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RIOX2 (ribosomal oxygenase 2)

Written2010-04Makoto Tsuneoka, Kengo Okamoto, Yuji Tanaka
Laboratory of Molecular, Cellular Biology, Department of Molecular Pharmacology, Faculty of Pharmacy, Takasaki University of Health, Welfare, 60 Nakaorui-machi, Takasaki-shi, Gunma 370-0033, Japan

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)MINA53
FLJ14393
mdig
Other aliasMINA (MYC induced nuclear antigen)
DKFZp762O1912
MDIG
NO52
HGNC (Hugo) RIOX2
LocusID (NCBI) 84864
Atlas_Id 44409
Location 3q11.2  [Link to chromosome band 3q11]
Location_base_pair Starts at 97941817 and ends at 97972451 bp from pter ( according to hg19-Feb_2009)  [Mapping RIOX2.png]
Note MINA (myc induced nuclear antigen) is a gene whose expression is directly induced by c-MYC protein. The MINA gene encodes a protein with a molecular weight of 53 kDa that is localized in the nucleoplasm and nucleolus.

DNA/RNA

 
  a. Exon-intron structure of the MINA gene. There are two transcription initiation sites at exon 1a and exon 1b. b. mRNA for human MINA that encodes MINA protein. The protein is coded from exon 2 to exon 10.
Description The human MINA gene consists of twelve exons spanning a 30 kb. The translation start site locates in exon 2, which follows two distinct exons, exon 1a and exon 1b. Thus, there are two transcription initiation sites in the human MINA gene. The exon 1b exists 0.25 kb downstream of the exon 1a. The stop codon (TAG) exists in the last exon, exon 10. The open reading frame of the coding region is 1398 bp, encoding 465 amino acids. mRNA encoding 464 amino acids (lacking 297Q) is also generated by alternative splicing due to the lack of the first three bp of exon 7.
Transcription The human MINA coding sequence consists of 1398 bp from the start codon to the stop codon. In addition to the 1395 bp-coding sequence, multiple alternative spliced transcript variants have been found for this gene. c-MYC protein stimulates the transcription of MINA through the E-box near the transcription start sites (Tsuneoka et al., 2002). The expression of MINA is also induced by serum (Tsuneoka et al., 2002).

Protein

 
  Structural features of MINA protein. The positions of the JmjC domain is shown (green).
Description Structure: MINA is a member of the jumonji C (JmjC) protein family, and suspected to hydroxylate some proteins to control gene expression.

Activation: The expression of mRNA is elevated by c-MYC protein, and frequently increased in various types of cancers, including human colon cancer, esophageal squamous cell carcinoma (ESCC). In some types of cancers such as ESCC, patients with high expression of MINA53 had shorter survival periods. MINA expression is also activated not only MYC but also by other factors, because there are lymphoma and lung cancer tissues where the expression of MYC is downregulated but the expression of MINA is elevated (Teye et al., 2007; Komiya et al., 2010). The expression of MINA is also activated and mineral dust in human alveolar macrophage and human lung cancer cell line, A549 (Zhange et al., 2005).

Expression MINA is ubiquitously expressed. The expression of MINA is frequently increased in various types of human cancers. In mice, MINA expression is high in some non-neoplastic tissues, including spleen, thymus, colon and testis, but low in skeletal muscle, cerebellum, and seminal vesicle. In testis the expression of MINA is high in spermatogonia and mitotic prophase cells and weakly in early pachytene spermatocyte but absent in late pachytene spermatocytes (Tsuneoka et al., 2006).
Localisation MINA is diffusely nucleoplasmic and some portion is accumulated in nucleolus (Tsuneoka et al., 2002).
Function Specific inhibition of MINA expression suppressed cell proliferation in some cultured cell lines (Tsuneoka et al., 2002). Forced expression of MINA in NIH/3T3 cells induces cell transformation, and MINA-transfected NIH/3T3 clones produce tumor in nude mice (Komiya et al., 2010). Therefore, MINA has oncogenic potential. MINA is a nuclear protein and a member of the jumonji C (JmjC) protein family. Thus, MINA is suspected to hydroxylate some proteins to control gene expression, but its substrate is not clear.

Gene activation: MINA regulates several genes which are also regulated by MYC. Genes regulated by MINA but not by MYC include HGF, EGFR, and IL6 (Komiya et al., 2010).

