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HGNC Approved Gene Symbol: RPN1
Cytogenetic location: 3q21.3 Genomic coordinates (GRCh38): 3:128,619,969-128,650,818 (from NCBI)
Ribophorins I and II (180490) represent proteins that appear to be involved in ribosome binding. They are abundant, highly conserved glycoproteins located exclusively in the membranes of the rough endoplasmic reticulum.
Using probes derived from a human liver expression library, Crimaudo et al. (1987) isolated and sequenced full-length human cDNA clones encoding ribophorins I and II. The cDNA clones hybridize to mRNA species of 2.5 kb and encode polypeptides of 68.5 and 69.3 kD, respectively. Sequence comparisons and immunoblotting with specific antibodies showed both proteins to be highly conserved throughout a variety of species. However, no relationship between the 2 proteins could be deduced from their primary sequences.
Kelleher et al. (1992) reported that mammalian oligosaccharyltransferase activity is associated with a protein complex composed of ribophorin I, ribophorin II, and a 48-kD oligosaccharyltransferase protein (602202).
Rpn1 is a component of the proteasome base. Using in vitro binding assays with purified yeast proteasomes, Elsasser et al. (2002) found that the ubiquitin-like (UBL) domain of recombinant Rad23 (see 600061) interacted with proteasomes through the leucine-rich repeat domain of Rpn1. Yeast Dsk2 (see 300264) also contains a UBL domain, and it competed with Rad23 for proteasome binding.
Oligosaccharyltransferase (OST) complexes catalyze N-glycosylation of nascent polypeptides in the endoplasmic reticulum (ER) lumen. Dumax-Vorzet et al. (2013) found that human OST4 (618932) assembled into distinct OST complexes through association with STT3A (601134) or STT3B (608605), as well as with the OST accessory subunit, ribophorin I. Knockdown experiments showed that OST4 preferentially stabilized STT3A and its interacting partner, KCP2 (KRTCAP2; 619029). STT3A and/or ribophorin I, in turn, stabilized OST4 in the complex. Depletion of OST4 destabilized both STT3A- and STT3B-containing OST complexes and released a ribophorin I-containing subcomplex. OST4 and ribophorin I stabilized whole OST complexes, and both proteins modulated the efficiency of N-glycosylation of endogenous prosaposin (PSAP; 176801) in HeLa cells.
Shi et al. (2016) found that the 5 proteasomal ubiquitin receptors known in yeast to that time are collectively nonessential for ubiquitin recognition and identified a sixth receptor, Rpn1. A site, T1, in the Rpn1 toroid recognized ubiquitin and UBL domains of substrate shuttling factors. T1 structures with monoubiquitin or lysine-48 diubiquitin show 3 neighboring outer helices engaging 2 ubiquitins. T1 contributes a distinct substrate-binding pathway with preference for lysine-48-linked chains. Proximal to T1 within the Rpn1 toroid is a second UBL-binding site, T2, that assists in ubiquitin chain disassembly, by binding the UBL of deubiquitinating enzyme Ubp6. Thus, a 2-site recognition domain intrinsic to the proteasome uses distinct ubiquitin-fold ligands to assemble substrates, shuttling factors, and a deubiquitinating enzyme.
Using cDNA clones, Barton et al. (1987) mapped the RPN1 gene to chromosome 3 in somatic cell hybrids. Pekarsky et al. (1997) reported that the RPN1 gene maps to chromosome 3q21.
In the UCSD-AML1 leukemia cell line, which has a t(3;3)(q21;q26) translocation, Pekarsky et al. (1997) identified several intergenic fusion transcripts involving EVI1 (165215), including an in-frame fusion of exon 1 of RBPH1 with exon 2 of EVI1.
Barton, D. E., Crimaudo, C., Hortsch, M., Francke, U. The genes for ribophorins I and II are on human chromosomes 3q and 20 and mouse chromosomes 6 and 12, respectively. (Abstract) Cytogenet. Cell Genet. 46: 577 only, 1987.
Crimaudo, C., Hortsch, M., Gausepohl, H., Meyer, D. I. Human ribophorins I and II: the primary structure and membrane topology of two highly conserved round endoplasmic reticulum-specific glycoproteins. EMBO J. 6: 75-82, 1987. [PubMed: 3034581] [Full Text: https://doi.org/10.1002/j.1460-2075.1987.tb04721.x]
Dumax-Vorzet, A., Roboti, P., High, S. OST4 is a subunit of the mammalian oligosaccharyltransferase required for efficient N-glycosylation. J. Cell Sci. 126: 2595-2606, 2013. [PubMed: 23606741] [Full Text: https://doi.org/10.1242/jcs.115410]
Elsasser, S., Gali, R. R., Schwickart, M., Larsen, C. N., Leggett, D. S., Muller, B., Feng, M. T., Tubing, F., Dittmar, G. A. G., Finley, D. Proteasome subunit Rpn1 binds ubiquitin-like protein domains. Nature Cell Biol. 4: 725-730, 2002. [PubMed: 12198498] [Full Text: https://doi.org/10.1038/ncb845]
Kelleher, D. J., Kreibich, G., Gilmore, R. Oligosaccharyltransferase activity is associated with a protein complex composed of ribophorins I and II and a 48 kd protein. Cell 69: 55-65, 1992. [PubMed: 1555242] [Full Text: https://doi.org/10.1016/0092-8674(92)90118-v]
Pekarsky, Y., Rynditch, A., Wieser, R., Fonatsch, C., Gardiner, K. Activation of a novel gene in 3q21 and identification of intergenic fusion transcripts with ecotropic viral insertion site I in leukemia. Cancer Res. 57: 3914-3919, 1997. [PubMed: 9307271]
Shi, Y., Chen, X., Elsasser, S., Stocks, B. B., Tian, G., Lee, B.-H., Shi, Y., Zhang, N., de Poot, S. A. H., Tuebing, F., Sun, S., Vannoy, J., Tarasov, S. G., Engen, J. R., Finley, D., Walters, K. J. Rpn1 provides adjacent receptor sites for substrate binding and deubiquitination by the proteasome. Science 351: aad9421, 2016. Note: Electronic Article. [PubMed: 26912900] [Full Text: https://doi.org/10.1126/science.aad9421]