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Protein

Apolipoprotein A-IV

Gene

APOA4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • antioxidant activity Source: HGNC
  • cholesterol binding Source: GO_Central
  • cholesterol transporter activity Source: BHF-UCL
  • copper ion binding Source: HGNC
  • identical protein binding Source: IntAct
  • lipid binding Source: BHF-UCL
  • lipid transporter activity Source: ProtInc
  • phosphatidylcholine binding Source: BHF-UCL
  • phosphatidylcholine-sterol O-acyltransferase activator activity Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL

GO - Biological processi

  • cellular protein metabolic process Source: Reactome
  • cholesterol biosynthetic process Source: GO_Central
  • cholesterol efflux Source: BHF-UCL
  • cholesterol homeostasis Source: BHF-UCL
  • cholesterol metabolic process Source: BHF-UCL
  • chylomicron assembly Source: BHF-UCL
  • chylomicron remodeling Source: Reactome
  • high-density lipoprotein particle assembly Source: GO_Central
  • high-density lipoprotein particle remodeling Source: BHF-UCL
  • hydrogen peroxide catabolic process Source: HGNC
  • innate immune response in mucosa Source: BHF-UCL
  • leukocyte cell-cell adhesion Source: BHF-UCL
  • lipid catabolic process Source: BHF-UCL
  • lipid homeostasis Source: BHF-UCL
  • lipid transport Source: BHF-UCL
  • lipoprotein metabolic process Source: InterPro
  • negative regulation of plasma lipoprotein oxidation Source: BHF-UCL
  • neuron projection regeneration Source: GO_Central
  • phosphatidylcholine metabolic process Source: BHF-UCL
  • phospholipid efflux Source: BHF-UCL
  • positive regulation of cholesterol esterification Source: BHF-UCL
  • positive regulation of fatty acid biosynthetic process Source: BHF-UCL
  • positive regulation of lipoprotein lipase activity Source: BHF-UCL
  • positive regulation of triglyceride catabolic process Source: BHF-UCL
  • protein-lipid complex assembly Source: BHF-UCL
  • regulation of cholesterol transport Source: BHF-UCL
  • regulation of intestinal cholesterol absorption Source: GO_Central
  • removal of superoxide radicals Source: HGNC
  • response to lipid hydroperoxide Source: HGNC
  • response to stilbenoid Source: Ensembl
  • retinoid metabolic process Source: Reactome
  • reverse cholesterol transport Source: BHF-UCL
  • triglyceride homeostasis Source: GO_Central
  • very-low-density lipoprotein particle remodeling Source: BHF-UCL

Keywordsi

Biological processLipid transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-8963888 Chylomicron assembly
R-HSA-8963889 Assembly of active LPL and LIPC lipase complexes
R-HSA-8963901 Chylomicron remodeling
R-HSA-975634 Retinoid metabolism and transport
R-HSA-977225 Amyloid fiber formation

Names & Taxonomyi

Protein namesi
Recommended name:
Apolipoprotein A-IV
Short name:
Apo-AIV
Short name:
ApoA-IV
Alternative name(s):
Apolipoprotein A4
Gene namesi
Name:APOA4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000110244.6
HGNCiHGNC:602 APOA4
MIMi107690 gene
neXtProtiNX_P06727

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chylomicron, HDL, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi337

Polymorphism and mutation databases

DMDMi93163358

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 201 PublicationAdd BLAST20
ChainiPRO_000000197521 – 396Apolipoprotein A-IVAdd BLAST376

Post-translational modificationi

Phosphorylation sites are present in the extracellular medium.

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP06727
MaxQBiP06727
PaxDbiP06727
PeptideAtlasiP06727
PRIDEiP06727

2D gel databases

DOSAC-COBS-2DPAGEP06727
REPRODUCTION-2DPAGEIPI00304273
SWISS-2DPAGEP06727

PTM databases

CarbonylDBiP06727
iPTMnetiP06727
PhosphoSitePlusiP06727

Miscellaneous databases

PMAP-CutDBA8MSL6

Expressioni

Tissue specificityi

Synthesized primarily in the intestine and secreted in plasma.

Gene expression databases

BgeeiENSG00000110244
CleanExiHS_APOA4
GenevisibleiP06727 HS

Organism-specific databases

HPAiCAB068250
CAB068251
CAB068252
HPA001352
HPA002549

Interactioni

Subunit structurei

Homodimer.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

DIPiDIP-38333N
IntActiP06727, 5 interactors
STRINGi9606.ENSP00000350425

Structurei

Secondary structure

1396
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi97 – 113Combined sources17
Helixi114 – 116Combined sources3
Helixi117 – 223Combined sources107
Helixi224 – 226Combined sources3
Helixi231 – 276Combined sources46
Beta strandi278 – 280Combined sources3
Helixi282 – 307Combined sources26
Helixi310 – 329Combined sources20

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3S84X-ray2.40A/B84-355[»]
ProteinModelPortaliP06727
SMRiP06727
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati33 – 541Add BLAST22
Repeati60 – 812Add BLAST22
Repeati82 – 1033Add BLAST22
Repeati115 – 1364Add BLAST22
Repeati137 – 1585Add BLAST22
Repeati159 – 1806Add BLAST22
Repeati181 – 2027Add BLAST22
Repeati203 – 2248Add BLAST22
Repeati225 – 2469Add BLAST22
Repeati247 – 26810Add BLAST22
Repeati269 – 28611Add BLAST18
Repeati287 – 30812Add BLAST22
Repeati309 – 33013Add BLAST22

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni33 – 33013 X 22 AA approximate tandem repeatsAdd BLAST298

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi372 – 389Gln/Glu-richAdd BLAST18

Domaini

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.

