Q6Q788 (APOA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Apolipoprotein A-V
Short name=Apo-AV
Short name=ApoA-V

Alternative name(s):
Apolipoprotein A5
Regeneration-associated protein 3

Gene names

Name:	APOA5
Synonyms:	RAP3
ORF Names:	UNQ411/PRO773

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	366 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	Minor apolipoprotein mainly associated with HDL and to a lesser extent with VLDL. May also be associated with chylomicrons. Important determinant of plasma triglyceride (TG) levels by both being a potent stimulator of apo-CII lipoprotein lipase (LPL) TG hydrolysis and a inhibitor of the hepatic VLDL-TG production rate (without affecting the VLDL-apoB production rate) By similarity. Activates poorly lecithin:cholesterol acyltransferase (LCAT) and does not enhance efflux of cholesterol from macrophages. Ref.6 Ref.7 Ref.10
Subunit structure	Interacts with GPIHBP1. Ref.11
Subcellular location	Secreted Ref.9.
Tissue specificity	Liver and plasma. Ref.1 Ref.6 Ref.10
Induction	Up-regulated by PPARA agonists, which are used clinically to lower serum TG (such as fibrates). Ref.8
Post-translational modification	Phosphorylation sites are present in the extracellular medium.
Polymorphism	Three common alleles are known: allele APOA5*1, APOA5*2 and APOA5*3. The APOA5*2 haplotype, which consists of 3 non-coding SNPs, is present in approximately 16% of Caucasians and is associated with increased plasma triglyceride concentrations. APOA5*3 haplotype is defined by the rare Ser-19-Trp substitution. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25 to 50% of African Americans, Hispanics, and Caucasians.
Involvement in disease	Hypertriglyceridemia, familial (FHTR) [MIM:145750]: A common inherited disorder in which the concentration of very low density lipoprotein (VLDL) is elevated in the plasma. This leads to increased risk of heart disease, obesity, and pancreatitis. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Hyperlipoproteinemia 5 (HLPP5) [MIM:144650]: Characterized by increased amounts of chylomicrons and very low density lipoprotein (VLDL) and decreased low density lipoprotein (LDL) and high density lipoprotein (HDL) in the plasma after a fast. Numerous conditions cause this phenotype, including insulin-dependent diabetes mellitus, contraceptive steroids, alcohol abuse, and glycogen storage disease type 1A (GSD1A). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15
Miscellaneous	Induced in early phase of liver regeneration.
Sequence similarities	Belongs to the apolipoprotein A1/A4/E family.
Caution	It is uncertain whether Met-1 or Met-4 is the initiator.
Sequence caution	The sequence AAF25661.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF25662.1 differs from that shown. Reason: Erroneous initiation. The sequence AAQ89109.1 differs from that shown. Reason: Erroneous termination at position 275. Translated as Gln.

Ontologies

Keywords
Biological process	Lipid transport Transport
Cellular component	Chylomicron HDL Secreted VLDL
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Coiled coil Signal
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol homeostasis Inferred from direct assay PubMed 19121291. Source: BHF-UCL lipid transport Inferred from direct assay PubMed 15178420. Source: BHF-UCL lipoprotein metabolic process Inferred from electronic annotation. Source: InterPro organ regeneration Inferred from electronic annotation. Source: Compara positive regulation of fatty acid biosynthetic process Inferred from direct assay PubMed 18635818. Source: BHF-UCL positive regulation of lipoprotein lipase activity Inferred from direct assay PubMed 15178420PubMed 16806135PubMed 18635818. Source: BHF-UCL positive regulation of receptor-mediated endocytosis Traceable author statement PubMed 18635818. Source: BHF-UCL positive regulation of triglyceride catabolic process Inferred from direct assay PubMed 18635818. Source: BHF-UCL positive regulation of very-low-density lipoprotein particle remodeling Inferred from direct assay PubMed 18635818. Source: BHF-UCL response to hormone stimulus Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome tissue regeneration Inferred from expression pattern Ref.1. Source: UniProtKB triglyceride catabolic process Inferred from mutant phenotype PubMed 15178420. Source: BHF-UCL triglyceride homeostasis Inferred from direct assay PubMed 19121291. Source: BHF-UCL triglyceride-rich lipoprotein particle remodeling Inferred from electronic annotation. Source: Compara
Cellular_component	chylomicron Inferred from direct assay Ref.10. Source: UniProtKB high-density lipoprotein particle Inferred from direct assay Ref.10. Source: BHF-UCL very-low-density lipoprotein particle Inferred from direct assay Ref.10. Source: BHF-UCL
Molecular_function	enzyme binding Inferred from direct assay PubMed 15178420. Source: BHF-UCL heparin binding Inferred from direct assay PubMed 15878877. Source: BHF-UCL lipoprotein lipase activator activity Inferred from direct assay PubMed 18635818. Source: BHF-UCL phosphatidylcholine binding Inferred from direct assay PubMed 16806135. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 366	343	Apolipoprotein A-V		PRO_0000001981
Regions
	Coiled coil	54 – 157	104	Potential
	Coiled coil	236 – 262	27	Potential
Natural variations
	Natural variant	19	1	S → W in allele APOA5*3; associated with high plasma triglyceride levels. Ref.2 Ref.12 Ref.13 Corresponds to variant rs3135506 [ dbSNP | Ensembl ].		VAR_021165
	Natural variant	37	1	D → E. Corresponds to variant rs34282181 [ dbSNP | Ensembl ].		VAR_035124
	Natural variant	153	1	V → M. Ref.2 Corresponds to variant rs3135507 [ dbSNP | Ensembl ].		VAR_021166
	Natural variant	185	1	G → C Associated with high plasma triglyceride levels. Ref.14 Corresponds to variant rs2075291 [ dbSNP | Ensembl ].		VAR_021167