Gene suppression: Recently, MINA was identified as a genetic determinant of T(H)2 bias. MINA specifically binds to and represses the IL4 promoter. MINA overexpression in transgenic mice impaired IL4 expression, whereas its knockdown in primary CD4(+) T cells led to IL4 de-repression. Therefore MINA controls helper T cell differentiation through an IL4-regulatory pathway (Okamoto et al,. 2009). These findings suggest that MINA may play a role on carcinogenesis also in the field of cancer immunology.

Ribosome biogenesis: MINA is accumulated in nucleolus (Tsuneoka et al., 2002). Immunolocalization studies revealed that MINA is highly concentrated in the granular component of nucleoli (Eilbracht et al., 2005). MINA is a constituent of free preribosomal particles but is absent from cytoplasmic ribosomes. MINA interacts with various ribosomal proteins as well as with a distinct set of non-ribosomal nucleolar proteins. These results suggest that MINA is directly involved in ribosome biogenesis, most likely during the assembly process of preribosomal particles (Eilbracht et al., 2005). MINA was also suggested to be involved in ribosomal RNA transcription (Lu et al., 2009).

Homology The primary sequence of MINA has similarity to nucleolar protein NO66, which also has a JmjC domain. The JmjC domain of MINA has 50% identity to that of NO66. In 2010, it was report that NO66 directly interacts with Osterix (Osx), which is an osteoblast-specific transcription factor required for osteoblast differentiation and bone formation. NO66 exhibits a JmjC-dependent histone demethylase activity, which is specific for both H3K4me and H3K36me in vitro and in vivo. It was suggested that interactions between NO66 and Osx regulate Osx-target genes in osteoblasts by modulating histone methylation states (Sinha et al., 2010).

Implicated in

Note
  
Entity Neoplasm diseases
Note Colon cancer, esophageal squamous cell carcinoma, gingival squamous cell carcinoma, subtypes of human lymphoma, renal cell carcinoma, neuroblastoma, gastric carcinoma, lung cancer and hepatoma.
Disease MINA expression is elevated in several types of carcinomas.
Prognosis MINA is preferentially expressed in some types of cancers with a poor prognosis, including esophageal squamous cell carcinoma, advanced renal cell carcinoma, neuroblastoma. The expression levels of MINA may be used as a prognositic marker in these cancers. On the other hand, elevated expression of MINA in lung cancer patients is associated with favorable prognosis.
  
  
Entity Colon cancer
Note The expression of MINA is elevated in all the adenocarcinomas compared to adjacent non-neoplastic tissues, which shows little staining. MINA is expressed in all pathological grades of cancer as well as in the adenoma. Staining patterns of Ki-67, a biomarker for cell proliferation, are similar to those of MINA in most cases. While anti-Ki-67 antibody strongly stains some well-proliferating non-neoplastic cells including cells in the deeper part of the crypts and in lymphoid germinal centers, antibody to MINA rarely stained those cells. These results indicate that the elevated expression of MINA is a characteristic feature in colon cancer (Teye et al., 2004).
  
  
Entity Esophageal cancer
Note The expression of MINA in tumors is increased compared with that in adjacent non-neoplastic tissues. MINA was highly expressed in more than 80% of specimens. Anti-MINA antibody stained tumors more efficiently than antibody against Ki-67, a cell proliferation biomarker, in some cancer specimens. Patients with high expression of MINA has shorter survival periods, whereas the expression level of Ki-67 in ESCC shows no relationship to patient outcome (Tsuneoka et al., 2004).
  
  
Entity Primary gingival squamous cell carcinoma
Note A significant correlation was found between the expression of MINA and that of Ki-67 in patients with gingival squamous cell carcinoma or dysplastic gingiva. No significant correlation was noted between the expression of MINA or Ki-67 and prognostic factors such as the degree of differentiation, lymph node metastasis, stage, and tumor diameter (Kuratomi et al., 2006).
  
  
Entity Lymphoma
Note Although MINA expression is not prominent in lymphoma in general, it is related to tumor progression of B cell lymphoma (Teye et al., 2007).
  
  
Entity Renal cell carcinoma (RCC)
Note MINA is expressed in the nuclei of tumor cells and tubular nuclei of normal renal tissue. The expression level of MINA is significantly higher in patients with poor prognostic factors (stage IV, MVI-positive, and sarcomatoid RCC, and high Ki-67 LI). The prognosis of high MINA-expressing tumors was significantly poorer than that of non-MINA-high tumors (Ishizaki et al., 2007).
  
