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Gene Review

Rpa2  -  replication protein A2

Mus musculus

Synonyms: 30-kDa protein, AA409079, AI325195, AU020965, RF-A protein 2, ...
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Disease relevance of Rpa2

  • In this study, we purified the 30-kDa protein from heart extract and identified it as cardiac troponin I (cTnI), encoded by a gene in which mutations can cause familial hypertrophic cardiomyopathy (HCM) [1].
  • We recently reported that mice deficient in the programmed cell death-1 (PD-1) immunoinhibitory coreceptor develop autoimmune dilated cardiomyopathy (DCM), with production of high-titer autoantibodies against a heart-specific, 30-kDa protein [1].
  • Antibodies present in these sera immunoprecipitate a triplet of proteins of 115,000 mol wt (p115), 80,000 mol wt (p80), and 32,000 mol wt (p32) from many but not all T cell lymphomas of mice [2].
  • The two alleles of the 30 kDa TATA-binding protein associated factor (TAF(II)30) gene, have been targeted by homologous recombination in murine F9 embryonal carcinoma cells and subsequently disrupted using a Cre recombinase-loxP strategy [3].
  • A murine mAb, STEGI 1, was generated against a 30-kDa raf protein purified from an Escherichia coli expression vector [4].

High impact information on Rpa2

  • Although apoptosis occurred in the absence or after crosslinking with anti-CD3 mAb, specific activation of CPP32, as assessed by the extent of proteolytic cleavage of the p32 zymogen, was only detected in thymocytes cultured in the presence of the immobilized antibody or dexamethasone [5].
  • The deduced amino acid sequence of p32 is identical to that of rat prohibitin. p37 is highly homologous to p32 [6].
  • To gain insight into the role of BRCA2 in the repair of DNA damage, we fused a single (BRC3, BRC4) or multiple BRC motifs to the large RPA subunit [7].
  • gACRP30, the globular subunit of adipocyte complement-related protein of 30 kDa (ACRP30), improves insulin sensitivity and increases fatty acid oxidation [8].
  • Cytosolic, full-length dbpB (50 kDa) was rapidly cleaved to a 30-kDa species upon thrombin stimulation of EC [9].

Chemical compound and disease context of Rpa2


Biological context of Rpa2

  • The properties of this enzyme suggest that it may take part in reactions mediated by RPA such as those predicted to occur at replication forks or alternatively may function during DNA repair or recombination [14].
  • Replication protein A (RPA), which is comprised of three subunits, is an important factor involved in DNA replication, repair, and transcription [15].
  • CfaRPA1 contains a zinc-finger motif that is also found in the RP-A large subunits from human, frog, and yeast [16].
  • This AID-RPA association, which requires phosphorylation, may provide a mechanism for allowing AID to access dsDNA targets in activated B cells [17].
  • Thus, AID from non-lymphoid cells can be functionally phosphorylated by recombinant PKA to allow interaction with RPA and promote deamination of transcribed dsDNA substrates [17].

Anatomical context of Rpa2

  • In an effort to identify cellular helicases that mimic the action of SV40 large T-antigen, we performed replication protein A (RPA) affinity chromatography on cell extracts from the mouse mammary carcinoma cell line FM3A [14].
  • The 32-kDa subunit of RPA interacts specifically with AID from activated B cells in a manner that seems to be dependent on post-translational AID modification [18].
  • Both 34-kDa and 30-kDa bands were also present in mitochondria isolated from transfected COS cells, whereas only the 30-kDa band was present in mitochondria isolated from normal human liver [19].
  • We have identified a 30-kDa isoform (p30) of C/EBP alpha that is expressed by 3T3-L1 adipocytes, mouse adipose tissue, and rat liver [20].
  • The N-terminal sequence determined directly on the 30-kDa soluble CA purified from transfected COS cells indicated that processing of the precursor to mature human CA V involves removal of a 38-aa mitochondrial leader sequence [19].

