 (22), 6861-6865 (1982)
PUBMED 6294659
REFERENCE 3 (sites)
AUTHORS Law,S.W., Gray,G. and Brewer,H.B. Jr.
TITLE cDNA cloning of human apoA-I: amino acid sequence of preproapoA-I
JOURNAL Biochem. Biophys. Res. Commun. 112 (1), 257-264 (1983)
PUBMED 6404278
REFERENCE 4 (bases 5020 to 5271)
AUTHORS Karathanasis,S.K., McPherson,J., Zannis,V.I. and Breslow,J.L.
TITLE Linkage of human apolipoproteins A-I and C-III genes
JOURNAL Nature 304 (5924), 371-373 (1983)
PUBMED 6308458
REFERENCE 5 (bases 1 to 2396)
AUTHORS Shoulders,C.C., Kornblihtt,A.R., Munro,B.S. and Baralle,F.E.
TITLE Gene structure of human apolipoprotein A1
JOURNAL Nucleic Acids Res. 11 (9), 2827-2837 (1983)
PUBMED 6406984
REFERENCE 6 (bases 684 to 745; 932 to 1088; 1677 to 2335)
AUTHORS Cheung,P. and Chan,L.
TITLE Nucleotide sequence of cloned cDNA of human apolipoprotein A-I
JOURNAL Nucleic Acids Res. 11 (11), 3703-3715 (1983)
PUBMED 6304641
REFERENCE 7 (bases 703 to 745; 932 to 960)
AUTHORS Zannis,V.I., Karathanasis,S.K., Keutmann,H.T., Goldberger,G. and
Breslow,J.L.
TITLE Intracellular and extracellular processing of human apolipoprotein
A-I: secreted apolipoprotein A-I isoprotein 2 is a propeptide
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 80 (9), 2574-2578 (1983)
PUBMED 6405383
REFERENCE 8 (bases 105 to 2338)
AUTHORS Karathanasis,S.K., Zannis,V.I. and Breslow,J.L.
TITLE Isolation and characterization of the human apolipoprotein A-I gene
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 80 (20), 6147-6151 (1983)
PUBMED 6413973
REFERENCE 9 (bases 431 to 2637)
AUTHORS Seilhamer,J.J., Protter,A.A., Frossard,P. and Levy-Wilson,B.
TITLE Isolation and DNA sequence of full-length cDNA and of the entire
gene for human apolipoprotein AI--discovery of a new genetic
polymorphism in the apo AI gene
JOURNAL DNA 3 (4), 309-317 (1984)
PUBMED 6207999
REFERENCE 10 (bases 5016 to 5323; 7161 to 7284; 7420 to 7487; 8113 to 8148)
AUTHORS Levy-Wilson,B., Appleby,V., Protter,A., Auperin,D. and
Seilhamer,J.J.
TITLE Isolation and DNA sequence of full-length cDNA for human
preapolipoprotein CIII
JOURNAL DNA 3 (5), 359-364 (1984)
PUBMED 6548954
REFERENCE 11 (bases 2272 to 8337)
AUTHORS Protter,A.A., Levy-Wilson,B., Miller,J., Bencen,G., White,T. and
Seilhamer,J.J.
TITLE Isolation and sequence analysis of the human apolipoprotein CIII
gene and the intergenic region between the apo AI and apo CIII
genes
JOURNAL DNA 3 (6), 449-456 (1984)
PUBMED 6439535
REFERENCE 12 (bases 4 to 900; 932 to 1088; 1677 to 2334; 5016 to 5323; 7161
to 7284; 7420 to 7474)
AUTHORS Sharpe,C.R., Sidoli,A., Shelley,C.S., Lucero,M.A., Shoulders,C.C.
and Baralle,F.E.
TITLE Human apolipoproteins AI, AII, CII and CIII. cDNA sequences and
mRNA abundance
JOURNAL Nucleic Acids Res. 12 (9), 3917-3932 (1984)
PUBMED 6328445
REFERENCE 13 (bases 474 to 486; 683 to 745; 932 to 1088; 1677 to 2318)
AUTHORS Law,S.W. and Brewer,H.B. Jr.
TITLE Nucleotide sequence and the encoded amino acids of human
apolipoprotein A-I mRNA
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 81 (1), 66-70 (1984)
PUBMED 6198645
REFERENCE 14 (sites)
AUTHORS Karathanasis,S.K.
