Full text data of CIB1
CIB1
(CIB, KIP, PRKDCIP)
[Confidence: high (present in two of the MS resources)]
Calcium and integrin-binding protein 1; CIB (Calcium- and integrin-binding protein; CIBP; Calmyrin; DNA-PKcs-interacting protein; Kinase-interacting protein; KIP; SNK-interacting protein 2-28; SIP2-28)
Calcium and integrin-binding protein 1; CIB (Calcium- and integrin-binding protein; CIBP; Calmyrin; DNA-PKcs-interacting protein; Kinase-interacting protein; KIP; SNK-interacting protein 2-28; SIP2-28)
hRBCD
IPI00018451
IPI00018451 Calcium and integrin-binding protein 1 Calcium and integrin-binding protein 1 membrane n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a Attached to the membrane by a GPI-anchor. n/a found at its expected molecular weight found at molecular weight
IPI00018451 Calcium and integrin-binding protein 1 Calcium and integrin-binding protein 1 membrane n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a Attached to the membrane by a GPI-anchor. n/a found at its expected molecular weight found at molecular weight
UniProt
Q99828
ID CIB1_HUMAN Reviewed; 191 AA.
AC Q99828; B5BU40; O00693; O00735; Q6IB49; Q96J54; Q99971;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 20-MAR-2007, sequence version 4.
DT 22-JAN-2014, entry version 135.
DE RecName: Full=Calcium and integrin-binding protein 1;
DE Short=CIB;
DE AltName: Full=Calcium- and integrin-binding protein;
DE Short=CIBP;
DE AltName: Full=Calmyrin;
DE AltName: Full=DNA-PKcs-interacting protein;
DE AltName: Full=Kinase-interacting protein;
DE Short=KIP;
DE AltName: Full=SNK-interacting protein 2-28;
DE Short=SIP2-28;
GN Name=CIB1; Synonyms=CIB, KIP, PRKDCIP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT THR-44.
RA Yuan O.;
RT "SNK, a Ser/Thr protein kinase, associated proteins.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT THR-44.
RX PubMed=9372844; DOI=10.1016/S0921-8777(97)00035-9;
RA Wu X., Lieber M.R.;
RT "Interaction between DNA-dependent protein kinase and a novel protein,
RT KIP.";
RL Mutat. Res. 385:13-20(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal liver;
RX PubMed=9030514; DOI=10.1074/jbc.272.8.4651;
RA Naik U.P., Patel P.M., Parise L.V.;
RT "Identification of a novel calcium-binding protein that interacts with
RT the integrin alphaIIb cytoplasmic domain.";
RL J. Biol. Chem. 272:4651-4654(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-44.
RX PubMed=10826701;
RA Hattori A., Seki N., Hayashi A., Kozuma S., Saito T.;
RT "Genomic structure of mouse and human genes for DNA-PKcs interacting
RT protein (KIP).";
RL DNA Seq. 10:415-418(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H.,
RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M.,
RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T.,
RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A.,
RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K.,
RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S.,
RA Isogai T., Imai J., Watanabe S., Nomura N.;
RT "Human protein factory for converting the transcriptome into an in
RT vitro-expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP MYRISTOYLATION AT GLY-2, AND INTERACTION WITH PSEN2.
RX PubMed=10366599; DOI=10.1083/jcb.145.6.1277;
RA Stabler S.M., Ostrowski L.L., Janicki S.M., Monteiro M.J.;
RT "A myristoylated calcium-binding protein that preferentially interacts
RT with the Alzheimer's disease presenilin 2 protein.";
RL J. Cell Biol. 145:1277-1292(1999).
RN [10]
RP INTERACTION WITH F8.
RX PubMed=11323029; DOI=10.1016/S0049-3848(01)00229-8;
RA Fang X., Chen C., Wang Q., Gu J., Chi C.;
RT "The interaction of the calcium- and integrin-binding protein (CIBP)
RT with the coagulation factor VIII.";
RL Thromb. Res. 102:177-185(2001).
RN [11]
RP INTERACTION WITH NBR1 AND FEZ1, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11856312; DOI=10.1046/j.0014-2956.2001.02681.x;
RA Whitehouse C., Chambers J., Howe K., Cobourne M., Sharpe P.,
RA Solomon E.;
RT "NBR1 interacts with fasciculation and elongation protein zeta-1
RT (FEZ1) and calcium and integrin binding protein (CIB) and shows
RT developmentally restricted expression in the neural tube.";
RL Eur. J. Biochem. 269:538-545(2002).
