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Q6Q788 (APOA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length366 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processLipid transport
Transport
   Cellular componentChylomicron
HDL
Secreted
VLDL
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainCoiled coil
Signal
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processacylglycerol homeostasis

Inferred from direct assay Ref.6. Source: BHF-UCL

cellular lipid metabolic process

Traceable author statement. Source: Reactome

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: Ensembl

positive regulation of fatty acid biosynthetic process

Inferred from direct assay PubMed 18635818. Source: BHF-UCL

positive regulation of lipid catabolic process

Inferred from direct assay PubMed 16806135. 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

Inferred from electronic annotation. Source: Ensembl

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 metabolic process

Inferred from direct assay Ref.6. Source: BHF-UCL

triglyceride-rich lipoprotein particle remodeling

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentchylomicron

Inferred from direct assay Ref.10. Source: UniProtKB

extracellular region

Inferred from direct assay Ref.1. Source: UniProtKB

extracellular space

Inferred from direct assay PubMed 18635818PubMed 19121291. Source: BHF-UCL

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_functionenzyme activator activity

Inferred from direct assay PubMed 16806135. Source: BHF-UCL

enzyme binding

Inferred from direct assay PubMed 15178420. Source: BHF-UCL

heparin binding

Inferred from direct assay PubMed 15878877. Source: BHF-UCL

lipase activator activity

Inferred from mutant phenotype PubMed 15178420. Source: BHF-UCL

lipase binding

Inferred from physical interaction PubMed 15178420. Source: BHF-UCL

lipid binding

Inferred from direct assay Ref.9. Source: UniProtKB

lipoprotein lipase activator activity

Inferred from direct assay PubMed 18635818. Source: BHF-UCL

lipoprotein particle receptor binding

Inferred from physical interaction PubMed 18635818. Source: BHF-UCL

low-density lipoprotein particle receptor binding

Inferred from physical interaction PubMed 17326667. Source: BHF-UCL

phosphatidylcholine binding

Inferred from direct assay PubMed 16806135. Source: BHF-UCL

phospholipid binding

Inferred from direct assay Ref.9. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 366343Apolipoprotein A-V
PRO_0000001981

Regions

Coiled coil54 – 157104 Potential
Coiled coil236 – 26227 Potential

Amino acid modifications

Modified residue591Phosphoserine By similarity

Natural variations

Natural variant191S → 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 variant371D → E.
Corresponds to variant rs34282181 [ dbSNP | Ensembl ].
VAR_035124
Natural variant1531V → M. Ref.2
Corresponds to variant rs3135507 [ dbSNP | Ensembl ].
VAR_021166
Natural variant1851G → C Associated with high plasma triglyceride levels. Ref.14
Corresponds to variant rs2075291 [ dbSNP | Ensembl ].
VAR_021167

Sequences

Sequence LengthMass (Da)Tools
Q6Q788 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: A1C9C207024D0DAF

FASTA36641,213
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
RefSeqNP_001160070.1. NM_001166598.1.
NP_443200.2. NM_052968.4.
UniGeneHs.283923.

3D structure databases

ProteinModelPortalQ6Q788.
SMRQ6Q788. Positions 18-316.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125518. 3 interactions.
IntActQ6Q788. 6 interactions.
STRING9606.ENSP00000227665.

PTM databases

PhosphoSiteQ6Q788.

Polymorphism databases

DMDM60391728.

Proteomic databases

PaxDbQ6Q788.
PRIDEQ6Q788.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000227665; ENSP00000227665; ENSG00000110243.
ENST00000542499; ENSP00000445002; ENSG00000110243.
GeneID116519.
KEGGhsa:116519.
UCSCuc001ppr.3. human.

Organism-specific databases

CTD116519.
GeneCardsGC11M116660.
HGNCHGNC:17288. APOA5.
MIM144650. phenotype.
145750. phenotype.
606368. gene.
neXtProtNX_Q6Q788.
Orphanet413. Hyperlipoproteinemia type 4.
70470. Hyperlipoproteinemia type 5.
PharmGKBPA24888.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46095.
HOGENOMHOG000253942.
HOVERGENHBG050545.
InParanoidQ6Q788.
KOK09025.
OMAHRSVAPH.
OrthoDBEOG7K9K48.
PhylomeDBQ6Q788.
TreeFamTF334458.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ6Q788.
BgeeQ6Q788.
CleanExHS_APOA5.
GenevestigatorQ6Q788.

Family and domain databases

InterProIPR000074. ApoA1_A4_E.
[Graphical view]
PfamPF01442. Apolipoprotein. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiAPOA5.
GenomeRNAi116519.
NextBio79962.
PROQ6Q788.
SOURCESearch...

Entry information

Entry nameAPOA5_HUMAN
AccessionPrimary (citable) accession number: Q6Q788
Secondary accession number(s): B0YIV9 expand/collapse secondary AC list , Q3MIK6, Q6UWK9, Q9UBJ3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: July 5, 2004
Last modified: April 16, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM