Full text data of APOA4
APOA4
[Confidence: low (only semi-automatic identification from reviews)]
Apolipoprotein A-IV; Apo-AIV; ApoA-IV (Apolipoprotein A4; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Apolipoprotein A-IV; Apo-AIV; ApoA-IV (Apolipoprotein A4; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P06727
ID APOA4_HUMAN Reviewed; 396 AA.
AC P06727; A8MSL6; Q14CW8; Q6Q787;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-MAR-2006, sequence version 3.
DT 22-JAN-2014, entry version 158.
DE RecName: Full=Apolipoprotein A-IV;
DE Short=Apo-AIV;
DE Short=ApoA-IV;
DE AltName: Full=Apolipoprotein A4;
DE Flags: Precursor;
GN Name=APOA4;
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], AND VARIANT LYS-279.
RX PubMed=3755616; DOI=10.1021/bi00361a034;
RA Karathanasis S.K., Yunis I.;
RT "Structure, evolution, and tissue-specific synthesis of human
RT apolipoprotein AIV.";
RL Biochemistry 25:3962-3970(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LYS-279.
RX PubMed=3095836; DOI=10.1073/pnas.83.22.8457;
RA Karathanasis S.K., Oettgen P., Haddad I.A., Antonarakis S.E.;
RT "Structure, evolution, and polymorphisms of the human apolipoprotein
RT A4 gene (APOA4).";
RL Proc. Natl. Acad. Sci. U.S.A. 83:8457-8461(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT APOA-IV*2 HIS-380.
RX PubMed=3036793;
RA Elshourbagy N.A., Walker D.W., Paik Y.K., Boguski M.S., Freeman M.,
RA Gordon J.I., Taylor J.M.;
RT "Structure and expression of the human apolipoprotein A-IV gene.";
RL J. Biol. Chem. 262:7973-7981(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Intestine;
RX PubMed=2930771; DOI=10.1016/0005-2760(89)90292-0;
RA Yang C., Gu Z.W., Xiong W., Rosseneu M., Yang H.X., Lee B.M.,
RA Gotto A.M. Jr., Chan L.;
RT "The primary structure of human apolipoprotein A-IV.";
RL Biochim. Biophys. Acta 1002:231-237(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-13; HIS-77;
RP SER-147; SER-161; SER-367 AND HIS-380.
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 GENOMIC DNA], AND VARIANT SER-147.
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Colon;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 21-396, AND VARIANT APOA-IV*2 HIS-380.
RX PubMed=3080432;
RA Elshourbagy N.A., Walker D.W., Boguski M.S., Gordon J.I., Taylor J.M.;
RT "The nucleotide and derived amino acid sequence of human
RT apolipoprotein A-IV mRNA and the close linkage of its gene to the
RT genes of apolipoproteins A-I and C-III.";
RL J. Biol. Chem. 261:1998-2002(1986).
RN [9]
RP SIGNAL SEQUENCE CLEAVAGE SITE.
RX PubMed=6706947;
RA Gordon J.I., Bisgaier C.L., Sims H.F., Sachdev O.P., Glickman R.M.,
RA Strauss A.W.;
RT "Biosynthesis of human preapolipoprotein A-IV.";
RL J. Biol. Chem. 259:468-474(1984).
RN [10]
RP REVIEW ON POLYMORPHISM.
RA Lohse P., Brewer H.B. Jr.;
RT "Genetic polymorphism of apolipoprotein A-IV.";
RL Curr. Opin. Lipidol. 2:90-95(1991).
RN [11]
RP ALLELES APOA-IV*1 AND APOA-IV*2, AND VARIANT HIS-380.
RX PubMed=2351649;
RA Lohse P., Kindt M.R., Rader D.J., Brewer H.B. Jr.;
RT "Genetic polymorphism of human plasma apolipoprotein A-IV is due to
RT nucleotide substitutions in the apolipoprotein A-IV gene.";
RL J. Biol. Chem. 265:10061-10064(1990).
RN [12]
RP ALLELES A-IV*0 AND A-IV*3, AND VARIANTS LYS-250 AND
RP GLU-GLN-GLN-GLN-381 INS.
RX PubMed=1973689;
RA Lohse P., Kindt M.R., Rader D.J., Brewer H.B. Jr.;
RT "Human plasma apolipoproteins A-IV-0 and A-IV-3. Molecular basis for
RT two rare variants of apolipoprotein A-IV-1.";
RL J. Biol. Chem. 265:12734-12739(1990).
RN [13]
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 [14]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 84-355, AND SUBUNIT.
RX PubMed=22579246; DOI=10.1016/j.str.2012.02.020;
RA Deng X., Morris J., Dressmen J., Tubb M.R., Tso P., Jerome W.G.,
RA Davidson W.S., Thompson T.B.;
RT "The structure of dimeric apolipoprotein A-IV and its mechanism of
RT self-association.";
RL Structure 20:767-779(2012).
RN [15]
RP VARIANT HIS-380.
RX PubMed=2065039;
RA Tenkanen H., Lukka M., Jauhiainen M., Metso J., Baumann M.,
RA Peltonen L., Ehnholm C.;
RT "The mutation causing the common apolipoprotein A-IV polymorphism is a
RT glutamine to histidine substitution of amino acid 360.";
RL Arterioscler. Thromb. 11:851-856(1991).
RN [16]
RP ALLELES A-IV*0; A-IV*1; A-IV*2 AND A-IV*3, AND VARIANTS LYS-185;
RP GLU-187; SER-367 AND HIS-380.
RX PubMed=1677358;
RA Lohse P., Kindt M.R., Rader D.J., Brewer H.B. Jr.;
RT "Three genetic variants of human plasma apolipoprotein A-IV: apoA-IV-
RT 1(Thr-347-->Ser), apoA-IV-0(Lys-167-->Glu,Gln-360-->His), and apoA-IV-
RT 3(Glu-165-->Lys).";
RL J. Biol. Chem. 266:13513-13518(1991).
RN [17]
RP ERRATUM.
RA Lohse P., Kindt M.R., Rader D.J., Brewer H.B. Jr.;
RL J. Biol. Chem. 266:19866-19866(1991).
RN [18]
RP VARIANT MET-13.
RX PubMed=1349197;
RA von Eckardstein A., Funke H., Schulte M., Erren M., Schulte H.,
RA Assmann G.;
RT "Nonsynonymous polymorphic sites in the apolipoprotein (apo) A-IV gene
RT are associated with changes in the concentration of apo B- and apo A-
RT I-containing lipoproteins in a normal population.";
RL Am. J. Hum. Genet. 50:1115-1128(1992).
RN [19]
RP VARIANT SER-147.
RX PubMed=1737067; DOI=10.1016/0925-4439(92)90147-F;
RA Tenkanen H., Koskinen P., Metso J., Baumann M., Lukka M.,
RA Kauppinen-Makelin R., Kontula K., Taskinen M.R., Manttari M.,
RA Manninen V., Ehnholm C.;
RT "A novel polymorphism of apolipoprotein A-IV is the result of an
RT asparagine to serine substitution at residue 127.";
RL Biochim. Biophys. Acta 1138:27-33(1992).
RN [20]
RP ALLELE A-IV*5, AND VARIANT GLU-GLN-GLN-GLN-381 INS.
RX PubMed=1487136; DOI=10.1002/gepi.1370090602;
RA Kamboh M.I., Williams E.R., Law J.C., Aston C.E., Bunker C.H.,
RA Ferrell R.E., Pollitzer W.S.;
RT "Molecular basis of a unique African variant (A-IV 5) of human
RT apolipoprotein A-IV and its significance in lipid metabolism.";
RL Genet. Epidemiol. 9:379-388(1992).
RN [21]
RP VARIANTS BUDAPEST-2 LYS-44; BUDAPEST-1 CYS-305 AND SER-367.
RX PubMed=7728150; DOI=10.1002/humu.1380050108;
RA Menzel H.J., Dieplinger H., Sandholzer C., Karadi I., Utermann G.,
RA Csaszar A.;
RT "Apolipoprotein A-IV polymorphism in the Hungarian population: gene
RT frequencies, effect on lipid levels, and sequence of two new
RT variants.";
RL Hum. Mutat. 5:58-65(1995).
RN [22]
RP VARIANTS SEATTLE-3 SER-161; SEATTLE-1 LEU-178 AND SEATTLE-2 GLN-264.
RX PubMed=8956036;
RX DOI=10.1002/(SICI)1098-1004(1996)8:4<319::AID-HUMU4>3.3.CO;2-T;
RA Deeb S.S., Nevin D.N., Iwasaki L., Brunzell J.D.;
RT "Two novel apolipoprotein A-IV variants in individuals with familial
RT combined hyperlipidemia and diminished levels of lipoprotein lipase
RT activity.";
RL Hum. Mutat. 8:319-325(1996).
