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RNF7 (RING finger protein-7)

Written2007-11Yi Sun
Department of Radiation Oncology, University of Michigan, 4304 CCGC, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0010, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_nameszinc RING finger protein SAG
regulator of cullins 2
Alias_symbol (synonym)SAG
ROC2
CKBBP1
Other aliasRBX2
SAG (Sensitive to Apoptosis Gene)
HGNC (Hugo) RNF7
LocusID (NCBI) 9616
Atlas_Id 44108
Location 3q23  [Link to chromosome band 3q23]
Location_base_pair Starts at 141738209 and ends at 141746803 bp from pter ( according to hg19-Feb_2009)  [Mapping RNF7.png]
 
  A) Location. B) Local order
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ATP1B3 (3q23) / RNF7 (3q23)RNF7 (3q23) / BRI3BP (12q24.31)

DNA/RNA

 
Description The gene encoding RNF7/SAG consists of four exons and three introns.
Transcription About 0.8 kb mRNA with 342 bp open reading frame; three alternative splicing variants; induced by redox compound, tumor promoter (TPA), and hypoxia.
Pseudogene Two psuedogenes, SAGp1 and SAGp2.

Protein

 
Description 113 amino acids; 14 kDa protein; contains a RING domain (Cys-X2-Cys-X9-39-Cys-X1-3-His-X2-3-Cys/His-X2-Cys-X4-48-Cys-X2-Cys) at the C-terminus (50-102); Subjected to CK2 phosphorylation at Thr-10.
Expression Ubiquitously expressed with the highest expression in heart, skeleton muscle, and testis in humans.
Localisation Both cytoplasm and nucleus
Function 1) In vitro test tube assays using purified protein showed that RNF7/SAG scavenges hydrogen peroxide at the expense of self oligomerization; has thiol-linked peroxidase activity; inhibits peroxynitrite-induced DNA damage. When complexed with the components of SCF E3 ubiquitin ligase, SAG has E3 ubiquitin ligase activity.
2) In cultured cells, SAG over-expression inhibits apoptosis induced by redox, nitric oxide, ischemia/hypoxia, neurotoxin, MPP, and UV-irradiation (unpublished data). SAG over-expression also promotes the S-phase entry and cell growth under serum starved conditions and inhibits TPA-induced neoplastic transformation. Silencing SAG expression by anti-sense or siRNA inhibits tumor cell growth, enhanced apoptosis induced by etoposide and TRAIL, and enhances TPA-induced neoplastic transformation.
3) In whole animals, SAG over-expression via injection of SAG expressing recombinant adenovirus protects mouse brain tissues from ischemia/hypoxia-induced damage. Targeted expression of SAG in mouse skin inhibits tumor formation at the early stage, but enhances tumor growth at the later stage in a SAG-transgenic DMBA-TPA carcinogenesis model.
4) In yeast, SAG is a growth essential gene whose targeted deletion causes death, which can be rescued by human SAG.
Homology SAG is an evolutionarily conserved gene with 96% protein sequence identity between human and mouse, 70% identify between human and C-elegans and 50% between human and yeast. Two family members are found in human and mouse, four in Drosophila, three in C-elegans, one in Arabidopsis and in yeast.

Mutations

Germinal Not known
Somatic Not known

Implicated in

Note
  
Entity lung and colon cancer
Disease SAG/RNF7 over-expression was found in lung cancer and a subset of colon cancer tissues.
Prognosis Lung cancer patients with SAG/RNF7 over-expression have a worse prognosis.
Oncogenesis Targeted over-expression of SAG/RNF7 in mouse skin by K14 promoter inhibits tumor formation, but enhances tumor growth in DMBA-TPA-induced skin carcinogenesis.
  

