RNF7 (RING finger protein-7)

Identity

Other names	CKBBP1
	RBX2
	ROC2
	SAG (Sensitive to Apoptosis Gene)
HGNC	RNF7
Location	3q22-24
	A) Location. B) Local order

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inhibits apoptosis induced by redox, nitric oxide, ischemia/hypoxia, neurotoxin, MPP, and UV-irradiation (unpublished data).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

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.

External links

	Nomenclature
HGNC	RNF7   10070
Entrez_Gene	RNF7  9616  ring finger protein 7
	Cards
Atlas	RNF7ID44108ch3q22
GeneCards	RNF7
Ensembl	RNF7 [Search_View]   ENSG00000114125 [Gene_View]
Genatlas	RNF7
GeneLynx	RNF7
eGenome	RNF7
euGene	9616
	Genomic and cartography
GoldenPath	RNF7  -     chr3:142939741-142947933 +  3q22-q24   [Description]    (hg18-Mar_2006)
Ensembl	RNF7 - 3q22-q24 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	RNF7
	Gene and transcription
Genbank	AF092878 [ ENTREZ ]
Genbank	AF142060 [ ENTREZ ]
Genbank	AF164679 [ ENTREZ ]
Genbank	AF312226 [ ENTREZ ]
Genbank	AK311982 [ ENTREZ ]
RefSeq	NM_014245 [ SRS ]    NM_014245 [ ENTREZ ]
RefSeq	NM_183237 [ SRS ]    NM_183237 [ ENTREZ ]
RefSeq	AC_000046 [ SRS ]    AC_000046 [ ENTREZ ]
RefSeq	AC_000135 [ SRS ]    AC_000135 [ ENTREZ ]
RefSeq	NC_000003 [ SRS ]    NC_000003 [ ENTREZ ]
RefSeq	NT_005612 [ SRS ]    NT_005612 [ ENTREZ ]
RefSeq	NW_001838884 [ SRS ]    NW_001838884 [ ENTREZ ]
RefSeq	NW_921807 [ SRS ]    NW_921807 [ ENTREZ ]
AceView	RNF7 AceView - NCBI
Unigene	Hs.134623 [ SRS ]    Hs.134623 [ NCBI ]     HS134623 [ spliceNest ]
Fast-db	13582 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q9UBF6 [ SRS]    Q9UBF6 [ EXPASY ]     Q9UBF6 [ INTERPRO ]     Q9UBF6 [ UNIPROT ]
Prosite	PS50089 ZF_RING_2 [ SRS ]    PS50089 ZF_RING_2 [ Expasy ]
Interpro	IPR001841 Znf_RING [ SRS ]    IPR001841 Znf_RING [ EBI ]
Interpro	IPR013083 Znf_RING/FYVE/PHD [ SRS ]    IPR013083 Znf_RING/FYVE/PHD [ EBI ]
CluSTr	Q9UBF6
Pfam	PF00097 zf-C3HC4 [ SRS ]    PF00097 zf-C3HC4 [ Sanger ]    pfam00097 [ NCBI-CDD ]
Smart	SM00184 RING [EMBL]
Blocks	Q9UBF6
PDB	2ECL [ SRS ]    2ECL [ PdbSum ],   2ECL [ IMB ]   2ECL [ RSDB ]
HPRD	04840
	Protein Interaction databases
DIP	Q9UBF6
IntAct	Q9UBF6
	Polymorphism : SNP, mutations, diseases
OMIM	603863    [ map ]
GENECLINICS	603863
SNP	RNF7 [dbSNP-NCBI]
SNP	NM_014245 [SNP-NCI]
SNP	NM_183237 [SNP-NCI]
SNP	RNF7 [GeneSNPs - Utah]  RNF7] [HGBASE - SRS]
HAPMAP	RNF7 [HAPMAP]
COSMIC	RNF7 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	RNF7
	General knowledge
Family Browser	RNF7 [UCSC Family Browser]
SOURCE	NM_014245
SOURCE	NM_183237
SMD	Hs.134623
SAGE	Hs.134623
GO	copper ion binding [Amigo]  copper ion binding
GO	protein binding [Amigo]  protein binding
GO	nucleus [Amigo]  nucleus
GO	cytoplasm [Amigo]  cytoplasm
GO	anti-apoptosis [Amigo]  anti-apoptosis
GO	redox signal response [Amigo]  redox signal response
GO	zinc ion binding [Amigo]  zinc ion binding
GO	induction of apoptosis by oxidative stress [Amigo]  induction of apoptosis by oxidative stress
GO	metal ion binding [Amigo]  metal ion binding
PubGene	RNF7
TreeFam	RNF7
CTD	9616 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	RNF7 Related clones (RZPD - Berlin)
	PubMed
PubMed	23 Pubmed reference(s) in LocusLink

Bibliography

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

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

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

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

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

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

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

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

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

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

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 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

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

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

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

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

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

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

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Last year publications	automatic search in PubMed

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Contributor(s)

Written	11-2007	Yi Sun
		Department of Radiation Oncology, University of Michigan, 4304 CCGC, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0010, USA

Citation

This paper should be referenced as such :

Sun Y . RNF7 (RING finger protein-7). Atlas Genet Cytogenet Oncol Haematol. November 2007 . URL : http://AtlasGeneticsOncology.org/Genes/RNF7ID44108ch3q22.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:17:16 2008