Skip to main content


We’d like to understand how you use our websites in order to improve them. Register your interest.

Functional characterization of human Kindlin-2 core promoter identifies a key role of SP1 in Kindlin-2 transcriptional regulation


Kindlin-2 is a recently identified FERM and PH domain containing integrin interacting protein. Kindlin-2 is ubiquitously expressed in normal tissues. So far, much effort has been spent exploring the functional aspects of Kindlin-2. However, the transcriptional regulation of Kindlin-2 has not yet been investigated. In this study we identified and functionally characterized the promoter of the human Kindlin-2 gene. We show that the core promoter of Kindlin-2 is a 39 base pair long GC rich fragment located −122/-83 upstream of the Kindlin-2 transcription start site. Functional characterization of this core promoter region by both in silico as well as in vitro/in vivo analysis shows that the transcription factor SP1 plays an important role in regulation of Kindlin-2 expression.



database for transcription start site


4.1 protein, ezrin, radixin and moesin


mitogen-induced gene-2


pleckstrin homology


  1. 1.

    Khan, A.A., Janke, A., Shimokawa, T. and Zhang, H. Phylogenetic analysis of kindlins suggests subfunctionalization of an ancestral unduplicated kindlin into three paralogs in vertebrates. Evol. Bioinform. Online 7 (2011) 7–19.

  2. 2.

    Siegel, D.H., Ashton, G.H., Penagos, H.G., Lee, J.V., Feiler, H.S., Wilhelmsen, K.C., South, A.P., Smith, F.J., Prescott, A.R., Wessagowit, V., Oyama, N., Akiyama, M., Al Aboud, D., Al Aboud, K., Al Githami, A., Al Hawsawi, K., Al Ismaily, A., Al-Suwaid, R., Atherton, D.J., Caputo, R., Fine, J.D., Frieden, I.J., Fuchs, E., Haber, R.M., Harada, T., Kitajima, Y., Mallory, S.B., Ogawa, H., Sahin, S., Shimizu, H., Suga, Y., Tadini, G., Tsuchiya, K., Wiebe, C.B., Wojnarowska, F., Zaghloul, A.B., Hamada, T., Mallipeddi, R., Eady, R.A., McLean, W.H., McGrath, J.A. and Epstein, E.H. Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actinextracellular-matrix linker protein UNC-112, causes Kindler syndrome. Am. J. Hum. Genet. 73 (2003) 174–187.

  3. 3.

    Rogalski, T.M., Mullen, G.P., Gilbert, M.M., Williams, B.D. and Moerman, D.G. The UNC-112 gene in Caenorhabditis elegans encodes a novel component of cell-matrix adhesion structures required for integrin localization in the muscle cell membrane. J. Cell Biol. 150 (2000) 253–264.

  4. 4.

    Tu, Y., Wu, W., Wu, T., Cao, Z., Wilkins, R., Toh, B.H., Cooper, M.E. and Chai, Z. Antiproliferative autoantigen CDA1 transcriptionally up-regulates p21(Waf1/Cip1) by activating p53 and MEK/ERK1/2 MAPK pathways. J. Biol. Chem. 282 (2007) 11722–11731.

  5. 5.

    Mackinnon, A.C., Qadota, H., Norman, K.R., Moerman, D.G. and Williams, B.D. C. elegans PAT-4/ILK functions as an adaptor protein within integrin adhesion complexes. Curr. Biol. 12 (2002) 787–797.

  6. 6.

    Shi, X., Ma, Y.Q., Tu, Y., Chen, K., Wu, S., Fukuda, K., Qin, J., Plow, E.F. and Wu, C. The MIG-2/integrin interaction strengthens cell-matrix adhesion and modulates cell motility. J. Biol. Chem. 282 (2007) 20455–20466.

  7. 7.

    Dowling, J.J., Gibbs, E., Russell, M., Goldman, D., Minarcik, J., Golden, J.A. and Feldman, E.L. Kindlin-2 is an essential component of intercalated discs and is required for vertebrate cardiac structure and function. Circ. Res. 102 (2008) 423–431.

  8. 8.

    An, Z., Dobra, K., Lock, J.G., Stromblad, S., Hjerpe, A. and Zhang, H. Kindlin-2 is expressed in malignant mesothelioma and is required for tumor cell adhesion and migration. Int. J. Cancer 127 (2010) 1999–2008.