Bibliography

SAG attenuates apoptotic cell death caused by simulated ischaemia/reoxygenation in rat cardiomyocytes.
Chanalaris A, Sun Y, Latchman DS, Stephanou A
Journal of molecular and cellular cardiology. 2003 ; 35 (3) : 257-264.
PMID 12676540
 
Promotion of S-phase entry and cell growth under serum starvation by SAG/ROC2/Rbx2/Hrt2, an E3 ubiquitin ligase component: association with inhibition of p27 accumulation.
Duan H, Tsvetkov LM, Liu Y, Song Y, Swaroop M, Wen R, Kung HF, Zhang H, Sun Y
Molecular carcinogenesis. 2001 ; 30 (1) : 37-46.
PMID 11255262
 
SAG, a novel zinc RING finger protein that protects cells from apoptosis induced by redox agents.
Duan H, Wang Y, Aviram M, Swaroop M, Loo JA, Bian J, Tian Y, Mueller T, Bisgaier CL, Sun Y
Molecular and cellular biology. 1999 ; 19 (4) : 3145-3155.
PMID 10082581
 
SAG/ROC2 E3 ligase regulates skin carcinogenesis by stage-dependent targeting of c-Jun/AP1 and IkappaB-alpha/NF-kappaB.
Gu Q, Bowden GT, Normolle D, Sun Y
The Journal of cell biology. 2007 ; 178 (6) : 1009-1023.
PMID 17846172
 
SAG/ROC2/Rbx2 is a novel activator protein-1 target that promotes c-Jun degradation and inhibits 12-O-tetradecanoylphorbol-13-acetate-induced neoplastic transformation.
Gu Q, Tan M, Sun Y
Cancer research. 2007 ; 67 (8) : 3616-3625.
PMID 17440073
 
CK2 phosphorylation of SAG at Thr10 regulates SAG stability, but not its E3 ligase activity.
He H, Tan M, Pamarthy D, Wang G, Ahmed K, Sun Y
Molecular and cellular biochemistry. 2007 ; 295 (1-2) : 179-188.
PMID 16874460
 
Elevated expression of SAG/ROC2/Rbx2/Hrt2 in human colon carcinomas: SAG does not induce neoplastic transformation, but antisense SAG transfection inhibits tumor cell growth.
Huang Y, Duan H, Sun Y
Molecular carcinogenesis. 2001 ; 30 (1) : 62-70.
PMID 11255265
 
Thiol-linked peroxidase activity of human sensitive to apoptosis gene (SAG) protein.
Kim SY, Bae YS, Park JW
Free radical research. 2002 ; 36 (1) : 73-78.
PMID 11999705
 
SAG protects human neuroblastoma SH-SY5Y cells against 1-methyl-4-phenylpyridinium ion (MPP+)-induced cytotoxicity via the downregulation of ROS generation and JNK signaling.
Kim SY, Kim MY, Mo JS, Park JW, Park HS
Neuroscience letters. 2007 ; 413 (2) : 132-136.
PMID 17240529
 
Human sensitive to apoptosis gene protein inhibits peroxynitrite-induced DNA damage.
Kim SY, Lee JH, Yang ES, Kil IS, Park JW
Biochemical and biophysical research communications. 2003 ; 301 (3) : 671-674.
PMID 12565832
 
Phosphorylation of threonine 10 on CKBBP1/SAG/ROC2/Rbx2 by protein kinase CKII promotes the degradation of IkappaBalpha and p27Kip1.
Kim YS, Lee JY, Son MY, Park W, Bae YS
The Journal of biological chemistry. 2003 ; 278 (31) : 28462-28469.
PMID 12748192
 
Expression of the sensitive to apoptosis gene, SAG, as a prognostic marker in nonsmall cell lung cancer.
Sasaki H, Yukiue H, Kobayashi Y, Moriyama S, Nakashima Y, Kaji M, Fukai I, Kiriyama M, Yamakawa Y, Fujii Y
International journal of cancer. Journal international du cancer. 2001 ; 95 (6) : 375-377.
PMID 11668520
 
Alterations of SAG mRNA in human cancer cell lines: requirement for the RING finger domain for apoptosis protection.
Sun Y
Carcinogenesis. 1999 ; 20 (10) : 1899-1903.
PMID 10506102
 
SAG/ROC/Rbx/Hrt, a zinc RING finger gene family: molecular cloning, biochemical properties, and biological functions.
Sun Y, Tan M, Duan H, Swaroop M
Antioxidants & redox signaling. 2001 ; 3 (4) : 635-650.
PMID 11554450
 
Expression, purification, and biochemical characterization of SAG, a ring finger redox-sensitive protein.
Swaroop M, Bian J, Aviram M, Duan H, Bisgaier CL, Loo JA, Sun Y
Free radical biology & medicine. 1999 ; 27 (1-2) : 193-202.
PMID 10443936
 
