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Gene Review

CIB1  -  calcium and integrin binding 1 (calmyrin)

Homo sapiens

Synonyms: CALMYRIN, CIB, CIBP, Calcium and integrin-binding protein 1, Calcium-and integrin-binding protein, ...
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Disease relevance of CIB1


High impact information on CIB1


Chemical compound and disease context of CIB1


Biological context of CIB1

  • The crystal structure for Ca(2+)-bound CIB1 has been determined at 2.0 A resolution and reveals a compact alpha-helical protein containing four EF-hands, the last two of which bind calcium ions in the standard fashion seen in many other EF-hand proteins [10].
  • Differences in structure, oligomeric state, and phylogeny define a new family of CIB1-related proteins that extends from arthropods to humans [10].
  • These results allude to several provocative possibilities for a dynamic role of calmyrin in signaling, cell death, and AD [8].
  • The collective data in this paper suggest that KIP plays a positive role in telomere length maintenance and/or regulation and may represent a novel target for anti-cancer drug development [11].
  • Calmyrin is a myristoylated calcium binding protein that contains four putative EF-hands [12].

Anatomical context of CIB1


Associations of CIB1 with chemical compounds

  • In contrast, overexpression of CIB1 or CaBP1 attenuated InsP(3)R-dependent Ca(2+) signaling, and in vitro pre-exposure to CIB1 reduced the number of channels available for subsequent stimulation by InsP(3) [15].
  • Glutathione bound in this fashion suggests CIB1 may be redox regulated [16].
  • CIB binding to alpha(IIb) cytoplasmic tail peptides, as measured by intrinsic tryptophan fluorescence, indicates a CIB-binding site within a hydrophobic, 15-amino acid, membrane-proximal region of alpha(IIb) [17].
  • CIB engineered to contain alanine substitutions in the implicated regions retained wild type secondary structure as determined by circular dichroism, yet failed to bind alpha(IIb) in 11 of 12 cases, whereas CIB mutated within the N terminus retained binding activity [17].
  • CIB1 (CIB) is an EF-hand-containing protein that binds multiple effector proteins, including the platelet alphaIIbbeta3 integrin and several serine/threonine kinases and potentially modulates their function [10].

Physical interactions of CIB1


Co-localisations of CIB1

  • Third, immunolocalization experiments demonstrate that KIP is a nuclear protein that co-localizes with hTERT in cells [11].
  • Also, CIB co-localized with active Rac3 to the periphery of cells adhering to fibrinogen [18].

Regulatory relationships of CIB1

  • Taken together, our results suggest that CIB regulates platelet spreading through the regulation of FAK activation [13].
  • Calcium binding sequences in calmyrin regulates interaction with presenilin-2 [12].

Other interactions of CIB1

  • Immunoprecipitation analysis indicates that CIB associates with focal adhesion kinase (FAK), a key regulator in focal complex formation, and up-regulates its activity [13].
  • Second, antibodies specific to KIP immunoprecipitate human telomerase in cell-free extracts [11].
  • Previously, we have shown that, when bound to glycoprotein IIb (GPIIb), calcium- and integrin-binding protein (CIB) regulates platelet spreading on immobilized fibrinogen (Fg) [13].
  • Binding of V12Rac3 to CIB was mediated by the C-terminal end of Rac3 and by Rac3 membrane localization [18].
  • CIB1 has been implicated in alphaIIb beta3 activation and outside-in signaling through the integrin [20].

