P06727 (APOA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Apolipoprotein A-IV
Short name=Apo-AIV
Short name=ApoA-IV

Alternative name(s):
Apolipoprotein A4

Gene names

Name:

APOA4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	396 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subcellular location	Secreted.
Tissue specificity	Synthesized primarily in the intestine and secreted in plasma. Ref.11
Domain	Nine of the thirteen 22-amino acid tandem repeats (each 22-mer is actually a tandem array of two, A and B, related 11-mers) occurring in this sequence are predicted to be highly alpha-helical, and many of these helices are amphipathic. They may therefore serve as lipid-binding domains with lecithin:cholesterol acyltransferase (LCAT) activating abilities.
Post-translational modification	Phosphorylation sites are present in the extracelllular medium.
Polymorphism	Eight alleles have been characterized (APOA-IV*0 to APOA-IV*7). APOA-IV*1 is the major allele (90%), APOA-IV*2 is also common (8%), the others are rare alleles. The sequence shown represents allele APOA-IV*1.
Sequence similarities	Belongs to the apolipoprotein A1/A4/E family.

Ontologies

Keywords
Biological process	Lipid transport Transport
Cellular component	Chylomicron HDL Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat Signal
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cholesterol efflux Inferred from direct assay. Source: BHF-UCL cholesterol homeostasis Inferred from direct assay. Source: BHF-UCL cholesterol metabolic process Inferred from direct assay. Source: BHF-UCL chylomicron assembly Traceable author statement. Source: BHF-UCL chylomicron remodeling Inferred by curator. Source: BHF-UCL high-density lipoprotein particle remodeling Inferred by curator. Source: BHF-UCL hydrogen peroxide catabolic process Inferred from direct assay. Source: HGNC innate immune response in mucosa Inferred from direct assay. Source: BHF-UCL leukocyte cell-cell adhesion Inferred from direct assay. Source: BHF-UCL lipoprotein metabolic process Traceable author statement. Source: Reactome multicellular organismal lipid catabolic process Inferred from direct assay. Source: BHF-UCL negative regulation of plasma lipoprotein particle oxidation Inferred from direct assay. Source: BHF-UCL phosphatidylcholine metabolic process Inferred from direct assay. Source: BHF-UCL phospholipid efflux Inferred from direct assay. Source: BHF-UCL positive regulation of cholesterol esterification Inferred from direct assay. Source: BHF-UCL positive regulation of fatty acid biosynthetic process Inferred from direct assay. Source: BHF-UCL positive regulation of lipoprotein lipase activity Inferred from direct assay. Source: BHF-UCL positive regulation of triglyceride catabolic process Inferred from direct assay. Source: BHF-UCL removal of superoxide radicals Inferred from direct assay. Source: HGNC response to lipid hydroperoxide Inferred from direct assay. Source: HGNC reverse cholesterol transport Inferred from direct assay. Source: BHF-UCL very-low-density lipoprotein particle remodeling Inferred from direct assay. Source: BHF-UCL
Cellular component	centrosome Inferred from direct assay. Source: HPA chylomicron Inferred from direct assay. Source: BHF-UCL endoplasmic reticulum lumen Traceable author statement. Source: Reactome high-density lipoprotein particle Inferred from direct assay. Source: BHF-UCL very-low-density lipoprotein particle Inferred from direct assay. Source: BHF-UCL
