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Apolipoprotein A-I



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


Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT). As part of the SPAP complex, activates spermatozoa motility.1 Publication

GO - Molecular functioni

  • amyloid-beta binding Source: BHF-UCL
  • apolipoprotein A-I receptor binding Source: BHF-UCL
  • apolipoprotein receptor binding Source: BHF-UCL
  • chemorepellent activity Source: UniProtKB
  • cholesterol binding Source: BHF-UCL
  • cholesterol transporter activity Source: BHF-UCL
  • enzyme binding Source: BHF-UCL
  • heat shock protein binding Source: CAFA
  • high-density lipoprotein particle binding Source: Ensembl
  • high-density lipoprotein particle receptor binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • lipase inhibitor activity Source: Ensembl
  • phosphatidylcholine binding Source: GO_Central
  • phosphatidylcholine-sterol O-acyltransferase activator activity Source: BHF-UCL
  • phospholipid binding Source: BHF-UCL
  • phospholipid transporter activity Source: Ensembl

GO - Biological processi

  • adrenal gland development Source: Ensembl
  • animal organ regeneration Source: Ensembl
  • blood vessel endothelial cell migration Source: Ensembl
  • cellular protein metabolic process Source: Reactome
  • cholesterol biosynthetic process Source: GO_Central
  • cholesterol efflux Source: BHF-UCL
  • cholesterol homeostasis Source: BHF-UCL
  • cholesterol import Source: BHF-UCL
  • cholesterol metabolic process Source: BHF-UCL
  • cholesterol transport Source: MGI
  • chylomicron assembly Source: Reactome
  • chylomicron remodeling Source: Reactome
  • endothelial cell proliferation Source: Ensembl
  • glucocorticoid metabolic process Source: Ensembl
  • G-protein coupled receptor signaling pathway Source: BHF-UCL
  • high-density lipoprotein particle assembly Source: BHF-UCL
  • high-density lipoprotein particle clearance Source: Reactome
  • high-density lipoprotein particle remodeling Source: BHF-UCL
  • integrin-mediated signaling pathway Source: UniProtKB
  • lipid storage Source: Ensembl
  • lipoprotein biosynthetic process Source: Ensembl
  • lipoprotein metabolic process Source: GO_Central
  • negative chemotaxis Source: UniProtKB
  • negative regulation of cell adhesion molecule production Source: BHF-UCL
  • negative regulation of cytokine secretion involved in immune response Source: BHF-UCL
  • negative regulation of heterotypic cell-cell adhesion Source: BHF-UCL
  • negative regulation of inflammatory response Source: BHF-UCL
  • negative regulation of interleukin-1 beta secretion Source: BHF-UCL
  • negative regulation of lipase activity Source: Ensembl
  • negative regulation of response to cytokine stimulus Source: BHF-UCL
  • negative regulation of tumor necrosis factor-mediated signaling pathway Source: BHF-UCL
  • negative regulation of very-low-density lipoprotein particle remodeling Source: BHF-UCL
  • neuron projection regeneration Source: GO_Central
  • peptidyl-methionine modification Source: UniProtKB
  • peripheral nervous system axon regeneration Source: Ensembl
  • phosphatidylcholine biosynthetic process Source: BHF-UCL
  • phospholipid efflux Source: BHF-UCL
  • phospholipid homeostasis Source: BHF-UCL
  • platelet degranulation Source: Reactome
  • positive regulation of cholesterol esterification Source: BHF-UCL
  • positive regulation of fatty acid biosynthetic process Source: GO_Central
  • positive regulation of hydrolase activity Source: BHF-UCL
  • positive regulation of lipoprotein lipase activity Source: GO_Central
  • positive regulation of Rho protein signal transduction Source: UniProtKB
  • positive regulation of stress fiber assembly Source: UniProtKB
  • positive regulation of substrate adhesion-dependent cell spreading Source: UniProtKB
  • positive regulation of triglyceride catabolic process Source: GO_Central
  • post-translational protein modification Source: Reactome
  • protein oxidation Source: UniProtKB
  • protein stabilization Source: BHF-UCL
  • receptor-mediated endocytosis Source: Reactome
  • regulation of Cdc42 protein signal transduction Source: BHF-UCL
  • regulation of intestinal cholesterol absorption Source: GO_Central
  • regulation of lipid metabolic process Source: Reactome
  • regulation of protein phosphorylation Source: Ensembl
  • response to drug Source: Ensembl
  • response to estrogen Source: Ensembl
  • response to nutrient Source: Ensembl
  • retinoid metabolic process Source: Reactome
  • reverse cholesterol transport Source: BHF-UCL
  • triglyceride catabolic process Source: GO_Central
  • triglyceride homeostasis Source: BHF-UCL
  • vitamin transport Source: AgBase


