| Structural highlights
Disease
ALBU_HUMAN Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM:103600. FDH is a form of euthyroid hyperthyroxinemia that is due to increased affinity of ALB for T(4). It is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasian population.[1] [2] [3] [4]
Function
ALBU_HUMAN Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.[5]
Publication Abstract from PubMed
CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.
Discovery and characterization of an endogenous CXCR4 antagonist.,Zirafi O, Kim KA, Standker L, Mohr KB, Sauter D, Heigele A, Kluge SF, Wiercinska E, Chudziak D, Richter R, Moepps B, Gierschik P, Vas V, Geiger H, Lamla M, Weil T, Burster T, Zgraja A, Daubeuf F, Frossard N, Hachet-Haas M, Heunisch F, Reichetzeder C, Galzi JL, Perez-Castells J, Canales-Mayordomo A, Jimenez-Barbero J, Gimenez-Gallego G, Schneider M, Shorter J, Telenti A, Hocher B, Forssmann WG, Bonig H, Kirchhoff F, Munch J Cell Rep. 2015 May 5;11(5):737-47. doi: 10.1016/j.celrep.2015.03.061. Epub 2015, Apr 23. PMID:25921529[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sunthornthepvarakul T, Angkeow P, Weiss RE, Hayashi Y, Refetoff S. An identical missense mutation in the albumin gene results in familial dysalbuminemic hyperthyroxinemia in 8 unrelated families. Biochem Biophys Res Commun. 1994 Jul 29;202(2):781-7. PMID:8048949
- ↑ Rushbrook JI, Becker E, Schussler GC, Divino CM. Identification of a human serum albumin species associated with familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab. 1995 Feb;80(2):461-7. PMID:7852505
- ↑ Wada N, Chiba H, Shimizu C, Kijima H, Kubo M, Koike T. A novel missense mutation in codon 218 of the albumin gene in a distinct phenotype of familial dysalbuminemic hyperthyroxinemia in a Japanese kindred. J Clin Endocrinol Metab. 1997 Oct;82(10):3246-50. PMID:9329347
- ↑ Sunthornthepvarakul T, Likitmaskul S, Ngowngarmratana S, Angsusingha K, Kitvitayasak S, Scherberg NH, Refetoff S. Familial dysalbuminemic hypertriiodothyroninemia: a new, dominantly inherited albumin defect. J Clin Endocrinol Metab. 1998 May;83(5):1448-54. PMID:9589637
- ↑ Lu J, Stewart AJ, Sadler PJ, Pinheiro TJ, Blindauer CA. Albumin as a zinc carrier: properties of its high-affinity zinc-binding site. Biochem Soc Trans. 2008 Dec;36(Pt 6):1317-21. doi: 10.1042/BST0361317. PMID:19021548 doi:10.1042/BST0361317
- ↑ Zirafi O, Kim KA, Standker L, Mohr KB, Sauter D, Heigele A, Kluge SF, Wiercinska E, Chudziak D, Richter R, Moepps B, Gierschik P, Vas V, Geiger H, Lamla M, Weil T, Burster T, Zgraja A, Daubeuf F, Frossard N, Hachet-Haas M, Heunisch F, Reichetzeder C, Galzi JL, Perez-Castells J, Canales-Mayordomo A, Jimenez-Barbero J, Gimenez-Gallego G, Schneider M, Shorter J, Telenti A, Hocher B, Forssmann WG, Bonig H, Kirchhoff F, Munch J. Discovery and characterization of an endogenous CXCR4 antagonist. Cell Rep. 2015 May 5;11(5):737-47. doi: 10.1016/j.celrep.2015.03.061. Epub 2015, Apr 23. PMID:25921529 doi:http://dx.doi.org/10.1016/j.celrep.2015.03.061
|
