RNF7 (RING finger protein-7)

2007-11-01   Yi Sun 

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


Atlas Image
A) Location. B) Local order


Atlas Image


The gene encoding RNF7/SAG consists of four exons and three introns.


About 0.8 kb mRNA with 342 bp open reading frame; three alternative splicing variants; induced by redox compound, tumor promoter (TPA), and hypoxia.


Two psuedogenes, SAGp1 and SAGp2.


Atlas Image


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.


Ubiquitously expressed with the highest expression in heart, skeleton muscle, and testis in humans.


Both cytoplasm and nucleus


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inhibits apoptosis induced by redox, nitric oxide, ischemia/hypoxia, neurotoxin, MPP, and UV-irradiation (unpublished data).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


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.



Not known


Not known

Implicated in

Entity name
lung and colon cancer
SAG/RNF7 over-expression was found in lung cancer and a subset of colon cancer tissues.
Lung cancer patients with SAG/RNF7 over-expression have a worse prognosis.
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.


Pubmed IDLast YearTitleAuthors
126765402003SAG attenuates apoptotic cell death caused by simulated ischaemia/reoxygenation in rat cardiomyocytes.Chanalaris A et al
112552622001Promotion 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 et al
100825811999SAG, a novel zinc RING finger protein that protects cells from apoptosis induced by redox agents.Duan H et al
178461722007SAG/ROC2 E3 ligase regulates skin carcinogenesis by stage-dependent targeting of c-Jun/AP1 and IkappaB-alpha/NF-kappaB.Gu Q et al
174400732007SAG/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 et al
168744602007CK2 phosphorylation of SAG at Thr10 regulates SAG stability, but not its E3 ligase activity.He H et al
112552652001Elevated 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 et al
119997052002Thiol-linked peroxidase activity of human sensitive to apoptosis gene (SAG) protein.Kim SY et al
172405292007SAG 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 et al
125658322003Human sensitive to apoptosis gene protein inhibits peroxynitrite-induced DNA damage.Kim SY et al
127481922003Phosphorylation of threonine 10 on CKBBP1/SAG/ROC2/Rbx2 by protein kinase CKII promotes the degradation of IkappaBalpha and p27Kip1.Kim YS et al
116685202001Expression of the sensitive to apoptosis gene, SAG, as a prognostic marker in nonsmall cell lung cancer.Sasaki H et al
105061021999Alterations of SAG mRNA in human cancer cell lines: requirement for the RING finger domain for apoptosis protection.Sun Y et al
115544502001SAG/ROC/Rbx/Hrt, a zinc RING finger gene family: molecular cloning, biochemical properties, and biological functions.Sun Y et al
104439361999Expression, purification, and biochemical characterization of SAG, a ring finger redox-sensitive protein.Swaroop M et al
115067062001SAG/ROC2/Rbx2/Hrt2, a component of SCF E3 ubiquitin ligase: genomic structure, a splicing variant, and two family pseudogenes.Swaroop M et al
108510892000Yeast 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 et al
172176222006SAG/ROC-SCF beta-TrCP E3 ubiquitin ligase promotes pro-caspase-3 degradation as a mechanism of apoptosis protection.Tan M et al
178283032008SAG/ROC2/RBX2 is a HIF-1 target gene that promotes HIF-1 alpha ubiquitination and degradation.Tan M et al
164840442006Regulation of nitric oxide-induced apoptosis by sensitive to apoptosis gene protein.Yang ES et al
114885412001Attenuation of ischemia-induced mouse brain injury by SAG, a redox-inducible antioxidant protein.Yang GY et al

Other Information

Locus ID:

NCBI: 9616
MIM: 603863
HGNC: 10070
Ensembl: ENSG00000114125


dbSNP: 9616
ClinVar: 9616
TCGA: ENSG00000114125


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Ubiquitin mediated proteolysisKEGGko04120
Ubiquitin mediated proteolysisKEGGhsa04120
ECS complexKEGGhsa_M00388
ECS complexKEGGM00388
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Class I MHC mediated antigen processing & presentationREACTOMER-HSA-983169
Antigen processing: Ubiquitination & Proteasome degradationREACTOMER-HSA-983168

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
201036732010Validation of SAG/RBX2/ROC2 E3 ubiquitin ligase as an anticancer and radiosensitizing target.53
172176222006SAG/ROC-SCF beta-TrCP E3 ubiquitin ligase promotes pro-caspase-3 degradation as a mechanism of apoptosis protection.48
178283032008SAG/ROC2/RBX2 is a HIF-1 target gene that promotes HIF-1 alpha ubiquitination and degradation.47
228417842012Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection.46
244301842014Inactivation of SAG/RBX2 E3 ubiquitin ligase suppresses KrasG12D-driven lung tumorigenesis.37
184549452008Regulation of heat shock-induced apoptosis by sensitive to apoptosis gene protein.18
252165162014SAG/RBX2 is a novel substrate of NEDD4-1 E3 ubiquitin ligase and mediates NEDD4-1 induced chemosensitization.15
260308422015A fluorescent bimolecular complementation screen reveals MAF1, RNF7 and SETD3 as PCNA-associated proteins in human cells.10
279108722016SAG/RBX2 E3 ligase complexes with UBCH10 and UBE2S E2s to ubiquitylate β-TrCP1 via K11-linkage for degradation.10
127481922003Phosphorylation of threonine 10 on CKBBP1/SAG/ROC2/Rbx2 by protein kinase CKII promotes the degradation of IkappaBalpha and p27Kip1.6


Yi Sun

RNF7 (RING finger protein-7)

Atlas Genet Cytogenet Oncol Haematol. 2007-11-01

Online version: http://atlasgeneticsoncology.org/gene/44108/rnf7