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RSF1 (remodeling and spacing factor 1)

Identity

Other namesHBXAP
XAP8
RSF-1
p325
HGNC (Hugo) RSF1
LocusID (NCBI) 51773
Location 11q14.1
Location_base_pair Starts at 77377274 and ends at 77531880 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order gene orientation: centromere -3' RSF1 5'- telomere.

DNA/RNA

 
  Genomic organization of human RSF1.
Description Rsf1 gene is encoded by 16 exons spanning 154.607 Mb that are located on chromosome 11p14.1.
Transcription 5.131 Kb mRNA, the coding sequence is from 121 bp-4446 bp.

Protein

Note 1441 amino acids, highly acidic protein (pI 4.94), with calculated molecular mass of 164 kD. SDS-PAGE detected native RSF1 at molecular mass of 200 to 300 kD
Contain a DDT domain, Zinc finger PHD-type domain which was found in nuclear proteins thought to be involved in chromatin-mediated transcriptional regulation.
RSF1 also contains 3 nuclear localization signal near C-terminus.
 
  Diagram of the RSF1 protein.
Description Using a variation of the yeast 2-hybrid screen aiming to identify proteins interacting with hepatitis B virus X protein (HBX), Shamay et al (2002a) cloned RSF1 from a spleen cDNA library. Therefore, the initial name of RSF1 was called Hepatitis B virus X-Associated Protein (HBXAP). Using 5'RACE, 3 splice variants were cloned and named HBXAP-alpha, -beta, -gamma, which contains 1431, 1400, and 1189 amino acids, respectively. By characterizing a protein remodeling complex RSF, Loyola A et al has identified two interacting subunits: RSF1 and SNF2H. They used peptide sequence information of RSF1 to clone the full-length cDNA. The deduced sequence contains 1441 amino acids which includes 252 additional amino acids at N-terminus as compared to HBXAP-gamma. Reconstitute experiment by isolating protein complex from coinfection of viruses caring each subunit can recapitulate the chromatin assembly ability and ATPase activity of native complex. They also showed that SNF2H binds to DNA independently of histones. However, RSF1 couldn't bind to DNA unless histones are present.
Expression Highly expressed in heart, skeletal muscle, kidney, and placenta, and expressed weakly in brain and colon.
Localisation Mainly located at cell nucleus. During mitosis, the expression in the nucleus is decreased.
Function RSF1 functions as transcription coactivator when associated with hepatitis B virus X protein (HBX). Shamay et al (2002b) observed the direct interaction between the RSF1 variant, HBXAP-gamma, and HBX. HBXAP-gamma increased hepatitis B viral transcription in an HBX-dependent manner. Furthermore, in the presence of both HBX and HBXAP, the transcription of a nuclear factor kappa-B ( NFKB ) was significantly increased. However, in the presence of HBXAP alone, the transcription of a NFKB was decreased in a dose-dependent manner. Examination of HBXAP-gamma deletion mutants showed that the interaction between HBX and HBXAP-gamma was mediated by the PHD domain in HBXAP-gamma.
RSF1 functions as chromatin remodeling and spacing when associated with SNF2H. Loyola et al reconstituted the RSF complex by overexpressing two subunits, RSF1 and SNF2H. RSF1 assembled nucleosome randomly as a histone chaperone in the nuclei. The resulting nucleosomes were then redistributed into a regularly spaced nucleosome array by the ATP-utilizing nucleosome mobilization factor SNF2H. At the cellular level, Rsf1/SNF2H complex participated in chromatin remodeling by mobilizing nucleosomes in response to a variety of growth modifying signals and environmental cues. Sheu JJ et al found that the induction of RSF1 expression affected the molecular partnership of SNF2H and translocated SNF2H into nuclei where it colocalized with RSF1. To determine which domain in the RSF1 is involved in the binding to SNF2H, a series of RSF1-deletion mutants were generated. Only the fragment that contains DDT, Glu-rich, and PHD motifs could be immunoprecipitated with SNF2H. Ectopic expression of this RSF1 fragment disrupted RSF1/SNF2H complex and resulted in remarkable growth inhibition in ovarian cancer cells with RSF1 gene amplification and overexpression, but not in the cells without detectable RSF1 expression. This finding suggests that interaction between RSF1 and SNF2H may define a survival signal in the tumors overexpressing RSF1.

