2msd

Structural highlights

Disease

[APOA1_HUMAN] Defects in APOA1 are a cause of high density lipoprotein deficiency type 2 (HDLD2) [MIM:604091]; also known as familial hypoalphalipoproteinemia (FHA). Inheritance is autosomal dominant.^{[1] [2]} Defects in APOA1 are a cause of the low HDL levels observed in high density lipoprotein deficiency type 1 (HDLD1) [MIM:205400]; also known as analphalipoproteinemia or Tangier disease (TGD). HDLD1 is a recessive disorder characterized by the absence of plasma HDL, accumulation of cholesteryl esters, premature coronary artery disease, hepatosplenomegaly, recurrent peripheral neuropathy and progressive muscle wasting and weakness. In HDLD1 patients, ApoA-I fails to associate with HDL probably because of the faulty conversion of pro-ApoA-I molecules into mature chains, either due to a defect in the converting enzyme activity or a specific structural defect in Tangier ApoA-I.^{[3] [4]} Note=A mutation in APOA1 is the cause of amyloid polyneuropathy-nephropathy Iowa type (AMYLIOWA); also known as amyloidosis van Allen type or familial amyloid polyneuropathy type III. AMYLIOWA is a hereditary generalized amyloidosis due to deposition of amyloid mainly constituted by apolipoprotein A1. 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. Severe peptic ulcer disease can occurr in some and hearing loss is frequent. Cataracts is present in several, but vitreous opacities are not observed.^{[5] [6] [7] [8]} Defects in APOA1 are a cause of amyloidosis type 8 (AMYL8) [MIM:105200]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is 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.^{[9] [10] [11]}

Function

[APOA1_HUMAN] 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.^[12]

See Also

• GTPase KRas

References

1. ↑ Nakata K, Kobayashi K, Yanagi H, Shimakura Y, Tsuchiya S, Arinami T, Hamaguchi H. Autosomal dominant hypoalphalipoproteinemia due to a completely defective apolipoprotein A-I gene. Biochem Biophys Res Commun. 1993 Oct 29;196(2):950-5. PMID:8240372 doi:http://dx.doi.org/S0006-291X(83)72341-7
2. ↑ Ng DS, Leiter LA, Vezina C, Connelly PW, Hegele RA. Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia. J Clin Invest. 1994 Jan;93(1):223-9. PMID:8282791 doi:http://dx.doi.org/10.1172/JCI116949
3. ↑ Nakata K, Kobayashi K, Yanagi H, Shimakura Y, Tsuchiya S, Arinami T, Hamaguchi H. Autosomal dominant hypoalphalipoproteinemia due to a completely defective apolipoprotein A-I gene. Biochem Biophys Res Commun. 1993 Oct 29;196(2):950-5. PMID:8240372 doi:http://dx.doi.org/S0006-291X(83)72341-7
4. ↑ Ng DS, Leiter LA, Vezina C, Connelly PW, Hegele RA. Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia. J Clin Invest. 1994 Jan;93(1):223-9. PMID:8282791 doi:http://dx.doi.org/10.1172/JCI116949
5. ↑ Nakata K, Kobayashi K, Yanagi H, Shimakura Y, Tsuchiya S, Arinami T, Hamaguchi H. Autosomal dominant hypoalphalipoproteinemia due to a completely defective apolipoprotein A-I gene. Biochem Biophys Res Commun. 1993 Oct 29;196(2):950-5. PMID:8240372 doi:http://dx.doi.org/S0006-291X(83)72341-7
6. ↑ Ng DS, Leiter LA, Vezina C, Connelly PW, Hegele RA. Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia. J Clin Invest. 1994 Jan;93(1):223-9. PMID:8282791 doi:http://dx.doi.org/10.1172/JCI116949
7. ↑ Nichols WC, Dwulet FE, Liepnieks J, Benson MD. Variant apolipoprotein AI as a major constituent of a human hereditary amyloid. Biochem Biophys Res Commun. 1988 Oct 31;156(2):762-8. PMID:3142462
8. ↑ Nichols WC, Gregg RE, Brewer HB Jr, Benson MD. A mutation in apolipoprotein A-I in the Iowa type of familial amyloidotic polyneuropathy. Genomics. 1990 Oct;8(2):318-23. PMID:2123470
9. ↑ Nakata K, Kobayashi K, Yanagi H, Shimakura Y, Tsuchiya S, Arinami T, Hamaguchi H. Autosomal dominant hypoalphalipoproteinemia due to a completely defective apolipoprotein A-I gene. Biochem Biophys Res Commun. 1993 Oct 29;196(2):950-5. PMID:8240372 doi:http://dx.doi.org/S0006-291X(83)72341-7
10. ↑ Ng DS, Leiter LA, Vezina C, Connelly PW, Hegele RA. Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia. J Clin Invest. 1994 Jan;93(1):223-9. PMID:8282791 doi:http://dx.doi.org/10.1172/JCI116949
11. ↑ Soutar AK, Hawkins PN, Vigushin DM, Tennent GA, Booth SE, Hutton T, Nguyen O, Totty NF, Feest TG, Hsuan JJ, et al.. Apolipoprotein AI mutation Arg-60 causes autosomal dominant amyloidosis. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7389-93. PMID:1502149
12. ↑ Akerlof E, Jornvall H, Slotte H, Pousette A. Identification of apolipoprotein A1 and immunoglobulin as components of a serum complex that mediates activation of human sperm motility. Biochemistry. 1991 Sep 17;30(37):8986-90. PMID:1909888
13. ↑ Mazhab-Jafari MT, Marshall CB, Smith MJ, Gasmi-Seabrook GM, Stathopulos PB, Inagaki F, Kay LE, Neel BG, Ikura M. Oncogenic and RASopathy-associated K-RAS mutations relieve membrane-dependent occlusion of the effector-binding site. Proc Natl Acad Sci U S A. 2015 May 26;112(21):6625-30. doi:, 10.1073/pnas.1419895112. Epub 2015 May 4. PMID:25941399 doi:http://dx.doi.org/10.1073/pnas.1419895112