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RPN2
Identifiers
Aliases	RPN2, RIBIIR, RPN-II, RPNII, SWP1, ribophorin II
External IDs	OMIM: 180490; MGI: 98085; HomoloGene: 2214; GeneCards: RPN2; OMA:RPN2 - orthologs
Gene location (Human) Chr. Chromosome 20 (human) Band 20q11.23 Start 37,178,410 bp End 37,241,619 bp
Gene location (Mouse) Chr. Chromosome 2 (mouse) Band 2 H1|2 78.2 cM Start 157,120,937 bp End 157,168,239 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in corpus epididymis pylorus placenta pericardium mucosa of ileum stromal cell of endometrium islet of Langerhans caput epididymis pancreatic ductal cell trachea Top expressed in Ileal epithelium spermatocyte spermatid yolk sac seminal vesicula corneal stroma lacrimal gland calvaria stroma of bone marrow parotid gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function dolichyl-diphosphooligosaccharide-protein glycotransferase activity ribosome binding protein binding Cellular component integral component of membrane rough endoplasmic reticulum autophagosome membrane membrane endoplasmic reticulum membrane oligosaccharyltransferase complex endoplasmic reticulum Biological process ageing protein N-linked glycosylation via asparagine protein glycosylation protein N-linked glycosylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6185 20014 Ensembl ENSG00000118705 ENSMUSG00000027642 UniProt P04844 Q9DBG6 RefSeq (mRNA) NM_001135771 NM_002951 NM_001324299 NM_001324301 NM_001324302 NM_001324303 NM_001324304 NM_001324305 NM_001324306 NM_019642 NM_001355163 NM_001355164 NM_001355165 RefSeq (protein) NP_001129243 NP_001311228 NP_001311230 NP_001311231 NP_001311232 NP_001311233 NP_001311234 NP_001311235 NP_002942 NP_062616 NP_001342092 NP_001342093 NP_001342094 Location (UCSC) Chr 20: 37.18 – 37.24 Mb Chr 2: 157.12 – 157.17 Mb PubMed search
Wikidata
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Dolichyl-diphosphooligosaccharide—protein glycosyltransferase subunit 2, also called ribophorin ǁ is an enzyme that in humans is encoded by the RPN2 gene.

Function

This gene encodes a type I integral ribophorin membrane protein found only in the rough endoplasmic reticulum. The encoded protein is part of an N-oligosaccharyl transferase complex that links high mannose oligosaccharides to asparagine residues found in the Asn-X-Ser/Thr consensus motif of nascent polypeptide chains. This protein is similar in sequence to the yeast oligosaccharyl transferase subunit SWP1. RPN2 has been demonstrated to be a prognostic marker of human cancer, and may be a potential target of clinical importance.

Structure

Gene

The RPN2 gene lies on the chromosome location of 20q11.23 and consists of 19 exons.

Protein

RPN2 consists of 631 amino acid residues and weighs 69284Da.

Function

RPN2 is a unique integral glycoprotein in rough ER membrane that is involved in translocation and the maintenance of the structural uniqueness of the rough ER. It is also an essential subunit of N-oligosaccharyl transferase complex that conjugates high mannose oligosaccharides to asparagine residues in the N-X-S/T consensus motif of nascent polypeptide chains. RPN2 regulates the glycosylation of multi-drug resistance, and thus its interference could decrease the membrane localization of P-glycoprotein by reducing its glycosylation status and restored the sensitivity to docetaxel.

Clinical significance

RPN2 has been demonstrated to be a prognostic marker of human cancer. RPN2 is highly expressed in breast cancer stem cells and is associated with tumor metastasis. Recent study has shown that its expression is correlated with clinically aggressive features of breast cancer, implying a possible application in personalized medicine. RPN2 silencing has been reported to repress tumorigenicity and to sensitize the tumors to cisplatin treatment, which led to the longer survival of NSCLC-bearing mice, suggesting that RPN2 may represent a promising new target for RNAi-based medicine against NSCLC. Similar potential application has also been shown in osteosarcoma, esophageal squamous cell carcinoma and colorectal cancer. RPN2 is also reported to be one of the prothrombin-binding proteins on monocyte surfaces, suggesting that its involvement in the pathophysiology of thrombosis in patients with APS.

