May have a role in chylomicrons and VLDL secretion and catabolism. Required for efficient activation of lipoprotein lipase by ApoC-II; potent activator of LCAT. Apoa-IV is a major component of HDL and chylomicrons. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

Publication	Identification ¹	Uniprot mapping ²	Not mapped / Obsolete	TrEMBL	Swiss-Prot
Goodman (2013)	2289 (gene list)	2278	53	20599	2269
Lange (2014)	1234	1234	7	28	1224
Hegedus (2015)	2638	2622	0	235	2387
Wilson (2016)	1658	1528	170	291	1068
d'Alessandro (2017)	1826	1817	2	0	1815
Bryk (2017)	2090	2060	10	108	1942
Chu (2018)	1853	1804	55	362	1387

¹ as available in the article and/or in supplementary material
² uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Protein sequence (FASTA)

Protein coevolution profile (FreeContact)

Multiple Sequence Alignment (Muscle)

Total structural coverage: 69%

Model score: 30

(right-click above to access to more options from the contextual menu)

Variant	Description
	allele APOA-IV*1D
	Budapest-2
	dbSNP:rs5102
	dbSNP:rs12721042
	dbSNP:rs5104
	Seattle-3
	Seattle-1
	allele APOA-IV*3
	allele APOA-IV*0A
	allele APOA-IV*3A
	Seattle-2
	dbSNP:rs1042372
	Budapest-1
	dbSNP:rs5108
	allele APOA-IV*1A and allele Budapest-1
	allele APOA-IV2 and allele APOA-IV0A

No binding partner found

Biological Process

Amyloid fibril formation

Cellular protein metabolic process

Cholesterol biosynthetic process

Cholesterol efflux

Cholesterol homeostasis

Cholesterol metabolic process

Chylomicron assembly

Chylomicron remodeling

High-density lipoprotein particle assembly

High-density lipoprotein particle remodeling

Hydrogen peroxide catabolic process

Innate immune response in mucosa

Leukocyte cell-cell adhesion

Lipid catabolic process

Lipid homeostasis

Lipid transport

Lipoprotein metabolic process

Multicellular organismal lipid catabolic process

Negative regulation of plasma lipoprotein oxidation

Neuron projection regeneration

Phosphatidylcholine metabolic process

Phospholipid efflux

Phototransduction, visible light

Positive regulation of cholesterol esterification

Positive regulation of fatty acid biosynthetic process

Positive regulation of lipid biosynthetic process

Positive regulation of lipoprotein lipase activity

Positive regulation of triglyceride catabolic process

Protein-lipid complex assembly

Regulation of cholesterol transport

Regulation of intestinal cholesterol absorption

Removal of superoxide radicals

Response to lipid hydroperoxide

Response to stilbenoid

Retinoid metabolic process

Reverse cholesterol transport

Small molecule metabolic process

Triglyceride catabolic process

Triglyceride homeostasis

Very-low-density lipoprotein particle remodeling

Cellular Component

Blood microparticle

Chylomicron

Collagen-containing extracellular matrix

Cytosol

Early endosome

Endoplasmic reticulum lumen

Extracellular exosome

Extracellular matrix

Extracellular region

Extracellular space

High-density lipoprotein particle

Very-low-density lipoprotein particle

Molecular Function

Antioxidant activity

Cholesterol binding

Cholesterol transfer activity

Cholesterol transporter activity

Copper ion binding

Identical protein binding

Lipid binding

Lipid transporter activity

Phosphatidylcholine binding

Phosphatidylcholine-sterol O-acyltransferase activator activity

Phospholipid binding

Protein homodimerization activity

The reference OMIM entry for this protein is 107690

Apolipoprotein a-iv; apoa4

CLONING

Apolipoprotein A-IV is a component of chylomicrons and high-density lipoproteins. 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 ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 107690 was added.

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed

Apolipoprotein A-IV (APOA4)