Calcium and integrin-binding protein 1

Details

Name
Calcium and integrin-binding protein 1
Synonyms
  • Calcium- and integrin-binding protein
  • Calmyrin
  • CIB
  • CIBP
  • DNA-PKcs-interacting protein
  • Kinase-interacting protein
  • KIP
  • PRKDCIP
  • SIP2-28
  • SNK-interacting protein 2-28
Gene Name
CIB1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0049476|Calcium and integrin-binding protein 1
MGGSGSRLSKELLAEYQDLTFLTKQEILLAHRRFCELLPQEQRSVESSLRAQVPFEQILS
LPELKANPFKERICRVFSTSPAKDSLSFEDFLDLLSVFSDTATPDIKSHYAFRIFDFDDD
GTLNREDLSRLVNCLTGEGEDTRLSASEMKQLIDNILEESDIDRDGTINLSEFQHVISRS
PDFASSFKIVL
Number of residues
191
Molecular Weight
21703.07
Theoretical pI
Not Available
GO Classification
Functions
calcium ion binding / calcium-dependent protein kinase inhibitor activity / ion channel binding / protein anchor / protein C-terminus binding / protein kinase binding / protein serine/threonine kinase inhibitor activity / Ras GTPase binding
Processes
angiogenesis / apoptotic process / cell adhesion / cell division / cellular response to DNA damage stimulus / cellular response to growth factor stimulus / cellular response to nerve growth factor stimulus / cellular response to tumor necrosis factor / cytoplasmic microtubule organization / double-strand break repair / endomitotic cell cycle / extrinsic apoptotic signaling pathway / negative regulation of apoptotic process / negative regulation of cell proliferation / negative regulation of megakaryocyte differentiation / negative regulation of microtubule depolymerization / negative regulation of neuron projection development / negative regulation of protein kinase B signaling / negative regulation of protein phosphorylation / platelet formation / positive regulation of calcineurin-NFAT signaling cascade / positive regulation of catalytic activity / positive regulation of cell adhesion mediated by integrin / positive regulation of cell growth / positive regulation of cell migration / positive regulation of cell migration involved in sprouting angiogenesis / positive regulation of cell proliferation / positive regulation of cell-matrix adhesion / positive regulation of ERK1 and ERK2 cascade / positive regulation of establishment of protein localization to plasma membrane / positive regulation of male germ cell proliferation / positive regulation of NF-kappaB transcription factor activity / positive regulation of protein phosphorylation / positive regulation of protein serine/threonine kinase activity / positive regulation of protein targeting to membrane / positive regulation of substrate adhesion-dependent cell spreading / regulation of cell division / regulation of cell proliferation / response to ischemia / spermatid development / thrombopoietin-mediated signaling pathway
Components
apical plasma membrane / axon / cell periphery / centrosome / cytoplasm / dendrite / endoplasmic reticulum / extracellular exosome / filopodium tip / Golgi apparatus / growth cone / lamellipodium / membrane / neuron projection / neuronal cell body / nucleoplasm / nucleus / perinuclear region of cytoplasm / plasma membrane / ruffle membrane / sarcolemma / vesicle
General Function
Calcium-binding protein that plays a role in the regulation of numerous cellular processes, such as cell differentiation, cell division, cell proliferation, cell migration, thrombosis, angiogenesis, cardiac hypertrophy and apoptosis. Involved in bone marrow megakaryocyte differentiation by negatively regulating thrombopoietin-mediated signaling pathway. Participates in the endomitotic cell cycle of megakaryocyte, a form of mitosis in which both karyokinesis and cytokinesis are interrupted. Plays a role in integrin signaling by negatively regulating alpha-IIb/beta3 activation in thrombin-stimulated megakaryocytes preventing platelet aggregation. Up-regulates PTK2/FAK1 activity, and is also needed for the recruitment of PTK2/FAK1 to focal adhesions; it thus appears to play an important role in focal adhesion formation. Positively regulates cell migration on fibronectin in a CDC42-dependent manner, the effect being negatively regulated by PAK1. Functions as a negative regulator of stress activated MAP kinase (MAPK) signaling pathways. Down-regulates inositol 1,4,5-trisphosphate receptor-dependent calcium signaling. Involved in sphingosine kinase SPHK1 translocation to the plasma membrane in a N-myristoylation-dependent manner preventing TNF-alpha-induced apoptosis. Regulates serine/threonine-protein kinase PLK3 activity for proper completion of cell division progression. Plays a role in microtubule (MT) dynamics during neuronal development; disrupts the MT depolymerization activity of STMN2 attenuating NGF-induced neurite outgrowth and the MT reorganization at the edge of lamellipodia. Promotes cardiomyocyte hypertrophy via activation of the calcineurin/NFAT signaling pathway. Stimulates calcineurin PPP3R1 activity by mediating its anchoring to the sarcolemma. In ischemia-induced (pathological or adaptive) angiogenesis, stimulates endothelial cell proliferation, migration and microvessel formation by activating the PAK1 and ERK1/ERK2 signaling pathway. Promotes also cancer cell survival and proliferation. May regulate cell cycle and differentiation of spermatogenic germ cells, and/or differentiation of supporting Sertoli cells.
