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Gene Review

RFC2  -  replication factor C (activator 1) 2, 40kDa

Homo sapiens

Synonyms: A1, A1 40 kDa subunit, Activator 1 40 kDa subunit, Activator 1 subunit 2, RF-C 40 kDa subunit, ...
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Disease relevance of RFC2


High impact information on RFC2

  • At gastrulation, however, both A1 and A2 proteins turn over rapidly during interphase of the cell cycle [6].
  • Here we show that hnRNP A1 inhibits splicing of this intron via a novel heterogeneous nuclear ribonucleoprotein (hnRNP) A1-responsive intron splicing silencer (ISS) that can function independently of the previously characterized exon splicing silencer (ESS3) [7].
  • However, CT activation as determined by its reduction to form the A1 peptide and CT activity as measured by cyclic AMP accumulation were inhibited in filipin-treated cells [8].
  • The amino acid sequence of A1 contains two RNP motif RNA-binding domains (RBDs) at the amino terminus and a glycine-rich domain at the carboxyl terminus [9].
  • The RBDs and another RNA binding motif found in the glycine-rich domain, the RGG box, are not required for A1 nuclear localization [9].

Chemical compound and disease context of RFC2

  • In PA-1 human teratocarcinoma cells HOX A1 is the earliest HOX A gene to be expressed after treatment with RA [10].
  • Protein content in cholesterol gallstones ranged from 50 to 5700 micrograms/g, with median, quartile, and three quartile values being 250, 111, and 740; apolipoprotein A1 content ranged from 9 to 9000 ng/g (200, 41, 647) [11].

Biological context of RFC2


Anatomical context of RFC2

  • In humans, apo A-1 Milano infusion has led to rapid regression of atherosclerosis in coronary arteries [16].
  • The heterogeneous nuclear RNP (hnRNP) A1 protein is one of the major pre-mRNA/mRNA binding proteins in eukaryotic cells and one of the most abundant proteins in the nucleus [9].
  • Monocyte-derived dendritic cells infected with a recombinant canarypoxvirus (ALVAC) containing the entire MAGE-A1 gene were used to stimulate CD8+ T lymphocytes from the blood of individuals without cancer [17].
  • The A1 chain is not degraded in the cytosol, as demonstrated by the fact that proteasome inhibitors do not stimulate its activity [18].
  • Cholera toxin travels from the cell surface of affected mammalian cells to the endoplasmic reticulum (ER), where the A1 chain is released and retro-translocated across the ER membrane into the cytosol [18].

Associations of RFC2 with chemical compounds

  • Complementary functions of the antiapoptotic protein A1 and serine/threonine kinase pim-1 in the BCR/ABL-mediated leukemogenesis [14].
  • We show here that expression of the antiapoptotic protein A1, a member of the Bcl-2 family, and the serine/threonine kinase pim-1 are enhanced by BCR/ABL [14].
  • Direct assignment of vitamin K1 as the secondary acceptor A1 in photosystem I [19].
  • Cyclic AMP regulates the expression and nuclear translocation of RFC40 in MCF7 cells [20].
  • It was demonstrated in the early 1990s that adenosine exerts many physiological functions through the interaction with four different receptors, named A1, A2A, A2B, and A3 [21].

Regulatory relationships of RFC2


Other interactions of RFC2

  • Activator 1 (A1; also called replication factor C), in conjunction with proliferating-cell nuclear antigen (PCNA), is essential for the elongation of primed DNA templates by DNA polymerases delta and epsilon [2].
  • Within this region we have completely characterized 200 kb containing the genes LIMK1, WBSCR1, and RFC2 [12].
  • Here we describe the genetic analysis of the rfc2 +gene of the fission yeast Schizosaccharomyces pombe encoding a structural homologue of the budding yeast Rfc2p and human hRFC37 proteins [13].
  • We have recently identified a novel interaction between RIalpha and RFC40, the second subunit of Replication Factor C (RFC), and have demonstrated that this interaction may be associated with cell survival [4].
  • Additionally, the nuclear to cytoplasmic ratio of RFC40 increased by 26% followed by a parallel increase in the percentage of S phase cells by 33% [20].