Sequences

	Sequence		Length	Mass (Da)
	Q6Q788 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: A1C9C207024D0DAF	FASTA	366	41,213
	10 20 30 40 50 60 MASMAAVLTW ALALLSAFSA TQARKGFWDY FSQTSGDKGR VEQIHQQKMA REPATLKDSL 70 80 90 100 110 120 EQDLNNMNKF LEKLRPLSGS EAPRLPQDPV GMRRQLQEEL EEVKARLQPY MAEAHELVGW 130 140 150 160 170 180 NLEGLRQQLK PYTMDLMEQV ALRVQELQEQ LRVVGEDTKA QLLGGVDEAW ALLQGLQSRV 190 200 210 220 230 240 VHHTGRFKEL FHPYAESLVS GIGRHVQELH RSVAPHAPAS PARLSRCVQV LSRKLTLKAK 250 260 270 280 290 300 ALHARIQQNL DQLREELSRA FAGTGTEEGA GPDPQMLSEE VRQRLQAFRQ DTYLQIAAFT 310 320 330 340 350 360 RAIDQETEEV QQQLAPPPPG HSAFAPEFQQ TDSGKVLSKL QARLDDLWED ITHSLHDQGH SHLGDP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Apolipoprotein A-V. A novel apolipoprotein associated with an early phase of liver regeneration." van Der Vliet H.N., Sammels M.G., Leegwater A.C.J., Levels J.H.M., Reitsma P.H., Boers W., Chamuleau R.A.F.M. J. Biol. Chem. 276:44512-44520(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Liver.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TRP-19 AND MET-153.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	NHLBI resequencing and genotyping service (RS&G) Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[6]	"An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing." Pennacchio L.A., Olivier M., Hubacek J.A., Cohen J.C., Cox D.R., Fruchart J.-C., Krauss R.M., Rubin E.M. Science 294:169-173(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[7]	"Structure-function studies of human apolipoprotein A-V: a regulator of plasma lipid homeostasis." Beckstead J.A., Oda M.N., Martin D.D.O., Forte T.M., Bielicki J.K., Berger T., Luty R., Kay C.M., Ryan R.O. Biochemistry 42:9416-9423(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"The human apolipoprotein AV gene is regulated by peroxisome proliferator-activated receptor-alpha and contains a novel farnesoid X-activated receptor response element." Prieur X., Coste H., Rodriguez J.C. J. Biol. Chem. 278:25468-25480(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[9]	"Structure and interfacial properties of human apolipoprotein A-V." Weinberg R.B., Cook V.R., Beckstead J.A., Martin D.D.O., Gallagher J.W., Shelness G.S., Ryan R.O. J. Biol. Chem. 278:34438-34444(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[10]	"The novel apolipoprotein A5 is present in human serum, is associated with VLDL, HDL, and chylomicrons, and circulates at very low concentrations compared with other apolipoproteins." O'Brien P.J., Alborn W.E., Sloan J.H., Ulmer M., Boodhoo A., Knierman M.D., Schultze A.E., Konrad R.J. Clin. Chem. 51:351-359(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[11]	"Normal binding of lipoprotein lipase, chylomicrons, and apo-AV to GPIHBP1 containing a G56R amino acid substitution." Gin P., Beigneux A.P., Davies B., Young M.F., Ryan R.O., Bensadoun A., Fong L.G., Young S.G. Biochim. Biophys. Acta 1771:1464-1468(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GPIHBP1.
[12]	"Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels." Pennacchio L.A., Olivier M., Hubacek J.A., Krauss R.M., Rubin E.M., Cohen J.C. Hum. Mol. Genet. 11:3031-3038(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TRP-19.
