APOA4_HUMAN
ID APOA4_HUMAN Reviewed; 396 AA.
AC P06727; A8MSL6; Q14CW8; Q6Q787;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 17-JUN-2020, sequence version 4.
DT 03-AUG-2022, entry version 226.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ASN-147 AND 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 VARIANTS ASN-147 AND 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 A4
RT gene (APOA4).";
RL Proc. Natl. Acad. Sci. U.S.A. 83:8457-8461(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM, AND VARIANTS ASN-147 AND
RP HIS-380.
RX PubMed=3036793; DOI=10.1016/s0021-9258(18)47513-8;
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], AND VARIANT ASN-147.
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; ASN-147;
RP 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 ASN-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., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., 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], AND VARIANT ASN-147.
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 21-396, AND VARIANTS ASN-147 AND HIS-380.
RX PubMed=3080432; DOI=10.1016/s0021-9258(17)35888-x;
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 apolipoprotein A-
RT IV mRNA and the close linkage of its gene to the genes of apolipoproteins
RT A-I and C-III.";
RL J. Biol. Chem. 261:1998-2002(1986).
RN [9]
RP SIGNAL SEQUENCE CLEAVAGE SITE.
RX PubMed=6706947; DOI=10.1016/s0021-9258(17)43684-2;
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 POLYMORPHISM, ALLELES APOA-IV*1 AND APOA-IV*2, AND VARIANT HIS-380.
RX PubMed=2351649; DOI=10.1016/s0021-9258(19)38779-4;
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 POLYMORPHISM, ALLELES A-IV*0 AND A-IV*3, AND VARIANTS LYS-250 AND
RP GLU-GLN-GLN-GLN-381 INS.
RX PubMed=1973689; DOI=10.1016/s0021-9258(19)38406-6;
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 two
RT 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., Buerckstuemmer T.,
RA 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 self-
RT association.";
RL Structure 20:767-779(2012).
RN [15]
RP VARIANT HIS-380.
RX PubMed=2065039; DOI=10.1161/01.atv.11.4.851;
RA Tenkanen H., Lukka M., Jauhiainen M., Metso J., Baumann M., Peltonen L.,
RA 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 POLYMORPHISM, ALLELES A-IV*0; A-IV*1; A-IV*2 AND A-IV*3, AND VARIANTS
RP LYS-185; GLU-187; SER-367 AND HIS-380.
RX PubMed=1677358; DOI=10.1016/s0021-9258(18)92728-6;
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-1(Thr-
RT 347-->Ser), apoA-IV-0(Lys-167-->Glu,Gln-360-->His), and apoA-IV-3(Glu-
RT 165-->Lys).";
RL J. Biol. Chem. 266:13513-13518(1991).
RN [17]
RP ERRATUM OF PUBMED:1677358.
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., Assmann G.;
RT "Nonsynonymous polymorphic sites in the apolipoprotein (apo) A-IV gene are
RT associated with changes in the concentration of apo B- and apo A-I-
RT containing lipoproteins in a normal population.";
RL Am. J. Hum. Genet. 50:1115-1128(1992).
RN [19]
RP VARIANT ASN-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., Manninen V.,
RA Ehnholm C.;
RT "A novel polymorphism of apolipoprotein A-IV is the result of an asparagine
RT to serine substitution at residue 127.";
RL Biochim. Biophys. Acta 1138:27-33(1992).
RN [20]
RP POLYMORPHISM, 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 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>3.0.co;2-2;
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 blood-
RT 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 lipase by
CC ApoC-II; potent activator of LCAT. Apoa-IV is a major component of HDL
CC and chylomicrons.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:22579246}.
CC -!- INTERACTION:
CC P06727; Q6RW13-2: AGTRAP; NbExp=3; IntAct=EBI-1222447, EBI-11522760;
CC P06727; P06727: APOA4; NbExp=10; IntAct=EBI-1222447, EBI-1222447;
CC P06727; P55212: CASP6; NbExp=3; IntAct=EBI-1222447, EBI-718729;
CC P06727; Q8IZR5-2: CMTM4; NbExp=3; IntAct=EBI-1222447, EBI-17278014;
CC P06727; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-1222447, EBI-11522780;
CC P06727; P43360: MAGEA6; NbExp=3; IntAct=EBI-1222447, EBI-1045155;
CC P06727; P20393: NR1D1; NbExp=3; IntAct=EBI-1222447, EBI-2811738;
CC P06727; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-1222447, EBI-2623095;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Synthesized primarily in the intestine and secreted
CC in plasma.
