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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox gene}}
{{PBB_Controls
'''Dolichyl-diphosphooligosaccharide—protein glycosyltransferase subunit 2,''' also called '''ribophorin ǁ''' is an [[enzyme]] that in humans is encoded by the ''RPN2'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: RPN2 ribophorin II| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6185| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
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.<ref name="entrez" /> RPN2 has been demonstrated to be a prognostic marker of human [[cancer]], and may be a potential target of clinical importance.
| image =
| image_source =
| PDB =  
| Name = Ribophorin II
| HGNCid = 10382
| Symbol = RPN2
| AltSymbols =; RIBIIR; RPN-II; RPNII; SWP1
| OMIM = 180490
| ECnumber = 
| Homologene = 2214
| MGIid = 98085
| GeneAtlas_image1 = PBB_GE_RPN2_208689_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_RPN2_213399_x_at_tn.png
| GeneAtlas_image3 = PBB_GE_RPN2_213491_x_at_tn.png
| Function = {{GNF_GO|id=GO:0004579 |text = dolichyl-diphosphooligosaccharide-protein glycotransferase activity}} {{GNF_GO|id=GO:0016740 |text = transferase activity}}
| Component = {{GNF_GO|id=GO:0005783 |text = endoplasmic reticulum}} {{GNF_GO|id=GO:0008250 |text = oligosaccharyl transferase complex}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process = {{GNF_GO|id=GO:0006464 |text = protein modification process}} {{GNF_GO|id=GO:0018279 |text = protein amino acid N-linked glycosylation via asparagine}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 6185
    | Hs_Ensembl = ENSG00000118705
    | Hs_RefseqProtein = NP_002942
    | Hs_RefseqmRNA = NM_002951
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 20
    | Hs_GenLoc_start = 35240888
    | Hs_GenLoc_end = 35303440
    | Hs_Uniprot = P04844
    | Mm_EntrezGene = 20014
    | Mm_Ensembl = ENSMUSG00000027642
    | Mm_RefseqmRNA = XM_977943
    | Mm_RefseqProtein = XP_983037
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 2
    | Mm_GenLoc_start = 156970500
    | Mm_GenLoc_end = 157017760
    | Mm_Uniprot = Q3U505
  }}
}}
'''Ribophorin II''', also known as '''RPN2''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: RPN2 ribophorin II| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6185| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Structure ==
{{PBB_Summary
=== Gene ===
| section_title =  
| summary_text = This gene encodes a type I integral 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.<ref name="entrez">{{cite web | title = Entrez Gene: RPN2 ribophorin II| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6185| accessdate = }}</ref>
}}


==References==
The ''RPN2'' gene lies on the [[chromosome]] location of 20q11.23 and consists of 19 [[exons]].
{{reflist|2}}
 
==Further reading==
=== Protein ===
{{refbegin | 2}}
RPN2 consists of 631 [[amino acid residues]] and weighs 69284Da.
{{PBB_Further_reading
 
