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Protein

Apolipoprotein A-IV

Gene

APOA4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • 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: BHF-UCL
  • 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 homeostasis Source: BHF-UCL
  • lipid transport Source: BHF-UCL
  • lipoprotein biosynthetic process Source: Reactome
  • lipoprotein metabolic process Source: Reactome
  • multicellular organism lipid catabolic process Source: BHF-UCL
  • negative regulation of plasma lipoprotein particle 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
Complete GO annotation...

Keywords - Biological processi

Lipid transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000110244-MONOMER.
ReactomeiR-HSA-174800. Chylomicron-mediated lipid transport.
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

HGNCiHGNC:602. APOA4.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • chylomicron Source: BHF-UCL
  • cytosol Source: Reactome
  • early endosome Source: Reactome
  • endoplasmic reticulum lumen Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: BHF-UCL
  • high-density lipoprotein particle Source: BHF-UCL
  • very-low-density lipoprotein particle Source: BHF-UCL
Complete GO annotation...

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

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

WithEntry#Exp.IntActNotes
NR1D1P203933EBI-1222447,EBI-2811738

GO - Molecular functioni

  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

DIPiDIP-38333N.
IntActiP06727. 4 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

InterProiIPR000074. ApoA_E.
[Graphical view]
PfamiPF01442. Apolipoprotein. 3 hits.
[Graphical view]

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 rs5102dbSNPEnsembl.1
Natural variantiVAR_02544477Q → H.1 Publication1
Natural variantiVAR_000628147N → S in allele APOA-IV*1B. Combined sources3 PublicationsCorresponds to variant rs5104dbSNPEnsembl.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 rs2238008dbSNPEnsembl.1
Natural variantiVAR_025443279R → K.2 PublicationsCorresponds to variant rs1042372dbSNPEnsembl.1
Natural variantiVAR_000635305R → C in Budapest-1. 1 Publication1
Natural variantiVAR_014611307V → L.Corresponds to variant rs5108dbSNPEnsembl.1
Natural variantiVAR_000636367T → S in allele APOA-IV*1A and allele Budapest-1. 3 PublicationsCorresponds to variant rs675dbSNPEnsembl.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 rs5110dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

SHMPD

The Singapore human mutation and polymorphism database

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.

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...

Protein-protein interaction databases

DIPiDIP-38333N.
IntActiP06727. 4 interactors.
STRINGi9606.ENSP00000350425.

PTM databases

iPTMnetiP06727.
PhosphoSitePlusiP06727.

Polymorphism and mutation databases

DMDMi93163358.

2D gel databases

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

Proteomic databases

EPDiP06727.
MaxQBiP06727.
PaxDbiP06727.
PeptideAtlasiP06727.
PRIDEiP06727.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357780; ENSP00000350425; ENSG00000110244.
UCSCiuc001pps.2. human.

Organism-specific databases

DisGeNETi337.
GeneCardsiAPOA4.
HGNCiHGNC:602. APOA4.
HPAiCAB068250.
CAB068251.
CAB068252.
HPA001352.
HPA002549.
MIMi107690. gene.
neXtProtiNX_P06727.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKU1. Eukaryota.
ENOG41119VI. LUCA.
HOGENOMiHOG000037942.
HOVERGENiHBG105707.
InParanoidiP06727.
OrthoDBiEOG091G0IA5.
PhylomeDBiP06727.
TreeFamiTF334458.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000110244-MONOMER.
ReactomeiR-HSA-174800. Chylomicron-mediated lipid transport.
R-HSA-975634. Retinoid metabolism and transport.
R-HSA-977225. Amyloid fiber formation.

Miscellaneous databases

PMAP-CutDBA8MSL6.
PROiP06727.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000110244.
CleanExiHS_APOA4.
GenevisibleiP06727. HS.

Family and domain databases

InterProiIPR000074. ApoA_E.
[Graphical view]
PfamiPF01442. Apolipoprotein. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAPOA4_HUMAN
AccessioniPrimary (citable) accession number: P06727
Secondary accession number(s): A8MSL6, Q14CW8, Q6Q787
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: March 7, 2006
Last modified: November 30, 2016
This is version 187 of the entry and version 3 of the sequence. [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

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.