RN [23]
RP VARIANT HIS-380.
RX PubMed=10391210; DOI=10.1038/10297;
RA Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A.,
RA Cooper R., Lipshutz R., Chakravarti A.;
RT "Patterns of single-nucleotide polymorphisms in candidate genes for
RT blood-pressure homeostasis.";
RL Nat. Genet. 22:239-247(1999).
CC -!- FUNCTION: May have a role in chylomicrons and VLDL secretion and
CC catabolism. Required for efficient activation of lipoprotein
CC lipase by ApoC-II; potent activator of LCAT. Apoa-IV is a major
CC component of HDL and chylomicrons.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Synthesized primarily in the intestine and
CC secreted in plasma.
CC -!- DOMAIN: Nine of the thirteen 22-amino acid tandem repeats (each
CC 22-mer is actually a tandem array of two, A and B, related 11-
CC mers) occurring in this sequence are predicted to be highly alpha-
CC helical, and many of these helices are amphipathic. They may
CC therefore serve as lipid-binding domains with lecithin:cholesterol
CC acyltransferase (LCAT) activating abilities.
CC -!- PTM: Phosphorylation sites are present in the extracellular
CC medium.
CC -!- POLYMORPHISM: Eight alleles have been characterized (APOA-IV*0 to
CC APOA-IV*7). APOA-IV*1 is the major allele (90%), APOA-IV*2 is also
CC common (8%), the others are rare alleles. The sequence shown
CC represents allele APOA-IV*1.
CC -!- SIMILARITY: Belongs to the apolipoprotein A1/A4/E family.
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;=APOA4";
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DR EMBL; M13654; AAA51744.1; -; mRNA.
DR EMBL; M14642; AAA51745.1; -; Genomic_DNA.
DR EMBL; J02758; AAA96731.1; -; Genomic_DNA.
DR EMBL; X13629; CAA31955.1; -; mRNA.
DR EMBL; AY422950; AAQ91809.1; -; Genomic_DNA.
DR EMBL; AY555191; AAS68228.1; -; Genomic_DNA.
DR EMBL; AP006216; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC074764; AAH74764.1; -; mRNA.
DR EMBL; BC113594; AAI13595.1; -; mRNA.
DR EMBL; BC113596; AAI13597.1; -; mRNA.
DR EMBL; M14566; AAA51748.1; -; mRNA.
DR PIR; A94137; LPHUA4.
DR UniGene; Hs.1247; -.
DR PDB; 3S84; X-ray; 2.40 A; A/B=84-355.
DR PDBsum; 3S84; -.
DR ProteinModelPortal; P06727; -.
DR SMR; P06727; 25-389.
DR DIP; DIP-38333N; -.
DR IntAct; P06727; 1.
DR STRING; 9606.ENSP00000350425; -.
DR PhosphoSite; P06727; -.
DR DMDM; 93163358; -.
DR DOSAC-COBS-2DPAGE; P06727; -.
DR REPRODUCTION-2DPAGE; IPI00304273; -.
DR SWISS-2DPAGE; P06727; -.
DR PaxDb; P06727; -.
DR PeptideAtlas; P06727; -.
DR PRIDE; P06727; -.
DR Ensembl; ENST00000357780; ENSP00000350425; ENSG00000110244.
DR UCSC; uc001pps.1; human.
DR GeneCards; GC11M116692; -.
DR HGNC; HGNC:602; APOA4.
DR HPA; HPA001352; -.
DR HPA; HPA002549; -.
DR MIM; 107690; gene.
DR neXtProt; NX_P06727; -.
DR eggNOG; NOG42418; -.
DR HOGENOM; HOG000037942; -.
DR HOVERGEN; HBG105707; -.
DR InParanoid; P06727; -.
DR OrthoDB; EOG7K9K48; -.
DR PhylomeDB; P06727; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR PMAP-CutDB; A8MSL6; -.
DR PRO; PR:P06727; -.
DR Bgee; P06727; -.
DR CleanEx; HS_APOA4; -.
DR Genevestigator; P06727; -.
DR GO; GO:0042627; C:chylomicron; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005769; C:early endosome; TAS:Reactome.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0034364; C:high-density lipoprotein particle; IDA:BHF-UCL.
DR GO; GO:0034361; C:very-low-density lipoprotein particle; IDA:BHF-UCL.
DR GO; GO:0016209; F:antioxidant activity; IDA:HGNC.
DR GO; GO:0017127; F:cholesterol transporter activity; IDA:BHF-UCL.
DR GO; GO:0005507; F:copper ion binding; IDA:HGNC.
DR GO; GO:0031210; F:phosphatidylcholine binding; IDA:BHF-UCL.
DR GO; GO:0060228; F:phosphatidylcholine-sterol O-acyltransferase activator activity; IDA:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0033344; P:cholesterol efflux; IDA:BHF-UCL.
DR GO; GO:0042632; P:cholesterol homeostasis; IDA:BHF-UCL.
DR GO; GO:0008203; P:cholesterol metabolic process; IDA:BHF-UCL.
DR GO; GO:0034378; P:chylomicron assembly; TAS:BHF-UCL.
DR GO; GO:0034371; P:chylomicron remodeling; IC:BHF-UCL.
DR GO; GO:0034375; P:high-density lipoprotein particle remodeling; IC:BHF-UCL.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:HGNC.
DR GO; GO:0002227; P:innate immune response in mucosa; IDA:BHF-UCL.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:0042157; P:lipoprotein metabolic process; TAS:Reactome.
DR GO; GO:0044240; P:multicellular organismal lipid catabolic process; IDA:BHF-UCL.
DR GO; GO:0034445; P:negative regulation of plasma lipoprotein particle oxidation; IDA:BHF-UCL.
DR GO; GO:0046470; P:phosphatidylcholine metabolic process; 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:0010873; P:positive regulation of cholesterol esterification; IDA:BHF-UCL.
DR GO; GO:0045723; P:positive regulation of fatty acid biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0051006; P:positive regulation of lipoprotein lipase activity; IDA:BHF-UCL.
DR GO; GO:0010898; P:positive regulation of triglyceride catabolic process; IDA:BHF-UCL.
DR GO; GO:0032374; P:regulation of cholesterol transport; IDA:BHF-UCL.
DR GO; GO:0030300; P:regulation of intestinal cholesterol absorption; IEA:Ensembl.
DR GO; GO:0019430; P:removal of superoxide radicals; IDA:HGNC.
DR GO; GO:0006982; P:response to lipid hydroperoxide; IDA:HGNC.
DR GO; GO:0035634; P:response to stilbenoid; IEA:Ensembl.
DR GO; GO:0001523; P:retinoid metabolic process; TAS:Reactome.
DR GO; GO:0043691; P:reverse cholesterol transport; IDA:BHF-UCL.
DR GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; IDA:BHF-UCL.
DR InterPro; IPR000074; ApoA1_A4_E.
DR Pfam; PF01442; Apolipoprotein; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Chylomicron; Complete proteome; HDL; Lipid transport;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; Secreted;
KW Signal; Transport.
FT SIGNAL 1 20
FT CHAIN 21 396 Apolipoprotein A-IV.
FT /FTId=PRO_0000001975.
FT REPEAT 33 54 1.
FT REPEAT 60 81 2.
FT REPEAT 82 103 3.
FT REPEAT 115 136 4.
FT REPEAT 137 158 5.
FT REPEAT 159 180 6.
FT REPEAT 181 202 7.
FT REPEAT 203 224 8.
FT REPEAT 225 246 9.
FT REPEAT 247 268 10.
FT REPEAT 269 286 11.
FT REPEAT 287 308 12.
FT REPEAT 309 330 13.
FT REGION 33 330 13 X 22 AA approximate tandem repeats.
FT COMPBIAS 372 389 Gln/Glu-rich.
FT VARIANT 13 13 V -> M (in allele APOA-IV*1D).
FT /FTId=VAR_000626.
FT VARIANT 44 44 E -> K (in Budapest-2).
FT /FTId=VAR_000627.
FT VARIANT 74 74 G -> S (in dbSNP:rs5102).
FT /FTId=VAR_014610.
FT VARIANT 77 77 Q -> H.
FT /FTId=VAR_025444.
FT VARIANT 147 147 N -> S (in allele APOA-IV*1B;
FT dbSNP:rs5104).
FT /FTId=VAR_000628.
FT VARIANT 161 161 A -> S (in Seattle-3).
FT /FTId=VAR_000629.
FT VARIANT 178 178 S -> L (in Seattle-1; may contribute to
FT the development of familial combined
FT hyperlipidemia).
FT /FTId=VAR_000630.
FT VARIANT 185 185 E -> K (in allele APOA-IV*3).
FT /FTId=VAR_000631.
FT VARIANT 187 187 K -> E (in allele APOA-IV*0A; associated
FT with H-380).
