ApoA-I Human Active Protein

This gene encodes apolipoprotein A-I, which is the major protein component of high density lipoprotein (HDL) in plasma. The protein promotes cholesterol efflux from tissues to the liver for excretion, and it is a cofactor for lecithin cholesterolacyltransferase (LCAT) which is responsible for the formation of most plasma cholesteryl esters. This gene is closely linked with two other apolipoprotein genes on chromosome 11. Defects in this gene are associated with HDL deficiencies, including Tangier disease, and with systemic non-neuropathic amyloidosis. [provided by RefSeq, Jul 2008]

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. Ref.20

Subunit structure: Interacts with APOA1BP and CLU. Component of a sperm activating protein complex (SPAP), consisting of APOA1, an immunoglobulin heavy chain, an immunoglobulin light chain and albumin. Interacts with NDRG1. Ref.20 Ref.25 Ref.31 Ref.34

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. Ref.32

Post-translational modification: Palmitoylated. Ref.28Met-110 and Met-136 are oxidized to methionine sulfoxides.Phosphorylation sites are present in the extracellular medium.

Polymorphism: Genetic variations in APOA1 can result in APOA1 deficiency and are associated with low levels of HDL cholesterol [

MIM:107680].

Involvement in disease: High density lipoprotein deficiency 2 (HDLD2) [MIM:604091]: Inherited 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.38 Ref.39High density lipoprotein deficiency 1 (HDLD1) [MIM:205400]: Recessive 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.38 Ref.39APOA1 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 (Ref.44 and Ref.45). 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. Ref.38 Ref.39Amyloidosis 8 (AMYL8) [MIM:105200]: A hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.38 Ref.39 Ref.44 Ref.45 Ref.47 Ref.52

Sequence similarities: Belongs to the apolipoprotein A1/A4/E family.

Mass spectrometry: Molecular mass is 28081 Da from positions 25 - 267. Determined by ESI. Without methionine sulfoxide. Ref.32Molecular mass is 28098 Da from positions 25 - 267. Determined by ESI. With 1 methionine sulfoxide, oxidation at Met-110. Ref.32Molecular mass is 28095 Da from positions 25 - 267. Determined by ESI. With 1 methionine sulfoxide, oxidation at Met-136. Ref.32Molecular mass is 28114 Da from positions 25 - 267. Determined by ESI. With 2 methionine sulfoxides, oxidation at Met-110 and Met-136. Ref.32