  9. 9.

    Ussar, S., Wang, H.V., Linder, S., Fassler, R. and Moser, M. The Kindlins: subcellular localization and expression during murine development. Exp. Cell Res. 312 (2006) 3142–3151.

  10. 10.

    Montanez, E., Ussar, S., Schifferer, M., Bosl, M., Zent, R., Moser, M. and Fassler, R. Kindlin-2 controls bidirectional signaling of integrins. Genes Dev. 22 (2008) 1325–1330.

  11. 11.

    Kruger, M., Moser, M., Ussar, S., Thievessen, I., Luber, C.A., Forner, F., Schmidt, S., Zanivan, S., Fassler, R. and Mann, M. SILAC mouse for quantitative proteomics uncovers kindlin-3 as an essential factor for red blood cell function. Cell 134 (2008) 353–364.

  12. 12.

    Moser, M., Nieswandt, B., Ussar, S., Pozgajova, M. and Fassler, R. Kindlin-3 is essential for integrin activation and platelet aggregation. Nat. Med. 14 (2008) 325–330.

  13. 13.

    Malinin, N.L., Zhang, L., Choi, J., Ciocea, A., Razorenova, O., Ma, Y.Q., Podrez, E.A., Tosi, M., Lennon, D.P., Caplan, A.I., Shurin, S.B., Plow, E.F. and Byzova, T.V. A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans. Nat. Med. 15 (2009) 313–318.

  14. 14.

    Suzuki, Y., Yamashita, R., Nakai, K. and Sugano, S. DBTSS: DataBase of human Transcriptional Start Sites and full-length cDNAs. Nucleic Acids Res. 30 (2002) 328–331.

  15. 15.

    Sandelin, A., Wasserman, W.W. and Lenhard, B. ConSite: web-based prediction of regulatory elements using cross-species comparison. Nucleic Acids Res. 32 (2004) W249–252.

  16. 16.

    Mayor, C., Brudno, M., Schwartz, J.R., Poliakov, A., Rubin, E.M., Frazer, K.A., Pachter, L.S. and Dubchak, I. VISTA: visualizing global DNA sequence alignments of arbitrary length. Bioinformatics 16 (2000) 1046–1047.

  17. 17.

    Wick, M., Burger, C., Brusselbach, S., Lucibello, F.C. and Muller, R. Identification of serum-inducible genes: different patterns of gene regulation during G0→S and G1→S progression. J. Cell Sci. 107(Pt 3) (1994) preceding table of contents.

  18. 18.

    Zhu, J., He, F., Hu, S. and Yu, J. On the nature of human housekeeping genes. Trends Genet. 24 (2008) 481–484.

  19. 19.

    Fisher, S., Grice, E.A., Vinton, R.M., Bessling, S.L. and McCallion, A.S. Conservation of RET regulatory function from human to zebrafish without sequence similarity. Science 312 (2006) 276–279.

  20. 20.