RN [12]
RP INTERACTION WITH UBR5.
RX PubMed=12011095; DOI=10.1074/jbc.M203527200;
RA Henderson M.J., Russell A.J., Hird S., Munoz M., Clancy J.L.,
RA Lehrbach G.M., Calanni S.T., Jans D.A., Sutherland R.L., Watts C.K.;
RT "EDD, the human hyperplastic discs protein, has a role in progesterone
RT receptor coactivation and potential involvement in DNA damage
RT response.";
RL J. Biol. Chem. 277:26468-26478(2002).
RN [13]
RP INTERACTION WITH ITGA2B, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP PHE-115; LEU-131; ILE-153 AND PHE-173.
RX PubMed=12023286; DOI=10.1074/jbc.M202983200;
RA Barry W.T., Boudignon-Proudhon C., Shock D.D., McFadden A.,
RA Weiss J.M., Sondek J., Parise L.V.;
RT "Molecular basis of CIB binding to the integrin alpha IIb cytoplasmic
RT domain.";
RL J. Biol. Chem. 277:28877-28883(2002).
RN [14]
RP FUNCTION.
RX PubMed=12714504; DOI=10.1182/blood-2003-02-0591;
RA Naik U.P., Naik M.U.;
RT "Association of CIB with GPIIb/IIIa during outside-in signaling is
RT required for platelet spreading on fibrinogen.";
RL Blood 102:1355-1362(2003).
RN [15]
RP SUBCELLULAR LOCATION, INTERACTION WITH PSEN2, AND MUTAGENESIS OF
RP ASP-127 AND GLU-172.
RX PubMed=15475008; DOI=10.1016/j.yexcr.2004.07.020;
RA Zhu J., Stabler S.M., Ames J.B., Baskakov I., Monteiro M.J.;
RT "Calcium binding sequences in calmyrin regulates interaction with
RT presenilin-2.";
RL Exp. Cell Res. 300:440-454(2004).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PTK2/FAK1.
RX PubMed=12881299; DOI=10.1182/blood-2003-05-1703;
RA Naik M.U., Naik U.P.;
RT "Calcium-and integrin-binding protein regulates focal adhesion kinase
RT activity during platelet spreading on immobilized fibrinogen.";
RL Blood 102:3629-3636(2003).
RN [17]
RP SUBUNIT.
RX PubMed=15933764;
RA Sobczak A., Blazejczyk M., Piszczek G., Zhao G., Kuznicki J.,
RA Wojda U.;
RT "Calcium-binding calmyrin forms stable covalent dimers in vitro, but
RT in vivo is found in monomeric form.";
RL Acta Biochim. Pol. 52:469-476(2005).
RN [18]
RP FUNCTION, AND INTERACTION WITH IFI6 AND BCL2.
RX PubMed=15685448; DOI=10.1007/s00262-004-0645-2;
RA Tahara E. Jr., Tahara H., Kanno M., Naka K., Takeda Y., Matsuzaki T.,
RA Yamazaki R., Ishihara H., Yasui W., Barrett J.C., Ide T., Tahara E.;
RT "G1P3, an interferon inducible gene 6-16, is expressed in gastric
RT cancers and inhibits mitochondrial-mediated apoptosis in gastric
RT cancer cell line TMK-1 cell.";
RL Cancer Immunol. Immunother. 54:729-740(2005).
RN [19]
RP INTERACTION WITH ITPR3.
RX PubMed=16723353; DOI=10.1074/jbc.M602175200;
RA White C., Yang J., Monteiro M.J., Foskett J.K.;
RT "CIB1, a ubiquitously expressed Ca2+-binding protein ligand of the
RT InsP3 receptor Ca2+ release channel.";
RL J. Biol. Chem. 281:20825-20833(2006).
RN [20]
RP FUNCTION, INTERACTION WITH TAS1R2, AND SUBCELLULAR LOCATION.
RX PubMed=18627437; DOI=10.1111/j.1471-4159.2008.05563.x;
RA Hennigs J.K., Burhenne N., Staehler F., Winnig M., Walter B.,
RA Meyerhof W., Schmale H.;
RT "Sweet taste receptor interacting protein CIB1 is a general inhibitor
RT of InsP3-dependent Ca2+ release in vivo.";
RL J. Neurochem. 106:2249-2262(2008).
RN [21]
RP FUNCTION, AND INTERACTION WITH MAP3K5.
