Jump to content

RPN2

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by 1234qwer1234qwer4 (talk | contribs) at 11:29, 4 March 2023 (Importing Wikidata short description: Protein-coding gene in the species Homo sapiens (shortdescs-in-category)). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

RPN2
Identifiers
AliasesRPN2, RIBIIR, RPN-II, RPNII, SWP1, ribophorin II
External IDsOMIM: 180490; MGI: 98085; HomoloGene: 2214; GeneCards: RPN2; OMA:RPN2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

6185

20014

Ensembl

ENSG00000118705

ENSMUSG00000027642

UniProt

P04844

Q9DBG6

RefSeq (mRNA)

NM_019642
NM_001355163
NM_001355164
NM_001355165

RefSeq (protein)

NP_062616
NP_001342092
NP_001342093
NP_001342094

Location (UCSC)Chr 20: 37.18 – 37.24 MbChr 2: 157.12 – 157.17 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Dolichyl-diphosphooligosaccharide—protein glycosyltransferase subunit 2, also called ribophorin ǁ is an enzyme that in humans is encoded by the RPN2 gene.[5]

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.[5] 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.[6][7][8][9] 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.[10]

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.[11] 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.[10] Similar potential application has also been shown in osteosarcoma, esophageal squamous cell carcinoma and colorectal cancer.[12][13][14] 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.[15]

Interactions

P53[11]

tetraspanin CD63 [16]

prothrombin [15]

Model organisms

Model organisms have been used in the study of RPN2 function. A conditional knockout mouse line, called Rpn2tm1a(EUCOMM)Wtsi[21][22] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[23][24][25]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[19][26] Twenty six tests were carried out on mutant mice and two significant abnormalities were observed.[19] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals.[19]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000118705 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b "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. ^ a b 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. ^ a b 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: 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  15. ^ a b 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  17. ^ "Salmonella infection data for Rpn2". Wellcome Trust Sanger Institute.
  18. ^ "Citrobacter infection data for Rpn2". Wellcome Trust Sanger Institute.
  19. ^ a b c d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
  20. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  21. ^ "International Knockout Mouse Consortium".
  22. ^ "Mouse Genome Informatics".
  23. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  24. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  25. ^ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  26. ^ van der Weyden L, White JK, Adams DJ, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.{{cite journal}}: CS1 maint: unflagged free DOI (link)

Further reading

Retrieved from "https://en.wikipedia.org/w/index.php?title=RPN2&oldid=1142790375"