Specific Function
Calcium ion binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0049477|Calcium and integrin-binding protein 1 (CIB1)
ATGGGGGGCTCGGGCAGTCGCCTGTCCAAGGAGCTGCTGGCCGAGTACCAGGACTTGACG
TTCCTGACGAAGCAGGAGATCCTCCTAGCCCACAGGCGGTTTTGTGAGCTGCTTCCCCAG
GAGCAGCGGAGCGTGGAGTCGTCACTTCGGGCACAAGTGCCCTTCGAGCAGATTCTCAGC
CTTCCAGAGCTCAAGGCCAACCCCTTCAAGGAGCGAATCTGCAGGGTCTTCTCCACATCC
CCAGCCAAAGACAGCCTTAGCTTTGAGGACTTCCTGGATCTCCTCAGTGTGTTCAGTGAC
ACAGCCACGCCAGACATCAAGTCCCATTATGCCTTCCGCATCTTTGACTTTGATGATGAC
GGAACCTTGAACAGAGAAGACCTGAGCCGGCTGGTGAACTGCCTCACGGGAGAGGGCGAG
GACACACGGCTTAGTGCGTCTGAGATGAAGCAGCTCATCGACAACATCCTGGAGGAGTCT
GACATTGACAGGGATGGAACCATCAACCTCTCTGAGTTCCAGCACGTCATCTCCCGTTCT
CCAGACTTTGCCAGCTCCTTTAAGATTGTCCTGTGA
Chromosome Location
15
Locus
15q26.1
External Identifiers
ResourceLink
UniProtKB IDQ99828
UniProtKB Entry NameCIB1_HUMAN
HGNC IDHGNC:16920
General References
  1. Naik UP, Patel PM, Parise LV: Identification of a novel calcium-binding protein that interacts with the integrin alphaIIb cytoplasmic domain. J Biol Chem. 1997 Feb 21;272(8):4651-4. [Article]
  2. Wu X, Lieber MR: Interaction between DNA-dependent protein kinase and a novel protein, KIP. Mutat Res. 1997 Oct;385(1):13-20. [Article]
  3. Hattori A, Seki N, Hayashi A, Kozuma S, Saito T: Genomic structure of mouse and human genes for DNA-PKcs interacting protein (KIP). DNA Seq. 2000;10(6):415-8. [Article]
  4. Armacki M, Joodi G, Nimmagadda SC, de Kimpe L, Pusapati GV, Vandoninck S, Van Lint J, Illing A, Seufferlein T: A novel splice variant of calcium and integrin-binding protein 1 mediates protein kinase D2-stimulated tumour growth by regulating angiogenesis. Oncogene. 2014 Feb 27;33(9):1167-80. doi: 10.1038/onc.2013.43. Epub 2013 Mar 18. [Article]
  5. Goshima N, Kawamura Y, Fukumoto A, Miura A, Honma R, Satoh R, Wakamatsu A, Yamamoto J, Kimura K, Nishikawa T, Andoh T, Iida Y, Ishikawa K, Ito E, Kagawa N, Kaminaga C, Kanehori K, Kawakami B, Kenmochi K, Kimura R, Kobayashi M, Kuroita T, Kuwayama H, Maruyama Y, Matsuo K, Minami K, Mitsubori M, Mori M, Morishita R, Murase A, Nishikawa A, Nishikawa S, Okamoto T, Sakagami N, Sakamoto Y, Sasaki Y, Seki T, Sono S, Sugiyama A, Sumiya T, Takayama T, Takayama Y, Takeda H, Togashi T, Yahata K, Yamada H, Yanagisawa Y, Endo Y, Imamoto F, Kisu Y, Tanaka S, Isogai T, Imai J, Watanabe S, Nomura N: Human protein factory for converting the transcriptome into an in vitro-expressed proteome,. Nat Methods. 2008 Dec;5(12):1011-7. [Article]
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  7. Shock DD, Naik UP, Brittain JE, Alahari SK, Sondek J, Parise LV: Calcium-dependent properties of CIB binding to the integrin alphaIIb cytoplasmic domain and translocation to the platelet cytoskeleton. Biochem J. 1999 Sep 15;342 Pt 3:729-35. [Article]
