Fetuin-A

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-A Related Areas

Enzyme>>Protease & Regulator>>Cysteine Protease & Regulator>>Fetuin-A/AHSG

Fetuin-A Alternative Names

Fetuin-A, AHSG, A2HS, AHS, FETUA, HSGA [Homo sapiens]

Fetuin-A, Ahsg [Mus musculus] [Mus musculus]

Summaries for Fetuin-A

Entrez Gene summary for AHSG:

Alpha2-HS glycoprotein (AHSG), a glycoprotein present in the serum, is synthesized by hepatocytes. The AHSG molecule consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. Fetuin-A is involved in several functions, such as endocytosis, brain development and the formation of bone tissue. Fetuin-A 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. [provided by RefSeq, Jul 2008]

Wikipedia summary for Fetuin-A:

Alpha-2-HS-glycoprotein (AHSG) also known as fetuin-A is a protein that in humans is encoded by the AHSG gene. Fetuin-A belongs to the fetuin class of plasma binding proteins and is more abundant in fetal than adult blood.

Human Fetuin-A Protein General Information

 

• Protein names: Fetuin-A
• Sequence length: 367 AA.
• Sequence similarities: Fetuin-A belongs to the fetuin family. Fetuin-A contains 2 cystatin fetuin-A-type domains.
• Post-translational modification: Phosphorylation sites are present in the extracelllular medium.
  O- and N-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. N-glycan at Asn-156: Hex5HexNAc4; N-glycan heterogeneity at Asn-176: Hex5HexNAc4 (major) and Hex6HexNAc5 (minor).
• Subunit structure: Fetuin-A derives from this precursor, when the connecting peptide is cleaved off. The two chains A and B are held together by a single disulfide bond.
• Subcellular location: Secreted.
• Tissue specificity: Fetuin-A is synthesized in liver and selectively concentrated in bone matrix. Secreted in plasma. Fetuin-A is also found in dentin in much higher quantities than other plasma proteins.
• Polymorphism: There are two common alleles, AHSG*1 and AHSG*2. AHSG*1 has Thr-248/Thr-256; AHSG*2 has Met-248/Ser-256.

General information above from UniProt

Function for Fetuin-A Protein

UniProtKB:

Fetuin-A promotes endocytosis, possesses opsonic properties and influences the mineral phase of bone. Fetuin-A shows affinity for calcium and barium ions.

Genatlas:

• Fetuin-A is the inhibitor of the insulin-receptor tyrosine kinase
• Fetuin-A is involved in skeletal development and chronic disorder such as vascular calcifications
• phosphate level is negatively correlated with Fetuin-A level
• Fetuin-A is implicated in the regulation of body fat and insulin sensitivity
• Fetuin-A is negative acute phase protein involved in inflammatory diseases, thus being a potential physiological regulator of meprin (MEP1A, MEP1B) activity (Pubmed 20806899)
• CST3 an Fetuin-A are endogenous inhibitors of human meprin metalloproteases(Pubmed 20806899)

Homology for human Fetuin-A

• homolog to collagen
• paralog to fetuin b