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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)


SAG (Sensitive to Apoptosis Gene)
HGNC (Hugo) RNF7
HGNC Alias symbSAG
HGNC Alias namesensitive to apoptosis, zinc RING finger protein SAG, regulator of cullins 2
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 GRCh38/hg38-Dec_2013)  [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)


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.


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inhibits apoptosis induced by redox, nitric oxide, ischemia/hypoxia, neurotoxin, MPP, and UV-irradiation (unpublished data).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.


Germinal Not known
Somatic Not known

Implicated in

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.


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


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 ]

External links


HGNC (Hugo)RNF7   10070
Atlas Explorer : (Salamanque)RNF7
Entrez_Gene (NCBI)RNF7    ring finger protein 7
AliasesCKBBP1; ROC2; SAG; rbx2
GeneCards (Weizmann)RNF7
Ensembl hg19 (Hinxton)ENSG00000114125 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000114125 [Gene_View]  ENSG00000114125 [Sequence]  chr3:141738209-141746803 [Contig_View]  RNF7 [Vega]
ICGC DataPortalENSG00000114125
TCGA cBioPortalRNF7
AceView (NCBI)RNF7
Genatlas (Paris)RNF7
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)
GoldenPathRNF7 - 3q23 [CytoView hg19]  RNF7 - 3q23 [CytoView hg38]
Genome Data Viewer NCBIRNF7 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AF092878 AF142060 AF164679 AF312226 AK289894
RefSeq transcript (Entrez)NM_001201370 NM_014245 NM_183063 NM_183237
Consensus coding sequences : CCDS (NCBI)RNF7
Gene ExpressionRNF7 [ NCBI-GEO ]   RNF7 [ EBI - ARRAY_EXPRESS ]   RNF7 [ SEEK ]   RNF7 [ MEM ]
Gene Expression Viewer (FireBrowse)RNF7 [ Firebrowse - Broad ]
GenevisibleExpression of RNF7 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
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
PDB Europe2ECL   
Structural Biology KnowledgeBase2ECL   
SCOP (Structural Classification of Proteins)2ECL   
CATH (Classification of proteins structures)2ECL   
AlphaFold pdb e-kbQ9UBF6   
Human Protein Atlas [tissue]ENSG00000114125-RNF7 [tissue]
Protein Interaction databases
IntAct (EBI)Q9UBF6
Ontologies - Pathways
Ontology : AmiGOcopper ion binding  protein binding  nucleus  nucleus  nucleoplasm  cytoplasm  cytosol  cytosol  ubiquitin-dependent protein catabolic process  zinc ion binding  protein ubiquitination  protein ubiquitination  NEDD8 transferase activity  cullin-RING ubiquitin ligase complex  Cul5-RING ubiquitin ligase complex  Cul5-RING ubiquitin ligase complex  post-translational protein modification  protein neddylation  response to redox state  ubiquitin protein ligase activity  NEDD8 ligase activity  cullin family protein binding  cullin family protein binding  
Ontology : EGO-EBIcopper ion binding  protein binding  nucleus  nucleus  nucleoplasm  cytoplasm  cytosol  cytosol  ubiquitin-dependent protein catabolic process  zinc ion binding  protein ubiquitination  protein ubiquitination  NEDD8 transferase activity  cullin-RING ubiquitin ligase complex  Cul5-RING ubiquitin ligase complex  Cul5-RING ubiquitin ligase complex  post-translational protein modification  protein neddylation  response to redox state  ubiquitin protein ligase activity  NEDD8 ligase activity  cullin family protein binding  cullin family protein binding  
REACTOMEQ9UBF6 [protein]
REACTOME PathwaysR-HSA-983168 [pathway]   
NDEx NetworkRNF7
Atlas of Cancer Signalling NetworkRNF7
Wikipedia pathwaysRNF7
Orthology - Evolution
GeneTree (enSembl)ENSG00000114125
Phylogenetic Trees/Animal Genes : TreeFamRNF7
Homologs : HomoloGeneRNF7
Homology/Alignments : Family Browser (UCSC)RNF7
Gene fusions - Rearrangements
Fusion : FusionHubATP1B3--RNF7    CEP63--RNF7    PDE3A--RNF7    RNF7--BRI3BP    RNF7--RAB10    RNF7--RPL26    RPRD1B--RNF7    RYBP--RNF7    SNX2--RNF7    TFDP2--RNF7   
Fusion : QuiverRNF7
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRNF7 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RNF7
Exome Variant ServerRNF7
GNOMAD BrowserENSG00000114125
Varsome BrowserRNF7
ACMGRNF7 variants
Genomic Variants (DGV)RNF7 [DGVbeta]
DECIPHERRNF7 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisRNF7 
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]  
Somatic Mutations in Cancer : COSMIC3DRNF7
Mutations and Diseases : HGMDRNF7
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)RNF7
DoCM (Curated mutations)RNF7
CIViC (Clinical Interpretations of Variants in Cancer)RNF7
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry RNF7
NextProtQ9UBF6 [Medical]
Target ValidationRNF7
Huge Navigator RNF7 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDRNF7
Pharm GKB GenePA34444
Clinical trialRNF7
DataMed IndexRNF7
PubMed94 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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