FT /FTId=VAR_000632.
FT VARIANT 250 250 E -> K (in allele APOA-IV*3A).
FT /FTId=VAR_000633.
FT VARIANT 264 264 R -> Q (in Seattle-2; may contribute to
FT the development of familial combined
FT hyperlipidemia; dbSNP:rs2238008).
FT /FTId=VAR_000634.
FT VARIANT 279 279 R -> K (in dbSNP:rs1042372).
FT /FTId=VAR_025443.
FT VARIANT 305 305 R -> C (in Budapest-1).
FT /FTId=VAR_000635.
FT VARIANT 307 307 V -> L (in dbSNP:rs5108).
FT /FTId=VAR_014611.
FT VARIANT 367 367 T -> S (in allele APOA-IV*1A and allele
FT Budapest-1; dbSNP:rs675).
FT /FTId=VAR_000636.
FT VARIANT 380 380 Q -> H (in allele APOA-IV*2 and allele
FT APOA-IV*0A; associated with E-187 in
FT allele APOA-IV*0A; dbSNP:rs5110).
FT /FTId=VAR_000637.
FT VARIANT 381 381 Q -> QEQQQ (in allele APOA-IV*0 and
FT allele APOA-IV*5; allele APOA-IV*5 is
FT further defined by a silent nucleotide
FT substitution).
FT /FTId=VAR_000638.
FT CONFLICT 158 160 TPY -> DPL (in Ref. 1; AAA51744 and 2;
FT AAA51745).
FT CONFLICT 327 327 Q -> T (in Ref. 3; AAA96731 and 8;
FT AAA51748).
FT HELIX 97 113
FT HELIX 114 116
FT HELIX 117 223
FT HELIX 224 226
FT HELIX 231 276
FT STRAND 278 280
FT HELIX 282 307
FT HELIX 310 329
SQ SEQUENCE 396 AA; 45399 MW; 193753196CA2FA4A CRC64;
MFLKAVVLTL ALVAVAGARA EVSADQVATV MWDYFSQLSN NAKEAVEHLQ KSELTQQLNA
LFQDKLGEVN TYAGDLQKKL VPFATELHER LAKDSEKLKE EIGKELEELR ARLLPHANEV
SQKIGDNLRE LQQRLEPYAD QLRTQVNTQA EQLRRQLTPY AQRMERVLRE NADSLQASLR
PHADELKAKI DQNVEELKGR LTPYADEFKV KIDQTVEELR RSLAPYAQDT QEKLNHQLEG
LTFQMKKNAE ELKARISASA EELRQRLAPL AEDVRGNLRG NTEGLQKSLA ELGGHLDQQV
EEFRRRVEPY GENFNKALVQ QMEQLRQKLG PHAGDVEGHL SFLEKDLRDK VNSFFSTFKE
KESQDKTLSL PELEQQQEQQ QEQQQEQVQM LAPLES
//
ID APOA4_HUMAN Reviewed; 396 AA.
AC P06727; A8MSL6; Q14CW8; Q6Q787;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-MAR-2006, sequence version 3.
DT 22-JAN-2014, entry version 158.
DE RecName: Full=Apolipoprotein A-IV;
DE Short=Apo-AIV;
DE Short=ApoA-IV;
DE AltName: Full=Apolipoprotein A4;
DE Flags: Precursor;
GN Name=APOA4;
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], AND VARIANT LYS-279.
RX PubMed=3755616; DOI=10.1021/bi00361a034;
RA Karathanasis S.K., Yunis I.;
RT "Structure, evolution, and tissue-specific synthesis of human
RT apolipoprotein AIV.";
RL Biochemistry 25:3962-3970(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LYS-279.
RX PubMed=3095836; DOI=10.1073/pnas.83.22.8457;
RA Karathanasis S.K., Oettgen P., Haddad I.A., Antonarakis S.E.;
RT "Structure, evolution, and polymorphisms of the human apolipoprotein
RT A4 gene (APOA4).";
RL Proc. Natl. Acad. Sci. U.S.A. 83:8457-8461(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT APOA-IV*2 HIS-380.
RX PubMed=3036793;
RA Elshourbagy N.A., Walker D.W., Paik Y.K., Boguski M.S., Freeman M.,
RA Gordon J.I., Taylor J.M.;
RT "Structure and expression of the human apolipoprotein A-IV gene.";
RL J. Biol. Chem. 262:7973-7981(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Intestine;
RX PubMed=2930771; DOI=10.1016/0005-2760(89)90292-0;
RA Yang C., Gu Z.W., Xiong W., Rosseneu M., Yang H.X., Lee B.M.,
RA Gotto A.M. Jr., Chan L.;
RT "The primary structure of human apolipoprotein A-IV.";
RL Biochim. Biophys. Acta 1002:231-237(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-13; HIS-77;
RP SER-147; SER-161; SER-367 AND HIS-380.
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 GENOMIC DNA], AND VARIANT SER-147.
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Colon;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 21-396, AND VARIANT APOA-IV*2 HIS-380.
RX PubMed=3080432;
RA Elshourbagy N.A., Walker D.W., Boguski M.S., Gordon J.I., Taylor J.M.;
RT "The nucleotide and derived amino acid sequence of human
RT apolipoprotein A-IV mRNA and the close linkage of its gene to the
RT genes of apolipoproteins A-I and C-III.";
RL J. Biol. Chem. 261:1998-2002(1986).
RN [9]
RP SIGNAL SEQUENCE CLEAVAGE SITE.
RX PubMed=6706947;
RA Gordon J.I., Bisgaier C.L., Sims H.F., Sachdev O.P., Glickman R.M.,
RA Strauss A.W.;
RT "Biosynthesis of human preapolipoprotein A-IV.";
RL J. Biol. Chem. 259:468-474(1984).
RN [10]
RP REVIEW ON POLYMORPHISM.
RA Lohse P., Brewer H.B. Jr.;
RT "Genetic polymorphism of apolipoprotein A-IV.";
RL Curr. Opin. Lipidol. 2:90-95(1991).
RN [11]
RP ALLELES APOA-IV*1 AND APOA-IV*2, AND VARIANT HIS-380.
RX PubMed=2351649;
RA Lohse P., Kindt M.R., Rader D.J., Brewer H.B. Jr.;
RT "Genetic polymorphism of human plasma apolipoprotein A-IV is due to
RT nucleotide substitutions in the apolipoprotein A-IV gene.";
RL J. Biol. Chem. 265:10061-10064(1990).
RN [12]
RP ALLELES A-IV*0 AND A-IV*3, AND VARIANTS LYS-250 AND
RP GLU-GLN-GLN-GLN-381 INS.
RX PubMed=1973689;
RA Lohse P., Kindt M.R., Rader D.J., Brewer H.B. Jr.;
RT "Human plasma apolipoproteins A-IV-0 and A-IV-3. Molecular basis for
RT two rare variants of apolipoprotein A-IV-1.";
RL J. Biol. Chem. 265:12734-12739(1990).
RN [13]
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 [14]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 84-355, AND SUBUNIT.
RX PubMed=22579246; DOI=10.1016/j.str.2012.02.020;
RA Deng X., Morris J., Dressmen J., Tubb M.R., Tso P., Jerome W.G.,
RA Davidson W.S., Thompson T.B.;
RT "The structure of dimeric apolipoprotein A-IV and its mechanism of
RT self-association.";
RL Structure 20:767-779(2012).
RN [15]
RP VARIANT HIS-380.
RX PubMed=2065039;
RA Tenkanen H., Lukka M., Jauhiainen M., Metso J., Baumann M.,
RA Peltonen L., Ehnholm C.;
RT "The mutation causing the common apolipoprotein A-IV polymorphism is a
RT glutamine to histidine substitution of amino acid 360.";
RL Arterioscler. Thromb. 11:851-856(1991).
RN [16]
RP ALLELES A-IV*0; A-IV*1; A-IV*2 AND A-IV*3, AND VARIANTS LYS-185;
RP GLU-187; SER-367 AND HIS-380.
RX PubMed=1677358;
RA Lohse P., Kindt M.R., Rader D.J., Brewer H.B. Jr.;
RT "Three genetic variants of human plasma apolipoprotein A-IV: apoA-IV-
RT 1(Thr-347-->Ser), apoA-IV-0(Lys-167-->Glu,Gln-360-->His), and apoA-IV-
RT 3(Glu-165-->Lys).";
RL J. Biol. Chem. 266:13513-13518(1991).
RN [17]
RP ERRATUM.
RA Lohse P., Kindt M.R., Rader D.J., Brewer H.B. Jr.;
RL J. Biol. Chem. 266:19866-19866(1991).
RN [18]
RP VARIANT MET-13.
