alpha-2-HS-glycoprotein (AHSG, Alpha-2-Heremans-Schmid Glycoprotein) also known as fetuin-A is a protein that in humans is encoded by the AHSG gene. [4] [5] [6] Fetuin-A belongs to the fetuin class of plasma binding proteins and is more abundant in fetal than adult blood.
Alpha2-HS glycoprotein, a glycoprotein present in the serum, is synthesized by hepatocytes and adipocytes. [7] The AHSG molecule consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. It is involved in several functions, such as endocytosis, brain development and the formation of bone tissue. The protein is commonly present in the cortical plate of the immature cerebral cortex and bone marrow hemopoietic matrix, and it has therefore been postulated that it participates in the development of the tissues. However, its exact significance is still obscure. [6]
The choroid plexus is an established extrahepatic expression site. The mature circulating AHSG molecule consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. Multiple post-translational modifications have been reported. [8] Thus AHSG is a secreted partially phosphorylated glycoprotein with complex proteolytic processing that circulates in blood and extracellular fluids. In the test tube AHSG can bind multiple ligands and therefore has been claimed to be involved in several functions, such as endocytosis, brain development and the formation of bone tissue. Most of these functions await confirmation in vivo.
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. [9] [10] [11] Thus fetuin-A is a potent inhibitor of pathological calcification, in particular Calciphylaxis. [12] Mice deficient in fetuin-A show systemic calcification of soft tissues. [13] [14] Fetuin-A can inhibit calcification, and inhibits osteogenesis in bone. [11] Fetuin-A appears to promote calcification in coronary artery disease, but oppose calcification in peripheral artery disease. [11]
High levels of Fetuin-A are associated with obesity and insulin resistance. [11] [7] Fetuin-A promotes insulin resistance by enhancing the binding of free fatty acids to TLR4. [11] [7] In adipose tissue, Fetuin-A downregulates the expression of adiponectin, thereby increasing inflammation and insulin resistance. [11] Also in adipose tissue, Fetuin-A reduces lipogenesis and increases lipolysis, thereby increasing obesity and insulin resistance. [7]
Supervised exercise (that is not associated with weight reduction) reduces Fetuin-A. [7]
α2-Macroglobulin (α2M) or alpha-2-macroglobulin is a large plasma protein found in the blood. It is mainly produced by the liver, and also locally synthesized by macrophages, fibroblasts, and adrenocortical cells. In humans it is encoded by the A2M gene.
Fetuins are blood proteins that are made in the liver and secreted into the bloodstream. They belong to a large group of binding proteins mediating the transport and availability of a wide variety of cargo substances in the bloodstream. Fetuin-A is a major carrier protein of free fatty acids in the circulation. The best known representative of carrier proteins is serum albumin, the most abundant protein in the blood plasma of adult animals. Fetuin is more abundant in fetal blood, hence the name "fetuin". Fetal bovine serum contains more fetuin than albumin, while adult serum contains more albumin than fetuin.
HLA class II histocompatibility antigen, DR alpha chain is a protein that in humans is encoded by the HLA-DRA gene. HLA-DRA encodes the alpha subunit of HLA-DR. Unlike the alpha chains of other Human MHC class II molecules, the alpha subunit is practically invariable. However it can pair with, in any individual, the beta chain from 3 different DR beta loci, DRB1, and two of any DRB3, DRB4, or DRB5 alleles. Thus there is the potential that any given individual can form 4 different HLA-DR isoforms.
Sodium channel protein type 4 subunit alpha is a protein that in humans is encoded by the SCN4A gene.
Insulin-like growth factor-binding protein 1 (IBP-1) also known as placental protein 12 (PP12) is a protein that in humans is encoded by the IGFBP1 gene.
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 is an enzyme that in humans is encoded by the ENPP1 gene.
Collagen alpha-1(VI) chain is a protein that in humans is encoded by the COL6A1 gene.
Laminin subunit alpha-2 is a protein that in humans is encoded by the LAMA2 gene.
Zinc-alpha-2-glycoprotein is a protein that in humans is encoded by the AZGP1 gene.
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-3 is an enzyme that in humans is encoded by the PLCB3 gene.
Collagen alpha-1(XIV) chain is a protein that in humans is encoded by the COL14A1 gene. It likely plays a role in collagen binding and cell-cell adhesion.
Collagen alpha-2(IX) chain is a protein that in humans is encoded by the COL9A2 gene.
Collagen alpha-1(VIII) chain is a protein that in humans is encoded by the COL8A1 gene.
CD109 is a human gene.
Inter-alpha-trypsin inhibitor heavy chain H4 is a protein that in humans is encoded by the ITIH4 gene.
Fetuin-B is a protein that in humans is encoded by the FETUB gene.
Alpha-1-acid glycoprotein 1 is a protein that in humans is encoded by the ORM1 gene.
Glycoprotein hormone alpha-2 is a protein that in humans is encoded by the GPHA2 gene.
Dystrobrevin beta is a protein which in humans is encoded by the DTNB gene.
Hepatokines are proteins produced by liver cells (hepatocytes) that are secreted into the circulation and function as hormones across the organism. Research is mostly focused on hepatokines that play a role in the regulation of metabolic diseases such as diabetes and fatty liver and include: Adropin, ANGPTL4, Fetuin-A, Fetuin-B, FGF-21, Hepassocin, LECT2, RBP4,Selenoprotein P, Sex hormone-binding globulin.