Mutations

Somatic Chromosome 11q is one of the most common targets for allelic imbalance alteration in human cancers. Several candidate tumor-promoting genes were postulated previously. In ovarian carcinoma, Shih et al, has pinpointed a minimal amplicon spanning from 76.6 to 78.4 Mb on the chromosome 11q, which harbor 13 genes. Rsf1 was identified as the gene with most consistent correlation between gene amplification and transcription up-regulation.

Implicated in

Entity Ovarian cancer
Prognosis Shih et al found that amplification of Rsf1 locus was correlated with shorter overall survival of ovarian cancer patients.
Cytogenetics Amplification of 11q13 detected an ovarian cancer cell line, OVCAR3.
Oncogenesis Shih et al found that the amplification of chr11q13 is associated with RSF1 protein over-expression. siRNA knockdown experiment in OVCAR3 cell, which harbor Rsf-1 amplification, demonstrated it is essential for tumor cell survival.
Mao TL et al found that RSF1 overexpression was observed in 25% of high-grade ovarian serous carcinomas and in less than 7% of low-grade ovarian serous carcinoma and ovarian endometrioid. RSF1 does not express in any of the ovarian serous borderline tumors, ovarian clear cell carcinomas, ovarian mucinous carcinomas, and normal ovaries. Overexpression of RSF1 was significantly associated with high-grade ovarian serous carcinoma (P < 0.05) as compared with other types of ovarian tumors, demonstrating that RSF1 expression is primarily confined to high-grade serous carcinoma, the most aggressive ovarian cancer.
  

External links

Nomenclature
HGNC (Hugo)RSF1   18118
Cards
AtlasRSF1ID44107ch11q13
Entrez_Gene (NCBI)RSF1  51773  remodeling and spacing factor 1
GeneCards (Weizmann)RSF1
Ensembl (Hinxton)ENSG00000048649 [Gene_View]  chr11:77377274-77531880 [Contig_View]  RSF1 [Vega]
ICGC DataPortalENSG00000048649
cBioPortalRSF1
AceView (NCBI)RSF1
Genatlas (Paris)RSF1
WikiGenes51773
SOURCE (Princeton)NM_016578
Genomic and cartography
GoldenPath (UCSC)RSF1  -  11q14.1   chr11:77377274-77531880 -  11q14.1   [Description]    (hg19-Feb_2009)
EnsemblRSF1 - 11q14.1 [CytoView]
Mapping of homologs : NCBIRSF1 [Mapview]
OMIM608522   
Gene and transcription
Genbank (Entrez)AF059317 AF227948 AF380176 AK001268 AL602953
RefSeq transcript (Entrez)NM_016578
RefSeq genomic (Entrez)AC_000143 NC_000011 NC_018922 NT_167190 NW_001838028 NW_004929380
Consensus coding sequences : CCDS (NCBI)RSF1
Cluster EST : UnigeneHs.420229 [ NCBI ]
CGAP (NCI)Hs.420229
Alternative Splicing : Fast-db (Paris)GSHG0006040
Alternative Splicing GalleryENSG00000048649
Gene ExpressionRSF1 [ NCBI-GEO ]     RSF1 [ SEEK ]   RSF1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ96T23 (Uniprot)
NextProtQ96T23  [Medical]
With graphics : InterProQ96T23
Splice isoforms : SwissVarQ96T23 (Swissvar)
Domaine pattern : Prosite (Expaxy)DDT (PS50827)    ZF_PHD_1 (PS01359)    ZF_PHD_2 (PS50016)   
Domains : Interpro (EBI)Zinc_finger_PHD-type_CS [organisation]   Znf_FYVE_PHD [organisation]   Znf_PHD [organisation]   Znf_PHD-finger [organisation]   Znf_RING/FYVE/PHD [organisation]  
Related proteins : CluSTrQ96T23
Domain families : Pfam (Sanger)PHD (PF00628)   
Domain families : Pfam (NCBI)pfam00628   
Domain families : Smart (EMBL)PHD (SM00249)  
DMDM Disease mutations51773
Blocks (Seattle)Q96T23
Human Protein AtlasENSG00000048649 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ96T23
HPRD10537
IPIIPI00290652   IPI00514411   IPI00982445   IPI01010155   IPI00977965   IPI00976511   IPI00981883   
Protein Interaction databases
DIP (DOE-UCLA)Q96T23
IntAct (EBI)Q96T23
FunCoupENSG00000048649
BioGRIDRSF1
InParanoidQ96T23
Interologous Interaction database Q96T23
IntegromeDBRSF1
STRING (EMBL)RSF1
Ontologies - Pathways
Ontology : AmiGOprotein binding  nucleus  nucleoplasm  nucleosome assembly  nucleosome assembly  chromatin remodeling  DNA-dependent transcription, initiation  zinc ion binding  nucleosome positioning  ATPase activity  RSF complex  CENP-A containing nucleosome assembly at centromere  histone binding  negative regulation of DNA binding  negative regulation of transcription, DNA-dependent  positive regulation of transcription, DNA-dependent  positive regulation of viral transcription  
Ontology : EGO-EBIprotein binding  nucleus  nucleoplasm  nucleosome assembly  nucleosome assembly  chromatin remodeling  DNA-dependent transcription, initiation  zinc ion binding  nucleosome positioning  ATPase activity  RSF complex  CENP-A containing nucleosome assembly at centromere  histone binding  negative regulation of DNA binding  negative regulation of transcription, DNA-dependent  positive regulation of transcription, DNA-dependent  positive regulation of viral transcription  
Protein Interaction DatabaseRSF1
Wikipedia pathwaysRSF1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)RSF1
snp3D : Map Gene to Disease51773
SNP (GeneSNP Utah)RSF1
SNP : HGBaseRSF1
Genetic variants : HAPMAPRSF1
Exome VariantRSF1
1000_GenomesRSF1 
ICGC programENSG00000048649 
Somatic Mutations in Cancer : COSMICRSF1 
CONAN: Copy Number AnalysisRSF1 
Mutations and Diseases : HGMDRSF1
Genomic VariantsRSF1  RSF1 [DGVbeta]
dbVarRSF1
ClinVarRSF1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM608522   
MedgenRSF1
GENETestsRSF1
Disease Genetic AssociationRSF1
Huge Navigator RSF1 [HugePedia]  RSF1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneRSF1
Homology/Alignments : Family Browser (UCSC)RSF1
Phylogenetic Trees/Animal Genes : TreeFamRSF1
Chemical/Protein Interactions : CTD51773
Chemical/Pharm GKB GenePA29210
Clinical trialRSF1
Cancer Resource (Charite)ENSG00000048649
Other databases
Probes
Litterature
PubMed48 Pubmed reference(s) in Entrez
CoreMineRSF1
iHOPRSF1

