UniProt functional annotation for P02647



	UniProt functional annotation for P02647

UniProt code: P02647.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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. {ECO:0000269|PubMed:1909888}.

Subunit: Homodimer (By similarity). Interacts with NAXE 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). Interacts with NAXE and YJEFN3 (PubMed:23719382). {ECO:0000250|UniProtKB:G5BQH5, ECO:0000269|PubMed:11991719, ECO:0000269|PubMed:12847263, ECO:0000269|PubMed:15922294, ECO:0000269|PubMed:1742316, ECO:0000269|PubMed:1909888, ECO:0000269|PubMed:23719382}.

Subcellular location: Secreted.

Tissue specificity: 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. {ECO:0000269|PubMed:12576517}.

Ptm: Glycosylated. {ECO:0000250}.

Ptm: Palmitoylated. {ECO:0000269|PubMed:3005308}.

Ptm: Phosphorylation sites are present in the extracellular medium.

Mass spectrometry: [Apolipoprotein A-I]: Mass=28081; Method=Electrospray; Note=Without methionine sulfoxide.; Evidence={ECO:0000269|PubMed:12576517};

Mass spectrometry: [Apolipoprotein A-I]: Mass=28098; Method=Electrospray; Note=With 1 methionine sulfoxide, oxidation at Met-110.; Evidence={ECO:0000269|PubMed:12576517};

Mass spectrometry: [Apolipoprotein A-I]: Mass=28095; Method=Electrospray; Note=With 1 methionine sulfoxide, oxidation at Met-136.; Evidence={ECO:0000269|PubMed:12576517};

Mass spectrometry: [Apolipoprotein A-I]: Mass=28114; Method=Electrospray; Note=With 2 methionine sulfoxides, oxidation at Met-110 and Met-136.; Evidence={ECO:0000269|PubMed:12576517};

Polymorphism: Genetic variations in APOA1 can result in APOA1 deficiency and are associated with low levels of HDL cholesterol [MIM:107680]. {ECO:0000305}.

Disease: Hypoalphalipoproteinemia, primary, 2 (FHA2) [MIM:618463]: A rare disorder of lipoprotein metabolism, biochemically characterized by complete or partial apoA-I deficiency and mild to severe reduction of serum high-density lipoprotein cholesterol (HDL-C). Severe hypoalphalipoproteinemia characterized by undetectable levels of apoA-I is an autosomal recessive condition, generally associated with markedly increased atherosclerotic cardiovascular disease, xanthomas and corneal opacities. Mild hypoalphalipoproteinemia characterized by half the normal plasma apoA-I and HDL-C levels is inherited as an autosomal dominant trait, may be associated with xanthomas and corneal opacities, but most patients do not have increased cardiovascular risk. {ECO:0000269|PubMed:1898657, ECO:0000269|PubMed:1901417, ECO:0000269|PubMed:8282791}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Note=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.

Disease: Amyloidosis 8 (AMYL8) [MIM:105200]: A 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. {ECO:0000269|PubMed:10198255, ECO:0000269|PubMed:10487826, ECO:0000269|PubMed:12050338, ECO:0000269|PubMed:1502149, ECO:0000269|PubMed:2123470, ECO:0000269|PubMed:3142462, ECO:0000269|PubMed:8208902}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the apolipoprotein A1/A4/E family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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. {ECO:0000269\|PubMed:1909888}.


Subunit:		Homodimer (By similarity). Interacts with NAXE 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). Interacts with NAXE and YJEFN3 (PubMed:23719382). {ECO:0000250\|UniProtKB:G5BQH5, ECO:0000269\|PubMed:11991719, ECO:0000269\|PubMed:12847263, ECO:0000269\|PubMed:15922294, ECO:0000269\|PubMed:1742316, ECO:0000269\|PubMed:1909888, ECO:0000269\|PubMed:23719382}.
Subcellular location:		Secreted.
Tissue specificity:		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. {ECO:0000269\|PubMed:12576517}.
Ptm:		Glycosylated. {ECO:0000250}.
Ptm:		Palmitoylated. {ECO:0000269\|PubMed:3005308}.
Ptm:		Phosphorylation sites are present in the extracellular medium.
Mass spectrometry:		[Apolipoprotein A-I]: Mass=28081; Method=Electrospray; Note=Without methionine sulfoxide.; Evidence={ECO:0000269\|PubMed:12576517};
Mass spectrometry:		[Apolipoprotein A-I]: Mass=28098; Method=Electrospray; Note=With 1 methionine sulfoxide, oxidation at Met-110.; Evidence={ECO:0000269\|PubMed:12576517};
Mass spectrometry:		[Apolipoprotein A-I]: Mass=28095; Method=Electrospray; Note=With 1 methionine sulfoxide, oxidation at Met-136.; Evidence={ECO:0000269\|PubMed:12576517};
Mass spectrometry:		[Apolipoprotein A-I]: Mass=28114; Method=Electrospray; Note=With 2 methionine sulfoxides, oxidation at Met-110 and Met-136.; Evidence={ECO:0000269\|PubMed:12576517};
Polymorphism:		Genetic variations in APOA1 can result in APOA1 deficiency and are associated with low levels of HDL cholesterol [MIM:107680]. {ECO:0000305}.
Disease:		Hypoalphalipoproteinemia, primary, 2 (FHA2) [MIM:618463]: A rare disorder of lipoprotein metabolism, biochemically characterized by complete or partial apoA-I deficiency and mild to severe reduction of serum high-density lipoprotein cholesterol (HDL-C). Severe hypoalphalipoproteinemia characterized by undetectable levels of apoA-I is an autosomal recessive condition, generally associated with markedly increased atherosclerotic cardiovascular disease, xanthomas and corneal opacities. Mild hypoalphalipoproteinemia characterized by half the normal plasma apoA-I and HDL-C levels is inherited as an autosomal dominant trait, may be associated with xanthomas and corneal opacities, but most patients do not have increased cardiovascular risk. {ECO:0000269\|PubMed:1898657, ECO:0000269\|PubMed:1901417, ECO:0000269\|PubMed:8282791}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Note=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.
Disease:		Amyloidosis 8 (AMYL8) [MIM:105200]: A 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. {ECO:0000269\|PubMed:10198255, ECO:0000269\|PubMed:10487826, ECO:0000269\|PubMed:12050338, ECO:0000269\|PubMed:1502149, ECO:0000269\|PubMed:2123470, ECO:0000269\|PubMed:3142462, ECO:0000269\|PubMed:8208902}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the apolipoprotein A1/A4/E family. {ECO:0000305}.