Associations of Rpa2 with chemical compounds

  • When [35S]methionine-labeled proteins synthesized after the addition of TPA were analyzed by one- or two-dimensional polyacrylamide gel electrophoresis, the increased synthesis of a 32,000-dalton protein (designated p32) was noted as one of the earliest changes [21].
  • The increased rate of the synthesis of p32 was considered to be regulated at the transcriptional level, because the increase in synthesis of p32 was inhibited by actinomycin D, and TPA-treated cells were shown to contain a higher level of translatable mRNA coding for p32 than do control cells [21].
  • The pool levels of the 42- and 30-kDa isoforms were high in control nuclear extracts and decreased significantly after lipopolysaccharide (LPS) treatment [22].
  • We observed that one of the major initial signaling events associated with Fc epsilon RI-mediated activation of human mast cells (HuMCs) is the rapid tyrosine phosphorylation of a protein of 25 to 30 kDa [23].
  • In a limited trypsin digestion assay, complexation of RAR alpha with retinoic acid or several other agonistic retinoids altered the degradation of the receptor such that a 30-kDa proteolytic fragment became resistant to proteolysis [24].

Physical interactions of Rpa2


Regulatory relationships of Rpa2

  • Comparison of two-dimensional gel electrophoresis patterns of proteins from wst/wst and control mouse thymus revealed that an acidic protein with a molecular mass of approximately 30 kDa was consistently expressed at lower levels in wasted mice than in controls [29].
  • PDGF-activated binding to the 27-mer is shown to involve a single 30-kDa protein by UV-cross-linking analysis [30].
  • Both CTLL contain a [3H]DFP-labeled protein that migrates with a molecular mass of 60 kDa under nonreducing conditions and with 30 kDa under reducing conditions and which can be inactivated by the TSP-1-specific inhibitor H-D-Pro-Phe-Arg-chloromethylketone [31].

Other interactions of Rpa2

  • In biochemical assays, replication protein A (RPA), a ssDNA-binding protein, associates with phosphorylated AID from activated B cells and enhances AID activity on transcribed double-stranded (ds)DNA containing somatic hypermutation or CSR target sequences [17].
  • Levels of c-jun mRNA and AP-1 DNA binding activity, however, remain elevated from the outset, while C/EBP alpha mRNA expression is down-regulated, resulting in a decrease in the steady-state levels of the 42- and 30-kDa C/EBP alpha polypeptides and C/EBP alpha DNA binding activity [32].
  • The mouse Cig30 gene codes for a 30-kDa membrane glycoprotein, which appears to have a role in the recruitment of brown adipose tissue [33].
  • The 30-kDa form of the steroidogenic acute regulatory (StAR) protein was quantitated, by Western blot, in Leydig cells and was found to decrease in a time-dependent manner [34].
  • To further assess whether chitin has Th1 adjuvant effects, interleukin-10 (IL-10)-knockout (KO) mice and their wild-type (WT, C57BL/6) controls were immunized with a 30-kDa MPB-59 mycobacterial protein mixed with chitin [35].