CC -!- DOMAIN: Nine of the thirteen 22-amino acid tandem repeats (each 22-mer
CC is actually a tandem array of two, A and B, related 11-mers) occurring
CC in this sequence are predicted to be highly alpha-helical, and many of
CC these helices are amphipathic. They may therefore serve as lipid-
CC binding domains with lecithin:cholesterol acyltransferase (LCAT)
CC activating abilities.
CC -!- PTM: Phosphorylation sites are present in the extracellular medium.
CC -!- POLYMORPHISM: Eight alleles have been characterized (APOA-IV*0 to APOA-
CC IV*7). APOA-IV*1 is the major allele (90%), APOA-IV*2 is also common
CC (8%), the others are rare alleles. {ECO:0000269|PubMed:1487136,
CC ECO:0000269|PubMed:1677358, ECO:0000269|PubMed:1973689,
CC ECO:0000269|PubMed:2351649, ECO:0000269|PubMed:3036793,
CC ECO:0000269|Ref.10}.
CC -!- SIMILARITY: Belongs to the apolipoprotein A1/A4/E family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 CCDS; CCDS31681.1; -.
DR PIR; A94137; LPHUA4.
DR RefSeq; NP_000473.2; NM_000482.3.
DR PDB; 3S84; X-ray; 2.40 A; A/B=84-355.
DR PDBsum; 3S84; -.
DR AlphaFoldDB; P06727; -.
DR SMR; P06727; -.
DR DIP; DIP-38333N; -.
DR IntAct; P06727; 14.
DR STRING; 9606.ENSP00000350425; -.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB11886; Infigratinib.
DR DrugBank; DB00877; Sirolimus.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR CarbonylDB; P06727; -.
DR GlyGen; P06727; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P06727; -.
DR PhosphoSitePlus; P06727; -.
DR BioMuta; APOA4; -.
DR DMDM; 93163358; -.
DR DOSAC-COBS-2DPAGE; P06727; -.
DR REPRODUCTION-2DPAGE; IPI00304273; -.
DR SWISS-2DPAGE; P06727; -.
DR CPTAC; non-CPTAC-1077; -.
DR CPTAC; non-CPTAC-1078; -.
DR CPTAC; non-CPTAC-1079; -.
DR EPD; P06727; -.
DR jPOST; P06727; -.
DR MassIVE; P06727; -.
DR MaxQB; P06727; -.
DR PaxDb; P06727; -.
DR PeptideAtlas; P06727; -.
DR PRIDE; P06727; -.
DR ProteomicsDB; 51912; -.
DR Antibodypedia; 18421; 494 antibodies from 37 providers.
DR DNASU; 337; -.
DR Ensembl; ENST00000357780.5; ENSP00000350425.3; ENSG00000110244.7.
DR GeneID; 337; -.
DR KEGG; hsa:337; -.
DR MANE-Select; ENST00000357780.5; ENSP00000350425.3; NM_000482.4; NP_000473.2.
DR UCSC; uc001pps.2; human.
DR CTD; 337; -.
DR GeneCards; APOA4; -.
DR HGNC; HGNC:602; APOA4.
DR HPA; ENSG00000110244; Tissue enriched (intestine).
DR MIM; 107690; gene.
DR neXtProt; NX_P06727; -.
DR OpenTargets; ENSG00000110244; -.
DR VEuPathDB; HostDB:ENSG00000110244; -.
DR eggNOG; ENOG502QSC5; Eukaryota.
DR GeneTree; ENSGT00950000182929; -.
DR HOGENOM; CLU_058447_0_0_1; -.
DR InParanoid; P06727; -.
DR OMA; KGHLTPY; -.
DR PhylomeDB; P06727; -.
DR TreeFam; TF334458; -.
DR PathwayCommons; P06727; -.
DR Reactome; R-HSA-8963888; Chylomicron assembly.
DR Reactome; R-HSA-8963889; Assembly of active LPL and LIPC lipase complexes.
DR Reactome; R-HSA-8963901; Chylomicron remodeling.
DR Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SignaLink; P06727; -.
DR Pharos; P06727; Tbio.
DR PRO; PR:P06727; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P06727; protein.
DR Bgee; ENSG00000110244; Expressed in jejunal mucosa and 106 other tissues.
DR Genevisible; P06727; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0042627; C:chylomicron; IDA:BHF-UCL.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA: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:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0034364; C:high-density lipoprotein particle; IDA:BHF-UCL.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0034361; C:very-low-density lipoprotein particle; IDA:BHF-UCL.
DR GO; GO:0016209; F:antioxidant activity; IDA:HGNC-UCL.
DR GO; GO:0015485; F:cholesterol binding; IBA:GO_Central.
DR GO; GO:0120020; F:cholesterol transfer activity; IDA:BHF-UCL.