  
Entity Neuroblastoma
Note Surgically obtained neuroblastoma specimens were immunohistochemically stained to determine the MINA and Cap43 expression levels. A significant relationship was found between MINA and Ki-67, between MINA and neurotrophic tyrosine kinase, receptor, type 1 (TrkA), and between Cap43 and TrkA. The prognosis is significantly favorable in the Cap43 high-expression cases, whereas it is significantly poor in the MINA high-expression cases (Fukahori et al., 2007).
  
  
Entity Gastric carcinomas
Note Elevated expression of MINA was observed in 91.1% of the gastric carcinomas. No significant associations were found between MINA and clinicopathological characteristics such as sex, age, histological differentiation, distant metastasis and lymph node metastasis. However, there was a significant association with depth of invasion and TMN stage. MINA expression was positively associated with a proliferation marker, PCNA, level (Zhang et al., 2008).
  
  
Entity Lung cancers
Note The expression of MINA is elevated in lung cancer tissues (Lu et al., 2009; Komiya et al., 2010). The overexpression of MINA is an early event in lung cancer occurence (Lu et al., 2009; Komiya et al., 2010). Further, patients with negative staining for MINA has shorter survival than patients with positive staining for MINA, especially in stage I or with squamous cell carcinoma. These results suggest that overexpression of MINA in lung cancer patients is associated with favorable prognosis (Komiya et al., 2009). MINA may inhibit lung cancer cell invasion (Komiya et al., 2009).
  
  
Entity Hepatoma
Note MINA is diffusely expressed in the nuclei of cancer cells in the tumor nodule, and is often strong at the periphery of tumor nodules. MINA expression is higher in poorly differentiated hepatocellular carcinoma (HCC) than in well-differentiated HCC, and there is significant relationship between MINA expression and histological grade. The high MINA expression is associated with high expression of a proliferation marker, antibody to Ki-67. MINA expression is high in the tumors of > 2 cm of diameter than in ≤ 2 cm (Ogasawara et al., 2010 in press).
  

Bibliography

Protein NO52--a constitutive nucleolar component sharing high sequence homologies to protein NO66.
Eilbracht J, Kneissel S, Hofmann A, Schmidt-Zachmann MS.
Eur J Cell Biol. 2005 Mar;84(2-3):279-94.
PMID 15819408
 
Immunohistochemical expressions of Cap43 and Mina53 proteins in neuroblastoma.
Fukahori S, Yano H, Tsuneoka M, Tanaka Y, Yagi M, Kuwano M, Tajiri T, Taguchi T, Tsuneyoshi M, Kojiro M.
J Pediatr Surg. 2007 Nov;42(11):1831-40.
PMID 18022432
 
T(H)2 bias: Mina tips the balance.
Hemmers S, Mowen KA.
Nat Immunol. 2009 Aug;10(8):806-8.
PMID 19621039
 
Overexpression of the myc target gene Mina53 in advanced renal cell carcinoma.
Ishizaki H, Yano H, Tsuneoka M, Ogasawara S, Akiba J, Nishida N, Kojiro S, Fukahori S, Moriya F, Matsuoka K, Kojiro M.
Pathol Int. 2007 Oct;57(10):672-80.
PMID 17803656
 
Mina53, a novel c-Myc target gene, is frequently expressed in lung cancers and exerts oncogenic property in NIH/3T3 cells.
Komiya K, Sueoka-Aragane N, Sato A, Hisatomi T, Sakuragi T, Mitsuoka M, Sato T, Hayashi S, Izumi H, Tsuneoka M, Sueoka E.
J Cancer Res Clin Oncol. 2010 Mar;136(3):465-73. Epub 2009 Sep 16.
PMID 19756735
 
Immunohistochemical expression of Mina53 and Ki67 proteins in human primary gingival squamous cell carcinoma.
Kuratomi K, Yano H, Tsuneoka M, Sakamoto K, Kusukawa J, Kojiro M.
Kurume Med J. 2006;53(3-4):71-8.
PMID 17317935
 
Mina, an Il4 repressor, controls T helper type 2 bias.
Okamoto M, Van Stry M, Chung L, Koyanagi M, Sun X, Suzuki Y, Ohara O, Kitamura H, Hijikata A, Kubo M, Bix M.
Nat Immunol. 2009 Aug;10(8):872-9. Epub 2009 Jun 28.
PMID 19561615
 