Molecular function	antioxidant activity Inferred from direct assay. Source: HGNC cholesterol transporter activity Inferred from direct assay. Source: BHF-UCL copper ion binding Inferred from direct assay. Source: HGNC phosphatidylcholine binding Inferred from direct assay. Source: BHF-UCL phosphatidylcholine-sterol O-acyltransferase activator activity Inferred from direct assay. Source: BHF-UCL protein homodimerization activity Inferred from direct assay. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20
	Chain	21 – 396	376	Apolipoprotein A-IV		PRO_0000001975
Regions
	Repeat	33 – 54	22	1
	Repeat	60 – 81	22	2
	Repeat	82 – 103	22	3
	Repeat	115 – 136	22	4
	Repeat	137 – 158	22	5
	Repeat	159 – 180	22	6
	Repeat	181 – 202	22	7
	Repeat	203 – 224	22	8
	Repeat	225 – 246	22	9
	Repeat	247 – 268	22	10
	Repeat	269 – 286	18	11
	Repeat	287 – 308	22	12
	Repeat	309 – 330	22	13
	Region	33 – 330	298	13 X 22 AA approximate tandem repeats
	Compositional bias	372 – 389	18	Gln/Glu-rich
Amino acid modifications
	Modified residue	259	1	Phosphoserine Ref.11
Natural variations
	Natural variant	13	1	V → M in allele APOA-IV*1D. Ref.5 Ref.17		VAR_000626
	Natural variant	44	1	E → K in Budapest-2. Ref.20		VAR_000627
	Natural variant	74	1	G → S. Corresponds to variant rs5102 [ dbSNP | Ensembl ].		VAR_014610
	Natural variant	77	1	Q → H. Ref.5		VAR_025444
	Natural variant	147	1	N → S in allele APOA-IV*1B. Ref.5 Ref.6 Ref.18 Corresponds to variant rs5104 [ dbSNP | Ensembl ].		VAR_000628
	Natural variant	161	1	A → S in Seattle-3. Ref.5 Ref.21		VAR_000629
	Natural variant	178	1	S → L in Seattle-1; may contribute to the development of familial combined hyperlipidemia. Ref.21		VAR_000630
	Natural variant	185	1	E → K in allele APOA-IV*3. Ref.15		VAR_000631
	Natural variant	187	1	K → E in allele APOA-IV*0A; associated with H-380. Ref.15		VAR_000632
	Natural variant	250	1	E → K in allele APOA-IV*3A. Ref.13		VAR_000633
	Natural variant	264	1	R → Q in Seattle-2; may contribute to the development of familial combined hyperlipidemia. Ref.21 Corresponds to variant rs2238008 [ dbSNP | Ensembl ].		VAR_000634
	Natural variant	279	1	R → K. Ref.1 Ref.2 Corresponds to variant rs1042372 [ dbSNP | Ensembl ].		VAR_025443
	Natural variant	305	1	R → C in Budapest-1. Ref.20		VAR_000635
	Natural variant	307	1	V → L. Corresponds to variant rs5108 [ dbSNP | Ensembl ].		VAR_014611
	Natural variant	367	1	T → S in allele APOA-IV*1A and allele Budapest-1. Ref.5 Ref.15 Ref.20 Corresponds to variant rs675 [ dbSNP | Ensembl ].		VAR_000636
	Natural variant	380	1	Q → H in allele APOA-IV*2 and allele APOA-IV*0A; associated with E-187 in allele APOA-IV*0A. Ref.3 Ref.5 Ref.8 Ref.12 Ref.14 Ref.15 Ref.22 Corresponds to variant rs5110 [ dbSNP | Ensembl ].		VAR_000637
	Natural variant	381	1	Q → QEQQQ in allele APOA-IV*0 and allele APOA-IV*5; allele APOA-IV*5 is further defined by a silent nucleotide substitution.		VAR_000638
Experimental info
	Sequence conflict	158 – 160	3	TPY → DPL in AAA51744. Ref.1
	Sequence conflict	158 – 160	3	TPY → DPL in AAA51745. Ref.2
	Sequence conflict	327	1	Q → T in AAA96731. Ref.3
	Sequence conflict	327	1	Q → T in AAA51748. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	P06727 [UniParc]. Last modified March 7, 2006. Version 3. Checksum: 193753196CA2FA4A	FASTA	396	45,399
	10 20 30 40 50 60 MFLKAVVLTL ALVAVAGARA EVSADQVATV MWDYFSQLSN NAKEAVEHLQ KSELTQQLNA 70 80 90 100 110 120 LFQDKLGEVN TYAGDLQKKL VPFATELHER LAKDSEKLKE EIGKELEELR ARLLPHANEV 130 140 150 160 170 180 SQKIGDNLRE LQQRLEPYAD QLRTQVNTQA EQLRRQLTPY AQRMERVLRE NADSLQASLR 190 200 210 220 230 240 PHADELKAKI DQNVEELKGR LTPYADEFKV KIDQTVEELR RSLAPYAQDT QEKLNHQLEG 250 260 270 280 290 300 LTFQMKKNAE ELKARISASA EELRQRLAPL AEDVRGNLRG NTEGLQKSLA ELGGHLDQQV 310 320 330 340 350 360 EEFRRRVEPY GENFNKALVQ QMEQLRQKLG PHAGDVEGHL SFLEKDLRDK VNSFFSTFKE 370 380 390 KESQDKTLSL PELEQQQEQQ QEQQQEQVQM LAPLES

