Fetuin-A, also known as Alpha-2-HS-Glycoprotein (AHSG), belongs to the Fetuin family, is a plasma binding protein, and is more abundant in fetal than adult blood. It is involved in several functions, such as endocytosis, brain development and the formation of bone tissue. Fetuins are carrier proteins like albumin. Fetuin-A forms soluble complexes with calcium and phosphate and thus is a carrier of otherwise insoluble calcium phosphate. Thus Fetuin-A is a potent inhibitor of pathological calcification. The circulating levels of fetuin-A, a well-described inhibitor of calcification, regulate the cell-dependent process of osteogenesis. The low circulating fetuin-A levels are associated with a greater prevalence and/or severity of Vascular calcification (VC) and increased risk for all-cause and cardiovascular mortality. However, high circulating fetuin-A levels appear to induce insulin resistance and, in non-dialyzed subjects with diabetic nephropathy, are directly related to VC burden. The emerging role of fetuin-A deficiency as a risk factor in dialysis patients was documented in cross-sectional studies demonstrating a significant correlation with all-cause and cardiovascular mortality. Additionally, Human fetuin-A is a negative acute phase protein involved in inflammatory diseases, thus being a potential physiological regulator of meprin activity. Fetuin-A is a broad-range protease inhibitor. Fetuin-A and cystatin C as endogenous proteolytic regulators of meprin activity broadens our understanding of the proteolytic network in plasma.
Fetuin-B is a member of the Fetuin family that is part of the Cystatin superfamily of Cysteine Protease inhibitors. It is reported that Fetuin-B is highly expressed in liver tissue, in tongue and placenta tissues. Fetuin-B is a paralogue of Fetuin-A. Fetuin-A and Fetuin-B display similarities and differences in their characteristics, however, they share only 20% amino acid sequence identity. The amounts of Fetuin-B in human serum, unlike Fetuin-A, vary with gender and are higher in females than in males. Fetuin-B is an inhibitor of basic calcium phosphate precipitation but is less active than Fetuin-A. Fetuin-B expression is decreased in Fetuin-A deficient knock-out mice. The expression of Fetuin-B has been shown to be regulated by FXR (Farnesoid X Receptor), a nuclear receptor activated by bile acids. Evidence has shown that overexpression of Fetuin-B in skin squamous carcinoma cells suppresses tumor growth in nude mice. The function of Fetuin B is still not fully characterized.
Fetuin-B , also known as Fetuin-like protein IRL685 and FETUB , is a secreted protein which belongs to thefetuin family. Fetuin-B / FETUB contains twocystatin domains. Fetuin-B is a member of the fetuin family , part of the cystatin superfamily of cysteine protease inhibitors. Fetuins have been implicated in several diverse functions , including osteogenesis and bone resorption. Fetuin-A has been identified as a major protein during fetal life and is also involved in important functions such as protease inhibitory activities and development-associated regulation of calcium metabolism and osteogenesis. Fetuin-A is a key partner in the recovery phase of an acute inflammatory response. Fetuin-B / FETUB is found at least in Human and rodents. It is unambiguously a paralogue of Fetuin-A. Fetuin-A and Fetuin-B exhibit significant differences at the amino acid sequence level , notably including variations with respect to the archetypal fetuin-specific signature.
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