APOA4

Apolipoprotein A-IV
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3S84
Identifiers
Symbols	APOA4; MGC142154; MGC142156
External IDs	OMIM: 107690 MGI: 88051 HomoloGene: 47927 GeneCards: APOA4 Gene
Gene Ontology Molecular function • lipid transporter activity • copper ion binding • lipid binding • antioxidant activity • cholesterol transporter activity • phosphatidylcholine binding • protein homodimerization activity • eukaryotic cell surface binding • phosphatidylcholine-sterol O-acyltransferase activator activity Cellular component • extracellular region • extracellular space • early endosome • endoplasmic reticulum lumen • cytosol • cell surface • very-low-density lipoprotein particle • high-density lipoprotein particle • chylomicron Biological process • retinoid metabolic process • innate immune response in mucosa • lipid metabolic process • lipid transport • response to lipid hydroperoxide • leukocyte cell-cell adhesion • phototransduction, visible light • cholesterol metabolic process • positive regulation of cholesterol esterification • positive regulation of triglyceride catabolic process • removal of superoxide radicals • regulation of intestinal cholesterol absorption • regulation of cholesterol transport • cholesterol efflux • phospholipid efflux • chylomicron remodeling • very-low-density lipoprotein particle remodeling • high-density lipoprotein particle remodeling • chylomicron assembly • negative regulation of plasma lipoprotein particle oxidation • response to stilbenoid • lipoprotein metabolic process • cholesterol homeostasis • hydrogen peroxide catabolic process • reverse cholesterol transport • multicellular organismal lipid catabolic process • small molecule metabolic process • positive regulation of fatty acid biosynthetic process • phosphatidylcholine metabolic process • positive regulation of lipoprotein lipase activity • lipid homeostasis • protein-lipid complex assembly Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	337	11808
Ensembl	ENSG00000110244	ENSMUSG00000032080
UniProt	P06727	P06728
RefSeq (mRNA)	NM_000482	NM_007468
RefSeq (protein)	NP_000473	NP_031494
Location (UCSC)	Chr 11: 116.69 – 116.69 Mb	Chr 9: 46.24 – 46.24 Mb
PubMed search	[1]	[2]

Apolipoprotein A-IV (also known as apoA-IV, apoAIV, or apoA4) is plasma protein that is the product of the human gene APOA4.

Gene

APOA4 resides on chromosome 11 in close linkage to APOA1 and APOC3. APOA4 contains 3 exons separated by two introns, and is polymorphic, although most of the reported sequence polymorphisms occur in exon 3. The best validated and studied non-synonymous SNPs are a glutamine → histidine substitution at codon 360 and a threonine → serine substitution at codon 347; a sequence polymorphism has also been identified in the 3'UTR of the third exon. Intra-species comparative gene sequence analysis suggests that the APOA4 gene arose from APOA1 by gene duplication approximately 270 MYA.

Function

The primary translation product of the APOA4 gene is a 396-residue preprotein, which undergoes proteolytic processing to yield apo A-IV, a 376-reside mature O-linked glycoprotein. In most mammals, including humans, apo A-IV synthesis is confined to the intestine; however in mice and rats hepatic synthesis also occurs. Apo A-IV is secreted into circulation on the surface of newly synthesized chylomicron particles. Intestinal fat absorption dramatically increases the synthesis and secretion of apo A-IV. Although its primary function in human lipid metabolism has not been established, apo A-IV has been found to: 1) activate lecithin-cholesterol acyltransferase and cholesterylester transfer protein in vitro; 2) play a role in the regulation of appetite and satiety in rodent models; 3) display anti-oxidant and anti-atherogenic properties in vitro and in rodent models; 4) modulate the efficiency of enterocyte and hepatic transcellular lipid transport in vitro. Human apo A-IV deficiency has not been reported.

Interactions

APOA4 has been shown to interact with GPLD1.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.