DR GO; GO:0005507; F:copper ion binding; IDA:HGNC-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008289; F:lipid binding; IMP:BHF-UCL.
DR GO; GO:0005319; F:lipid transporter activity; TAS:ProtInc.
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:0005543; F:phospholipid binding; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IBA:GO_Central.
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:0034380; P:high-density lipoprotein particle assembly; IBA:GO_Central.
DR GO; GO:0034375; P:high-density lipoprotein particle remodeling; IDA:BHF-UCL.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:HGNC-UCL.
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:0016042; P:lipid catabolic process; IDA:BHF-UCL.
DR GO; GO:0055088; P:lipid homeostasis; IDA:BHF-UCL.
DR GO; GO:0006869; P:lipid transport; IDA:BHF-UCL.
DR GO; GO:0042157; P:lipoprotein metabolic process; IBA:GO_Central.
DR GO; GO:0034445; P:negative regulation of plasma lipoprotein oxidation; IDA:BHF-UCL.
DR GO; GO:0014012; P:peripheral nervous system axon regeneration; IEA:Ensembl.
DR GO; GO:0046470; P:phosphatidylcholine metabolic process; IDA:BHF-UCL.
DR GO; GO:0033700; P:phospholipid efflux; IDA:BHF-UCL.
DR GO; GO:0010873; P:positive regulation of cholesterol esterification; IBA:GO_Central.
DR GO; GO:1905920; P:positive regulation of CoA-transferase activity; IDA:ARUK-UCL.
DR GO; GO:0045723; P:positive regulation of fatty acid biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; IBA:GO_Central.
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:0065005; P:protein-lipid complex assembly; IMP:BHF-UCL.
DR GO; GO:0032374; P:regulation of cholesterol transport; IDA:BHF-UCL.
DR GO; GO:0030300; P:regulation of intestinal cholesterol absorption; IBA:GO_Central.
DR GO; GO:0019430; P:removal of superoxide radicals; IDA:HGNC-UCL.
DR GO; GO:0006982; P:response to lipid hydroperoxide; IDA:HGNC-UCL.
DR GO; GO:0035634; P:response to stilbenoid; IEA:Ensembl.
DR GO; GO:0034014; P:response to triglyceride; IEA:Ensembl.
DR GO; GO:0043691; P:reverse cholesterol transport; IDA:BHF-UCL.
DR GO; GO:0070328; P:triglyceride homeostasis; IBA:GO_Central.
DR GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; IDA:BHF-UCL.
DR InterPro; IPR000074; ApoA_E.
DR Pfam; PF01442; Apolipoprotein; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Chylomicron; HDL; Lipid transport; Phosphoprotein;
KW Reference proteome; Repeat; Secreted; Signal; Transport.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:6706947"
FT CHAIN 21..396
FT /note="Apolipoprotein A-IV"
FT /id="PRO_0000001975"
FT REPEAT 33..54
FT /note="1"
FT REPEAT 60..81
FT /note="2"
FT REPEAT 82..103
FT /note="3"
FT REPEAT 115..136
FT /note="4"
FT REPEAT 137..158
FT /note="5"
FT REPEAT 159..180
FT /note="6"
FT REPEAT 181..202
FT /note="7"
FT REPEAT 203..224
FT /note="8"
FT REPEAT 225..246
FT /note="9"
FT REPEAT 247..268
FT /note="10"
FT REPEAT 269..286
FT /note="11"
FT REPEAT 287..308
FT /note="12"
FT REPEAT 309..330
FT /note="13"
FT REGION 33..330
FT /note="13 X 22 AA approximate tandem repeats"
FT REGION 361..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 369..396
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 13
FT /note="V -> M (in allele APOA-IV*1D; dbSNP:rs12721041)"
FT /evidence="ECO:0000269|PubMed:1349197,
FT ECO:0000269|PubMed:15108119"
FT /id="VAR_000626"
FT VARIANT 44
FT /note="E -> K (in Budapest-2)"
FT /evidence="ECO:0000269|PubMed:7728150"
FT /id="VAR_000627"
FT VARIANT 74
FT /note="G -> S (in dbSNP:rs5102)"
FT /id="VAR_014610"
FT VARIANT 77