RX PubMed=19805025; DOI=10.1073/pnas.0812259106;
RA Yoon K.W., Cho J.H., Lee J.K., Kang Y.H., Chae J.S., Kim Y.M., Kim J.,
RA Kim E.K., Kim S.E., Baik J.H., Naik U.P., Cho S.G., Choi E.J.;
RT "CIB1 functions as a Ca(2+)-sensitive modulator of stress-induced
RT signaling by targeting ASK1.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:17389-17394(2009).
RN [22]
RP SUBUNIT, AND CALCIUM-BINDING.
RX PubMed=19388079; DOI=10.1002/pro.104;
RA Yamniuk A.P., Anderson K.L., Fraser M.E., Vogel H.J.;
RT "Auxiliary Ca2+ binding sites can influence the structure of CIB1.";
RL Protein Sci. 18:1128-1134(2009).
RN [23]
RP INTERACTION WITH PLK3.
RX PubMed=20473878; DOI=10.1002/ijc.25388;
RA Naik M.U., Pham N.T., Beebe K., Dai W., Naik U.P.;
RT "Calcium-dependent inhibition of polo-like kinase 3 activity by CIB1
RT in breast cancer cells.";
RL Int. J. Cancer 128:587-596(2011).
RN [24]
RP FUNCTION, AND INTERACTION WITH PLK3.
RX PubMed=21264284; DOI=10.1371/journal.pone.0014513;
RA Kostyak J.C., Naik U.P.;
RT "Calcium- and integrin-binding protein 1 regulates endomitosis and its
RT interaction with Polo-like kinase 3 is enhanced in endomitotic Dami
RT cells.";
RL PLoS ONE 6:E14513-E14513(2011).
RN [25]
RP STRUCTURE BY NMR OF 9-191.
RX PubMed=10822252;
RX DOI=10.1002/(SICI)1099-1352(200003/04)13:2<83::AID-JMR491>3.3.CO;2-1;
RA Hwang P.M., Vogel H.J.;
RT "Structures of the platelet calcium- and integrin-binding protein and
RT the alphaIIb-integrin cytoplasmic domain suggest a mechanism for
RT calcium-regulated recognition; homology modelling and NMR studies.";
RL J. Mol. Recognit. 13:83-92(2000).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 9-191 IN COMPLEX WITH
RP CALCIUM IONS, AND SUBUNIT.
RX PubMed=15574431; DOI=10.1074/jbc.M411515200;
RA Gentry H.R., Singer A.U., Betts L., Yang C., Ferrara J.D., Sondek J.,
RA Parise L.V.;
RT "Structural and biochemical characterization of CIB1 delineates a new
RT family of EF-hand-containing proteins.";
RL J. Biol. Chem. 280:8407-8415(2005).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 9-191.
RX PubMed=15840829; DOI=10.1110/ps.041270805;
RA Blamey C.J., Ceccarelli C., Naik U.P., Bahnson B.J.;
RT "The crystal structure of calcium- and integrin-binding protein 1:
RT insights into redox regulated functions.";
RL Protein Sci. 14:1214-1221(2005).
CC -!- FUNCTION: May convert the inactive conformation of integrin alpha-
CC IIb/beta3 to an active form through binding to the integrin
CC cytoplasmic domain. Induces cell migration and spreading mediated
CC through integrin (possibly via focal adhesion complexes).
CC Functions as a negative regulator of stress activated MAP kinase
CC (MAPK) signaling pathways. May play a role in regulation of
CC apoptosis. Interacts with and up-regulates PTK2/FAK1 activity.
CC Down regulates inositol 1,4,5-trisphosphate receptor-dependent
CC calcium signaling. Participates in endomitotic cell cycle, a form
CC of mitosis in which both karyokinesis and cytokinesis are
CC interrupted and is a hallmark of megakaryocyte differentiation.
CC -!- SUBUNIT: Monomer. Interacts with the heterodimeric integrin alpha-
CC IIb/beta3. Interacts with the protein kinases PLK2/SNK and with
CC the region immediately upstream of the kinase domain of DNA-PK.
CC Interacts with PLK3; leading to inhibit PLK3 kinase activity.
CC Interacts with PSEN2. Interacts with MYO1C (By similarity).
CC Interacts (via C-terminus) with F8. Interacts with NBR1 (via C-
CC terminus). Interacts with FEZ1 (via C-terminus). Interacts with
CC UBR5 (via C-terminus); the interaction is sensitive to DNA damage,
CC and may target CIB1 for ubiquitin-mediated degradation. Interacts
CC with IFI6. Interacts with BCL2. Interacts with TAS1R2 (via C-
CC terminus); this interaction is independent of the myristoylation
CC state of CIB1. Interacts with ITPR3; in a calcium dependent
CC manner. Interacts with PTK2/FAK1. Interacts with MAP3K5;
CC inhibiting MAP3K5 activation by phosphorylation, and its
CC subsequent interaction with TRAF2.