  8. Stabler SM, Ostrowski LL, Janicki SM, Monteiro MJ: A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein. J Cell Biol. 1999 Jun 14;145(6):1277-92. [Article]
  9. Fang X, Chen C, Wang Q, Gu J, Chi C: The interaction of the calcium- and integrin-binding protein (CIBP) with the coagulation factor VIII. Thromb Res. 2001 Apr 15;102(2):177-85. [Article]
  10. Whitehouse C, Chambers J, Howe K, Cobourne M, Sharpe P, Solomon E: 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. Eur J Biochem. 2002 Jan;269(2):538-45. [Article]
  11. Haataja L, Kaartinen V, Groffen J, Heisterkamp N: The small GTPase Rac3 interacts with the integrin-binding protein CIB and promotes integrin alpha(IIb)beta(3)-mediated adhesion and spreading. J Biol Chem. 2002 Mar 8;277(10):8321-8. Epub 2001 Dec 27. [Article]
  12. Henderson MJ, Russell AJ, Hird S, Munoz M, Clancy JL, Lehrbach GM, Calanni ST, Jans DA, Sutherland RL, Watts CK: EDD, the human hyperplastic discs protein, has a role in progesterone receptor coactivation and potential involvement in DNA damage response. J Biol Chem. 2002 Jul 19;277(29):26468-78. Epub 2002 May 13. [Article]
  13. Barry WT, Boudignon-Proudhon C, Shock DD, McFadden A, Weiss JM, Sondek J, Parise LV: Molecular basis of CIB binding to the integrin alpha IIb cytoplasmic domain. J Biol Chem. 2002 Aug 9;277(32):28877-83. Epub 2002 May 21. [Article]
  14. Naik UP, Naik MU: Association of CIB with GPIIb/IIIa during outside-in signaling is required for platelet spreading on fibrinogen. Blood. 2003 Aug 15;102(4):1355-62. Epub 2003 Apr 24. [Article]
  15. Yamniuk AP, Nguyen LT, Hoang TT, Vogel HJ: Metal ion binding properties and conformational states of calcium- and integrin-binding protein. Biochemistry. 2004 Mar 9;43(9):2558-68. [Article]
  16. Zhu J, Stabler SM, Ames JB, Baskakov I, Monteiro MJ: Calcium binding sequences in calmyrin regulates interaction with presenilin-2. Exp Cell Res. 2004 Nov 1;300(2):440-54. [Article]
  17. Naik MU, Naik UP: Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen. Blood. 2003 Nov 15;102(10):3629-36. Epub 2003 Jul 24. [Article]
  18. Sobczak A, Blazejczyk M, Piszczek G, Zhao G, Kuznicki J, Wojda U: Calcium-binding calmyrin forms stable covalent dimers in vitro, but in vivo is found in monomeric form. Acta Biochim Pol. 2005;52(2):469-76. Epub 2005 Jun 1. [Article]
  19. Tahara E Jr, Tahara H, Kanno M, Naka K, Takeda Y, Matsuzaki T, Yamazaki R, Ishihara H, Yasui W, Barrett JC, Ide T, Tahara E: G1P3, an interferon inducible gene 6-16, is expressed in gastric cancers and inhibits mitochondrial-mediated apoptosis in gastric cancer cell line TMK-1 cell. Cancer Immunol Immunother. 2005 Aug;54(8):729-40. Epub 2005 Feb 1. [Article]
  20. Leisner TM, Liu M, Jaffer ZM, Chernoff J, Parise LV: Essential role of CIB1 in regulating PAK1 activation and cell migration. J Cell Biol. 2005 Aug 1;170(3):465-76. [Article]