Analytical, diagnostic and therapeutic context of CIB1


  1. NBR1 interacts with fasciculation and elongation protein zeta-1 (FEZ1) and calcium and integrin binding protein (CIB) and shows developmentally restricted expression in the neural tube. Whitehouse, C., Chambers, J., Howe, K., Cobourne, M., Sharpe, P., Solomon, E. Eur. J. Biochem. (2002) [Pubmed]
  2. Randomized trial of cisplatin and ifosfamide with or without bleomycin in squamous carcinoma of the cervix: a gynecologic oncology group study. Bloss, J.D., Blessing, J.A., Behrens, B.C., Mannel, R.S., Rader, J.S., Sood, A.K., Markman, M., Benda, J. J. Clin. Oncol. (2002) [Pubmed]
  3. Downregulation of the KIP family members p27(KIP1) and p57(KIP2) by SKP2 and the role of methylation in p57(KIP2) inactivation in nonsmall cell lung cancer. Pateras, I.S., Apostolopoulou, K., Koutsami, M., Evangelou, K., Tsantoulis, P., Liloglou, T., Nikolaidis, G., Sigala, F., Kittas, C., Field, J.K., Kotsinas, A., Gorgoulis, V.G. Int. J. Cancer (2006) [Pubmed]
  4. Expression of second class of KIP protein p57KIP2 in human colorectal carcinoma. Noura, S., Yamamoto, H., Sekimoto, M., Takemasa, I., Miyake, Y., Ikenaga, M., Matsuura, N., Monden, M. Int. J. Oncol. (2001) [Pubmed]
  5. The influence of interferon-alpha on the pharmacokinetics of cyclophosphamide and its 4-hydroxy metabolite in patients with multiple myeloma. Hassan, M., Nilsson, C., Olsson, H., Lundin, J., Osterborg, A. Eur. J. Haematol. (1999) [Pubmed]
  6. CIB1 is an endogenous inhibitor of agonist-induced integrin alphaIIbbeta3 activation. Yuan, W., Leisner, T.M., McFadden, A.W., Wang, Z., Larson, M.K., Clark, S., Boudignon-Proudhon, C., Lam, S.C., Parise, L.V. J. Cell Biol. (2006) [Pubmed]
  7. Essential role of CIB1 in regulating PAK1 activation and cell migration. Leisner, T.M., Liu, M., Jaffer, Z.M., Chernoff, J., Parise, L.V. J. Cell Biol. (2005) [Pubmed]
  8. A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein. Stabler, S.M., Ostrowski, L.L., Janicki, S.M., Monteiro, M.J. J. Cell Biol. (1999) [Pubmed]
  9. Phase II study of cyclophosphamide, interferon-alpha and betamethasone (CIB) as induction therapy for patients 60-75 years of age with multiple myeloma stages II and III. Lundin, J., Osterborg, A., Björkholm, M., Björkstrand, B., Celsing, F., Hjalmar, V., Linder, O., Luthman, M., Merup, M., Tidefelt, U., Mellstedt, H. Hematol. J. (2003) [Pubmed]
  10. Structural and biochemical characterization of CIB1 delineates a new family of EF-hand-containing proteins. Gentry, H.R., Singer, A.U., Betts, L., Yang, C., Ferrara, J.D., Sondek, J., Parise, L.V. J. Biol. Chem. (2005) [Pubmed]
  11. DNA-protein kinase catalytic subunit-interacting protein KIP binds telomerase by interacting with human telomerase reverse transcriptase. Lee, G.E., Yu, E.Y., Cho, C.H., Lee, J., Muller, M.T., Chung, I.K. J. Biol. Chem. (2004) [Pubmed]
  12. Calcium binding sequences in calmyrin regulates interaction with presenilin-2. Zhu, J., Stabler, S.M., Ames, J.B., Baskakov, I., Monteiro, M.J. Exp. Cell Res. (2004) [Pubmed]
  13. Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen. Naik, M.U., Naik, U.P. Blood (2003) [Pubmed]
  14. The Alzheimer disease-related calcium-binding protein Calmyrin is present in human forebrain with an altered distribution in Alzheimer's as compared to normal ageing brains. Bernstein, H.G., Blazejczyk, M., Rudka, T., Gundelfinger, E.D., Dobrowolny, H., Bogerts, B., Kreutz, M.R., Kuznicki, J., Wojda, U. Neuropathol. Appl. Neurobiol. (2005) [Pubmed]
  15. CIB1, a ubiquitously expressed Ca2+-binding protein ligand of the InsP3 receptor Ca2+ release channel. White, C., Yang, J., Monteiro, M.J., Foskett, J.K. J. Biol. Chem. (2006) [Pubmed]
  16. The crystal structure of calcium- and integrin-binding protein 1: insights into redox regulated functions. Blamey, C.J., Ceccarelli, C., Naik, U.P., Bahnson, B.J. Protein Sci. (2005) [Pubmed]
  17. Molecular basis of CIB binding to the integrin alpha IIb cytoplasmic domain. Barry, W.T., Boudignon-Proudhon, C., Shock, D.D., McFadden, A., Weiss, J.M., Sondek, J., Parise, L.V. J. Biol. Chem. (2002) [Pubmed]
  18. The small GTPase Rac3 interacts with the integrin-binding protein CIB and promotes integrin alpha(IIb)beta(3)-mediated adhesion and spreading. Haataja, L., Kaartinen, V., Groffen, J., Heisterkamp, N. J. Biol. Chem. (2002) [Pubmed]
  19. Association of CIB with GPIIb/IIIa during outside-in signaling is required for platelet spreading on fibrinogen. Naik, U.P., Naik, M.U. Blood (2003) [Pubmed]
  20. Cytoplasmic binding partners of the platelet integrin alphaIIb beta3. Bonner, M.A., Naik, U.P. Front. Biosci. (2007) [Pubmed]
  21. Identification of a novel calcium-binding protein that interacts with the integrin alphaIIb cytoplasmic domain. Naik, U.P., Patel, P.M., Parise, L.V. J. Biol. Chem. (1997) [Pubmed]
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