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure, evolution, and tissue-specific synthesis of human apolipoprotein AIV." Karathanasis S.K., Yunis I. Biochemistry 25:3962-3970(1986) [PubMed: 3755616] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LYS-279.
[2]	"Structure, evolution, and polymorphisms of the human apolipoprotein A4 gene (APOA4)." Karathanasis S.K., Oettgen P., Haddad I.A., Antonarakis S.E. Proc. Natl. Acad. Sci. U.S.A. 83:8457-8461(1986) [PubMed: 3095836] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-279.
[3]	"Structure and expression of the human apolipoprotein A-IV gene." Elshourbagy N.A., Walker D.W., Paik Y.K., Boguski M.S., Freeman M., Gordon J.I., Taylor J.M. J. Biol. Chem. 262:7973-7981(1987) [PubMed: 3036793] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT APOA-IV*2 HIS-380.
[4]	"The primary structure of human apolipoprotein A-IV." Yang C., Gu Z.W., Xiong W., Rosseneu M., Yang H.X., Lee B.M., Gotto A.M. Jr., Chan L. Biochim. Biophys. Acta 1002:231-237(1989) [PubMed: 2930771] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Intestine.
[5]	"The effects of scale: variation in the APOA1/C3/A4/A5 gene cluster." Fullerton S.M., Buchanan A.V., Sonpar V.A., Taylor S.L., Smith J.D., Carlson C.S., Salomaa V., Stengaard J.H., Boerwinkle E., Clark A.G., Nickerson D.A., Weiss K.M. Hum. Genet. 115:36-56(2004) [PubMed: 15108119] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MET-13; HIS-77; SER-147; SER-161; SER-367 AND HIS-380.
[6]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed: 16554811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT SER-147.
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Colon.
[8]	"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." Elshourbagy N.A., Walker D.W., Boguski M.S., Gordon J.I., Taylor J.M. J. Biol. Chem. 261:1998-2002(1986) [PubMed: 3080432] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 21-396, VARIANT APOA-IV*2 HIS-380.
[9]	"Biosynthesis of human preapolipoprotein A-IV." Gordon J.I., Bisgaier C.L., Sims H.F., Sachdev O.P., Glickman R.M., Strauss A.W. J. Biol. Chem. 259:468-474(1984) [PubMed: 6706947] [Abstract] Cited for: SIGNAL SEQUENCE CLEAVAGE SITE.
[10]	"Genetic polymorphism of apolipoprotein A-IV." Lohse P., Brewer H.B. Jr. Curr. Opin. Lipidol. 2:90-95(1991) Cited for: REVIEW ON POLYMORPHISM.
[11]	"An initial characterization of the serum phosphoproteome." Zhou W., Ross M.M., Tessitore A., Ornstein D., Vanmeter A., Liotta L.A., Petricoin E.F. III J. Proteome Res. 8:5523-5531(2009) [PubMed: 19824718] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259, TISSUE SPECIFICITY, MASS SPECTROMETRY. Tissue: Serum.
[12]	"Genetic polymorphism of human plasma apolipoprotein A-IV is due to nucleotide substitutions in the apolipoprotein A-IV gene." Lohse P., Kindt M.R., Rader D.J., Brewer H.B. Jr. J. Biol. Chem. 265:10061-10064(1990) [PubMed: 2351649] [Abstract] Cited for: ALLELES APOA-IV*1 AND APOA-IV*2, VARIANT HIS-380.
[13]	"Human plasma apolipoproteins A-IV-0 and A-IV-3. Molecular basis for two rare variants of apolipoprotein A-IV-1." Lohse P., Kindt M.R., Rader D.J., Brewer H.B. Jr. J. Biol. Chem. 265:12734-12739(1990) [PubMed: 1973689] [Abstract] Cited for: ALLELES A-IV*0 AND A-IV*3, VARIANTS LYS-250 AND GLU-GLN-GLN-GLN-381 INS.
[14]	"The mutation causing the common apolipoprotein A-IV polymorphism is a glutamine to histidine substitution of amino acid 360." Tenkanen H., Lukka M., Jauhiainen M., Metso J., Baumann M., Peltonen L., Ehnholm C. Arterioscler. Thromb. 11:851-856(1991) [PubMed: 2065039] [Abstract] Cited for: VARIANT HIS-380.
[15]	"Three genetic variants of human plasma apolipoprotein A-IV: apoA-IV-1(Thr-347-->Ser), apoA-IV-0(Lys-167-->Glu,Gln-360-->His), and apoA-IV-3(Glu-165-->Lys)." Lohse P., Kindt M.R., Rader D.J., Brewer H.B. Jr. J. Biol. Chem. 266:13513-13518(1991) [PubMed: 1677358] [Abstract] Cited for: ALLELES A-IV*0; A-IV*1; A-IV*2 AND A-IV*3, VARIANTS LYS-185; GLU-187; SER-367 AND HIS-380.
[16]	Erratum Lohse P., Kindt M.R., Rader D.J., Brewer H.B. Jr. J. Biol. Chem. 266:19866-19866(1991)
[17]	"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." von Eckardstein A., Funke H., Schulte M., Erren M., Schulte H., Assmann G. Am. J. Hum. Genet. 50:1115-1128(1992) [PubMed: 1349197] [Abstract] Cited for: VARIANT MET-13.
[18]	"A novel polymorphism of apolipoprotein A-IV is the result of an asparagine to serine substitution at residue 127." Tenkanen H., Koskinen P., Metso J., Baumann M., Lukka M., Kauppinen-Makelin R., Kontula K., Taskinen M.R., Manttari M., Manninen V., Ehnholm C. Biochim. Biophys. Acta 1138:27-33(1992) [PubMed: 1737067] [Abstract] Cited for: VARIANT SER-147.
[19]	"Molecular basis of a unique African variant (A-IV 5) of human apolipoprotein A-IV and its significance in lipid metabolism." Kamboh M.I., Williams E.R., Law J.C., Aston C.E., Bunker C.H., Ferrell R.E., Pollitzer W.S. Genet. Epidemiol. 9:379-388(1992) [PubMed: 1487136] [Abstract] Cited for: ALLELE A-IV*5, VARIANT GLU-GLN-GLN-GLN-381 INS.
[20]	"Apolipoprotein A-IV polymorphism in the Hungarian population: gene frequencies, effect on lipid levels, and sequence of two new variants." Menzel H.J., Dieplinger H., Sandholzer C., Karadi I., Utermann G., Csaszar A. Hum. Mutat. 5:58-65(1995) [PubMed: 7728150] [Abstract] Cited for: VARIANTS BUDAPEST-2 LYS-44; BUDAPEST-1 CYS-305 AND SER-367.
[21]	"Two novel apolipoprotein A-IV variants in individuals with familial combined hyperlipidemia and diminished levels of lipoprotein lipase activity." Deeb S.S., Nevin D.N., Iwasaki L., Brunzell J.D. Hum. Mutat. 8:319-325(1996) [PubMed: 8956036] [Abstract] Cited for: VARIANTS SEATTLE-3 SER-161; SEATTLE-1 LEU-178 AND SEATTLE-2 GLN-264.
[22]	"Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis." Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A. Nat. Genet. 22:239-247(1999) [PubMed: 10391210] [Abstract] Cited for: VARIANT HIS-380.
+	Additional computationally mapped references.

