HGNC Approved Gene Symbol: FETUB
Cytogenetic location: 3q27.3 Genomic coordinates (GRCh38) : 3:186,635,969-186,653,141 (from NCBI)
The fetuin family, which includes FETUB, is part of the cystatin superfamily and encompasses a series of tightly related proteins that are synthesized mostly in the liver. Fetuins have been implicated in several diverse functions, including osteogenesis and bone resorption, regulation of the insulin and hepatocyte growth factor receptors (147670 and 164860, respectively), and response to systemic inflammation (summary by Olivier et al., 2000).
In an effort to identify hepatic genes preferentially expressed during acute inflammation, Olivier et al. (1999) identified a partial cDNA encoding rat fetuin B (Fetub). Northern blot analysis detected liver-specific expression of rat Fetub.
By searching an EST database using the full-length rat sequence as the probe, Olivier et al. (2000) identified cDNAs encoding human and mouse FETUB. The 382-amino acid human FETUB protein shares sequence and structural similarity with fetuin A (FETUA; 138680). The human, mouse, and rat FETUB proteins share 61% amino acid identity. Northern blot analysis detected a developmentally regulated expression pattern for Fetub in mouse and rat liver that differed between species. In response to inflammatory stimulus, hepatic levels of rat Fetua and Fetub were downregulated.
Using Northern blot analysis, Denecke et al. (2003) showed that fetuin A and B transcripts were expressed predominantly in human liver, with lower levels in placenta. Mouse fetuin A and B also showed predominant expression in liver. Immunoblot analysis demonstrated that fetuin A and B were secreted into sera of human, rat, and mouse. In human serum, fetuin B was more abundant in females than males. Fetuin A and B proteins had apparent molecular masses of 60 kD, higher than the calculated molecular masses, likely due to N-glycosylation and other posttranslational modifications.
Using ESTs, Olivier et al. (2000) mapped the FETUB gene to chromosome 3q27, where the FETUA gene is localized.
Denecke et al. (2003) mapped the Fetub gene to mouse chromosome 13, next to the Fetua gene.
Denecke et al. (2003) showed that recombinant mouse fetuin A and B inhibited precipitation of basic calcium phosphate, although fetuin B was less active than fetuin A.
Dietzel et al. (2013) found no apparent differences in Fetub -/- mice compared with wildtype except that Fetub -/- females were completely infertile due to an early block in fertilization. Fertility of Fetub -/- mouse ovaries could be restored by transplanting them into wildtype recipients, as liver-derived Fetub could reach ovaries through blood circulation. Infertility of Fetub -/- ovaries could also be rescued by laser-assisted in vitro fertilization, as Fetub -/- ovaries underwent premature zona pellucid hardening due to lack of ovastacin (ASTL; 608860) inhibition.
Denecke, B., Graber, S., Schafer, C., Heiss, A., Woltje, M., Jahnen-Dechent, W. Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A. Biochem. J. 376: 135-145, 2003. [PubMed: 12943536] [Full Text: https://doi.org/10.1042/BJ20030676]
Dietzel, E., Wessling, J., Floehr, J., Schafer, C., Ensslen, S., Denecke, B., Rosing, B., Neulen, J., Veitinger, T., Spehr, M., Tropartz, T., Tolba, R., and 9 others. Fetuin-B, a liver-derived plasma protein is essential for fertilization. Dev. Cell 25: 106-112, 2013. [PubMed: 23562279] [Full Text: https://doi.org/10.1016/j.devcel.2013.03.001]
Olivier, E., Soury, E., Risler, J. L., Smith, F., Schneider, K., Lochner, K., Jouzeau, J. Y., Fey, G. H., Salier, J. P. A novel set of hepatic mRNAs preferentially expressed during an acute inflammation in rat represents mostly intracellular proteins. Genomics 57: 352-364, 1999. [PubMed: 10329001] [Full Text: https://doi.org/10.1006/geno.1999.5795]
Olivier, E., Soury, E., Ruminy, P., Husson, A., Parmentier, F., Daveau, M., Salier, J.-P. Fetuin-B, a second member of the fetuin family in mammals. Biochem. J. 350: 589-597, 2000. [PubMed: 10947975]