CC -!- INTERACTION:
CC O00401:WASL; NbExp=7; IntAct=EBI-372594, EBI-957615;
CC -!- SUBCELLULAR LOCATION: Membrane; Lipid-anchor. Cytoplasm. Nucleus.
CC Cell projection, filopodium. Apical cell membrane. Note=Localizes
CC to the perinuclear region in the presence of NBR1. Colocalizes
CC with TAS1R2 in apical regions of taste receptor cells.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SIMILARITY: Contains 2 EF-hand domains.
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DR EMBL; U83236; AAB39758.1; -; mRNA.
DR EMBL; U85611; AAB53387.1; -; mRNA.
DR EMBL; U82226; AAC51106.1; -; mRNA.
DR EMBL; AB021866; BAA36281.1; -; Genomic_DNA.
DR EMBL; CR456955; CAG33236.1; -; mRNA.
DR EMBL; AB451276; BAG70090.1; -; mRNA.
DR EMBL; AB451406; BAG70220.1; -; mRNA.
DR EMBL; CH471101; EAX02090.1; -; Genomic_DNA.
DR EMBL; BC000846; AAH00846.1; -; mRNA.
DR RefSeq; NP_006375.2; NM_006384.3.
DR UniGene; Hs.715556; -.
DR PDB; 1DGU; NMR; -; A=9-191.
DR PDB; 1DGV; NMR; -; A=9-191.
DR PDB; 1XO5; X-ray; 1.99 A; A/B=9-191.
DR PDB; 1Y1A; X-ray; 2.30 A; A/B=9-191.
DR PDB; 2L4H; NMR; -; A=1-191.
DR PDB; 2L4I; NMR; -; A=1-191.
DR PDB; 2LM5; NMR; -; A=1-191.
DR PDBsum; 1DGU; -.
DR PDBsum; 1DGV; -.
DR PDBsum; 1XO5; -.
DR PDBsum; 1Y1A; -.
DR PDBsum; 2L4H; -.
DR PDBsum; 2L4I; -.
DR PDBsum; 2LM5; -.
DR ProteinModelPortal; Q99828; -.
DR SMR; Q99828; 9-191.
DR DIP; DIP-31260N; -.
DR IntAct; Q99828; 14.
DR MINT; MINT-95290; -.
DR STRING; 9606.ENSP00000333873; -.
DR PhosphoSite; Q99828; -.
DR DMDM; 134047806; -.
DR PaxDb; Q99828; -.
DR PRIDE; Q99828; -.
DR DNASU; 10519; -.
DR Ensembl; ENST00000328649; ENSP00000333873; ENSG00000185043.
DR GeneID; 10519; -.
DR KEGG; hsa:10519; -.
DR UCSC; uc002bpb.4; human.
DR CTD; 10519; -.
DR GeneCards; GC15M090773; -.
DR H-InvDB; HIX0012576; -.
DR HGNC; HGNC:16920; CIB1.
DR HPA; CAB012991; -.
DR MIM; 602293; gene.
DR neXtProt; NX_Q99828; -.
DR PharmGKB; PA38423; -.
DR eggNOG; NOG257993; -.
DR HOVERGEN; HBG107344; -.
DR InParanoid; Q99828; -.
DR KO; K17259; -.
DR OMA; ILQYPEL; -.
DR OrthoDB; EOG7KM5V7; -.
DR PhylomeDB; Q99828; -.
DR ChiTaRS; CIB1; human.
DR EvolutionaryTrace; Q99828; -.
DR GeneWiki; CIB1; -.
DR GenomeRNAi; 10519; -.
DR NextBio; 39892; -.
DR PRO; PR:Q99828; -.
DR Bgee; Q99828; -.
DR CleanEx; HS_CIB1; -.
DR Genevestigator; Q99828; -.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IMP:HGNC.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IMP:HGNC.
DR GO; GO:0042383; C:sarcolemma; IDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IMP:HGNC.
DR GO; GO:0043495; F:protein anchor; IGI:BHF-UCL.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0006302; P:double-strand break repair; TAS:ProtInc.
DR GO; GO:0007113; P:endomitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; TAS:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; IDA:BHF-UCL.
DR GO; GO:0090004; P:positive regulation of establishment of protein localization to plasma membrane; IGI:BHF-UCL.