RX PubMed=1349197;
RA von Eckardstein A., Funke H., Schulte M., Erren M., Schulte H.,
RA Assmann G.;
RT "Nonsynonymous polymorphic sites in the apolipoprotein (apo) A-IV gene
RT are associated with changes in the concentration of apo B- and apo A-
RT I-containing lipoproteins in a normal population.";
RL Am. J. Hum. Genet. 50:1115-1128(1992).
RN [19]
RP VARIANT SER-147.
RX PubMed=1737067; DOI=10.1016/0925-4439(92)90147-F;
RA Tenkanen H., Koskinen P., Metso J., Baumann M., Lukka M.,
RA Kauppinen-Makelin R., Kontula K., Taskinen M.R., Manttari M.,
RA Manninen V., Ehnholm C.;
RT "A novel polymorphism of apolipoprotein A-IV is the result of an
RT asparagine to serine substitution at residue 127.";
RL Biochim. Biophys. Acta 1138:27-33(1992).
RN [20]
RP ALLELE A-IV*5, AND VARIANT GLU-GLN-GLN-GLN-381 INS.
RX PubMed=1487136; DOI=10.1002/gepi.1370090602;
RA Kamboh M.I., Williams E.R., Law J.C., Aston C.E., Bunker C.H.,
RA Ferrell R.E., Pollitzer W.S.;
RT "Molecular basis of a unique African variant (A-IV 5) of human
RT apolipoprotein A-IV and its significance in lipid metabolism.";
RL Genet. Epidemiol. 9:379-388(1992).
RN [21]
RP VARIANTS BUDAPEST-2 LYS-44; BUDAPEST-1 CYS-305 AND SER-367.
RX PubMed=7728150; DOI=10.1002/humu.1380050108;
RA Menzel H.J., Dieplinger H., Sandholzer C., Karadi I., Utermann G.,
RA Csaszar A.;
RT "Apolipoprotein A-IV polymorphism in the Hungarian population: gene
RT frequencies, effect on lipid levels, and sequence of two new
RT variants.";
RL Hum. Mutat. 5:58-65(1995).
RN [22]
RP VARIANTS SEATTLE-3 SER-161; SEATTLE-1 LEU-178 AND SEATTLE-2 GLN-264.
RX PubMed=8956036;
RX DOI=10.1002/(SICI)1098-1004(1996)8:4<319::AID-HUMU4>3.3.CO;2-T;
RA Deeb S.S., Nevin D.N., Iwasaki L., Brunzell J.D.;
RT "Two novel apolipoprotein A-IV variants in individuals with familial
RT combined hyperlipidemia and diminished levels of lipoprotein lipase
RT activity.";
RL Hum. Mutat. 8:319-325(1996).
RN [23]
RP VARIANT HIS-380.
RX PubMed=10391210; DOI=10.1038/10297;
RA Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A.,
RA Cooper R., Lipshutz R., Chakravarti A.;
RT "Patterns of single-nucleotide polymorphisms in candidate genes for
RT blood-pressure homeostasis.";
RL Nat. Genet. 22:239-247(1999).
CC -!- FUNCTION: May have a role in chylomicrons and VLDL secretion and
CC catabolism. Required for efficient activation of lipoprotein
CC lipase by ApoC-II; potent activator of LCAT. Apoa-IV is a major
CC component of HDL and chylomicrons.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Synthesized primarily in the intestine and
CC secreted in plasma.
CC -!- DOMAIN: Nine of the thirteen 22-amino acid tandem repeats (each
CC 22-mer is actually a tandem array of two, A and B, related 11-
CC mers) occurring in this sequence are predicted to be highly alpha-
CC helical, and many of these helices are amphipathic. They may
CC therefore serve as lipid-binding domains with lecithin:cholesterol
CC acyltransferase (LCAT) activating abilities.
CC -!- PTM: Phosphorylation sites are present in the extracellular
CC medium.
CC -!- POLYMORPHISM: Eight alleles have been characterized (APOA-IV*0 to
CC APOA-IV*7). APOA-IV*1 is the major allele (90%), APOA-IV*2 is also
CC common (8%), the others are rare alleles. The sequence shown
CC represents allele APOA-IV*1.
CC -!- SIMILARITY: Belongs to the apolipoprotein A1/A4/E family.
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;=APOA4";
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DR EMBL; M13654; AAA51744.1; -; mRNA.
DR EMBL; M14642; AAA51745.1; -; Genomic_DNA.
DR EMBL; J02758; AAA96731.1; -; Genomic_DNA.
DR EMBL; X13629; CAA31955.1; -; mRNA.
DR EMBL; AY422950; AAQ91809.1; -; Genomic_DNA.
DR EMBL; AY555191; AAS68228.1; -; Genomic_DNA.
DR EMBL; AP006216; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC074764; AAH74764.1; -; mRNA.
DR EMBL; BC113594; AAI13595.1; -; mRNA.
DR EMBL; BC113596; AAI13597.1; -; mRNA.
DR EMBL; M14566; AAA51748.1; -; mRNA.
DR PIR; A94137; LPHUA4.
DR UniGene; Hs.1247; -.
DR PDB; 3S84; X-ray; 2.40 A; A/B=84-355.
DR PDBsum; 3S84; -.
DR ProteinModelPortal; P06727; -.
DR SMR; P06727; 25-389.
DR DIP; DIP-38333N; -.
DR IntAct; P06727; 1.
DR STRING; 9606.ENSP00000350425; -.
DR PhosphoSite; P06727; -.
DR DMDM; 93163358; -.
DR DOSAC-COBS-2DPAGE; P06727; -.
DR REPRODUCTION-2DPAGE; IPI00304273; -.
DR SWISS-2DPAGE; P06727; -.
DR PaxDb; P06727; -.
DR PeptideAtlas; P06727; -.
DR PRIDE; P06727; -.
DR Ensembl; ENST00000357780; ENSP00000350425; ENSG00000110244.
DR UCSC; uc001pps.1; human.
DR GeneCards; GC11M116692; -.
DR HGNC; HGNC:602; APOA4.
DR HPA; HPA001352; -.
DR HPA; HPA002549; -.
DR MIM; 107690; gene.
DR neXtProt; NX_P06727; -.
DR eggNOG; NOG42418; -.
DR HOGENOM; HOG000037942; -.
DR HOVERGEN; HBG105707; -.
DR InParanoid; P06727; -.
DR OrthoDB; EOG7K9K48; -.
DR PhylomeDB; P06727; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR PMAP-CutDB; A8MSL6; -.
DR PRO; PR:P06727; -.
DR Bgee; P06727; -.
DR CleanEx; HS_APOA4; -.
DR Genevestigator; P06727; -.
DR GO; GO:0042627; C:chylomicron; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005769; C:early endosome; TAS:Reactome.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0034364; C:high-density lipoprotein particle; IDA:BHF-UCL.
DR GO; GO:0034361; C:very-low-density lipoprotein particle; IDA:BHF-UCL.
DR GO; GO:0016209; F:antioxidant activity; IDA:HGNC.
DR GO; GO:0017127; F:cholesterol transporter activity; IDA:BHF-UCL.
DR GO; GO:0005507; F:copper ion binding; IDA:HGNC.
DR GO; GO:0031210; F:phosphatidylcholine binding; IDA:BHF-UCL.
DR GO; GO:0060228; F:phosphatidylcholine-sterol O-acyltransferase activator activity; IDA:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0033344; P:cholesterol efflux; IDA:BHF-UCL.
DR GO; GO:0042632; P:cholesterol homeostasis; IDA:BHF-UCL.
DR GO; GO:0008203; P:cholesterol metabolic process; IDA:BHF-UCL.
DR GO; GO:0034378; P:chylomicron assembly; TAS:BHF-UCL.
DR GO; GO:0034371; P:chylomicron remodeling; IC:BHF-UCL.
DR GO; GO:0034375; P:high-density lipoprotein particle remodeling; IC:BHF-UCL.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:HGNC.
DR GO; GO:0002227; P:innate immune response in mucosa; IDA:BHF-UCL.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:0042157; P:lipoprotein metabolic process; TAS:Reactome.
DR GO; GO:0044240; P:multicellular organismal lipid catabolic process; IDA:BHF-UCL.
DR GO; GO:0034445; P:negative regulation of plasma lipoprotein particle oxidation; IDA:BHF-UCL.
DR GO; GO:0046470; P:phosphatidylcholine metabolic process; 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:0010873; P:positive regulation of cholesterol esterification; IDA:BHF-UCL.
DR GO; GO:0045723; P:positive regulation of fatty acid biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0051006; P:positive regulation of lipoprotein lipase activity; IDA:BHF-UCL.
DR GO; GO:0010898; P:positive regulation of triglyceride catabolic process; IDA:BHF-UCL.
DR GO; GO:0032374; P:regulation of cholesterol transport; IDA:BHF-UCL.