Analytical, diagnostic and therapeutic context of Rpa2


  1. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Okazaki, T., Tanaka, Y., Nishio, R., Mitsuiye, T., Mizoguchi, A., Wang, J., Ishida, M., Hiai, H., Matsumori, A., Minato, N., Honjo, T. Nat. Med. (2003) [Pubmed]
  2. P80: a tumor-related protein found in many lymphomas of mice. Grunwald, D.J., Miller, K., Risser, R. J. Exp. Med. (1982) [Pubmed]
  3. Mammalian TAF(II)30 is required for cell cycle progression and specific cellular differentiation programmes. Metzger, D., Scheer, E., Soldatov, A., Tora, L. EMBO J. (1999) [Pubmed]
  4. Characterization of a murine monoclonal antibody that detects a C-terminal fragment of the raf oncogene product. Giardina, S.L., Storm, S.M., Longo, D.L., Mathieson, B.J., Rapp, U., Varesio, L. J. Immunol. (1988) [Pubmed]
  5. Specific activation of the cysteine protease CPP32 during the negative selection of T cells in the thymus. Alam, A., Braun, M.Y., Hartgers, F., Lesage, S., Cohen, L., Hugo, P., Denis, F., Sékaly, R.P. J. Exp. Med. (1997) [Pubmed]
  6. The IgM antigen receptor of B lymphocytes is associated with prohibitin and a prohibitin-related protein. Terashima, M., Kim, K.M., Adachi, T., Nielsen, P.J., Reth, M., Köhler, G., Lamers, M.C. EMBO J. (1994) [Pubmed]
  7. Suppression of the DNA repair defects of BRCA2-deficient cells with heterologous protein fusions. Saeki, H., Siaud, N., Christ, N., Wiegant, W.W., van Buul, P.P., Han, M., Zdzienicka, M.Z., Stark, J.M., Jasin, M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Tomas, E., Tsao, T.S., Saha, A.K., Murrey, H.E., Zhang Cc, C., Itani, S.I., Lodish, H.F., Ruderman, N.B. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  9. Thrombin induces the release of the Y-box protein dbpB from mRNA: a mechanism of transcriptional activation. Stenina, O.I., Shaneyfelt, K.M., DiCorleto, P.E. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  10. Proteins of 30 and 36 kilodaltons, membrane constituents of the Staphylococcus aureus L form, induce production of tumor necrosis factor alpha and activate the human immunodeficiency virus type 1 long terminal repeat. Akashi, A., Ono, S., Kuwano, K., Arai, S. Infect. Immun. (1996) [Pubmed]
  11. Mycobacterial protein HbhA binds human complement component C3. Mueller-Ortiz, S.L., Wanger, A.R., Norris, S.J. Infect. Immun. (2001) [Pubmed]
  12. The vaccinia virus A41L protein is a soluble 30 kDa glycoprotein that affects virus virulence. Ng, A., Tscharke, D.C., Reading, P.C., Smith, G.L. J. Gen. Virol. (2001) [Pubmed]
  13. The Mycobacterium bovis homologous protein of the Mycobacterium tuberculosis serine/threonine protein kinase Mbk (PknD) is truncated. Peirs, P., Parmentier, B., De Wit, L., Content, J. FEMS Microbiol. Lett. (2000) [Pubmed]
  14. A DNA helicase purified by replication protein A (RPA) affinity chromatography from mouse FM3A cells. Hughes, P., Baldacci, G. Nucleic Acids Res. (1997) [Pubmed]
  15. Two types of replication protein A 70 kDa subunit in rice, Oryza sativa: molecular cloning, characterization, and cellular & tissue distribution. Ishibashi, T., Kimura, S., Furukawa, T., Hatanaka, M., Hashimoto, J., Sakaguchi, K. Gene (2001) [Pubmed]
  16. Isolation of the genes encoding the 51-kilodalton and 28-kilodalton subunits of Crithidia fasciculata replication protein A. Brown, G.W., Hines, J.C., Fisher, P., Ray, D.S. Mol. Biochem. Parasitol. (1994) [Pubmed]
  17. The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation. Basu, U., Chaudhuri, J., Alpert, C., Dutt, S., Ranganath, S., Li, G., Schrum, J.P., Manis, J.P., Alt, F.W. Nature (2005) [Pubmed]
  18. Replication protein A interacts with AID to promote deamination of somatic hypermutation targets. Chaudhuri, J., Khuong, C., Alt, F.W. Nature (2004) [Pubmed]
  19. Human mitochondrial carbonic anhydrase: cDNA cloning, expression, subcellular localization, and mapping to chromosome 16. Nagao, Y., Platero, J.S., Waheed, A., Sly, W.S. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  20. A 30-kDa alternative translation product of the CCAAT/enhancer binding protein alpha message: transcriptional activator lacking antimitotic activity. Lin, F.T., MacDougald, O.A., Diehl, A.M., Lane, M.D. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  21. Tumor promoters increase the synthesis of a 32,000-dalton protein in BALB/c 3T3 cells. Hiwasa, T., Fujimura, S., Sakiyama, S. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  22. Evidence for posttranscriptional regulation of C/EBPalpha and C/EBPbeta isoform expression during the lipopolysaccharide-mediated acute-phase response. An, M.R., Hsieh, C.C., Reisner, P.D., Rabek, J.P., Scott, S.G., Kuninger, D.T., Papaconstantinou, J. Mol. Cell. Biol. (1996) [Pubmed]