Analytical, diagnostic and therapeutic context of RFC2

  • After switching back to UFH for hemodialysis, these biochemical indices reverted to previous values during UFH treatment with a significant higher level in TC and Apo B while serum Apo A-1 remained elevated [23].
  • Reaction of factor VIIIa with EDC resulted in the formation of a cross-linked product of approximately 90 kD consisting of the A1 and A2 subunits as judged by Western blotting [24].
  • In situ hybridization revealed that the gene encoding clone A1 was expressed preferentially in the mushroom bodies and not in the optic lobes, antennal lobes and central bodies; in the mushroom body, it was expressed strongly in the large type Kenyon cells and weakly in the small type Kenyon cells [25].
  • In the present study, using an enzyme-linked immunosorbent assay of apolipoprotein A1, we determined the content of apolipoprotein A1 in cholesterol gallstones and samples of gallbladder bile collected simultaneously from 23 patients during cholecystectomy [11].
  • 1. Southern blot confirmed the emergence of the human apolipoprotein A1 (h-apoA1) gene (four to 15 copies) in newborn transgenic mice [26].


  1. The gene for replication factor C subunit 2 (RFC2) is within the 7q11.23 Williams syndrome deletion. Peoples, R., Perez-Jurado, L., Wang, Y.K., Kaplan, P., Francke, U. Am. J. Hum. Genet. (1996) [Pubmed]
  2. Sequence and expression in Escherichia coli of the 40-kDa subunit of activator 1 (replication factor C) of HeLa cells. Chen, M., Pan, Z.Q., Hurwitz, J. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  3. In vitro activity of hederacolchisid A1 compared with other saponins from Hedera colchica against proliferation of human carcinoma and melanoma cells. Barthomeuf, C., Debiton, E., Mshvildadze, V., Kemertelidze, E., Balansard, G. Planta Med. (2002) [Pubmed]
  4. RIalpha influences cellular proliferation in cancer cells by transporting RFC40 into the nucleus. Gupte, R.S., Pozarowski, P., Grabarek, J., Traganos, F., Darzynkiewicz, Z., Lee, M.Y. Cancer Biol. Ther. (2005) [Pubmed]
  5. Retroviral insertions downstream of the heterogeneous nuclear ribonucleoprotein A1 gene in erythroleukemia cells: evidence that A1 is not essential for cell growth. Ben-David, Y., Bani, M.R., Chabot, B., De Koven, A., Bernstein, A. Mol. Cell. Biol. (1992) [Pubmed]
  6. Identification of a developmental timer regulating the stability of embryonic cyclin A and a new somatic A-type cyclin at gastrulation. Howe, J.A., Howell, M., Hunt, T., Newport, J.W. Genes Dev. (1995) [Pubmed]
  7. The hnRNP A1 protein regulates HIV-1 tat splicing via a novel intron silencer element. Tange, T.O., Damgaard, C.K., Guth, S., Valcárcel, J., Kjems, J. EMBO J. (2001) [Pubmed]
  8. Filipin-dependent inhibition of cholera toxin: evidence for toxin internalization and activation through caveolae-like domains. Orlandi, P.A., Fishman, P.H. J. Cell Biol. (1998) [Pubmed]
  9. A nuclear localization domain in the hnRNP A1 protein. Siomi, H., Dreyfuss, G. J. Cell Biol. (1995) [Pubmed]
  10. Structure and function of the HOX A1 human homeobox gene cDNA. Hong, Y.S., Kim, S.Y., Bhattacharya, A., Pratt, D.R., Hong, W.K., Tainsky, M.A. Gene (1995) [Pubmed]
  11. Measurement of apolipoprotein A1 in cholesterol gallstones and gallbladder bile of patients with gallstones. Hasegawa, T., Makino, I. J. Gastroenterol. (1995) [Pubmed]