[13]	"Ser19Trp polymorphism within the apolipoprotein AV gene in hypertriglyceridaemic people." Vrablik M., Horinek A., Ceska R., Adamkova V., Poledne R., Hubacek J.A. J. Med. Genet. 40:E105-E105(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TRP-19.
[14]	"A novel genetic variant in the apolipoprotein A5 gene is associated with hypertriglyceridemia." Kao J.-T., Wen H.-C., Chien K.-L., Hsu H.-C., Lin S.-W. Hum. Mol. Genet. 12:2533-2539(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CYS-185.
[15]	"Apoa5 Q139X truncation predisposes to late-onset hyperchylomicronemia due to lipoprotein lipase impairment." Marcais C., Verges B., Charriere S., Pruneta V., Merlin M., Billon S., Perrot L., Drai J., Sassolas A., Pennacchio L.A., Fruchart-Najib J., Fruchart J.C., Durlach V., Moulin P. J. Clin. Invest. 115:2862-2869(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN HLPP5.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF202889 mRNA. Translation: AAF25661.1. Different initiation. AF202890 mRNA. Translation: AAF25662.1. Different initiation. AY555191 Genomic DNA. Translation: AAS68229.1. AY422949 Genomic DNA. Translation: AAQ91808.1. AY358749 mRNA. Translation: AAQ89109.1. Sequence problems. EF444949 Genomic DNA. Translation: ACA05937.1. EF444949 Genomic DNA. Translation: ACA05938.1. BC101787 mRNA. Translation: AAI01788.1. BC101789 mRNA. Translation: AAI01790.1.
IPI	IPI00465378.
RefSeq	NP_001160070.1. NM_001166598.1. NP_443200.2. NM_052968.4.
UniGene	Hs.283923.
3D structure databases
ProteinModelPortal	Q6Q788.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6Q788. 3 interactions.
STRING	9606.ENSP00000227665.
PTM databases
PhosphoSite	Q6Q788.
Polymorphism databases
DMDM	60391728.
Proteomic databases
PaxDb	Q6Q788.
PRIDE	Q6Q788.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000227665; ENSP00000227665; ENSG00000110243. ENST00000542499; ENSP00000445002; ENSG00000110243.
GeneID	116519.
KEGG	hsa:116519.
UCSC	uc001ppr.3. human.
Organism-specific databases
CTD	116519.
GeneCards	GC11M116660.
HGNC	HGNC:17288. APOA5.
HPA	CAB032848.
MIM	144650. phenotype. 145750. phenotype. 606368. gene.
neXtProt	NX_Q6Q788.
Orphanet	413. Hyperlipoproteinemia type 4. 70470. Hyperlipoproteinemia type 5.
PharmGKB	PA24888.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG46095.
HOGENOM	HOG000253942.
HOVERGEN	HBG050545.
InParanoid	Q6Q788.
KO	K09025.
OMA	HRSVAPH.
OrthoDB	EOG4T1HMQ.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q6Q788.
Bgee	Q6Q788.
CleanEx	HS_APOA5.
Genevestigator	Q6Q788.
GermOnline	ENSG00000110243. Homo sapiens.
Family and domain databases
InterPro	IPR013326. ApoA. IPR000074. ApoA1_A4_E. [Graphical view]
Pfam	PF01442. Apolipoprotein. 1 hit. [Graphical view]
SUPFAM	SSF47162. SSF47162. 2 hits.
ProtoNet	Search...
Other
GenomeRNAi	116519.
NextBio	79962.
SOURCE	Search...

Entry information

Entry name

APOA5_HUMAN

Accession

Primary (citable) accession number: Q6Q788
Secondary accession number(s): B0YIV9 , Q3MIK6, Q6UWK9, Q9UBJ3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 2005
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 92 of the entry and version 1 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.