| citations =  
== Function ==
*{{cite journal  | author=Stoffel M, Xiang K, Bell GI |title=Dinucleotide repeat polymorphism at the human ribophorin II locus (RPN2) on chromosome 20q. |journal=Hum. Mol. Genet. |volume=1 |issue= 8 |pages= 656 |year= 1993 |pmid= 1301181 |doi= }}
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]].<ref>{{cite journal | vauthors = Kelleher DJ, Kreibich G, Gilmore R | title = Oligosaccharyltransferase activity is associated with a protein complex composed of ribophorins I and II and a 48 kd protein | journal = Cell | volume = 69 | issue = 1 | pages = 55–65 | date = April 1992 | pmid = 1555242 | doi=10.1016/0092-8674(92)90118-v}}</ref><ref>{{cite journal | vauthors = Kelleher DJ, Gilmore R | title = An evolving view of the eukaryotic oligosaccharyltransferase | journal = Glycobiology | volume = 16 | issue = 4 | pages = 47R-62R | date = April 2006 | pmid = 16317064 | doi = 10.1093/glycob/cwj066 }}</ref><ref>{{cite journal | vauthors = Crimaudo C, Hortsch M, Gausepohl H, Meyer DI | title = Human ribophorins I and II: the primary structure and membrane topology of two highly conserved rough endoplasmic reticulum-specific glycoproteins | journal = The EMBO Journal | volume = 6 | issue = 1 | pages = 75–82 | date = January 1987 | pmid = 3034581 | pmc = 553359 }}</ref><ref>{{cite journal | vauthors = Yuan TM, Liang RY, Chueh PJ, Chuang SM | title = Role of ribophorin II in the response to anticancer drugs in gastric cancer cell lines | journal = Oncology Letters | volume = 9 | issue = 4 | pages = 1861–1868 | date = April 2015 | pmid = 25789057 | pmc = 4356382 | doi = 10.3892/ol.2015.2900 }}</ref> 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]].<ref name=":0">{{cite journal | vauthors = Fujita Y, Yagishita S, Takeshita F, Yamamoto Y, Kuwano K, Ochiya T | title = Prognostic and therapeutic impact of RPN2-mediated tumor malignancy in non-small-cell lung cancer | journal = Oncotarget | volume = 6 | issue = 5 | pages = 3335–45 | date = February 2015 | pmid = 25595901 | pmc = 4413657 | doi = 10.18632/oncotarget.2793 }}</ref>
*{{cite journal | author=Löffler C, Rao VV, Hansmann I |title=Mapping of the ribophorin II (RPN II) gene to human chromosome 20q12-q13.1 by in-situ hybridization. |journal=Hum. Genet. |volume=87 |issue= 2 |pages= 221-2 |year= 1991 |pmid= 2066112 |doi= }}
 
*{{cite journal | author=Crimaudo C, Hortsch M, Gausepohl H, Meyer DI |title=Human ribophorins I and II: the primary structure and membrane topology of two highly conserved rough endoplasmic reticulum-specific glycoproteins. |journal=EMBO J. |volume=6 |issue= 1 |pages= 75-82 |year= 1987 |pmid= 3034581 |doi=  }}
== Clinical significance ==
*{{cite journal | author=Kumar V, Heinemann FS, Ozols J |title=Interleukin-2 induces N-glycosylation in T-cells: characterization of human lymphocyte oligosaccharyltransferase. |journal=Biochem. Biophys. Res. Commun. |volume=247 |issue= 2 |pages= 524-9 |year= 1998 |pmid= 9642163 |doi= 10.1006/bbrc.1998.8780 }}
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.<ref name=":1">{{cite journal | vauthors = 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 | title = The expression and clinical significance of ribophorin II (RPN2) in human breast cancer | journal = Pathology International | volume = 65 | issue = 6 | pages = 301–8 | date = June 2015 | pmid = 25881688 | doi = 10.1111/pin.12297 }}</ref> 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.<ref name=":0" /> Similar potential application has also been shown in [[osteosarcoma]], [[esophagus|esophageal]] squamous cell carcinoma and [[colorectal cancer]].<ref>{{cite journal | vauthors = Fujiwara T, Takahashi RU, Kosaka N, Nezu Y, Kawai A, Ozaki T, Ochiya T | title = RPN2 Gene Confers Osteosarcoma Cell Malignant Phenotypes and Determines Clinical Prognosis | journal = Molecular Therapy. Nucleic Acids | volume = 3 | pages = e189 | date = September 2014 | pmid = 25181275 | pmc = 4222647 | doi = 10.1038/mtna.2014.35 }}</ref><ref>{{cite journal | vauthors = Kurashige J, Watanabe M, Iwatsuki M, Kinoshita K, Saito S, Nagai Y, Ishimoto T, Baba Y, Mimori K, Baba H | title = RPN2 expression predicts response to docetaxel in oesophageal squamous cell carcinoma | journal = British Journal of Cancer | volume = 107 | issue = 8 | pages = 1233–8 | date = October 2012 | pmid = 22955852 | pmc = 3494434 | doi = 10.1038/bjc.2012.396 }}</ref><ref>{{cite journal | vauthors = 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 | title = Integrated transcriptional profiling and genomic analyses reveal RPN2 and HMGB1 as promising biomarkers in colorectal cancer | journal = Cell & Bioscience | volume = 5 | pages = 53 | date = 2015-01-01 | pmid = 26388988 | pmc = 4574027 | doi = 10.1186/s13578-015-0043-9 }}</ref> 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 [[Antiphospholipid syndrome|APS]].<ref name=":2">{{cite journal | vauthors = 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 | title = Ribophorin II is involved in the tissue factor expression mediated by phosphatidylserine-dependent antiprothrombin antibody on monocytes | journal = Rheumatology | volume = 55 | issue = 6 | pages = 1117–26 | date = June 2016 | pmid = 26895716 | doi = 10.1093/rheumatology/kew005 }}</ref>
*{{cite journal | author=Fu J, Kreibich G |title=Retention of subunits of the oligosaccharyltransferase complex in the endoplasmic reticulum. |journal=J. Biol. Chem. |volume=275 |issue= 6 |pages= 3984-90 |year= 2000 |pmid= 10660554 |doi= }}
 
