Serum amyloid A protein

From Ganfyd

Serum amyloid A protein is a 122 amino acid peptide that is coded by the SAA1 and SAA2 genes at 11p15.1 and expressed by mainly by hepatocytes. There are several alleles and the SAA1 gene codes for the form that makes up the majority of SAA. The SAA3 gene seems to be inactive but the SAA4 gene, 11 kb from SAA2 and in the same orientation is functional. All SAA genes have 4 exons. The SAA1 and SAA2 genes are arranged in a head-to-head transcriptional orientation about 18 kb apart. The genes are under cytokine regulation as the protein is an acute phase reactant. The peptide is usually processed to amyloid protein A (Amyloid fibril protein, AA) by the removal of approximately 24 residues from the C-terminal end. This is an apolipoprotein of the HDL complex. Usually it is degraded by cathepsins. In secondary amyloidosis there is the extracellular accumulation in various tissues of the macrophage produced highly insoluble and resistant to proteolysis AA protein product from the N-terminal 66-76 amino acids that aggregates into insoluble antiparallel beta-pleated sheet fibrils. The fibrils become resistant to degradation by the binding of proteoglycans and proteins, such as heparan sulfate and serum amyloid P (SAP)^[1]. Other possible processed products are:

1. Serum amyloid protein A(2-104)
2. Serum amyloid protein A(3-104)
3. Serum amyloid protein A(2-103)
4. Serum amyloid protein A(2-102)
5. Serum amyloid protein A(4-101)

The protein has several functions but it is unclear at this time how important these are. It could be an opsonin for Gram-negative bacilli, a factor in leukocyte chemoattraction, and involved in cholesterol metabolism^[1]. N-terminal secreted soluble forms of APP (in particular sAPPβ) drive neural differentiation^[2].

Polymorphisms in the gene coding for SAA1 are associated with increased risk of amyloidosis. Two single nucleotide polymorphisms at exon 3 produce three isotypes:

1. SAA 1.1 (Val52–Ala57)
2. SAA 1.3 (Ala52–Ala57)
3. SAA 1.5 (Ala52–Val57)

The 1.1/1.1 genotype has up to a sevenfold increased risk for amyloidosis^[1].

References