Biological processCholesterol metabolism, Lipid metabolism, Lipid transport, Steroid metabolism, Sterol metabolism, Transport

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-1369062 ABC transporters in lipid homeostasis
R-HSA-1989781 PPARA activates gene expression
R-HSA-2168880 Scavenging of heme from plasma
R-HSA-3000471 Scavenging by Class B Receptors
R-HSA-3000480 Scavenging by Class A Receptors
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-8963888 Chylomicron assembly
R-HSA-8963896 HDL assembly
R-HSA-8963901 Chylomicron remodeling
R-HSA-8964011 HDL clearance
R-HSA-8964058 HDL remodeling
R-HSA-975634 Retinoid metabolism and transport
R-HSA-977225 Amyloid fiber formation

Names & Taxonomyi

Protein namesi
Recommended name:
Apolipoprotein A-I
Short name:
Short name:
Alternative name(s):
Apolipoprotein A1
Cleaved into the following 2 chains:
Proapolipoprotein A-I
Short name:
Alternative name(s):
Apolipoprotein A-I(1-242)
Gene namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

MIMi107680 gene+phenotype

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

Amyloid, HDL, Secreted

Pathology & Biotechi

Involvement in diseasei

High density lipoprotein deficiency 2 (HDLD2)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionInherited as autosomal dominant trait. It is characterized by moderately low HDL cholesterol, predilection toward premature coronary artery disease (CAD) and a reduction in cellular cholesterol efflux.
See also OMIM:604091
High density lipoprotein deficiency 1 (HDLD1)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRecessive disorder characterized by absence of high density lipoprotein (HDL) cholesterol from plasma, accumulation of cholesteryl esters, premature coronary artery disease (CAD), hepatosplenomegaly, recurrent peripheral neuropathy and progressive muscle wasting and weakness.
See also OMIM:205400
APOA1 mutations may be involved in the pathogenesis of amyloid polyneuropathy-nephropathy Iowa type, also known as amyloidosis van Allen type or familial amyloid polyneuropathy type III (PubMed:3142462 and PubMed:2123470). The clinical picture is dominated by neuropathy in the early stages of the disease and nephropathy late in the course. Death is due in most cases to renal amyloidosis.
Amyloidosis 8 (AMYL8)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of hereditary generalized amyloidosis. Clinical features include extensive visceral amyloid deposits, renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash. There is no involvement of the nervous system.
See also OMIM:105200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00060950G → R in AMYL8; also found in a family with amyloid polyneuropathy-nephropathy Iowa. 3 PublicationsCorresponds to variant dbSNP:rs28931574EnsemblClinVar.1
Natural variantiVAR_00061084L → R in AMYL8. 1 PublicationCorresponds to variant dbSNP:rs121912724EnsemblClinVar.1

Keywords - Diseasei

Amyloidosis, Atherosclerosis, Disease mutation, Neuropathy

Organism-specific databases

MIMi105200 phenotype
107680 gene+phenotype
205400 phenotype
604091 phenotype
Orphaneti425 Apolipoprotein A-I deficiency
93560 Familial renal amyloidosis due to Apolipoprotein AI variant
314701 Primary systemic amyloidosis

Chemistry databases


Polymorphism and mutation databases


PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 182 PublicationsAdd BLAST18
ChainiPRO_000042532319 – 267Proapolipoprotein A-IAdd BLAST249
ChainiPRO_000000193925 – 267Apolipoprotein A-IAdd BLAST243
ChainiPRO_000000194025 – 266Truncated apolipoprotein A-IAdd BLAST242

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei110Methionine sulfoxide1 Publication1
Modified residuei136Methionine sulfoxide1 Publication1
Glycosylationi263N-linked (Glc) (glycation) lysine1

Post-translational modificationi

Glycosylated.By similarity
Palmitoylated.1 Publication
Phosphorylation sites are present in the extracellular medium.