Bibliography

Hepatitis B virus pX interacts with HBXAP, a PHD finger protein to coactivate transcription.
Shamay M, Barak O, Doitsh G, Ben-Dor I, Shaul Y.
J Biol Chem. 2002b Mar 22;277(12):9982-8. Epub 2002 Jan 11.
PMID 11788598
 
HBXAP, a novel PHD-finger protein, possesses transcription repression activity.
Shamay M, Barak O, Shaul Y.
Genomics. 2002a Apr;79(4):523-9.
PMID 11944984
 
Functional analysis of the subunits of the chromatin assembly factor RSF.
Loyola A, Huang JY, LeRoy G, Hu S, Wang YH, Donnelly RJ, Lane WS, Lee SC, Reinberg D.
Mol Cell Biol. 2003 Oct;23(19):6759-68.
PMID 12972596
 
Amplification of a chromatin remodeling gene, Rsf-1/HBXAP, in ovarian carcinoma.
Shih IeM, Sheu JJ, Santillan A, Nakayama K, Yen MJ, Bristow RE, Vang R, Parmigiani G, Kurman RJ, Trope CG, Davidson B, Wang TL.
Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):14004-9. Epub 2005 Sep 19.
PMID 16172393
 
Expression of Rsf-1, a chromatin-remodeling gene, in ovarian and breast carcinoma.
Mao TL, Hsu CY, Yen MJ, Gilks B, Sheu JJ, Gabrielson E, Vang R, Cope L, Kurman RJ, Wang TL, Shih IeM.
Hum Pathol. 2006 Sep;37(9):1169-75. Epub 2006 Jul 7.
PMID 16938522
 
The roles of human sucrose nonfermenting protein 2 homologue in the tumor-promoting functions of Rsf-1.
Sheu JJ, Choi JH, Yildiz I, Tsai FJ, Shaul Y, Wang TL, Shih IeM.
Cancer Res. 2008 Jun 1;68(11):4050-7.
PMID 18519663
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written07-2008Tian-Li Wang, Joon T Park
Departments of Gynecology/Obstetrics and Oncology Johns Hopkins Medical Institutions CRBII, Rm: 306 1550 Orleans Street Baltimore, MD 21231, USA

Citation

This paper should be referenced as such :
Wang, TL ; Park, JT
RSF1 (remodeling and spacing factor 1)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(6):426-428.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/RSF1ID44107ch11q13.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Jul 11 17:13:53 CEST 2014

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