  21. Yamniuk AP, Vogel HJ: Calcium- and magnesium-dependent interactions between calcium- and integrin-binding protein and the integrin alphaIIb cytoplasmic domain. Protein Sci. 2005 Jun;14(6):1429-37. Epub 2005 May 9. [Article]
  22. White C, Yang J, Monteiro MJ, Foskett JK: CIB1, a ubiquitously expressed Ca2+-binding protein ligand of the InsP3 receptor Ca2+ release channel. J Biol Chem. 2006 Jul 28;281(30):20825-33. Epub 2006 May 24. [Article]
  23. Yuan W, Leisner TM, McFadden AW, Wang Z, Larson MK, Clark S, Boudignon-Proudhon C, Lam SC, Parise LV: CIB1 is an endogenous inhibitor of agonist-induced integrin alphaIIbbeta3 activation. J Cell Biol. 2006 Jan 16;172(2):169-75. [Article]
  24. Hennigs JK, Burhenne N, Stahler F, Winnig M, Walter B, Meyerhof W, Schmale H: Sweet taste receptor interacting protein CIB1 is a general inhibitor of InsP3-dependent Ca2+ release in vivo. J Neurochem. 2008 Sep;106(5):2249-62. doi: 10.1111/j.1471-4159.2008.05563.x. [Article]
  25. Yoon KW, Cho JH, Lee JK, Kang YH, Chae JS, Kim YM, Kim J, Kim EK, Kim SE, Baik JH, Naik UP, Cho SG, Choi EJ: CIB1 functions as a Ca(2+)-sensitive modulator of stress-induced signaling by targeting ASK1. Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17389-94. doi: 10.1073/pnas.0812259106. Epub 2009 Sep 29. [Article]
  26. Yamniuk AP, Anderson KL, Fraser ME, Vogel HJ: Auxiliary Ca2+ binding sites can influence the structure of CIB1. Protein Sci. 2009 May;18(5):1128-34. doi: 10.1002/pro.104. [Article]
  27. Jarman KE, Moretti PA, Zebol JR, Pitson SM: Translocation of sphingosine kinase 1 to the plasma membrane is mediated by calcium- and integrin-binding protein 1. J Biol Chem. 2010 Jan 1;285(1):483-92. doi: 10.1074/jbc.M109.068395. Epub 2009 Oct 23. [Article]
  28. Heineke J, Auger-Messier M, Correll RN, Xu J, Benard MJ, Yuan W, Drexler H, Parise LV, Molkentin JD: CIB1 is a regulator of pathological cardiac hypertrophy. Nat Med. 2010 Aug;16(8):872-9. doi: 10.1038/nm.2181. Epub 2010 Jul 18. [Article]
  29. Sobczak A, Debowska K, Blazejczyk M, Kreutz MR, Kuznicki J, Wojda U: Calmyrin1 binds to SCG10 protein (stathmin2) to modulate neurite outgrowth. Biochim Biophys Acta. 2011 May;1813(5):1025-37. doi: 10.1016/j.bbamcr.2010.12.023. Epub 2011 Jan 6. [Article]
  30. Naik MU, Naik UP: Calcium- and integrin-binding protein 1 regulates microtubule organization and centrosome segregation through polo like kinase 3 during cell cycle progression. Int J Biochem Cell Biol. 2011 Jan;43(1):120-9. doi: 10.1016/j.biocel.2010.10.003. Epub 2010 Oct 15. [Article]
  31. Naik MU, Pham NT, Beebe K, Dai W, Naik UP: Calcium-dependent inhibition of polo-like kinase 3 activity by CIB1 in breast cancer cells. Int J Cancer. 2011 Feb 1;128(3):587-96. doi: 10.1002/ijc.25388. [Article]