*{{cite journal  | author=Deloukas P, Matthews LH, Ashurst J, ''et al.'' |title=The DNA sequence and comparative analysis of human chromosome 20. |journal=Nature |volume=414 |issue= 6866 |pages= 865-71 |year= 2002 |pmid= 11780052 |doi= 10.1038/414865a }}
== Interactions ==
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
[[P53]] <ref name=":1" />
*{{cite journal | author=Gevaert K, Goethals M, Martens L, ''et al.'' |title=Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. |journal=Nat. Biotechnol. |volume=21 |issue= 5 |pages= 566-9 |year= 2004 |pmid= 12665801 |doi= 10.1038/nbt810 }}
 
*{{cite journal | author=Kelleher DJ, Karaoglu D, Mandon EC, Gilmore R |title=Oligosaccharyltransferase isoforms that contain different catalytic STT3 subunits have distinct enzymatic properties. |journal=Mol. Cell |volume=12 |issue= 1 |pages= 101-11 |year= 2003 |pmid= 12887896 |doi= }}
[[tetraspanin]] CD63 <ref>{{cite journal | vauthors = Tominaga N, Hagiwara K, Kosaka N, Honma K, Nakagama H, Ochiya T | title = RPN2-mediated glycosylation of tetraspanin CD63 regulates breast cancer cell malignancy | journal = Molecular Cancer | volume = 13 | pages = 134 | date = May 2014 | pmid = 24884960 | pmc = 4070641 | doi = 10.1186/1476-4598-13-134 }}</ref>
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
 
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
prothrombin <ref name=":2" />
*{{cite journal | author=Shibatani T, David LL, McCormack AL, ''et al.'' |title=Proteomic analysis of mammalian oligosaccharyltransferase reveals multiple subcomplexes that contain Sec61, TRAP, and two potential new subunits. |journal=Biochemistry |volume=44 |issue= 16 |pages= 5982-92 |year= 2005 |pmid= 15835887 |doi= 10.1021/bi047328f }}
 
*{{cite journal  | author=Tu LC, Yan X, Hood L, Lin B |title=Proteomics analysis of the interactome of N-myc downstream regulated gene 1 and its interactions with the androgen response program in prostate cancer cells. |journal=Mol. Cell Proteomics |volume=6 |issue= 4 |pages= 575-88 |year= 2007 |pmid= 17220478 |doi= 10.1074/mcp.M600249-MCP200 }}
== Model organisms ==
*{{cite journal  | author=Ewing RM, Chu P, Elisma F, ''et al.'' |title=Large-scale mapping of human protein-protein interactions by mass spectrometry. |journal=Mol. Syst. Biol. |volume=3 |issue=  |pages= 89 |year= 2007 |pmid= 17353931 |doi= 10.1038/msb4100134 }}
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
}}
|+ ''Rpn2'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
 