Regulation of the osteoblast-specific transcription factor Osterix by NO66, a Jumonji family histone demethylase.
Sinha KM, Yasuda H, Coombes MM, Dent SY, de Crombrugghe B.
EMBO J. 2010 Jan 6;29(1):68-79. Epub 2009 Nov 19.
PMID 19927124
 
Expression of Myc target gene mina53 in subtypes of human lymphoma.
Teye K, Arima N, Nakamura Y, Sakamoto K, Sueoka E, Kimura H, Tsuneoka M.
Oncol Rep. 2007 Oct;18(4):841-8.
PMID 17786344
 
Increased expression of a Myc target gene Mina53 in human colon cancer.
Teye K, Tsuneoka M, Arima N, Koda Y, Nakamura Y, Ueta Y, Shirouzu K, Kimura H.
Am J Pathol. 2004 Jan;164(1):205-16.
PMID 14695334
 
Expression of Mina53, a product of a Myc target gene in mouse testis.
Tsuneoka M, Nishimune Y, Ohta K, Teye K, Tanaka H, Soejima M, Iida H, Inokuchi T, Kimura H, Koda Y.
Int J Androl. 2006 Apr;29(2):323-30.
PMID 16533354
 
Expression of Mina53 and its significance in gastric carcinoma.
Zhang Q, Hu CM, Yuan YS, He CH, Zhao Q, Liu NZ.
Int J Biol Markers. 2008 Apr-Jun;23(2):83-8.
PMID 18629780
 
The Human mineral dust-induced gene, mdig, is a cell growth regulating gene associated with lung cancer.
Zhang Y, Lu Y, Yuan BZ, Castranova V, Shi X, Stauffer JL, Demers LM, Chen F.
Oncogene. 2005 Jul 21;24(31):4873-82.
PMID 15897898
 

Citation

This paper should be referenced as such :
Tsuneoka, M ; Okamoto, K ; Tanaka, Y
MINA (MYC induced nuclear antigen)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(1):15-18.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/MINAID44409ch3q11.html


