Alpha-2-HS-glycoprotein

alpha-2-HS-glycoprotein

alpha-2-HS-glycoprotein

Protein-coding gene in the species Homo sapiens

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.

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Function

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.

Clinical significance

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]

See also

References

  1. [1]
    GRCm38: Ensembl release 89: ENSMUSG00000022868 – Ensembl, May 2017
  2. [2]
    "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. [3]
    "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. [4]
    Rizzu P, Baldini A (1995). "Three members of the human cystatin gene superfamily, AHSG, HRG, and KNG, map within one megabase of genomic DNA at 3q27". Cytogenet. Cell Genet. 70 (1–2): 26–8. doi:10.1159/000133984. PMID 7736783.
  5. [5]
    Osawa M, Umetsu K, Sato M, Ohki T, Yukawa N, Suzuki T, Takeichi S (September 1997). "Structure of the gene encoding human alpha 2-HS glycoprotein (AHSG)". Gene. 196 (1–2): 121–5. doi:10.1016/S0378-1119(97)00216-3. PMID 9322749.
  6. [6]
    "Entrez Gene: AHSG alpha-2-HS-glycoprotein".
  7. [7]
    Ramírez-Vélez R, García-Hermoso A, Hackney AC, Izquierdo M (2019). "Effects of exercise training on Fetuin-a in obese, type 2 diabetes and cardiovascular disease in adults and elderly: a systematic review and Meta-analysis". Lipids in Health and Disease. 18 (1): 23. doi:10.1186/s12944-019-0962-2. PMC 6343360. PMID 30670052.
  8. [8]
    Jahnen-Dechent W, Trindl A, Godovac-Zimmermann J, Müller-Esterl W (November 1994). "Posttranslational processing of human alpha 2-HS glycoprotein (human fetuin). Evidence for the production of a phosphorylated single-chain form by hepatoma cells". Eur. J. Biochem. 226 (1): 59–69. doi:10.1111/j.1432-1033.1994.tb20026.x. PMID 7525288.
  9. [9]
    Heiss A, Eckert T, Aretz A, Richtering W, van Dorp W, Schäfer C, Jahnen-Dechent W (May 2008). "Hierarchical role of fetuin-A and acidic serum proteins in the formation and stabilization of calcium phosphate particles". J. Biol. Chem. 283 (21): 14815–25. doi:10.1074/jbc.M709938200. PMID 18364352.
  10. [10]
    Jahnen-Dechent W, Schäfer C, Ketteler M, McKee MD (April 2008). "Mineral chaperones: a role for fetuin-A and osteopontin in the inhibition and regression of pathologic calcification". J. Mol. Med. 86 (4): 379–89. doi:10.1007/s00109-007-0294-y. PMID 18080808. S2CID 20960971.
  11. [11]
    Bourebaba L, Marycz K (2019). "Pathophysiological Implication of Fetuin-A Glycoprotein in the Development of Metabolic Disorders: A Concise Review". Journal of Clinical Medicine. 8 (12): E2033. doi:10.3390/jcm8122033. PMC 6947209. PMID 31766373.
  12. [12]
    Bojincă, Violeta Claudia; Bojincă, Mihai; Iosif, Cristina Ileana; Bălănescu, Şerban Mihai; Bălănescu, Andra Rodica (2018). "Diagnostic challenges in a patient with calciphylaxia - a case report". Romanian Journal of Morphology and Embryology = Revue Roumaine de Morphologie et Embryologie. 59 (2): 591–594. ISSN 1220-0522. PMID 30173268.
  13. [13]
    Westenfeld R, Schäfer C, Smeets R, Brandenburg VM, Floege J, Ketteler M, Jahnen-Dechent W (June 2007). "Fetuin-A (AHSG) prevents extraosseous calcification induced by uraemia and phosphate challenge in mice". Nephrol. Dial. Transplant. 22 (6): 1537–46. doi:10.1093/ndt/gfm094. PMID 17389622.
  14. [14]
    Schafer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J, Muller-Esterl W, Schinke T, Jahnen-Dechent W (August 2003). "The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification". J. Clin. Invest. 112 (3): 357–66. doi:10.1172/JCI17202. PMC 166290. PMID 12897203.

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