|-
| [[Homozygote]] viability || bgcolor="#C40000"|Abnormal
|-
| [[Recessive]] lethal study || bgcolor="#C40000"|Abnormal
|-
| Fertility || bgcolor="#488ED3"|Normal
|-
| Body weight || bgcolor="#488ED3"|Normal
|-
| [[Open Field (animal test)|Anxiety]] || bgcolor="#488ED3"|Normal
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
|-
| Grip strength || bgcolor="#488ED3"|Normal
|-
| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#488ED3"|Normal
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
|-
| [[Blood plasma|Plasma]] [[immunoglobulin]]s || bgcolor="#488ED3"|Normal
|-
| [[Haematology]] || bgcolor="#488ED3"|Normal
|-
| [[Peripheral blood lymphocyte]]s || bgcolor="#488ED3"|Normal
|-
| [[Micronucleus test]] || bgcolor="#488ED3"|Normal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| Brain histopathology || bgcolor="#488ED3"|Normal
|-
| Eye Histopathology || bgcolor="#488ED3"|Normal
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBEJ/salmonella-challenge/ |title=''Salmonella'' infection data for Rpn2 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| ''[[Citrobacter]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Citrobacter'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBEJ/citrobacter-challenge/ |title=''Citrobacter'' infection data for Rpn2 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference">{{cite journal | doi = 10.1111/j.1755-3768.2010.4142.x | title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice | year = 2010 | author = Gerdin AK | journal = Acta Ophthalmologica | volume = 88 | pages =  925–7 }}</ref><ref>[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>
|}
[[Model organism]]s have been used in the study of RPN2 function. A conditional [[knockout mouse]] line, called ''Rpn2<sup>tm1a(EUCOMM)Wtsi</sup>''<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Rpn2 |title=International Knockout Mouse Consortium}}</ref><ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4432779 |title=Mouse Genome Informatics}}</ref> 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.<ref name="pmid21677750">{{cite journal | vauthors = 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 | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = June 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = June 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = January 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref>
 
Male and female animals underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="mgp_reference" /><ref name="pmid21722353">{{cite journal | vauthors = van der Weyden L, White JK, Adams DJ, Logan DW | title = The mouse genetics toolkit: revealing function and mechanism | journal = Genome Biology | volume = 12 | issue = 6 | pages = 224 | date = June 2011 | pmid = 21722353 | pmc = 3218837 | doi = 10.1186/gb-2011-12-6-224 }}</ref> Twenty six tests were carried out on [[mutant]] mice and two significant abnormalities were observed.<ref name="mgp_reference" />  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.<ref name="mgp_reference" />
 