SAG/ROC2/Rbx2/Hrt2, a component of SCF E3 ubiquitin ligase: genomic structure, a splicing variant, and two family pseudogenes.
Swaroop M, Gosink M, Sun Y
DNA and cell biology. 2001 ; 20 (7) : 425-434.
PMID 11506706
 
Yeast homolog of human SAG/ROC2/Rbx2/Hrt2 is essential for cell growth, but not for germination: chip profiling implicates its role in cell cycle regulation.
Swaroop M, Wang Y, Miller P, Duan H, Jatkoe T, Madore SJ, Sun Y
Oncogene. 2000 ; 19 (24) : 2855-2866.
PMID 10851089
 
SAG/ROC-SCF beta-TrCP E3 ubiquitin ligase promotes pro-caspase-3 degradation as a mechanism of apoptosis protection.
Tan M, Gallegos JR, Gu Q, Huang Y, Li J, Jin Y, Lu H, Sun Y
Neoplasia (New York, N.Y.). 2006 ; 8 (12) : 1042-1054.
PMID 17217622
 
SAG/ROC2/RBX2 is a HIF-1 target gene that promotes HIF-1 alpha ubiquitination and degradation.
Tan M, Gu Q, He H, Pamarthy D, Semenza GL, Sun Y
Oncogene. 2008 ; 27 (10) : 1404-1411.
PMID 17828303
 
Regulation of nitric oxide-induced apoptosis by sensitive to apoptosis gene protein.
Yang ES, Park JW
Free radical research. 2006 ; 40 (3) : 279-284.
PMID 16484044
 
Attenuation of ischemia-induced mouse brain injury by SAG, a redox-inducible antioxidant protein.
Yang GY, Pang L, Ge HL, Tan M, Ye W, Liu XH, Huang FP, Wu DC, Che XM, Song Y, Wen R, Sun Y
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2001 ; 21 (6) : 722-733.
PMID 11488541
 

Citation

This paper should be referenced as such :
Sun, Y
RNF7 (RING finger protein-7)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(4):289-291.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/RNF7ID44108ch3q22.html


