Yamabe et al. (1997) identified a novel gene, which they termed REP8, in the 8p12-p11 chromosome region. The full-length cDNA predicted a polypeptide of 270 amino acids. Northern blotting revealed transcript sizes of 1.5 and 2.0 kb. The gene was expressed abundantly in human ovary and testis, and weakly in all other tissues tested. Genomic analysis showed that the REP8 gene consists of 8 exons spanning 20 kb. By FISH, Yamabe et al. (1997) localized REP8 to chromosome 8p12-p11.2, near the PPP2CB gene.
General function
Cell cycle regulation
Comment
Perhaps it plays a role in reproduction, as it is most highly expressed in the ovary and testis.
Cellular localization
ER
Comment
Ovarian function
Comment
Expression regulated by
Comment
Ovarian localization
Granulosa
Comment
The Tissue-Specific Rep8/UBXD6 Tethers p97 to the Endoplasmic Reticulum Membrane for Degradation of Misfolded Proteins. Madsen L et al. The protein known as p97 or VCP in mammals and Cdc48 in yeast is a versatile ATPase complex involved in several biological functions including membrane fusion, protein folding, and activation of membrane-bound transcription factors. In addition, p97 plays a central role in degradation of misfolded secretory proteins via the ER-associated degradation pathway. This functional diversity of p97 depends on its association with various cofactors, and to further our understanding of p97 function it is important that these cofactors are identified and analyzed. Here, we isolate and characterize the human protein named Rep8 or Ubxd6 as a new cofactor of p97. Mouse Rep8 is highly tissue-specific and abundant in gonads. In testes, Rep8 is expressed in post-meiotic round spermatids, whereas in ovaries Rep8 is expressed in granulosa cells. Rep8 associates directly with p97 via its UBX domain. We show that Rep8 is a transmembrane protein that localizes to the ER membrane with its UBX domain facing the cytoplasm. Knock-down of Rep8 expression in human cells leads to a decreased association of p97 with the ER membrane and concomitantly a retarded degradation of misfolded ER-derived proteasome substrates. Thus, Rep8 tethers p97 to the ER membrane for efficient ER-associated degradation.