Interactions

P53

tetraspanin CD63

prothrombin

References

1. ^ GRCh38: Ensembl release 89: ENSG00000118705 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000027642 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. ^ "Entrez Gene: RPN2 ribophorin II".
6. Kelleher DJ, Kreibich G, Gilmore R (April 1992). "Oligosaccharyltransferase activity is associated with a protein complex composed of ribophorins I and II and a 48 kd protein". Cell. 69 (1): 55–65. doi:10.1016/0092-8674(92)90118-v. PMID 1555242. S2CID 46304250.
7. Kelleher DJ, Gilmore R (April 2006). "An evolving view of the eukaryotic oligosaccharyltransferase". Glycobiology. 16 (4): 47R–62R. doi:10.1093/glycob/cwj066. PMID 16317064.
8. Crimaudo C, Hortsch M, Gausepohl H, Meyer DI (January 1987). "Human ribophorins I and II: the primary structure and membrane topology of two highly conserved rough endoplasmic reticulum-specific glycoproteins". The EMBO Journal. 6 (1): 75–82. doi:10.1002/j.1460-2075.1987.tb04721.x. PMC 553359. PMID 3034581.
9. Yuan TM, Liang RY, Chueh PJ, Chuang SM (April 2015). "Role of ribophorin II in the response to anticancer drugs in gastric cancer cell lines". Oncology Letters. 9 (4): 1861–1868. doi:10.3892/ol.2015.2900. PMC 4356382. PMID 25789057.
10. ^ Fujita Y, Yagishita S, Takeshita F, Yamamoto Y, Kuwano K, Ochiya T (February 2015). "Prognostic and therapeutic impact of RPN2-mediated tumor malignancy in non-small-cell lung cancer". Oncotarget. 6 (5): 3335–45. doi:10.18632/oncotarget.2793. PMC 4413657. PMID 25595901.
11. ^ Ono M, Tsuda H, Kobayashi T, Takeshita F, Takahashi RU, Tamura K, Akashi-Tanaka S, Moriya T, Yamasaki T, Kinoshita T, Yamamoto J, Fujiwara Y, Ochiya T (June 2015). "The expression and clinical significance of ribophorin II (RPN2) in human breast cancer". Pathology International. 65 (6): 301–8. doi:10.1111/pin.12297. PMID 25881688. S2CID 36249480.
12. Fujiwara T, Takahashi RU, Kosaka N, Nezu Y, Kawai A, Ozaki T, Ochiya T (September 2014). "RPN2 Gene Confers Osteosarcoma Cell Malignant Phenotypes and Determines Clinical Prognosis". Molecular Therapy: Nucleic Acids. 3 (9): e189. doi:10.1038/mtna.2014.35. PMC 4222647. PMID 25181275.
13. Kurashige J, Watanabe M, Iwatsuki M, Kinoshita K, Saito S, Nagai Y, Ishimoto T, Baba Y, Mimori K, Baba H (October 2012). "RPN2 expression predicts response to docetaxel in oesophageal squamous cell carcinoma". British Journal of Cancer. 107 (8): 1233–8. doi:10.1038/bjc.2012.396. PMC 3494434. PMID 22955852.
14. Zhang J, Yan B, Späth SS, Qun H, Cornelius S, Guan D, Shao J, Hagiwara K, Van Waes C, Chen Z, Su X, Bi Y (1 January 2015). "Integrated transcriptional profiling and genomic analyses reveal RPN2 and HMGB1 as promising biomarkers in colorectal cancer". Cell & Bioscience. 5: 53. doi:10.1186/s13578-015-0043-9. PMC 4574027. PMID 26388988.
15. ^ Fujieda Y, Amengual O, Matsumoto M, Kuroki K, Takahashi H, Kono M, Kurita T, Otomo K, Kato M, Oku K, Bohgaki T, Horita T, Yasuda S, Maenaka K, Hatakeyama S, Nakayama KI, Atsumi T (June 2016). "Ribophorin II is involved in the tissue factor expression mediated by phosphatidylserine-dependent antiprothrombin antibody on monocytes". Rheumatology. 55 (6): 1117–26. doi:10.1093/rheumatology/kew005. PMID 26895716.
16. Tominaga N, Hagiwara K, Kosaka N, Honma K, Nakagama H, Ochiya T (May 2014). "RPN2-mediated glycosylation of tetraspanin CD63 regulates breast cancer cell malignancy". Molecular Cancer. 13: 134. doi:10.1186/1476-4598-13-134. PMC 4070641. PMID 24884960.

Further reading

• Stoffel M, Xiang K, Bell GI (November 1992). "Dinucleotide repeat polymorphism at the human ribophorin II locus (RPN2) on chromosome 20q". Human Molecular Genetics. 1 (8): 656. doi:10.1093/hmg/1.8.656. PMID 1301181.
• Löffler C, Rao VV, Hansmann I (June 1991). "Mapping of the ribophorin II (RPN II) gene to human chromosome 20q12-q13.1 by in-situ hybridization". Human Genetics. 87 (2): 221–2. doi:10.1007/BF00204188. PMID 2066112. S2CID 26258810.
• Kumar V, Heinemann FS, Ozols J (June 1998). "Interleukin-2 induces N-glycosylation in T-cells: characterization of human lymphocyte oligosaccharyltransferase". Biochemical and Biophysical Research Communications. 247 (2): 524–9. doi:10.1006/bbrc.1998.8780. PMID 9642163.
• Fu J, Kreibich G (February 2000). "Retention of subunits of the oligosaccharyltransferase complex in the endoplasmic reticulum". The Journal of Biological Chemistry. 275 (6): 3984–90. doi:10.1074/jbc.275.6.3984. PMID 10660554.
• Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology. 21 (5): 566–9. doi:10.1038/nbt810. PMID 12665801. S2CID 23783563.
• Kelleher DJ, Karaoglu D, Mandon EC, Gilmore R (July 2003). "Oligosaccharyltransferase isoforms that contain different catalytic STT3 subunits have distinct enzymatic properties". Molecular Cell. 12 (1): 101–11. doi:10.1016/S1097-2765(03)00243-0. PMID 12887896.
• Shibatani T, David LL, McCormack AL, Frueh K, Skach WR (April 2005). "Proteomic analysis of mammalian oligosaccharyltransferase reveals multiple subcomplexes that contain Sec61, TRAP, and two potential new subunits". Biochemistry. 44 (16): 5982–92. doi:10.1021/bi047328f. PMID 15835887.
• Tu LC, Yan X, Hood L, Lin B (April 2007). "Proteomics analysis of the interactome of N-myc downstream regulated gene 1 and its interactions with the androgen response program in prostate cancer cells". Molecular & Cellular Proteomics. 6 (4): 575–88. doi:10.1074/mcp.M600249-MCP200. PMID 17220478.

• Genes on human chromosome 20
• Genes mutated in mice