DR GO; GO:0030300; P:regulation of intestinal cholesterol absorption; IEA:Ensembl.
DR GO; GO:0019430; P:removal of superoxide radicals; IDA:HGNC.
DR GO; GO:0006982; P:response to lipid hydroperoxide; IDA:HGNC.
DR GO; GO:0035634; P:response to stilbenoid; IEA:Ensembl.
DR GO; GO:0001523; P:retinoid metabolic process; TAS:Reactome.
DR GO; GO:0043691; P:reverse cholesterol transport; IDA:BHF-UCL.
DR GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; IDA:BHF-UCL.
DR InterPro; IPR000074; ApoA1_A4_E.
DR Pfam; PF01442; Apolipoprotein; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Chylomicron; Complete proteome; HDL; Lipid transport;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; Secreted;
KW Signal; Transport.
FT SIGNAL 1 20
FT CHAIN 21 396 Apolipoprotein A-IV.
FT /FTId=PRO_0000001975.
FT REPEAT 33 54 1.
FT REPEAT 60 81 2.
FT REPEAT 82 103 3.
FT REPEAT 115 136 4.
FT REPEAT 137 158 5.
FT REPEAT 159 180 6.
FT REPEAT 181 202 7.
FT REPEAT 203 224 8.
FT REPEAT 225 246 9.
FT REPEAT 247 268 10.
FT REPEAT 269 286 11.
FT REPEAT 287 308 12.
FT REPEAT 309 330 13.
FT REGION 33 330 13 X 22 AA approximate tandem repeats.
FT COMPBIAS 372 389 Gln/Glu-rich.
FT VARIANT 13 13 V -> M (in allele APOA-IV*1D).
FT /FTId=VAR_000626.
FT VARIANT 44 44 E -> K (in Budapest-2).
FT /FTId=VAR_000627.
FT VARIANT 74 74 G -> S (in dbSNP:rs5102).
FT /FTId=VAR_014610.
FT VARIANT 77 77 Q -> H.
FT /FTId=VAR_025444.
FT VARIANT 147 147 N -> S (in allele APOA-IV*1B;
FT dbSNP:rs5104).
FT /FTId=VAR_000628.
FT VARIANT 161 161 A -> S (in Seattle-3).
FT /FTId=VAR_000629.
FT VARIANT 178 178 S -> L (in Seattle-1; may contribute to
FT the development of familial combined
FT hyperlipidemia).
FT /FTId=VAR_000630.
FT VARIANT 185 185 E -> K (in allele APOA-IV*3).
FT /FTId=VAR_000631.
FT VARIANT 187 187 K -> E (in allele APOA-IV*0A; associated
FT with H-380).
FT /FTId=VAR_000632.
FT VARIANT 250 250 E -> K (in allele APOA-IV*3A).
FT /FTId=VAR_000633.
FT VARIANT 264 264 R -> Q (in Seattle-2; may contribute to
FT the development of familial combined
FT hyperlipidemia; dbSNP:rs2238008).
FT /FTId=VAR_000634.
FT VARIANT 279 279 R -> K (in dbSNP:rs1042372).
FT /FTId=VAR_025443.
FT VARIANT 305 305 R -> C (in Budapest-1).
FT /FTId=VAR_000635.
FT VARIANT 307 307 V -> L (in dbSNP:rs5108).
FT /FTId=VAR_014611.
FT VARIANT 367 367 T -> S (in allele APOA-IV*1A and allele
FT Budapest-1; dbSNP:rs675).
FT /FTId=VAR_000636.
FT VARIANT 380 380 Q -> H (in allele APOA-IV*2 and allele
FT APOA-IV*0A; associated with E-187 in
FT allele APOA-IV*0A; dbSNP:rs5110).
FT /FTId=VAR_000637.
FT VARIANT 381 381 Q -> QEQQQ (in allele APOA-IV*0 and
FT allele APOA-IV*5; allele APOA-IV*5 is
FT further defined by a silent nucleotide
FT substitution).
FT /FTId=VAR_000638.
FT CONFLICT 158 160 TPY -> DPL (in Ref. 1; AAA51744 and 2;
FT AAA51745).
FT CONFLICT 327 327 Q -> T (in Ref. 3; AAA96731 and 8;
FT AAA51748).
FT HELIX 97 113
FT HELIX 114 116
FT HELIX 117 223
FT HELIX 224 226
FT HELIX 231 276
FT STRAND 278 280
FT HELIX 282 307
FT HELIX 310 329
SQ SEQUENCE 396 AA; 45399 MW; 193753196CA2FA4A CRC64;
MFLKAVVLTL ALVAVAGARA EVSADQVATV MWDYFSQLSN NAKEAVEHLQ KSELTQQLNA
LFQDKLGEVN TYAGDLQKKL VPFATELHER LAKDSEKLKE EIGKELEELR ARLLPHANEV
SQKIGDNLRE LQQRLEPYAD QLRTQVNTQA EQLRRQLTPY AQRMERVLRE NADSLQASLR
PHADELKAKI DQNVEELKGR LTPYADEFKV KIDQTVEELR RSLAPYAQDT QEKLNHQLEG
LTFQMKKNAE ELKARISASA EELRQRLAPL AEDVRGNLRG NTEGLQKSLA ELGGHLDQQV
EEFRRRVEPY GENFNKALVQ QMEQLRQKLG PHAGDVEGHL SFLEKDLRDK VNSFFSTFKE
KESQDKTLSL PELEQQQEQQ QEQQQEQVQM LAPLES
//
MIM
107690
*RECORD*
*FIELD* NO
107690
*FIELD* TI
*107690 APOLIPOPROTEIN A-IV; APOA4
*FIELD* TX
CLONING
Apolipoprotein A-IV is a component of chylomicrons and high-density
read morelipoproteins. By isoelectric focusing, 2 isoforms, designated A-IV-1 and
A-IV-2, can be identified. Menzel et al. (1982) demonstrated another
variant form.
Anderson and Anderson (1977) and Tracy et al. (1982) described genetic
polymorphism of an unidentified serum peptide with a molecular weight of
about 45,000. Schamaun et al. (1984) immunologically identified this
serum protein as apoA-IV.
Karathanasis et al. (1986) isolated and characterized the APOA4 gene.
Elshourbagy et al. (1986) determined the complete nucleotide sequence of
the human APOA4 mRNA. The derived amino acid sequence showed that mature
plasma APOA4 contained 376 residues. Throughout most of its length,
human APOA4 was found to contain multiple tandem 22-residue repeated
segments having amphipathic, alpha-helical potential.
GENE STRUCTURE
Karathanasis et al. (1986) found that, in contrast to APOA1 (107680) and
APOC3 (107720) genes, which contain 3 introns, the APOA4 gene contains
only 2. An intron interrupting the 5-prime noncoding region of the APOA1
and APOC3 mRNAs is absent from the corresponding position of the APOA4
mRNA. However, similar to APOA1 and APOC3 genes, the introns of the
APOA4 gene separate nucleotide sequences coding for the signal peptide
and the amphipathic domains in APOA4. The similarities suggested that
the 3 closely linked genes were derived from a common evolutionary
ancestor, and that during evolution, the APOA4 gene lost one of its
introns.
Elshourbagy et al. (1987) determined the complete nucleotide sequence of
the APOA4 gene and reported that, contrary to the findings of
Karathanasis et al. (1986), the gene contains 3 exons of 162, 127, and
1180 nucleotides separated by 2 introns of 357 and 777 nucleotides. They
stated that the human APOA4 gene lacks an intron in the area encoding
the 5-prime untranslated region of its mRNA, which distinguishes it from
all the other human apolipoprotein genes whose sequences are known.
GENE FUNCTION
Duverger et al. (1996) expressed the human APOA4 gene in the livers of
mice deficient in apoE (107741). They found that apoA-4 levels did not
affect the levels of HDL cholesterol in these mice. However, transgenic
mice had a significant reduction in the size of atherosclerotic lesions.
Duverger et al. (1996) suggested that apoA-IV protects against
atherosclerosis by a mechanism that does not involve an increase in HDL
cholesterol concentration. They stated that their data support other
evidence that suggests that apoA-IV may participate in reverse
cholesterol transport (from tissues to the liver for elimination).
Cohen et al. (1997) produced transgenic mice with inserts of several
copies of murine apoA-IV gene. They found 3-fold increases in plasma
apoA-IV levels in mice fed a chow diet and 6-fold increases in those fed
an atherogenic diet. Plasma triglycerides, total cholesterol, HDL
cholesterol, and free fatty acids were increased, while unesterified
cholesterol was decreased, in the atherogenic diet group. Transgenic
mice exhibited 70% fewer aortic lesions than controls. HDL-sized
lipoproteins from mice fed the atherogenic diet promoted greater
cholesterol efflux from cholesterol-loaded human monocytes than
controls, and plasma from these mice showed raised cholesterol
esterification rates. Cohen et al. (1997) suggested that apoA-IV levels
may influence metabolism of HDL and its effects on atherogenesis.