TITLE Apolipoprotein multigene family: tandem organization of human
apolipoprotein AI, CIII, and AIV genes
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 82 (19), 6374-6378 (1985)
PUBMED 3931073
REFERENCE 15 (bases 8145 to 8966)
AUTHORS Reue,K., Leff,T. and Breslow,J.L.
TITLE Human apolipoprotein CIII gene expression is regulated by positive
and negative cis-acting elements and tissue-specific protein
factors
JOURNAL J. Biol. Chem. 263 (14), 6857-6864 (1988)
PUBMED 2834395
COMMENT [3] sites; translational and post-translational A-I cleavage
sites.
[14] sites; gene order and transcription directions. Draft entry
and computer-readable sequence for [15] kindly provided by K.Reue,
22-MAR-1988 Apolipoprotein A-I is the major protein component of
high density lipoprotein (HDL) in the plasma. Synthesized in the
liver and small intestine, it consists of two identical chains of
77 amino acids; an 18-amino acid signal peptide is removed
co-translationally and a 6-amino acid propeptide is cleaved
post-translationally [7]. Variation in the latter step, in
addition to modifications leading to so-called isoforms, is
responsible for some of the polymorphism observed. The A-I gene
structure resembles the C-III gene structure included in this
entry, but most resembles the IV and E genes [14], suggesting that
these apolipoprotein gene sequences have arisen by intergenic and
intragenic duplication. In particular, a 66 bp repeat (starting at
base 1843) characterizes the fourth exon of the A-I, A-IV and E
genes [8],[14]. The mRNA initiation site for A-I has not been
exactly specified; if initiation is around base 469 as argued by
[9] and [12], a potential TATA box is found at 438-443. Because
some of the sequence differences are thought to be natural
polymorphisms, we have annotated all differences as variations. The
MspI site at base 1221 is responsible for RFLP [9]. The assignment
of the A-I, C-III and A-IV genes to chromosome 11 is from Bruns,
Karathanasis and Breslow (1984) Arteriosclerosis 4, 97-102. The
linkage of these genes is demonstrated by [4],[11] and [14]. The
A-I and A-IV genes are transcribed from the same strand (see
segment 2 of this entry), while the C-III gene is transcribed
convergently in relation to A-I. It remains open whether these
genes are coordinately controlled. The C-III gene product is a
major component of the very low density lipoprotein (VLDL) of
plasma, and a minor component of the HDL. It is a glycoprotein
existing as three or more isoforms. While it has a signal peptide,
no propeptide is observed. Variation in the C-III gene occurs at
5163 in such a way as to promote hypertriglyceridaemia [4] (SacI
site RFLP). A potential TATA box is seen at 8170-8176; potential
CAAT boxes are situated at 8229-8237 and 8243-8251; and a possible
polyadenylation signal can be found at 5037-5042 (all on the
complementary strand) [11]. Draft entry and clean copy of the
sequences for [9] kindly provided by J.Seilhamer, 23-MAY-1985.
Complete source information:
Human DNA [5],[8],[9],[12],[11] and liver, cDNA to mRNA [1],[2],
[6],[7],[4]-[13].
FEATURES Qualifiers
source /organism="Homo sapiens"
/mol_type="genomic DNA"
/db_xref="taxon:9606"
/map="11q23-qter"
protein /gene="APOA1"
/note="preproapolipoprotein A-I"
intron_pos 15:1 (1/2)
intron_pos 67:2 (2/2)
BEGIN
1 MKAAVLTLAV LFLTGSQARH FWQQDEPPQS PWDRVKDLAT VYVDVLKDSG RDYVSQFEGS
61 ALGKQLNLKL LDNWDSVTST FSKLREQLGP VTQEFWDNLE KETEGLRQEM SKDLEEVKAK
121 VQPYLDDFQK KWQEEMELYR QKVEPLRAEL QEGARQKLHE LQEKLSPLGE EMRDRARAHV
181 DALRTHLAPY SDELRQRLAA RLEALKENGG ARLAEYHAKA TEHLSTLSEK AKPALEDLRQ
241 GLLPVLESFK VSFLSALEEY TKKLNTQ
//