Sequence and functional relationships between androgen-binding protein/sex hormone-binding globulin and its homologs protein S, Gas6, laminin, and agrin.
Androgen-binding protein/sex hormone-binding globulin (ABP/SHBG) is an extracellular binding protein that regulates the bioavailability of sex steroids. ABP/SHBG is closely related to the globular (G) domain of vitamin K-dependent protein S family of proteins and more distantly related to the G domains of several extracellular matrix proteins. ABP/SHBG appears to have evolved from the fusion of two ancestral G domains. Expanding evidence suggests that ABP/SHBG has other functions that are mediated through membrane binding, including signal transduction; however, the types of binding proteins (receptors) have not been identified. Sequence comparisons of ABP/SHBG with G domains of its homologs protein S, Gas6, laminin, and agrin have identified regions of ABP/SHBG that may bind receptors related to homolog receptors. These membrane receptors include beta-integrins, alpha-dystroglycan, and receptor tyrosine kinases. The G domains of laminin and related proteins have clearly evolved from a common ancestor to interact with specific receptors and binding proteins. It remains to be determined if ABP/SHBG followed this evolutionary pathway.
Joseph
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Applied Genetics Laboratories, Inc., University of Florida, Alachua 32615, USA.
D018171:Agrin / Q000737:chemistry* / Q000502:physiology; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000727:Androgen-Binding Protein / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D003598:Cytoskeletal Proteins / Q000378:metabolism; D049030:Dystroglycans; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin / Q000737:chemistry* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D017293:Protein S / Q000737:chemistry* / Q000502:physiology; D011506:Proteins / Q000737:chemistry* / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017385:Sequence Homology; D012738:Sex Hormone-Binding Globulin / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D000099255:Growth Arrest-Specific Protein 6
D018171:Agrin; D000727:Androgen-Binding Protein; D003598:Cytoskeletal Proteins; D049030:Dystroglycans; D019812:Heparan Sulfate Proteoglycans; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; D008562:Membrane Glycoproteins; D017293:Protein S; D011506:Proteins; D020794:Receptor Protein-Tyrosine Kinases; D012738:Sex Hormone-Binding Globulin; D000099255:Growth Arrest-Specific Protein 6; C483081:DAG1 protein, human