External links

Nomenclature
HGNC (Hugo)RNF7   10070
Cards
AtlasRNF7ID44108ch3q22
Entrez_Gene (NCBI)RNF7  9616  ring finger protein 7
AliasesCKBBP1; ROC2; SAG
GeneCards (Weizmann)RNF7
Ensembl hg19 (Hinxton)ENSG00000114125 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000114125 [Gene_View]  chr3:141738209-141746803 [Contig_View]  RNF7 [Vega]
ICGC DataPortalENSG00000114125
TCGA cBioPortalRNF7
AceView (NCBI)RNF7
Genatlas (Paris)RNF7
WikiGenes9616
SOURCE (Princeton)RNF7
Genetics Home Reference (NIH)RNF7
Genomic and cartography
GoldenPath hg38 (UCSC)RNF7  -     chr3:141738209-141746803 +  3q23   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RNF7  -     3q23   [Description]    (hg19-Feb_2009)
EnsemblRNF7 - 3q23 [CytoView hg19]  RNF7 - 3q23 [CytoView hg38]
Mapping of homologs : NCBIRNF7 [Mapview hg19]  RNF7 [Mapview hg38]
OMIM603863   
Gene and transcription
Genbank (Entrez)AF092878 AF142060 AF164679 AF312226 AK289894
RefSeq transcript (Entrez)NM_001201370 NM_014245 NM_183063 NM_183237
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)RNF7
Cluster EST : UnigeneHs.134623 [ NCBI ]
CGAP (NCI)Hs.134623
Alternative Splicing GalleryENSG00000114125
Gene ExpressionRNF7 [ NCBI-GEO ]   RNF7 [ EBI - ARRAY_EXPRESS ]   RNF7 [ SEEK ]   RNF7 [ MEM ]
Gene Expression Viewer (FireBrowse)RNF7 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9616
GTEX Portal (Tissue expression)RNF7
Human Protein AtlasENSG00000114125-RNF7 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UBF6   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9UBF6  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9UBF6
Splice isoforms : SwissVarQ9UBF6
PhosPhoSitePlusQ9UBF6
Domaine pattern : Prosite (Expaxy)ZF_RING_2 (PS50089)   
Domains : Interpro (EBI)Znf_RING    Znf_RING/FYVE/PHD    Znf_RING_H2   
Domain families : Pfam (Sanger)zf-rbx1 (PF12678)   
Domain families : Pfam (NCBI)pfam12678   
Conserved Domain (NCBI)RNF7
DMDM Disease mutations9616
Blocks (Seattle)RNF7
PDB (SRS)2ECL   
PDB (PDBSum)2ECL   
PDB (IMB)2ECL   
PDB (RSDB)2ECL   
Structural Biology KnowledgeBase2ECL   
SCOP (Structural Classification of Proteins)2ECL   
CATH (Classification of proteins structures)2ECL   
SuperfamilyQ9UBF6
Human Protein Atlas [tissue]ENSG00000114125-RNF7 [tissue]
Peptide AtlasQ9UBF6
HPRD04840
IPIIPI00033132   IPI00030891   IPI00377253   IPI00945636   IPI00945323   
Protein Interaction databases
DIP (DOE-UCLA)Q9UBF6
IntAct (EBI)Q9UBF6
FunCoupENSG00000114125
BioGRIDRNF7
STRING (EMBL)RNF7
ZODIACRNF7
Ontologies - Pathways
QuickGOQ9UBF6
Ontology : AmiGOcopper ion binding  protein binding  nucleus  nucleoplasm  cytoplasm  cytosol  zinc ion binding  protein ubiquitination  NEDD8 transferase activity  Cul5-RING ubiquitin ligase complex  protein neddylation  response to redox state  cullin family protein binding  
Ontology : EGO-EBIcopper ion binding  protein binding  nucleus  nucleoplasm  cytoplasm  cytosol  zinc ion binding  protein ubiquitination  NEDD8 transferase activity  Cul5-RING ubiquitin ligase complex  protein neddylation  response to redox state  cullin family protein binding  
Pathways : KEGGUbiquitin mediated proteolysis   
REACTOMEQ9UBF6 [protein]
REACTOME PathwaysR-HSA-983168 [pathway]   
NDEx NetworkRNF7
Atlas of Cancer Signalling NetworkRNF7
Wikipedia pathwaysRNF7
Orthology - Evolution
OrthoDB9616
GeneTree (enSembl)ENSG00000114125
Phylogenetic Trees/Animal Genes : TreeFamRNF7
HOVERGENQ9UBF6
HOGENOMQ9UBF6
Homologs : HomoloGeneRNF7
Homology/Alignments : Family Browser (UCSC)RNF7
Gene fusions - Rearrangements
Fusion: TCGA_MDACCATP1B3 3q23 RNF7 3q23 LUSC
Tumor Fusion PortalRNF7
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRNF7 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RNF7
dbVarRNF7
ClinVarRNF7
1000_GenomesRNF7 
Exome Variant ServerRNF7
ExAC (Exome Aggregation Consortium)ENSG00000114125
GNOMAD BrowserENSG00000114125
Genetic variants : HAPMAP9616
Genomic Variants (DGV)RNF7 [DGVbeta]
DECIPHERRNF7 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisRNF7 
Mutations
ICGC Data PortalRNF7 
TCGA Data PortalRNF7 
Broad Tumor PortalRNF7
OASIS PortalRNF7 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRNF7  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDRNF7
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch RNF7
DgiDB (Drug Gene Interaction Database)RNF7
DoCM (Curated mutations)RNF7 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RNF7 (select a term)
intoGenRNF7
NCG5 (London)RNF7
Cancer3DRNF7(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603863   
Orphanet
DisGeNETRNF7
MedgenRNF7
Genetic Testing Registry RNF7
NextProtQ9UBF6 [Medical]
TSGene9616
GENETestsRNF7
Target ValidationRNF7
Huge Navigator RNF7 [HugePedia]
snp3D : Map Gene to Disease9616
BioCentury BCIQRNF7
ClinGenRNF7
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9616
Chemical/Pharm GKB GenePA34444
Clinical trialRNF7
Miscellaneous
canSAR (ICR)RNF7 (select the gene name)
Probes
Litterature
PubMed67 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRNF7
EVEXRNF7
GoPubMedRNF7
iHOPRNF7
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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