MAPPING
By Southern blot analyses of APOA4 gene-containing cosmids, Elshourbagy
et al. (1986) determined that the APOA4, APOA1, and APOC3 genes reside
within a 20-kilobase span of chromosome 11 DNA. The APOA4 gene is
located about 14 kilobases downstream from the APOA1 gene in the same
orientation, with the APOC3 gene located between them in the opposite
orientation.
MOLECULAR GENETICS
Karathanasis et al. (1986) found that a site in the second intron of
APOA4 and a site 9 kb 3-prime to the gene were polymorphic in
Mediterranean and other European populations.
Kamboh and Ferrell (1987) determined the frequency of polymorphism at
the APOA4 locus by a simple and rapid 1-dimensional isoelectric-focusing
technique followed by immunoblotting. In an Icelandic population, Menzel
et al. (1990) found a higher frequency of the APOA4*2 allele (0.117 vs
0.077) than in Tyroleans (Menzel et al., 1988). In both populations the
alleles at the APOA4 locus had significant effects on plasma
high-density lipoprotein cholesterol and triglyceride levels. In the
Icelandic population, the average effect of the APO4*2 allele was to
raise cholesterol by 4.9 mg/dl and to lower triglyceride levels by 19.4
mg/dl. Menzel et al. (1990) estimated that the genetic variability at
the APOA4 locus accounted for 3.1% of the total variability of HDL
cholesterol and for 2.8% of the total variability of triglycerides in
the Icelandic population. Genetically determined polymorphism of apoA-IV
has been reported in dogs, horses, and baboons, in addition to humans.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
In a Norwegian family with a mutant APOA1 gene and polymorphism of
APOA4, Schamaun et al. (1984) found close linkage of the APOA1 and APOA4
loci; for the sexes combined, the peak lod score was 3.01 at a
recombination fraction of 0.00. Rogne et al. (1986) raised the lod score
to 6.32 by using 2 DNA polymorphisms of an APOA1 probe to study families
informative for apoA-IV protein variants. Karathanasis (1985) showed
that the APOA4 gene is located 12 kb 3-prime to the APOA1 gene.
*FIELD* AV
.0001
APOLIPOPROTEIN A-IV POLYMORPHISM, APOA4*1/APOA4*2
APOA4, GLN360HIS
Lohse et al. (1990) demonstrated that the genetic polymorphism of plasma
apolipoprotein A-IV, detected by isoelectric focusing followed by
immunoblotting, results from a single nucleotide change. Specifically,
the difference between APOA4*1 and APOA4*2 is a G-to-T substitution
leading to a conversion of glutamine-360 to histidine in the mature
protein. The allelic change is predicted to cause the loss of 2
restriction enzyme sites in the formation of a new restriction site for
a third enzyme. In Caucasian populations, the APOA4*1 and APOA4*2
alleles have a frequency of about 0.9 and 0.08, respectively; 3 rare
alleles, APOA4*0 (107690.0002), APOA4*3 (107690.0003), and APOA4*4, have
been described. In a study of various polymorphisms of APOA4, von
Eckardstein et al. (1992) could not confirm the previously reported
association of elevated HDL cholesterol concentrations with the his360
allele; from other associations, the authors concluded that the APOA4
gene locus has an important role in the metabolism of apolipoprotein B
and, to a lesser extent, apolipoprotein A-I-containing lipoproteins.
.0002
APOLIPOPROTEIN A-IV RARE VARIANT, APOA4*0
APOA4, 12-BP INS, GLU-GLN-GLN-GLN INS, CODONS 361-362
Lohse et al. (1990) described the molecular basis of the rare variant
APOA4*0: an insertion of 12 nucleotides in the carboxyl-terminal region,
which is highly conserved among human, rat, and mouse A-IV
apolipoproteins. This in-frame insertion of 4 amino acids,
glu-gln-gln-gln, between residues 361 and 362 of the mature protein,
produces the 1-charge unit, more acidic APOA4*0 isoprotein (pI = 4.92).
.0003
APOLIPOPROTEIN A-IV RARE VARIANT, APOA4*3
APOA4, GLU230LYS
Lohse et al. (1990) identified a single G-to-A substitution that
converted the glutamic acid (GAG) at position 230 of the mature apoA-IV
protein to lysine (AAG). The change added 2 positive charge units to the
apoA-IV-1 isoprotein (pI = 4.97) to give the more basic APOA4*3
isoprotein (pI, 5.08).
.0004
APOLIPOPROTEIN A-IV RARE VARIANT, APOA4*5
APOA4, 12-BP INS, GLU-GLN-GLN-GLN INS
Kamboh et al. (1992) described the same in-frame insertion of 12
nucleotides (coding for the 4 amino acids glu-gln-gln-gln) near the
carboxy-terminal region of the mature protein as Lohse et al. (1990)
(see 107690.0002). This study also revealed a polymorphism (G to T,
codon 316, third position) that did not result in an amino acid
substitution. Kamboh et al. (1992) noted that finding the exact position
of the 12 inserted bases was difficult because the sequences of 2 of the
5 repeat units in the APOA4*5 allele are identical. Possible sites of
insertion are between codons 357 and 358, or between codons 361 and 362.
Using data obtained from 308 subjects, they estimated the frequency of
the APOA4*5 allele in African Americans to be 3.2%.
*FIELD* SA
Green et al. (1980)
*FIELD* RF
1. Anderson, L.; Anderson, N. G.: High resolution two-dimensional
electrophoresis of human plasma proteins. Proc. Nat. Acad. Sci. 12:
5421-5425, 1977.
2. Cohen, R. D.; Castellani, L. W.; Qiao, J.-H.; Van Lenten, B. J.;
Lusis, A. J.; Reue, K.: Reduced aortic lesions and elevated high
density lipoprotein levels in transgenic mice overexpressing mouse
apolipoprotein A-IV. J. Clin. Invest. 99: 1906-1916, 1997.
3. Duverger, N.; Tremp, G.; Caillaud, J.-M.; Emmanuel, F.; Castro,
G.; Fruchart, J.-C.; Steinmetz, A.; Denefle, P.: Protection against
atherogenesis in mice mediated by human apolipoprotein A-IV. Science 273:
966-968, 1996.
4. Elshourbagy, N. A.; Walker, D. W.; Boguski, M. S.; Gordon, J. I.;
Taylor, J. M.: The nucleotide and derived amino acid sequence of
human apolipoprotein A-IV mRNA and the close linkage of its gene to
the genes of apolipoproteins A-I and C-III. J. Biol. Chem. 261:
1998-2002, 1986.
5. Elshourbagy, N. A.; Walker, D. W.; Paik, Y.-K.; Boguski, M. S.;
Freeman, M.; Gordon, J. I.; Taylor, J. M.: Structure and expression
of the human apolipoprotein A-IV gene. J. Biol. Chem. 262: 7973-7981,
1987.
6. Green, P. H. R.; Glickman, R. M.; Riley, J. W.; Quinet, E.: Human
apolipoprotein A-IV: intestinal origin and distribution in plasma. J.
Clin. Invest. 65: 911-919, 1980.
7. Kamboh, M. I.; Ferrell, R. E.: Genetic studies of human apolipoproteins.
I. Polymorphism of apolipoprotein A-IV. Am. J. Hum. Genet. 41: 119-127,
1987.
8. Kamboh, M. I.; Williams, E. R.; Law, J. C.; Aston, C. E.; Bunker,
C. H.; Ferrell. R. E.; Pollitzer, W. S.: Molecular basis of a unique
African variant (A-IV 5) of human apolipoprotein A-IV and its significance
in lipid metabolism. Genet. Epidemiol. 9: 379-388, 1992.
9. Karathanasis, S. K.: Apolipoprotein multigene family: tandem organization
of human apolipoprotein AI, CIII, and AIV genes. Proc. Nat. Acad.
Sci. 82: 6374-6378, 1985.
10. Karathanasis, S. K.; Oettgen, P.; Haddad, I. A.; Antonarakis,
S. E.: Structure, evolution, and polymorphisms of the human apolipoprotein
A4 gene (APOA4). Proc. Nat. Acad. Sci. 83: 8457-8461, 1986.
11. Lohse, P.; Kindt, M. R.; Rader, D. J.; Brewer, H. B., Jr.: Genetic
polymorphism of human plasma apolipoprotein A-IV is due to nucleotide
substitutions in the apolipoprotein A-IV gene. J. Biol. Chem. 265:
10061-10064, 1990.
12. Lohse, P.; Kindt, M. R.; Rader, D. J.; Brewer, H. B., Jr.: Human
plasma apolipoproteins A-IV-0 and A-IV-3: molecular basis for two
rare variants of apolipoprotein A-IV-1. J. Biol. Chem. 265: 12734-12739,
1990.