FT /note="Q -> H (in dbSNP:rs12721042)"
FT /evidence="ECO:0000269|PubMed:15108119"
FT /id="VAR_025444"
FT VARIANT 147
FT /note="S -> N (in dbSNP:rs5104)"
FT /evidence="ECO:0000269|PubMed:15108119,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16554811,
FT ECO:0000269|PubMed:1737067, ECO:0000269|PubMed:2930771,
FT ECO:0000269|PubMed:3036793, ECO:0000269|PubMed:3080432,
FT ECO:0000269|PubMed:3095836, ECO:0000269|PubMed:3755616"
FT /id="VAR_000628"
FT VARIANT 161
FT /note="A -> S (in Seattle-3; dbSNP:rs12721043)"
FT /evidence="ECO:0000269|PubMed:15108119,
FT ECO:0000269|PubMed:8956036"
FT /id="VAR_000629"
FT VARIANT 178
FT /note="S -> L (in Seattle-1; may contribute to the
FT development of familial combined hyperlipidemia;
FT dbSNP:rs1181852696)"
FT /evidence="ECO:0000269|PubMed:8956036"
FT /id="VAR_000630"
FT VARIANT 185
FT /note="E -> K (in allele APOA-IV*3; dbSNP:rs201861136)"
FT /evidence="ECO:0000269|PubMed:1677358"
FT /id="VAR_000631"
FT VARIANT 187
FT /note="K -> E (in allele APOA-IV*0A; associated with H-380;
FT dbSNP:rs773492545)"
FT /evidence="ECO:0000269|PubMed:1677358"
FT /id="VAR_000632"
FT VARIANT 250
FT /note="E -> K (in allele APOA-IV*3A; dbSNP:rs121909576)"
FT /evidence="ECO:0000269|PubMed:1973689"
FT /id="VAR_000633"
FT VARIANT 264
FT /note="R -> Q (in Seattle-2; may contribute to the
FT development of familial combined hyperlipidemia;
FT dbSNP:rs2238008)"
FT /evidence="ECO:0000269|PubMed:8956036"
FT /id="VAR_000634"
FT VARIANT 279
FT /note="R -> K (in dbSNP:rs1042372)"
FT /evidence="ECO:0000269|PubMed:3095836,
FT ECO:0000269|PubMed:3755616"
FT /id="VAR_025443"
FT VARIANT 305
FT /note="R -> C (in Budapest-1; dbSNP:rs150264487)"
FT /evidence="ECO:0000269|PubMed:7728150"
FT /id="VAR_000635"
FT VARIANT 307
FT /note="V -> L (in dbSNP:rs5108)"
FT /id="VAR_014611"
FT VARIANT 367
FT /note="T -> S (in allele APOA-IV*1A and allele Budapest-1;
FT dbSNP:rs675)"
FT /evidence="ECO:0000269|PubMed:15108119,
FT ECO:0000269|PubMed:1677358, ECO:0000269|PubMed:7728150"
FT /id="VAR_000636"
FT VARIANT 380
FT /note="Q -> H (in allele APOA-IV*2 and allele APOA-IV*0A;
FT associated with E-187 in allele APOA-IV*0A; dbSNP:rs5110)"
FT /evidence="ECO:0000269|PubMed:10391210,
FT ECO:0000269|PubMed:15108119, ECO:0000269|PubMed:1677358,
FT ECO:0000269|PubMed:2065039, ECO:0000269|PubMed:2351649,
FT ECO:0000269|PubMed:3036793, ECO:0000269|PubMed:3080432"
FT /id="VAR_000637"
FT VARIANT 381
FT /note="Q -> QEQQQ (in allele APOA-IV*0 and allele APOA-
FT IV*5; allele APOA-IV*5 is further defined by a silent
FT nucleotide substitution)"
FT /evidence="ECO:0000269|PubMed:1487136"
FT /id="VAR_000638"
FT CONFLICT 158..160
FT /note="TPY -> DPL (in Ref. 1; AAA51744 and 2; AAA51745)"
FT /evidence="ECO:0000305"
FT CONFLICT 327
FT /note="Q -> T (in Ref. 3; AAA96731 and 8; AAA51748)"
FT /evidence="ECO:0000305"
FT HELIX 97..113
FT /evidence="ECO:0007829|PDB:3S84"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:3S84"
FT HELIX 117..223
FT /evidence="ECO:0007829|PDB:3S84"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:3S84"
FT HELIX 231..276
FT /evidence="ECO:0007829|PDB:3S84"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:3S84"
FT HELIX 282..307
FT /evidence="ECO:0007829|PDB:3S84"
FT HELIX 310..329
FT /evidence="ECO:0007829|PDB:3S84"
SQ SEQUENCE 396 AA; 45372 MW; 19307A196CAE0A4A CRC64;
MFLKAVVLTL ALVAVAGARA EVSADQVATV MWDYFSQLSN NAKEAVEHLQ KSELTQQLNA
LFQDKLGEVN TYAGDLQKKL VPFATELHER LAKDSEKLKE EIGKELEELR ARLLPHANEV
SQKIGDNLRE LQQRLEPYAD QLRTQVSTQA 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