    Waterston, R.H., Lindblad-Toh, K., Birney, E., Rogers, J., Abril, J.F., Agarwal, P., Agarwala, R., Ainscough, R., Alexandersson, M., An, P., Antonarakis, S.E., Attwood, J., Baertsch, R., Bailey, J., Barlow, K., Beck, S., Berry, E., Birren, B., Bloom, T., Bork, P., Botcherby, M., Bray, N., Brent, M.R., Brown, D.G., Brown, S.D., Bult, C., Burton, J., Butler, J., Campbell, R.D., Carninci, P., Cawley, S., Chiaromonte, F., Chinwalla, A.T., Church, D.M., Clamp, M., Clee, C., Collins, F.S., Cook, L.L., Copley, R.R., Coulson, A., Couronne, O., Cuff, J., Curwen, V., Cutts, T., Daly, M., David, R., Davies, J., Delehaunty, K.D., Deri, J., Dermitzakis, E.T., Dewey, C., Dickens, N.J., Diekhans, M., Dodge, S., Dubchak, I., Dunn, D.M., Eddy, S.R., Elnitski, L., Emes, R.D., Eswara, P., Eyras, E., Felsenfeld, A., Fewell, G.A., Flicek, P., Foley, K., Frankel, W.N., Fulton, L.A., Fulton, R.S., Furey, T.S., Gage, D., Gibbs, R.A., Glusman, G., Gnerre, S., Goldman, N., Goodstadt, L., Grafham, D., Graves, T.A., Green, E.D., Gregory, S., Guigo, R., Guyer, M., Hardison, R.C., Haussler, D., Hayashizaki, Y., Hillier, L.W., Hinrichs, A., Hlavina, W., Holzer, T., Hsu, F., Hua, A., Hubbard, T., Hunt, A., Jackson, I., Jaffe, D.B., Johnson, L.S., Jones, M., Jones, T.A., Joy, A., Kamal, M., Karlsson, E.K., Karolchik, D., Kasprzyk, A., Kawai, J., Keibler, E., Kells, C., Kent, W.J., Kirby, A., Kolbe, D.L., Korf, I., Kucherlapati, R.S., Kulbokas, E.J., Kulp, D., Landers, T., Leger, J.P., Leonard, S., Letunic, I., Levine, R., Li, J., Li, M., Lloyd, C., Lucas, S., Ma, B., Maglott, D.R., Mardis, E.R., Matthews, L., Mauceli, E., Mayer, J.H., McCarthy, M., McCombie, W.R., McLaren, S., McLay, K., McPherson, J.D., Meldrim, J., Meredith, B., Mesirov, J.P., Miller, W., Miner, T.L., Mongin, E., Montgomery, K.T., Morgan, M., Mott, R., Mullikin, J.C., Muzny, D.M., Nash, W.E., Nelson, J.O., Nhan, M.N., Nicol, R., Ning, Z., Nusbaum, C., O’Connor, M.J., Okazaki, Y., Oliver, K., Overton-Larty, E., Pachter, L., Parra, G., Pepin, K.H., Peterson, J., Pevzner, P., Plumb, R., Pohl, C.S., Poliakov, A., Ponce, T.C., Ponting, C.P., Potter, S., Quail, M., Reymond, A., Roe, B.A., Roskin, K.M., Rubin, E.M., Rust, A.G., Santos, R., Sapojnikov, V., Schultz, B., Schultz, J., Schwartz, M.S., Schwartz, S., Scott, C., Seaman, S., Searle, S., Sharpe, T., Sheridan, A., Shownkeen, R., Sims, S., Singer, J.B., Slater, G., Smit, A., Smith, D.R., Spencer, B., Stabenau, A., Stange-Thomann, N., Sugnet, C., Suyama, M., Tesler, G., Thompson, J., Torrents, D., Trevaskis, E., Tromp, J., Ucla, C., Ureta-Vidal, A., Vinson, J.P., Von Niederhausern, A.C., Wade, C.M., Wall, M., Weber, R.J., Weiss, R.B., Wendl, M.C., West, A.P., Wetterstrand, K., Wheeler, R., Whelan, S., Wierzbowski, J., Willey, D., Williams, S., Wilson, R.K., Winter, E., Worley, K.C., Wyman, D., Yang, S., Yang, S.P., Zdobnov, E.M., Zody, M.C. and Lander, E.S. Initial sequencing and comparative analysis of the mouse genome. Nature 420 (2002) 520–562.

  21. 21.

    Smale, S.T. and Kadonaga, J.T. The RNA polymerase II core promoter. Annu. Rev. Biochem. 72 (2003) 449–479.

  22. 22.

    Kadonaga, J.T., Carner, K.R., Masiarz, F.R. and Tjian, R. Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain. Cell 51 (1987) 1079–1090.

Download references

Author information



Corresponding author

Correspondence to Hongquan Zhang.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Khan, A.A., Shimokawa, T., Strömblad, S. et al. Functional characterization of human Kindlin-2 core promoter identifies a key role of SP1 in Kindlin-2 transcriptional regulation. Cell Mol Biol Lett 16, 638 (2011).

Download citation

Key words

  • Kindlin-2
  • FERMT2
  • Mig-2
  • Transcription factor SP1
  • Promoter
  • Transcription start site
  • Gene regulation
  • Cis-acting elements
  • CpG island
  • Cell migration
  • Integrin
  • Gene expression