RSF1 (remodeling and spacing factor 1)

2008-07-01   Tian-Li Wang , Joon T Park 

Departments of Gynecology\\\/Obstetrics, Oncology Johns Hopkins Medical Institutions CRBII, Rm: 306 1550 Orleans Street Baltimore, MD 21231, USA




Atlas Image
Genomic organization of human RSF1.


Rsf1 gene is encoded by 16 exons spanning 154.607 Mb that are located on chromosome 11p14.1.


5.131 Kb mRNA, the coding sequence is from 121 bp-4446 bp.



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.
Atlas Image
Diagram of the RSF1 protein.


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 5RACE, 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 couldnt bind to DNA unless histones are present.


Highly expressed in heart, skeletal muscle, kidney, and placenta, and expressed weakly in brain and colon.


Mainly located at cell nucleus. During mitosis, the expression in the nucleus is decreased.


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.



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 name
Ovarian cancer
Shih et al found that amplification of Rsf1 locus was correlated with shorter overall survival of ovarian cancer patients.
Amplification of 11q13 detected an ovarian cancer cell line, OVCAR3.
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.


Pubmed IDLast YearTitleAuthors
129725962003Functional analysis of the subunits of the chromatin assembly factor RSF.Loyola A et al
169385222006Expression of Rsf-1, a chromatin-remodeling gene, in ovarian and breast carcinoma.Mao TL et al
119449842002HBXAP, a novel PHD-finger protein, possesses transcription repression activity.Shamay M et al
185196632008The roles of human sucrose nonfermenting protein 2 homologue in the tumor-promoting functions of Rsf-1.Sheu JJ et al
161723932005Amplification of a chromatin remodeling gene, Rsf-1/HBXAP, in ovarian carcinoma.Shih IeM et al

Other Information

Locus ID:

NCBI: 51773
MIM: 608522
HGNC: 18118
Ensembl: ENSG00000048649


dbSNP: 51773
ClinVar: 51773
TCGA: ENSG00000048649


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Cell CycleREACTOMER-HSA-1640170
Chromosome MaintenanceREACTOMER-HSA-73886
Nucleosome assemblyREACTOMER-HSA-774815
Deposition of new CENPA-containing nucleosomes at the centromereREACTOMER-HSA-606279

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
183149092008Amplification of 11q13 in ovarian carcinoma.56
161723932005Amplification of a chromatin remodeling gene, Rsf-1/HBXAP, in ovarian carcinoma.54
202287822010Serous tubal intraepithelial carcinoma upregulates markers associated with high-grade serous carcinomas including Rsf-1 (HBXAP), cyclin E and fatty acid synthase.36
191903252009Functional analysis of 11q13.5 amplicon identifies Rsf-1 (HBXAP) as a gene involved in paclitaxel resistance in ovarian cancer.31
194756912009Overexpression of insulin receptor substrate-1 and hepatitis Bx genes causes premalignant alterations in the liver.28
209237752010Rsf-1, a chromatin remodeling protein, induces DNA damage and promotes genomic instability.24
239741062013Remodeling and spacing factor 1 (RSF1) deposits centromere proteins at DNA double-strand breaks to promote non-homologous end-joining.22
185196632008The roles of human sucrose nonfermenting protein 2 homologue in the tumor-promoting functions of Rsf-1.21
248007432014The RSF1 histone-remodelling factor facilitates DNA double-strand break repair by recruiting centromeric and Fanconi Anaemia proteins.19
215144512011Overexpression of a chromatin remodeling factor, RSF-1/HBXAP, correlates with aggressive oral squamous cell carcinoma.18


Tian-Li Wang ; Joon T Park

RSF1 (remodeling and spacing factor 1)

Atlas Genet Cytogenet Oncol Haematol. 2008-07-01

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