  32. Naik MU, Naik UP: Contra-regulation of calcium- and integrin-binding protein 1-induced cell migration on fibronectin by PAK1 and MAP kinase signaling. J Cell Biochem. 2011 Nov;112(11):3289-99. doi: 10.1002/jcb.23255. [Article]
  33. Kostyak JC, Naik UP: Calcium- and integrin-binding protein 1 regulates endomitosis and its interaction with Polo-like kinase 3 is enhanced in endomitotic Dami cells. PLoS One. 2011 Jan 14;6(1):e14513. doi: 10.1371/journal.pone.0014513. [Article]
  34. Huang H, Bogstie JN, Vogel HJ: Biophysical and structural studies of the human calcium- and integrin-binding protein family: understanding their functional similarities and differences. Biochem Cell Biol. 2012 Oct;90(5):646-56. doi: 10.1139/o2012-021. Epub 2012 Jul 11. [Article]
  35. Freeman TC Jr, Black JL, Bray HG, Dagliyan O, Wu YI, Tripathy A, Dokholyan NV, Leisner TM, Parise LV: Identification of novel integrin binding partners for calcium and integrin binding protein 1 (CIB1): structural and thermodynamic basis of CIB1 promiscuity. Biochemistry. 2013 Oct 8;52(40):7082-90. doi: 10.1021/bi400678y. Epub 2013 Sep 25. [Article]
  36. Leisner TM, Moran C, Holly SP, Parise LV: CIB1 prevents nuclear GAPDH accumulation and non-apoptotic tumor cell death via AKT and ERK signaling. Oncogene. 2013 Aug 22;32(34):4017-27. doi: 10.1038/onc.2012.408. Epub 2012 Sep 10. [Article]
  37. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  38. Hwang PM, Vogel HJ: Structures of the platelet calcium- and integrin-binding protein and the alphaIIb-integrin cytoplasmic domain suggest a mechanism for calcium-regulated recognition; homology modelling and NMR studies. J Mol Recognit. 2000 Mar-Apr;13(2):83-92. [Article]
  39. Gentry HR, Singer AU, Betts L, Yang C, Ferrara JD, Sondek J, Parise LV: Structural and biochemical characterization of CIB1 delineates a new family of EF-hand-containing proteins. J Biol Chem. 2005 Mar 4;280(9):8407-15. Epub 2004 Dec 1. [Article]
  40. Blamey CJ, Ceccarelli C, Naik UP, Bahnson BJ: The crystal structure of calcium- and integrin-binding protein 1: insights into redox regulated functions. Protein Sci. 2005 May;14(5):1214-21. [Article]
  41. Huang H, Ishida H, Yamniuk AP, Vogel HJ: Solution structures of Ca2+-CIB1 and Mg2+-CIB1 and their interactions with the platelet integrin alphaIIb cytoplasmic domain. J Biol Chem. 2011 May 13;286(19):17181-92. doi: 10.1074/jbc.M110.179028. Epub 2011 Mar 9. [Article]
  42. Huang H, Vogel HJ: Structural basis for the activation of platelet integrin alphaIIbbeta3 by calcium- and integrin-binding protein 1. J Am Chem Soc. 2012 Feb 29;134(8):3864-72. doi: 10.1021/ja2111306. Epub 2012 Feb 16. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB11093Calcium citrateapproved, investigationalunknownligandDetails
DB11348Calcium PhosphateapprovedunknownligandDetails
DB14481Calcium phosphate dihydrateapprovedunknownDetails