  12. Comparative genomic sequence analysis of the Williams syndrome region (LIMK1-RFC2) of human chromosome 7q11.23. Martindale, D.W., Wilson, M.D., Wang, D., Burke, R.D., Chen, X., Duronio, V., Koop, B.F. Mamm. Genome (2000) [Pubmed]
  13. A key role for replication factor C in DNA replication checkpoint function in fission yeast. Reynolds, N., Fantes, P.A., MacNeill, S.A. Nucleic Acids Res. (1999) [Pubmed]
  14. Complementary functions of the antiapoptotic protein A1 and serine/threonine kinase pim-1 in the BCR/ABL-mediated leukemogenesis. Nieborowska-Skorska, M., Hoser, G., Kossev, P., Wasik, M.A., Skorski, T. Blood (2002) [Pubmed]
  15. A combination of molecular cytogenetic analyses reveals complex genetic alterations in conventional renal cell carcinoma. Strefford, J.C., Stasevich, I., Lane, T.M., Lu, Y.J., Oliver, T., Young, B.D. Cancer Genet. Cytogenet. (2005) [Pubmed]
  16. Plasma delipidation process induces rapid regression of atherosclerosis and mobilisation of adipose tissue. Cham, B.E., Kostner, K.M., Shafey, T.M., Smith, J.L., Colquhoun, D.M. Journal of clinical apheresis. (2005) [Pubmed]
  17. Identification of five MAGE-A1 epitopes recognized by cytolytic T lymphocytes obtained by in vitro stimulation with dendritic cells transduced with MAGE-A1. Chaux, P., Luiten, R., Demotte, N., Vantomme, V., Stroobant, V., Traversari, C., Russo, V., Schultz, E., Cornelis, G.R., Boon, T., van der Bruggen, P. J. Immunol. (1999) [Pubmed]
  18. Role of ubiquitination in retro-translocation of cholera toxin and escape of cytosolic degradation. Rodighiero, C., Tsai, B., Rapoport, T.A., Lencer, W.I. EMBO Rep. (2002) [Pubmed]
  19. Direct assignment of vitamin K1 as the secondary acceptor A1 in photosystem I. Snyder, S.W., Rustandi, R.R., Biggins, J., Norris, J.R., Thurnauer, M.C. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  20. Cyclic AMP regulates the expression and nuclear translocation of RFC40 in MCF7 cells. Gupte, R.S., Sampson, V., Traganos, F., Darzynkiewicz, Z., Lee, M.Y. Exp. Cell Res. (2006) [Pubmed]
  21. 7-Substituted 5-amino-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as A2A adenosine receptor antagonists: a study on the importance of modifications at the side chain on the activity and solubility. Baraldi, P.G., Cacciari, B., Romagnoli, R., Spalluto, G., Monopoli, A., Ongini, E., Varani, K., Borea, P.A. J. Med. Chem. (2002) [Pubmed]
  22. Phosphorylation of RIalpha by cyclin-dependent kinase CDK 2/cyclin E modulates the dissociation of the RIalpha-RFC40 complex. Gupte, R.S., Traganos, F., Darzynkiewicz, Z., Lee, M.Y. Cell Cycle (2006) [Pubmed]
  23. Effect of low molecular weight heparin on bone metabolism and hyperlipidemia in patients on maintenance hemodialysis. Lai, K.N., Ho, K., Cheung, R.C., Lit, L.C., Lee, S.K., Fung, K.S., Tong, M.K., Lam, C.W. The International journal of artificial organs. (2001) [Pubmed]
  24. Interacting regions in the A1 and A2 subunits of factor VIIIa identified by zero-length cross-linking. O'Brien, L.M., Huggins, C.F., Fay, P.J. Blood (1997) [Pubmed]
  25. Preferential expression of the gene for a putative inositol 1,4,5-trisphosphate receptor homologue in the mushroom bodies of the brain of the worker honeybee Apis mellifera L. Kamikouchi, A., Takeuchi, H., Sawata, M., Ohashi, K., Natori, S., Kubo, T. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  26. Inhibition of intimal lipid deposition in human apolipoprotein A1 transgenic mice. She, M., Li, H., Yu, L., Gu, S., Wang, Z. Clin. Exp. Pharmacol. Physiol. (1999) [Pubmed]
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