Sequence similaritiesi

Belongs to the apolipoprotein A1/A4/E family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IKU1 Eukaryota
ENOG41119VI LUCA
HOGENOMiHOG000037942
HOVERGENiHBG105707
InParanoidiP06727
OrthoDBiEOG091G0IA5
PhylomeDBiP06727
TreeFamiTF334458

Family and domain databases

InterProiView protein in InterPro
IPR000074 ApoA_E
PfamiView protein in Pfam
PF01442 Apolipoprotein, 3 hits

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P06727-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFLKAVVLTL ALVAVAGARA EVSADQVATV MWDYFSQLSN NAKEAVEHLQ
60 70 80 90 100
KSELTQQLNA LFQDKLGEVN TYAGDLQKKL VPFATELHER LAKDSEKLKE
110 120 130 140 150
EIGKELEELR ARLLPHANEV SQKIGDNLRE LQQRLEPYAD QLRTQVNTQA
160 170 180 190 200
EQLRRQLTPY AQRMERVLRE NADSLQASLR PHADELKAKI DQNVEELKGR
210 220 230 240 250
LTPYADEFKV KIDQTVEELR RSLAPYAQDT QEKLNHQLEG LTFQMKKNAE
260 270 280 290 300
ELKARISASA EELRQRLAPL AEDVRGNLRG NTEGLQKSLA ELGGHLDQQV
310 320 330 340 350
EEFRRRVEPY GENFNKALVQ QMEQLRQKLG PHAGDVEGHL SFLEKDLRDK
360 370 380 390
VNSFFSTFKE KESQDKTLSL PELEQQQEQQ QEQQQEQVQM LAPLES
Length:396
Mass (Da):45,399
Last modified:March 7, 2006 - v3
Checksum:i193753196CA2FA4A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti158 – 160TPY → DPL in AAA51744 (PubMed:3755616).Curated3
Sequence conflicti158 – 160TPY → DPL in AAA51745 (PubMed:3095836).Curated3
Sequence conflicti327Q → T in AAA96731 (PubMed:3036793).Curated1
Sequence conflicti327Q → T in AAA51748 (PubMed:3080432).Curated1

Polymorphismi

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*1.6 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00062613V → M in allele APOA-IV*1D. 2 Publications1
Natural variantiVAR_00062744E → K in Budapest-2. 1 Publication1
Natural variantiVAR_01461074G → S. Corresponds to variant dbSNP:rs5102Ensembl.1
Natural variantiVAR_02544477Q → H1 Publication1
Natural variantiVAR_000628147N → S in allele APOA-IV*1B. Combined sources3 PublicationsCorresponds to variant dbSNP:rs5104Ensembl.1
Natural variantiVAR_000629161A → S in Seattle-3. 2 Publications1
Natural variantiVAR_000630178S → L in Seattle-1; may contribute to the development of familial combined hyperlipidemia. 1 Publication1
Natural variantiVAR_000631185E → K in allele APOA-IV*3. 1 Publication1
Natural variantiVAR_000632187K → E in allele APOA-IV*0A; associated with H-380. 1 Publication1
Natural variantiVAR_000633250E → K in allele APOA-IV*3A. 1 Publication1
Natural variantiVAR_000634264R → Q in Seattle-2; may contribute to the development of familial combined hyperlipidemia. 1 PublicationCorresponds to variant dbSNP:rs2238008Ensembl.1
Natural variantiVAR_025443279R → K2 PublicationsCorresponds to variant dbSNP:rs1042372Ensembl.1
Natural variantiVAR_000635305R → C in Budapest-1. 1 Publication1
Natural variantiVAR_014611307V → L. Corresponds to variant dbSNP:rs5108Ensembl.1
Natural variantiVAR_000636367T → S in allele APOA-IV*1A and allele Budapest-1. 3 PublicationsCorresponds to variant dbSNP:rs675Ensembl.1
Natural variantiVAR_000637380Q → H in allele APOA-IV*2 and allele APOA-IV*0A; associated with E-187 in allele APOA-IV*0A. 7 PublicationsCorresponds to variant dbSNP:rs5110EnsemblClinVar.1
Natural variantiVAR_000638381Q → QEQQQ in allele APOA-IV*0 and allele APOA-IV*5; allele APOA-IV*5 is further defined by a silent nucleotide substitution. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS31681.1
PIRiA94137 LPHUA4
UniGeneiHs.1247

Genome annotation databases

EnsembliENST00000357780; ENSP00000350425; ENSG00000110244
UCSCiuc001pps.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAPOA4_HUMAN
AccessioniPrimary (citable) accession number: P06727
Secondary accession number(s): A8MSL6, Q14CW8, Q6Q787
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: March 7, 2006
Last modified: May 23, 2018
This is version 198 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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