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Statin Pathway edit

Further reading

• von Eckardstein A, Funke H, Schulte M, et al. (1992). "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 (5): 1115–28. PMC 1682587. PMID 1349197. 
• Kamboh MI, Williams ER, Law JC, et al. (1993). "Molecular basis of a unique African variant (A-IV 5) of human apolipoprotein A-IV and its significance in lipid metabolism.". Genet. Epidemiol. 9 (6): 379–88. doi:10.1002/gepi.1370090602. PMID 1487136. 
• Lohse P, Kindt MR, Rader DJ, Brewer HB (1991). "Three genetic variants of human plasma apolipoprotein A-IV. apoA-IV-1(Thr347----Ser), apoA-IV-0(Lys167----Glu,Gln360----His), and apoA-IV-3(Glu165----Lys).". J. Biol. Chem. 266 (21): 13513–8. PMID 1677358. 
• Tenkanen H, Koskinen P, Metso J, et al. (1992). "A novel polymorphism of apolipoprotein A-IV is the result of an asparagine to serine substitution at residue 127.". Biochim. Biophys. Acta 1138 (1): 27–33. PMID 1737067. 
• Lohse P, Kindt MR, Rader DJ, Brewer HB (1990). "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 (21): 12734–9. PMID 1973689. 
• Tenkanen H, Lukka M, Jauhiainen M, et al. (1991). "The mutation causing the common apolipoprotein A-IV polymorphism is a glutamine to histidine substitution of amino acid 360.". Arterioscler. Thromb. 11 (4): 851–6. PMID 2065039. 
• de Temmerman P, Visvikis S, Boerwinkle E, Siest G (1990). "Study of the sequence tagged site (STS) in the beginning of human apo A4 gene region.". Nucleic Acids Res. 18 (18): 5576. doi:10.1093/nar/18.18.5576. PMC 332267. PMID 2216752. 
• Wei S, Rocchi M, Archidiacono N, et al. (1990). "Physical mapping of the human chromosome 11q23 region containing the ataxia-telangiectasia locus.". Cancer Genet. Cytogenet. 46 (1): 1–8. doi:10.1016/0165-4608(90)90002-R. PMID 2331673. 
• Lohse P, Kindt MR, Rader DJ, Brewer HB (1990). "Genetic polymorphism of human plasma apolipoprotein A-IV is due to nucleotide substitutions in the apolipoprotein A-IV gene.". J. Biol. Chem. 265 (17): 10061–4. PMID 2351649. 
• Yang CY, Gu ZW, Chong IS, et al. (1989). "The primary structure of human apolipoprotein A-IV.". Biochim. Biophys. Acta 1002 (2): 231–7. PMID 2930771. 
• Elshourbagy NA, Walker DW, Boguski MS, et al. (1986). "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 (5): 1998–2002. PMID 3080432. 
• Bisgaier CL, Sachdev OP, Lee ES, et al. (1987). "Effect of lecithin:cholesterol acyltransferase on distribution of apolipoprotein A-IV among lipoproteins of human plasma.". J. Lipid Res. 28 (6): 693–703. PMID 3611972. 
• Karathanasis SK, Yunis I, Zannis VI (1986). "Structure, evolution, and tissue-specific synthesis of human apolipoprotein AIV.". Biochemistry 25 (13): 3962–70. doi:10.1021/bi00361a034. PMID 3755616. 
• Karathanasis SK (1985). "Apolipoprotein multigene family: tandem organization of human apolipoprotein AI, CIII, and AIV genes.". Proc. Natl. Acad. Sci. U.S.A. 82 (19): 6374–8. doi:10.1073/pnas.82.19.6374. PMC 390718. PMID 3931073. 
• Gordon JI, Bisgaier CL, Sims HF, et al. (1984). "Biosynthesis of human preapolipoprotein A-IV.". J. Biol. Chem. 259 (1): 468–74. PMID 6706947. 
• Menzel HJ, Dieplinger H, Sandholzer C, et al. (1995). "Apolipoprotein A-IV polymorphism in the Hungarian population: gene frequencies, effect on lipid levels, and sequence of two new variants.". Hum. Mutat. 5 (1): 58–65. doi:10.1002/humu.1380050108. PMID 7728150. 
• Duverger N, Tremp G, Caillaud JM, et al. (1996). "Protection against atherogenesis in mice mediated by human apolipoprotein A-IV.". Science 273 (5277): 966–8. doi:10.1126/science.273.5277.966. PMID 8688083. 
• Deeb SS, Nevin DN, Iwasaki L, Brunzell JD (1997). "Two novel apolipoprotein A-IV variants in individuals with familial combined hyperlipidemia and diminished levels of lipoprotein lipase activity.". Hum. Mutat. 8 (4): 319–25. doi:10.1002/(SICI)1098-1004(1996)8:4<319::AID-HUMU4>3.0.CO;2-2. PMID 8956036. 

External links

• Apolipoprotein A-IV at the US National Library of Medicine Medical Subject Headings (MeSH)