Keywords - PTMi

Glycation, Glycoprotein, Lipoprotein, Oxidation, Palmitate, Phosphoprotein

Proteomic databases


2D gel databases


PTM databases


Miscellaneous databases



Tissue specificityi

Major protein of plasma HDL, also found in chylomicrons. Synthesized in the liver and small intestine. The oxidized form at Met-110 and Met-136 is increased in individuals with increased risk for coronary artery disease, such as in carrier of the eNOSa/b genotype and exposure to cigarette smoking. It is also present in increased levels in aortic lesions relative to native ApoA-I and increased levels are seen with increasing severity of disease.1 Publication

Gene expression databases

ExpressionAtlasiP02647 baseline and differential
GenevisibleiP02647 HS

Organism-specific databases



Subunit structurei

Interacts with APOA1BP and CLU (PubMed:1742316, PubMed:11991719). Component of a sperm activating protein complex (SPAP), consisting of APOA1, an immunoglobulin heavy chain, an immunoglobulin light chain and albumin (PubMed:1909888). Interacts with NDRG1 (PubMed:15922294). Interacts with SCGB3A2 (PubMed:12847263).5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • apolipoprotein A-I receptor binding Source: BHF-UCL
  • apolipoprotein receptor binding Source: BHF-UCL
  • chemorepellent activity Source: UniProtKB
  • enzyme binding Source: BHF-UCL
  • heat shock protein binding Source: CAFA
  • high-density lipoprotein particle receptor binding Source: BHF-UCL
  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi106832, 90 interactors
IntActiP02647, 70 interactors


Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi33 – 42Combined sources10
Helixi45 – 59Combined sources15
Helixi61 – 65Combined sources5
Helixi80 – 88Combined sources9
Helixi93 – 158Combined sources66
Turni159 – 164Combined sources6
Helixi166 – 203Combined sources38
Turni229 – 232Combined sources4
Helixi233 – 260Combined sources28

3D structure databases


Miscellaneous databases


Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati68 – 891Add BLAST22
Repeati90 – 1112Add BLAST22
Repeati112 – 1223; half-lengthAdd BLAST11
Repeati123 – 1444Add BLAST22
Repeati145 – 1665Add BLAST22
Repeati167 – 1886Add BLAST22
Repeati189 – 2107Add BLAST22
Repeati211 – 2328Add BLAST22
Repeati233 – 2439; half-lengthAdd BLAST11
Repeati244 – 26710Add BLAST24


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni68 – 26710 X approximate tandem repeatsAdd BLAST200

Sequence similaritiesi

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

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IWKR Eukaryota

Family and domain databases

InterProiView protein in InterPro
IPR000074 ApoA_E
PfamiView protein in Pfam
PF01442 Apolipoprotein, 1 hit


Sequence statusi: Complete.

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

P02647-1 [UniParc]FASTAAdd to basket

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110 120 130 140 150
160 170 180 190 200
210 220 230 240 250
Mass (Da):30,778
Last modified:July 21, 1986 - v1

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti32W → P AA sequence (PubMed:1742316).Curated1

Mass spectrometryi

Molecular mass is 28081 Da from positions 25 - 267. Determined by ESI. Without methionine sulfoxide.1 Publication
Molecular mass is 28098 Da from positions 25 - 267. Determined by ESI. With 1 methionine sulfoxide, oxidation at Met-110.1 Publication
Molecular mass is 28095 Da from positions 25 - 267. Determined by ESI. With 1 methionine sulfoxide, oxidation at Met-136.1 Publication
Molecular mass is 28114 Da from positions 25 - 267. Determined by ESI. With 2 methionine sulfoxides, oxidation at Met-110 and Met-136.1 Publication