== References ==
{{reflist|33em}}
 
== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Stoffel M, Xiang K, Bell GI | title = Dinucleotide repeat polymorphism at the human ribophorin II locus (RPN2) on chromosome 20q | journal = Human Molecular Genetics | volume = 1 | issue = 8 | pages = 656 | date = November 1992 | pmid = 1301181 | doi = 10.1093/hmg/1.8.656 }}
* {{cite journal | vauthors = Löffler C, Rao VV, Hansmann I | title = Mapping of the ribophorin II (RPN II) gene to human chromosome 20q12-q13.1 by in-situ hybridization | journal = Human Genetics | volume = 87 | issue = 2 | pages = 221–2 | date = June 1991 | pmid = 2066112 | doi = 10.1007/BF00204188 }}
* {{cite journal | vauthors = Kumar V, Heinemann FS, Ozols J | title = Interleukin-2 induces N-glycosylation in T-cells: characterization of human lymphocyte oligosaccharyltransferase | journal = Biochemical and Biophysical Research Communications | volume = 247 | issue = 2 | pages = 524–9 | date = June 1998 | pmid = 9642163 | doi = 10.1006/bbrc.1998.8780 }}
* {{cite journal | vauthors = Fu J, Kreibich G | title = Retention of subunits of the oligosaccharyltransferase complex in the endoplasmic reticulum | journal = The Journal of Biological Chemistry | volume = 275 | issue = 6 | pages = 3984–90 | date = February 2000 | pmid = 10660554 | doi = 10.1074/jbc.275.6.3984 }}
* {{cite journal | vauthors = Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J | title = Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides | journal = Nature Biotechnology | volume = 21 | issue = 5 | pages = 566–9 | date = May 2003 | pmid = 12665801 | doi = 10.1038/nbt810 }}
* {{cite journal | vauthors = Kelleher DJ, Karaoglu D, Mandon EC, Gilmore R | title = Oligosaccharyltransferase isoforms that contain different catalytic STT3 subunits have distinct enzymatic properties | journal = Molecular Cell | volume = 12 | issue = 1 | pages = 101–11 | date = July 2003 | pmid = 12887896 | doi = 10.1016/S1097-2765(03)00243-0 }}
* {{cite journal | vauthors = Shibatani T, David LL, McCormack AL, Frueh K, Skach WR | title = Proteomic analysis of mammalian oligosaccharyltransferase reveals multiple subcomplexes that contain Sec61, TRAP, and two potential new subunits | journal = Biochemistry | volume = 44 | issue = 16 | pages = 5982–92 | date = April 2005 | pmid = 15835887 | doi = 10.1021/bi047328f }}
* {{cite journal | vauthors = Tu LC, Yan X, Hood L, Lin B | title = Proteomics analysis of the interactome of N-myc downstream regulated gene 1 and its interactions with the androgen response program in prostate cancer cells | journal = Molecular & Cellular Proteomics | volume = 6 | issue = 4 | pages = 575–88 | date = April 2007 | pmid = 17220478 | doi = 10.1074/mcp.M600249-MCP200 }}
{{refend}}
{{refend}}
{{Use dmy dates|date=April 2017}}


{{protein-stub}}
[[Category:Genes mutated in mice]]
{{WikiDoc Sources}}

Latest revision as of 07:22, 10 January 2019

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

n/a

n/a

UniProt

n/a

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RefSeq (mRNA)

n/a

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RefSeq (protein)

n/a

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Dolichyl-diphosphooligosaccharide—protein glycosyltransferase subunit 2, also called ribophorin ǁ is an enzyme that in humans is encoded by the RPN2 gene.[1]

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.[1] 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.[2][3][4][5] 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.[6]

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.[7] 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.[6] Similar potential application has also been shown in osteosarcoma, esophageal squamous cell carcinoma and colorectal cancer.[8][9][10] 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.[11]

Interactions

P53 [7]

tetraspanin CD63 [12]

prothrombin [11]

Model organisms

Model organisms have been used in the study of RPN2 function. A conditional knockout mouse line, called Rpn2tm1a(EUCOMM)Wtsi[17][18] 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.[19][20][21]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[15][22] Twenty six tests were carried out on mutant mice and two significant abnormalities were observed.[15] 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.[15]

References

  1. ↑ 1.0 1.1 "Entrez Gene: RPN2 ribophorin II".
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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. PMC 553359. PMID 3034581.
  5. ↑ 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.
  6. ↑ 6.0 6.1 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.
  7. ↑ 7.0 7.1 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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 (2015-01-01). "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.
  11. ↑ 11.0 11.1 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.
  12. ↑ 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.
  13. ↑ "Salmonella infection data for Rpn2". Wellcome Trust Sanger Institute.
  14. ↑ "Citrobacter infection data for Rpn2". Wellcome Trust Sanger Institute.
  15. ↑ 15.0 15.1 15.2 15.3 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.
  16. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  17. ↑ "International Knockout Mouse Consortium".
  18. ↑ "Mouse Genome Informatics".
  19. ↑ 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.
  20. ↑ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  21. ↑ 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.
  22. ↑ 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.

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.
  • 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.
  • 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.

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