13. Menzel, H.-J.; Boerwinkle, E.; Schrangl-Will, S.; Utermann, G.
: Human apolipoprotein A-IV polymorphism: frequency and effect on
lipid and lipoprotein levels. Hum. Genet. 79: 368-372, 1988.
14. Menzel, H.-J.; Kovary, P. M.; Assmann, G.: Apolipoprotein A-IV
polymorphism in man. Hum. Genet. 62: 349-352, 1982.
15. Menzel, H.-J.; Sigurdsson, G.; Boerwinkle, E.; Schrangl-Will,
S.; Dieplinger, H.; Utermann, G.: Frequency and effect of human apolipoprotein
A-IV polymorphism on lipid and lipoprotein levels in an Icelandic
population. Hum. Genet. 84: 344-346, 1990.
16. Rogne, S.; Myklebost, O.; Olaisen, B.; Gedde-Dahl, T., Jr.; Prydz,
H.: Confirmation of the close linkage between the loci for human
apolipoproteins AI and AIV by the use of a cloned cDNA probe and two
restriction site polymorphisms. Hum. Genet. 72: 68-71, 1986.
17. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
18. Schamaun, O.; Olaisen, B.; Mevag, B.; Gedde-Dahl, T., Jr.; Ehnholm,
C.; Teisberg, P.: The two apolipoprotein loci apoA-I and apoA-IV
are closely linked in man. Hum. Genet. 68: 181-184, 1984.
19. Tracy, R. P.; Currie, R. M.; Young, D. S.: Two-dimensional gel
electrophoresis of serum specimens from a normal population. Clin.
Chem. 28: 890-899, 1982.
20. von Eckardstein, A.; Funke, H.; Schulte, M.; Erren, M.; Schulte,
H.; Assmann, G.: Nonsynonymous polymorphic sites in the apolipoprotein
(apo) A-IV gene are associated with changes in the concentration of
apo B- and apo A-I-containing lipoproteins in a normal population. Am.
J. Hum. Genet. 50: 1115-1128, 1992.
*FIELD* CN
Michael J. Wright - updated: 9/25/1997
Jennifer P. Macke - updated: 7/28/1997
Stylianos E. Antonarakis - updated: 7/8/1996
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 07/16/2012
terry: 6/1/1998
alopez: 11/11/1997
alopez: 11/10/1997
dholmes: 8/25/1997
dholmes: 8/4/1997
terry: 7/28/1997
terry: 7/9/1997
mark: 7/8/1996
mimadm: 4/9/1994
carol: 7/6/1992
supermim: 3/19/1992
supermim: 3/16/1992
carol: 1/27/1992
carol: 2/8/1991
*RECORD*
*FIELD* NO
107690
*FIELD* TI
*107690 APOLIPOPROTEIN A-IV; APOA4
*FIELD* TX
CLONING
Apolipoprotein A-IV is a component of chylomicrons and high-density
read morelipoproteins. By isoelectric focusing, 2 isoforms, designated A-IV-1 and
A-IV-2, can be identified. Menzel et al. (1982) demonstrated another
variant form.
Anderson and Anderson (1977) and Tracy et al. (1982) described genetic
polymorphism of an unidentified serum peptide with a molecular weight of
about 45,000. Schamaun et al. (1984) immunologically identified this
serum protein as apoA-IV.
Karathanasis et al. (1986) isolated and characterized the APOA4 gene.
Elshourbagy et al. (1986) determined the complete nucleotide sequence of
the human APOA4 mRNA. The derived amino acid sequence showed that mature
plasma APOA4 contained 376 residues. Throughout most of its length,
human APOA4 was found to contain multiple tandem 22-residue repeated
segments having amphipathic, alpha-helical potential.
GENE STRUCTURE
Karathanasis et al. (1986) found that, in contrast to APOA1 (107680) and
APOC3 (107720) genes, which contain 3 introns, the APOA4 gene contains
only 2. An intron interrupting the 5-prime noncoding region of the APOA1
and APOC3 mRNAs is absent from the corresponding position of the APOA4
mRNA. However, similar to APOA1 and APOC3 genes, the introns of the
APOA4 gene separate nucleotide sequences coding for the signal peptide
and the amphipathic domains in APOA4. The similarities suggested that
the 3 closely linked genes were derived from a common evolutionary
ancestor, and that during evolution, the APOA4 gene lost one of its
introns.
Elshourbagy et al. (1987) determined the complete nucleotide sequence of
the APOA4 gene and reported that, contrary to the findings of
Karathanasis et al. (1986), the gene contains 3 exons of 162, 127, and
1180 nucleotides separated by 2 introns of 357 and 777 nucleotides. They
stated that the human APOA4 gene lacks an intron in the area encoding
the 5-prime untranslated region of its mRNA, which distinguishes it from
all the other human apolipoprotein genes whose sequences are known.
GENE FUNCTION
Duverger et al. (1996) expressed the human APOA4 gene in the livers of
mice deficient in apoE (107741). They found that apoA-4 levels did not
affect the levels of HDL cholesterol in these mice. However, transgenic
mice had a significant reduction in the size of atherosclerotic lesions.
Duverger et al. (1996) suggested that apoA-IV protects against
atherosclerosis by a mechanism that does not involve an increase in HDL
cholesterol concentration. They stated that their data support other
evidence that suggests that apoA-IV may participate in reverse
cholesterol transport (from tissues to the liver for elimination).
Cohen et al. (1997) produced transgenic mice with inserts of several
copies of murine apoA-IV gene. They found 3-fold increases in plasma
apoA-IV levels in mice fed a chow diet and 6-fold increases in those fed
an atherogenic diet. Plasma triglycerides, total cholesterol, HDL
cholesterol, and free fatty acids were increased, while unesterified
cholesterol was decreased, in the atherogenic diet group. Transgenic
mice exhibited 70% fewer aortic lesions than controls. HDL-sized
lipoproteins from mice fed the atherogenic diet promoted greater
cholesterol efflux from cholesterol-loaded human monocytes than
controls, and plasma from these mice showed raised cholesterol
esterification rates. Cohen et al. (1997) suggested that apoA-IV levels
may influence metabolism of HDL and its effects on atherogenesis.
MAPPING
By Southern blot analyses of APOA4 gene-containing cosmids, Elshourbagy
et al. (1986) determined that the APOA4, APOA1, and APOC3 genes reside
within a 20-kilobase span of chromosome 11 DNA. The APOA4 gene is
located about 14 kilobases downstream from the APOA1 gene in the same
orientation, with the APOC3 gene located between them in the opposite
orientation.
MOLECULAR GENETICS
Karathanasis et al. (1986) found that a site in the second intron of
APOA4 and a site 9 kb 3-prime to the gene were polymorphic in
Mediterranean and other European populations.
Kamboh and Ferrell (1987) determined the frequency of polymorphism at
the APOA4 locus by a simple and rapid 1-dimensional isoelectric-focusing
technique followed by immunoblotting. In an Icelandic population, Menzel
et al. (1990) found a higher frequency of the APOA4*2 allele (0.117 vs
0.077) than in Tyroleans (Menzel et al., 1988). In both populations the
alleles at the APOA4 locus had significant effects on plasma
high-density lipoprotein cholesterol and triglyceride levels. In the
Icelandic population, the average effect of the APO4*2 allele was to
raise cholesterol by 4.9 mg/dl and to lower triglyceride levels by 19.4
mg/dl. Menzel et al. (1990) estimated that the genetic variability at
the APOA4 locus accounted for 3.1% of the total variability of HDL
cholesterol and for 2.8% of the total variability of triglycerides in
the Icelandic population. Genetically determined polymorphism of apoA-IV
has been reported in dogs, horses, and baboons, in addition to humans.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
In a Norwegian family with a mutant APOA1 gene and polymorphism of
APOA4, Schamaun et al. (1984) found close linkage of the APOA1 and APOA4
loci; for the sexes combined, the peak lod score was 3.01 at a
recombination fraction of 0.00. Rogne et al. (1986) raised the lod score
to 6.32 by using 2 DNA polymorphisms of an APOA1 probe to study families
informative for apoA-IV protein variants. Karathanasis (1985) showed
that the APOA4 gene is located 12 kb 3-prime to the APOA1 gene.