Web resources

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases
EMBL GenBank DDBJ	M13654 mRNA. Translation: AAA51744.1. M14642 Genomic DNA. Translation: AAA51745.1. J02758 Genomic DNA. Translation: AAA96731.1. X13629 mRNA. Translation: CAA31955.1. AY422950 Genomic DNA. Translation: AAQ91809.1. AY555191 Genomic DNA. Translation: AAS68228.1. AP006216 Genomic DNA. No translation available. BC074764 mRNA. Translation: AAH74764.1. BC113594 mRNA. Translation: AAI13595.1. BC113596 mRNA. Translation: AAI13597.1. M14566 mRNA. Translation: AAA51748.1.
IPI	IPI00304273.
PIR	LPHUA4. A94137.
UniGene	Hs.1247.
3D structure databases
ProteinModelPortal	P06727.
SMR	P06727. Positions 19-297.
ModBase	Search...
Protein-protein interaction databases
IntAct	P06727. 1 interaction.
STRING	P06727.
PTM databases
PhosphoSite	P06727.
Polymorphism databases
DMDM	93163358.
2D gel databases
SWISS-2DPAGE	P06727.
DOSAC-COBS-2DPAGE	P06727.
REPRODUCTION-2DPAGE	IPI00304273.
Proteomic databases
PeptideAtlas	P06727.
PRIDE	P06727.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000357780; ENSP00000350425; ENSG00000110244.
UCSC	uc003bnx.1. human.
Organism-specific databases
GeneCards	GC11M116692.
HGNC	HGNC:602. APOA4.
HPA	HPA001352. HPA002549.
MIM	107690. gene.
neXtProt	NX_P06727.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18920.
HOGENOM	HBG268609.
HOVERGEN	HBG105707.
InParanoid	P06727.
OrthoDB	EOG4G1MHJ.
PhylomeDB	P06727.
Enzyme and pathway databases
Reactome	REACT_22258. Metabolism of lipids and lipoproteins. REACT_75925. Amyloids.
Gene expression databases
ArrayExpress	P06727.
Bgee	P06727.
CleanEx	HS_APOA4.
Genevestigator	P06727.
GermOnline	ENSG00000110244. Homo sapiens.
Family and domain databases
InterPro	IPR013326. ApoA/E_ApoLp. IPR000074. ApoA1_A4_E. [Graphical view]
Gene3D	G3DSA:1.20.120.20. ApoA/E_ApoLp. 3 hits.
Pfam	PF01442. Apolipoprotein. 2 hits. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

APOA4_HUMAN

Accession

Primary (citable) accession number: P06727
Secondary accession number(s): A8MSL6, Q14CW8, Q6Q787

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	March 7, 2006
Last modified:	January 25, 2012
This is version 140 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.