Submitted July 23, 2002
Accepted November 25, 2002
UbcH5A, a Member of Human Ubiquitin Conjugating Enzymes E2, is Closely Related to SFT, a Stimulator of Iron Transport, and Up-regulated in Hereditary Hemochromatosis
Sven G Gehrke, Hans Dieter Riedel, Thomas Herrmann, Boris Hadaschik, Karin Bents, Claudia Veltkamp, and Wolfgang Stremmel*
Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany
* Corresponding author; email: stremmel{at}medizin-online.com.
SFT, a stimulator of Fe transport, has been described as a transmembrane protein that facilitates the uptake of ferrous and ferric iron in mammalian cells. This study was initiated to investigate the 5' regulatory region of SFT and its role in the etiology of hereditary hemochromatosis. Sequence analyses of the putative 5' regulatory region revealed that the SFT cDNA sequence corresponds to intron 6 / exon 7 of UbcH5A, a member of ubiquitin-conjugating enzymes E2, which is involved in the iron-dependent ubiquitination of the hypoxia-inducible factor (HIF) by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex. Further mRNA expression studies using a sequence-specific RT-PCR assay showed that UbcH5A is significantly up-regulated in the liver of iron-overloaded patients with hereditary hemochromatosis, as previously published for SFT. However, in vitro studies on HepG2 cells failed to demonstrate any significant UbcH5A regulation in response to iron loading or iron chelation. In conclusion, in vivo mRNA expression data previously obtained for SFT might be attributed to UbcH5A. The role of UbcH5A and the ubiquitination pathway in the etiology of hereditary hemochromatosis remains to be elucidated further.
