Alternative titles; symbols
HGNC Approved Gene Symbol: SFR1
Cytogenetic location: 10q25.1 Genomic coordinates (GRCh38): 10:104,120,166-104,126,383 (from NCBI)
SFR1 functions in gene transcription and DNA recombination and repair (Feng et al., 2013).
Akamatsu and Jasin (2010) cloned Sfr1 from mouse embryonic stem (ES) cells and identified human SFR1 by database analysis. The deduced 303-amino acid mouse protein has a repeated pro-rich motif near the N terminus and a coiled-coil domain near the C terminus. The deduced human SFR1 protein contains 307 amino acids. Repetition of the pro-rich motif appeared to be rodent specific, as the motif was found only once in other mammals, including human. Immunofluorescence analysis showed colocalization of Sfr1 with Swi5 (616528) in the nucleus of mouse ES cells and embryonic fibroblasts.
Yuan and Chen (2011) reported that human MEI5 contains 232 amino acids. Database analysis revealed orthologs from mammals to yeast, all of which have a conserved C-terminal MEI5 domain with a coiled-coil motif. RT-PCR analysis detected MEI5 expression in all cell lines tested, and EST database analysis suggested widespread MEI5 expression in human tissues.
Feng et al. (2013) identified 3 isoforms of human SFR1, which they called SFR1A, SFR1B, and SFR1C. The deduced 307-, 245-, and 232-amino acid proteins differ in the length of their N-terminal ends. All isoforms have a C-terminal coiled-coil domain, followed by corepressor/nuclear receptor (CoRNR)-like sequences and an NR box-like motif.
Akamatsu and Jasin (2010) found that mouse Sfr1 and Swi5 formed a complex in vivo and in vitro. The Swi5-Sfr1 complex also interacted with Rad51 (179617), a DNA strand-exchange protein that functions during homologous recombination repair, through Swi5. Knockout of either Swi5 or Sfr1 in mouse ES cells reduced expression of the other protein and increased cell sensitivity to agents that cause DNA strand breaks.
Independently, Yuan and Chen (2011) found that human SWI5 and MEI5 interacted in the nucleus and provided mutual stability. Protein pull-down experiments revealed that the SWI5-MEI5 complex also interacted with RAD51. In U2OS cells, the SWI5-MEI5 complex promoted RAD51 foci formation and homologous recombination on damaged DNA following ionizing radiation-induced DNA damage. Knockdown of SWI5 or MEI5 impaired RAD51 foci formation on damaged DNA following ionizing radiation.
Using yeast 2-hybrid analysis, Feng et al. (2013) found that full-length SFR1A, but not SFR1B or SFR1C, bound estrogen receptor-alpha (ESRA; 133430). Reciprocal coimmunoprecipitation of Ishikawa human endometrial cancer cells confirmed interaction between SFR1A and ESRA. SFR1A interacted with ESRA both in the presence and absence of estrogen and enhanced both ligand-dependent and ligand-independent ESRA activation of reporter gene activity. SFR1A also interacted with androgen receptor (AR; 313700) in a ligand-independent manner. SFR1A did not interact with estrogen receptor-beta (ESRB; 601663). Depletion of SFR1A via RNA interference significantly impaired estrogen- and ESRA-dependent reporter activity. Knockdown of SFR1A also reduced estrogen-dependent growth and increased apoptosis in MCF7 cells.
Yuan and Chen (2011) stated that the SFR1 gene maps to chromosome 10q25.1.
Akamatsu, Y., Jasin, M. Role for the mammalian Swi5-Sfr1 complex in DNA strand break repair through homologous recombination. PLoS Genet. 6: e1001160, 2010. Note: Electronic Article. [PubMed: 20976249] [Full Text: https://doi.org/10.1371/journal.pgen.1001160]
Feng, Y., Singleton, D., Guo, C., Gardner, A., Pakala, S., Kumar, R., Jensen, E., Zhang, J., Khan, S. DNA homologous recombination factor SFR1 physically and functionally interacts with estrogen receptor alpha. PLoS One 8: e68075, 2013. Note: Electronic Article. [PubMed: 23874500] [Full Text: https://doi.org/10.1371/journal.pone.0068075]
Hartz, P. A. Personal Communication. Baltimore, Md. 8/17/2015.
Yuan, J., Chen, J. The role of the human SWI5-MEI5 complex in homologous recombination repair. J. Biol. Chem. 286: 9888-9893, 2011. [PubMed: 21252223] [Full Text: https://doi.org/10.1074/jbc.M110.207290]