  23. NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and Fc epsilon RI aggregation. Tkaczyk, C., Horejsi, V., Iwaki, S., Draber, P., Samelson, L.E., Satterthwaite, A.B., Nahm, D.H., Metcalfe, D.D., Gilfillan, A.M. Blood (2004) [Pubmed]
  24. Different agonist- and antagonist-induced conformational changes in retinoic acid receptors analyzed by protease mapping. Keidel, S., LeMotte, P., Apfel, C. Mol. Cell. Biol. (1994) [Pubmed]
  25. Decreased carbonic anhydrase III levels in the liver of the mouse mutant 'toxic milk' (tx) due to copper accumulation. Grimes, A., Paynter, J., Walker, I.D., Bhave, M., Mercer, J.F. Biochem. J. (1997) [Pubmed]
  26. hPop4: a new protein subunit of the human RNase MRP and RNase P ribonucleoprotein complexes. van Eenennaam, H., Pruijn, G.J., van Venrooij, W.J. Nucleic Acids Res. (1999) [Pubmed]
  27. Cellular and subcellular distribution of galectin-3 in the epiphyseal cartilage and bone of fetal and neonatal mice. Colnot, C., Sidhu, S.S., Poirier, F., Balmain, N. Cell. Mol. Biol. (Noisy-le-grand) (1999) [Pubmed]
  28. Characterization of a novel cis-element that regulates Fas ligand expression in corneal endothelial cells. Zhang, J., Ma, B., Marshak-Rothstein, A., Fine, A. J. Biol. Chem. (1999) [Pubmed]
  29. Regulation of thymus PCNA expression is altered in radiation-sensitive wasted mice. Woloschak, G.E., Paunesku, T., Libertin, C.R., Chang-Liu, C.M., Churchill, M., Panozzo, J., Grdina, D., Gemmell, M.A., Giometti, C. Carcinogenesis (1996) [Pubmed]
  30. A new platelet-derived growth factor-regulated genomic element which binds a serine/threonine phosphoprotein mediates induction of the slow immediate-early gene MCP-1. Freter, R.R., Alberta, J.A., Lam, K.K., Stiles, C.D. Mol. Cell. Biol. (1995) [Pubmed]
  31. The T cell-specific serine proteinase TSP-1 is associated with cytoplasmic granules of cytolytic T lymphocytes. Fruth, U., Prester, M., Golecki, J.R., Hengartner, H., Simon, H.G., Kramer, M.D., Simon, M.M. Eur. J. Immunol. (1987) [Pubmed]
  32. Cell-extracellular matrix interactions can regulate the switch between growth and differentiation in rat hepatocytes: reciprocal expression of C/EBP alpha and immediate-early growth response transcription factors. Rana, B., Mischoulon, D., Xie, Y., Bucher, N.L., Farmer, S.R. Mol. Cell. Biol. (1994) [Pubmed]
  33. Cig30 and Pitx3 genes are arranged in a partially overlapping tail-to-tail array resulting in complementary transcripts. Tvrdik, P., Asadi, A., Kozak, L.P., Nuglozeh, E., Parente, F., Nedergaard, J., Jacobsson, A. J. Biol. Chem. (1999) [Pubmed]
  34. Diametric effects of bacterial endotoxin lipopolysaccharide on adrenal and Leydig cell steroidogenic acute regulatory protein. Hales, K.H., Diemer, T., Ginde, S., Shankar, B.K., Roberts, M., Bosmann, H.B., Hales, D.B. Endocrinology (2000) [Pubmed]
  35. Th1 adjuvant N-acetyl-D-glucosamine polymer up-regulates Th1 immunity but down-regulates Th2 immunity against a mycobacterial protein (MPB-59) in interleukin-10-knockout and wild-type mice. Shibata, Y., Honda, I., Justice, J.P., Van Scott, M.R., Nakamura, R.M., Myrvik, Q.N. Infect. Immun. (2001) [Pubmed]
  36. Involvement of a nucleolar component, perichromonucleolin, in the condensation and decondensation of chromosomes. Shi, L.J., Ni, Z.M., Zhao, S., Wang, G., Yang, Y. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  37. Cloning and expression of two related connexins from the perch retina define a distinct subgroup of the connexin family. O'Brien, J., Bruzzone, R., White, T.W., Al-Ubaidi, M.R., Ripps, H. J. Neurosci. (1998) [Pubmed]
  38. Increase in the synthesis of a Mr 32,000 protein in BALB/c 3T3 cells treated with tumor-promoting indole alkaloids or polyacetates. Hiwasa, T., Fujiki, H., Sugimura, T., Sakiyama, S. Cancer Res. (1983) [Pubmed]
  39. Cytokine mediation of the suppressive effect of ferritin on colony-stimulating factor-1-dependent monocytopoiesis. Kreisberg, R., Detrick, M.S., Osmand, A.P., Moore, R.N. J. Immunol. (1993) [Pubmed]
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