Genetic variations in APOA1 can result in APOA1 deficiency and are associated with low levels of HDL cholesterol [MIMi:107680].Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00060527P → H in Munster-3C. Corresponds to variant dbSNP:rs121912720EnsemblClinVar.1
Natural variantiVAR_00060627P → R1 PublicationCorresponds to variant dbSNP:rs121912720EnsemblClinVar.1
Natural variantiVAR_00060728P → R in Munster-3B. 1 PublicationCorresponds to variant dbSNP:rs121912721EnsemblClinVar.1
Natural variantiVAR_00060834R → L in Baltimore. 1 PublicationCorresponds to variant dbSNP:rs28929476EnsemblClinVar.1
Natural variantiVAR_00060950G → R in AMYL8; also found in a family with amyloid polyneuropathy-nephropathy Iowa. 3 PublicationsCorresponds to variant dbSNP:rs28931574EnsemblClinVar.1
Natural variantiVAR_02544561A → T1 PublicationCorresponds to variant dbSNP:rs12718465EnsemblClinVar.1
Natural variantiVAR_00061084L → R in AMYL8. 1 PublicationCorresponds to variant dbSNP:rs121912724EnsemblClinVar.1
Natural variantiVAR_01701792T → I Polymorphism; confirmed at protein level. 2 PublicationsCorresponds to variant dbSNP:rs766422306Ensembl.1
Natural variantiVAR_000611113D → E1 PublicationCorresponds to variant dbSNP:rs150243849Ensembl.1
Natural variantiVAR_000612119A → D in Hita. 1
Natural variantiVAR_016189126D → H. Corresponds to variant dbSNP:rs5077Ensembl.1
Natural variantiVAR_000613127D → N in Munster-3A. Corresponds to variant dbSNP:rs921646982Ensembl.1
Natural variantiVAR_000615131K → M1 PublicationCorresponds to variant dbSNP:rs4882Ensembl.1
Natural variantiVAR_000614131Missing in Marburg/Munster-2. 1
Natural variantiVAR_000616132W → R in Tsushima. 1
Natural variantiVAR_000617134E → K in Fukuoka. 1 Publication1
Natural variantiVAR_000618160E → K in Norway. 1 PublicationCorresponds to variant dbSNP:rs121912718EnsemblClinVar.1
Natural variantiVAR_000619163E → G1 PublicationCorresponds to variant dbSNP:rs758509542Ensembl.1
Natural variantiVAR_000620167P → R in Giessen. 1 PublicationCorresponds to variant dbSNP:rs121912719EnsemblClinVar.1
Natural variantiVAR_000621168L → R in Zaragoza. 1 Publication1
Natural variantiVAR_000622171E → V1 PublicationCorresponds to variant dbSNP:rs1015066427Ensembl.1
Natural variantiVAR_074073173R → S in Boston; no evidence of association with premature coronary heart disease; associated with decreased levels of HDL cholesterol; associated with decreased serum cellular cholesterol efflux; associated with decreased lecithin-cholesterol acyltransferase (LCAT) activity. 1 Publication1
Natural variantiVAR_021362180V → E in Oita; 60% of normal apoA-I and normal HDL cholesterol levels; rapidly cleared from plasma. 1 PublicationCorresponds to variant dbSNP:rs121912727EnsemblClinVar.1
Natural variantiVAR_014609184R → P. Corresponds to variant dbSNP:rs5078Ensembl.1
Natural variantiVAR_000623189P → R1 PublicationCorresponds to variant dbSNP:rs121912722EnsemblClinVar.1
Natural variantiVAR_000624197R → C in Milano; no evidence of association with premature vascular disease; associated with decreased HDL levels and moderate increase in triglycerides; allows the formation of disulfide-linked homodimers via the introduced cysteine; assembles properly in HDL; alters protein structure; has no tendency to form fibrils and aggregates. 2 PublicationsCorresponds to variant dbSNP:rs28931573EnsemblClinVar.1
Natural variantiVAR_000625222E → K in Munster-4. 1 PublicationCorresponds to variant dbSNP:rs121912717EnsemblClinVar.1

Sequence databases

Select the link destinations:
Links Updated
J00098 Genomic DNA Translation: AAB59514.1
X01038 Genomic DNA Translation: CAA25519.1
X02162 mRNA Translation: CAA26097.1
X00566 mRNA Translation: CAA25232.1
M11791 mRNA Translation: AAA35545.1
X07496 Genomic DNA Translation: CAA30377.1
M27875 mRNA Translation: AAA62829.1
M29068 mRNA Translation: AAA51747.1
AY422952 Genomic DNA Translation: AAQ91811.1
AY555191 Genomic DNA Translation: AAS68227.1
A14829 mRNA Translation: CAA01198.1
AK292231 mRNA Translation: BAF84920.1
EF444948 Genomic DNA Translation: ACA05932.1
EF444948 Genomic DNA Translation: ACA05933.1
EF444948 Genomic DNA Translation: ACA05934.1
EF444948 Genomic DNA Translation: ACA05935.1
EF444948 Genomic DNA Translation: ACA05936.1
CH471065 Genomic DNA Translation: EAW67274.1
BC005380 mRNA Translation: AAH05380.1
BC110286 mRNA Translation: AAI10287.1
RefSeqiNP_000030.1, NM_000039.2
NP_001304946.1, NM_001318017.1
NP_001304947.1, NM_001318018.1
NP_001304950.1, NM_001318021.1

Genome annotation databases

EnsembliENST00000236850; ENSP00000236850; ENSG00000118137
ENST00000359492; ENSP00000352471; ENSG00000118137
ENST00000375320; ENSP00000364469; ENSG00000118137
ENST00000375323; ENSP00000364472; ENSG00000118137
UCSCiuc001ppv.2 human

Keywords - Coding sequence diversityi


Similar proteinsi

Entry informationi

Entry nameiAPOA1_HUMAN
AccessioniPrimary (citable) accession number: P02647
Secondary accession number(s): A8K866
, Q6LDN9, Q6Q785, Q9UCS8, Q9UCT8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 18, 2018
This is version 235 of the entry and version 1 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.


Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome


  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

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