*FIELD* AV
.0001
APOLIPOPROTEIN A-IV POLYMORPHISM, APOA4*1/APOA4*2
APOA4, GLN360HIS
Lohse et al. (1990) demonstrated that the genetic polymorphism of plasma
apolipoprotein A-IV, detected by isoelectric focusing followed by
immunoblotting, results from a single nucleotide change. Specifically,
the difference between APOA4*1 and APOA4*2 is a G-to-T substitution
leading to a conversion of glutamine-360 to histidine in the mature
protein. The allelic change is predicted to cause the loss of 2
restriction enzyme sites in the formation of a new restriction site for
a third enzyme. In Caucasian populations, the APOA4*1 and APOA4*2
alleles have a frequency of about 0.9 and 0.08, respectively; 3 rare
alleles, APOA4*0 (107690.0002), APOA4*3 (107690.0003), and APOA4*4, have
been described. In a study of various polymorphisms of APOA4, von
Eckardstein et al. (1992) could not confirm the previously reported
association of elevated HDL cholesterol concentrations with the his360
allele; from other associations, the authors concluded that the APOA4
gene locus has an important role in the metabolism of apolipoprotein B
and, to a lesser extent, apolipoprotein A-I-containing lipoproteins.
.0002
APOLIPOPROTEIN A-IV RARE VARIANT, APOA4*0
APOA4, 12-BP INS, GLU-GLN-GLN-GLN INS, CODONS 361-362
Lohse et al. (1990) described the molecular basis of the rare variant
APOA4*0: an insertion of 12 nucleotides in the carboxyl-terminal region,
which is highly conserved among human, rat, and mouse A-IV
apolipoproteins. This in-frame insertion of 4 amino acids,
glu-gln-gln-gln, between residues 361 and 362 of the mature protein,
produces the 1-charge unit, more acidic APOA4*0 isoprotein (pI = 4.92).
.0003
APOLIPOPROTEIN A-IV RARE VARIANT, APOA4*3
APOA4, GLU230LYS
Lohse et al. (1990) identified a single G-to-A substitution that
converted the glutamic acid (GAG) at position 230 of the mature apoA-IV
protein to lysine (AAG). The change added 2 positive charge units to the
apoA-IV-1 isoprotein (pI = 4.97) to give the more basic APOA4*3
isoprotein (pI, 5.08).
.0004
APOLIPOPROTEIN A-IV RARE VARIANT, APOA4*5
APOA4, 12-BP INS, GLU-GLN-GLN-GLN INS
Kamboh et al. (1992) described the same in-frame insertion of 12
nucleotides (coding for the 4 amino acids glu-gln-gln-gln) near the
carboxy-terminal region of the mature protein as Lohse et al. (1990)
(see 107690.0002). This study also revealed a polymorphism (G to T,
codon 316, third position) that did not result in an amino acid
substitution. Kamboh et al. (1992) noted that finding the exact position
of the 12 inserted bases was difficult because the sequences of 2 of the
5 repeat units in the APOA4*5 allele are identical. Possible sites of
insertion are between codons 357 and 358, or between codons 361 and 362.
Using data obtained from 308 subjects, they estimated the frequency of
the APOA4*5 allele in African Americans to be 3.2%.
*FIELD* SA
Green et al. (1980)
*FIELD* RF
1. Anderson, L.; Anderson, N. G.: High resolution two-dimensional
electrophoresis of human plasma proteins. Proc. Nat. Acad. Sci. 12:
5421-5425, 1977.
2. Cohen, R. D.; Castellani, L. W.; Qiao, J.-H.; Van Lenten, B. J.;
Lusis, A. J.; Reue, K.: Reduced aortic lesions and elevated high
density lipoprotein levels in transgenic mice overexpressing mouse
apolipoprotein A-IV. J. Clin. Invest. 99: 1906-1916, 1997.
3. Duverger, N.; Tremp, G.; Caillaud, J.-M.; Emmanuel, F.; Castro,
G.; Fruchart, J.-C.; Steinmetz, A.; Denefle, P.: Protection against
atherogenesis in mice mediated by human apolipoprotein A-IV. Science 273:
966-968, 1996.
4. Elshourbagy, N. A.; Walker, D. W.; Boguski, M. S.; Gordon, J. I.;
Taylor, J. M.: The nucleotide and derived amino acid sequence of
human apolipoprotein A-IV mRNA and the close linkage of its gene to
the genes of apolipoproteins A-I and C-III. J. Biol. Chem. 261:
1998-2002, 1986.
5. Elshourbagy, N. A.; Walker, D. W.; Paik, Y.-K.; Boguski, M. S.;
Freeman, M.; Gordon, J. I.; Taylor, J. M.: Structure and expression
of the human apolipoprotein A-IV gene. J. Biol. Chem. 262: 7973-7981,
1987.
6. Green, P. H. R.; Glickman, R. M.; Riley, J. W.; Quinet, E.: Human
apolipoprotein A-IV: intestinal origin and distribution in plasma. J.
Clin. Invest. 65: 911-919, 1980.
7. Kamboh, M. I.; Ferrell, R. E.: Genetic studies of human apolipoproteins.
I. Polymorphism of apolipoprotein A-IV. Am. J. Hum. Genet. 41: 119-127,
1987.
8. Kamboh, M. I.; Williams, E. R.; Law, J. C.; Aston, C. E.; Bunker,
C. H.; Ferrell. R. E.; Pollitzer, W. S.: Molecular basis of a unique
African variant (A-IV 5) of human apolipoprotein A-IV and its significance
in lipid metabolism. Genet. Epidemiol. 9: 379-388, 1992.
9. Karathanasis, S. K.: Apolipoprotein multigene family: tandem organization
of human apolipoprotein AI, CIII, and AIV genes. Proc. Nat. Acad.
Sci. 82: 6374-6378, 1985.
10. Karathanasis, S. K.; Oettgen, P.; Haddad, I. A.; Antonarakis,
S. E.: Structure, evolution, and polymorphisms of the human apolipoprotein
A4 gene (APOA4). Proc. Nat. Acad. Sci. 83: 8457-8461, 1986.
11. Lohse, P.; Kindt, M. R.; Rader, D. J.; Brewer, H. B., Jr.: Genetic
polymorphism of human plasma apolipoprotein A-IV is due to nucleotide
substitutions in the apolipoprotein A-IV gene. J. Biol. Chem. 265:
10061-10064, 1990.
12. Lohse, P.; Kindt, M. R.; Rader, D. J.; Brewer, H. B., Jr.: Human
plasma apolipoproteins A-IV-0 and A-IV-3: molecular basis for two
rare variants of apolipoprotein A-IV-1. J. Biol. Chem. 265: 12734-12739,
1990.
13. Menzel, H.-J.; Boerwinkle, E.; Schrangl-Will, S.; Utermann, G.
: Human apolipoprotein A-IV polymorphism: frequency and effect on
lipid and lipoprotein levels. Hum. Genet. 79: 368-372, 1988.
14. Menzel, H.-J.; Kovary, P. M.; Assmann, G.: Apolipoprotein A-IV
polymorphism in man. Hum. Genet. 62: 349-352, 1982.
15. Menzel, H.-J.; Sigurdsson, G.; Boerwinkle, E.; Schrangl-Will,
S.; Dieplinger, H.; Utermann, G.: Frequency and effect of human apolipoprotein
A-IV polymorphism on lipid and lipoprotein levels in an Icelandic
population. Hum. Genet. 84: 344-346, 1990.
16. Rogne, S.; Myklebost, O.; Olaisen, B.; Gedde-Dahl, T., Jr.; Prydz,
H.: Confirmation of the close linkage between the loci for human
apolipoproteins AI and AIV by the use of a cloned cDNA probe and two
restriction site polymorphisms. Hum. Genet. 72: 68-71, 1986.
17. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
18. Schamaun, O.; Olaisen, B.; Mevag, B.; Gedde-Dahl, T., Jr.; Ehnholm,
C.; Teisberg, P.: The two apolipoprotein loci apoA-I and apoA-IV
are closely linked in man. Hum. Genet. 68: 181-184, 1984.
19. Tracy, R. P.; Currie, R. M.; Young, D. S.: Two-dimensional gel
electrophoresis of serum specimens from a normal population. Clin.
Chem. 28: 890-899, 1982.
20. von Eckardstein, A.; Funke, H.; Schulte, M.; Erren, M.; Schulte,
H.; Assmann, G.: Nonsynonymous polymorphic sites in the apolipoprotein
(apo) A-IV gene are associated with changes in the concentration of
apo B- and apo A-I-containing lipoproteins in a normal population. Am.
J. Hum. Genet. 50: 1115-1128, 1992.
*FIELD* CN
Michael J. Wright - updated: 9/25/1997
Jennifer P. Macke - updated: 7/28/1997
Stylianos E. Antonarakis - updated: 7/8/1996
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 07/16/2012
terry: 6/1/1998
alopez: 11/11/1997
alopez: 11/10/1997
dholmes: 8/25/1997
dholmes: 8/4/1997
terry: 7/28/1997
terry: 7/9/1997
mark: 7/8/1996
mimadm: 4/9/1994
carol: 7/6/1992
supermim: 3/19/1992
supermim: 3/16/1992
carol: 1/27/1992
carol: 2/8/1991