External links

Nomenclature
HGNC (Hugo)RIOX2   19441
Cards
AtlasMINAID44409ch3q11
Entrez_Gene (NCBI)RIOX2  84864  ribosomal oxygenase 2
AliasesJMJD10; MDIG; MINA; MINA53; 
NO52; ROX
GeneCards (Weizmann)RIOX2
Ensembl hg19 (Hinxton)ENSG00000170854 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000170854 [Gene_View]  chr3:97941817-97972451 [Contig_View]  RIOX2 [Vega]
ICGC DataPortalENSG00000170854
TCGA cBioPortalRIOX2
AceView (NCBI)RIOX2
Genatlas (Paris)RIOX2
WikiGenes84864
SOURCE (Princeton)RIOX2
Genetics Home Reference (NIH)RIOX2
Genomic and cartography
GoldenPath hg38 (UCSC)RIOX2  -     chr3:97941817-97972451 -  3q11.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RIOX2  -     3q11.2   [Description]    (hg19-Feb_2009)
EnsemblRIOX2 - 3q11.2 [CytoView hg19]  RIOX2 - 3q11.2 [CytoView hg38]
Mapping of homologs : NCBIRIOX2 [Mapview hg19]  RIOX2 [Mapview hg38]
OMIM612049   
Gene and transcription
Genbank (Entrez)AB083189 AB083190 AB083191 AB083192 AB083193
RefSeq transcript (Entrez)NM_001042533 NM_001261829 NM_032778 NM_153182
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)RIOX2
Cluster EST : UnigeneHs.742206 [ NCBI ]
CGAP (NCI)Hs.742206
Alternative Splicing GalleryENSG00000170854
Gene ExpressionRIOX2 [ NCBI-GEO ]   RIOX2 [ EBI - ARRAY_EXPRESS ]   RIOX2 [ SEEK ]   RIOX2 [ MEM ]
Gene Expression Viewer (FireBrowse)RIOX2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)84864
GTEX Portal (Tissue expression)RIOX2
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8IUF8   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8IUF8  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8IUF8
Splice isoforms : SwissVarQ8IUF8
Catalytic activity : Enzyme1.14.11.- [ Enzyme-Expasy ]   1.14.11.-1.14.11.- [ IntEnz-EBI ]   1.14.11.- [ BRENDA ]   1.14.11.- [ KEGG ]   
PhosPhoSitePlusQ8IUF8
Domaine pattern : Prosite (Expaxy)JMJC (PS51184)   
Domains : Interpro (EBI)JmjC_dom   
Domain families : Pfam (Sanger)Cupin_4 (PF08007)   
Domain families : Pfam (NCBI)pfam08007   
Conserved Domain (NCBI)RIOX2
DMDM Disease mutations84864
Blocks (Seattle)RIOX2
PDB (SRS)2XDV    4BU2    4BXF   
PDB (PDBSum)2XDV    4BU2    4BXF   
PDB (IMB)2XDV    4BU2    4BXF   
PDB (RSDB)2XDV    4BU2    4BXF   
Structural Biology KnowledgeBase2XDV    4BU2    4BXF   
SCOP (Structural Classification of Proteins)2XDV    4BU2    4BXF   
CATH (Classification of proteins structures)2XDV    4BU2    4BXF   
SuperfamilyQ8IUF8
Human Protein AtlasENSG00000170854
Peptide AtlasQ8IUF8
HPRD17575
IPIIPI00216737   IPI00383332   IPI00868858   IPI00395527   IPI00966893   IPI00967414   IPI00967681   
Protein Interaction databases
DIP (DOE-UCLA)Q8IUF8
IntAct (EBI)Q8IUF8
FunCoupENSG00000170854
BioGRIDRIOX2
STRING (EMBL)RIOX2
ZODIACRIOX2
Ontologies - Pathways
QuickGOQ8IUF8
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  transcriptional repressor activity, RNA polymerase II transcription factor binding  nucleus  nucleus  nucleoplasm  transcription factor complex  nucleolus  cytosol  chromatin remodeling  transcription, DNA-templated  peptidyl-arginine hydroxylation  histone demethylase activity  histone demethylase activity (H3-K4 specific)  histone H3-K4 demethylation  ribosome biogenesis  identical protein binding  negative regulation of transcription, DNA-templated  metal ion binding  histone demethylase activity (H3-K36 specific)  oxidation-reduction process  histone H3-K36 demethylation  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  transcriptional repressor activity, RNA polymerase II transcription factor binding  nucleus  nucleus  nucleoplasm  transcription factor complex  nucleolus  cytosol  chromatin remodeling  transcription, DNA-templated  peptidyl-arginine hydroxylation  histone demethylase activity  histone demethylase activity (H3-K4 specific)  histone H3-K4 demethylation  ribosome biogenesis  identical protein binding  negative regulation of transcription, DNA-templated  metal ion binding  histone demethylase activity (H3-K36 specific)  oxidation-reduction process  histone H3-K36 demethylation  
NDEx NetworkRIOX2
Atlas of Cancer Signalling NetworkRIOX2
Wikipedia pathwaysRIOX2
Orthology - Evolution
OrthoDB84864
GeneTree (enSembl)ENSG00000170854
Phylogenetic Trees/Animal Genes : TreeFamRIOX2
HOVERGENQ8IUF8
HOGENOMQ8IUF8
Homologs : HomoloGeneRIOX2
Homology/Alignments : Family Browser (UCSC)RIOX2
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRIOX2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RIOX2
dbVarRIOX2
ClinVarRIOX2
1000_GenomesRIOX2 
Exome Variant ServerRIOX2
ExAC (Exome Aggregation Consortium)RIOX2 (select the gene name)
Genetic variants : HAPMAP84864
Genomic Variants (DGV)RIOX2 [DGVbeta]
DECIPHERRIOX2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisRIOX2 
Mutations
ICGC Data PortalRIOX2 
TCGA Data PortalRIOX2 
Broad Tumor PortalRIOX2
OASIS PortalRIOX2 [ Somatic mutations - Copy number]
Mutations and Diseases : HGMDRIOX2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch RIOX2
DgiDB (Drug Gene Interaction Database)RIOX2
DoCM (Curated mutations)RIOX2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RIOX2 (select a term)
intoGenRIOX2
NCG5 (London)RIOX2
Cancer3DRIOX2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM612049   
Orphanet
MedgenRIOX2
Genetic Testing Registry RIOX2
NextProtQ8IUF8 [Medical]
TSGene84864
GENETestsRIOX2
Target ValidationRIOX2
Huge Navigator RIOX2 [HugePedia]
snp3D : Map Gene to Disease84864
BioCentury BCIQRIOX2
ClinGenRIOX2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD84864
Chemical/Pharm GKB GenePA134991047
Clinical trialRIOX2
Miscellaneous
canSAR (ICR)RIOX2 (select the gene name)
Probes
Litterature
PubMed37 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRIOX2
EVEXRIOX2
GoPubMedRIOX2
iHOPRIOX2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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