DR Gene3D; 1.10.238.10; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF13499; EF-hand_7; 1.
DR SMART; SM00054; EFh; 2.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell membrane; Cell projection;
KW Complete proteome; Cytoplasm; Lipoprotein; Membrane; Metal-binding;
KW Myristate; Nucleus; Polymorphism; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 191 Calcium and integrin-binding protein 1.
FT /FTId=PRO_0000073531.
FT DOMAIN 103 138 EF-hand 1.
FT DOMAIN 148 183 EF-hand 2.
FT CA_BIND 116 127 1.
FT CA_BIND 161 172 2.
FT LIPID 2 2 N-myristoyl glycine.
FT VARIANT 44 44 S -> T (in dbSNP:rs3210935).
FT /FTId=VAR_019565.
FT VARIANT 106 106 I -> T (in dbSNP:rs11551250).
FT /FTId=VAR_048636.
FT MUTAGEN 115 115 F->A: Loss of binding to ITGA2B.
FT MUTAGEN 127 127 D->N: Cytoplasmic localization.
FT MUTAGEN 131 131 L->A,T: Loss of binding to ITGA2B.
FT MUTAGEN 153 153 I->A: Loss of binding to ITGA2B.
FT MUTAGEN 172 172 E->Q: Cytoplasmic localization.
FT MUTAGEN 173 173 F->A: Loss of binding to ITGA2B.
FT CONFLICT 136 136 T -> M (in Ref. 5; CAG33236).
FT HELIX 14 16
FT TURN 18 20
FT HELIX 24 35
FT HELIX 40 42
FT HELIX 45 50
FT HELIX 55 59
FT HELIX 62 65
FT HELIX 70 77
FT STRAND 81 86
FT HELIX 88 98
FT HELIX 104 115
FT STRAND 120 123
FT HELIX 125 135
FT STRAND 137 139
FT STRAND 145 147
FT HELIX 149 160
FT STRAND 165 168
FT HELIX 170 179
FT HELIX 181 190
SQ SEQUENCE 191 AA; 21703 MW; 9AA19A0DE7AA1E05 CRC64;
MGGSGSRLSK ELLAEYQDLT FLTKQEILLA HRRFCELLPQ EQRSVESSLR AQVPFEQILS
LPELKANPFK ERICRVFSTS PAKDSLSFED FLDLLSVFSD TATPDIKSHY AFRIFDFDDD
GTLNREDLSR LVNCLTGEGE DTRLSASEMK QLIDNILEES DIDRDGTINL SEFQHVISRS
PDFASSFKIV L
//
ID CIB1_HUMAN Reviewed; 191 AA.
AC Q99828; B5BU40; O00693; O00735; Q6IB49; Q96J54; Q99971;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 20-MAR-2007, sequence version 4.
DT 22-JAN-2014, entry version 135.
DE RecName: Full=Calcium and integrin-binding protein 1;
DE Short=CIB;
DE AltName: Full=Calcium- and integrin-binding protein;
DE Short=CIBP;
DE AltName: Full=Calmyrin;
DE AltName: Full=DNA-PKcs-interacting protein;
DE AltName: Full=Kinase-interacting protein;
DE Short=KIP;
DE AltName: Full=SNK-interacting protein 2-28;
DE Short=SIP2-28;
GN Name=CIB1; Synonyms=CIB, KIP, PRKDCIP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT THR-44.
RA Yuan O.;
RT "SNK, a Ser/Thr protein kinase, associated proteins.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT THR-44.
RX PubMed=9372844; DOI=10.1016/S0921-8777(97)00035-9;
RA Wu X., Lieber M.R.;
RT "Interaction between DNA-dependent protein kinase and a novel protein,
RT KIP.";
RL Mutat. Res. 385:13-20(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal liver;
RX PubMed=9030514; DOI=10.1074/jbc.272.8.4651;
RA Naik U.P., Patel P.M., Parise L.V.;
RT "Identification of a novel calcium-binding protein that interacts with
RT the integrin alphaIIb cytoplasmic domain.";
RL J. Biol. Chem. 272:4651-4654(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-44.
RX PubMed=10826701;
RA Hattori A., Seki N., Hayashi A., Kozuma S., Saito T.;
RT "Genomic structure of mouse and human genes for DNA-PKcs interacting
RT protein (KIP).";
RL DNA Seq. 10:415-418(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H.,
RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M.,
RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T.,
RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A.,
RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K.,
RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S.,
RA Isogai T., Imai J., Watanabe S., Nomura N.;
RT "Human protein factory for converting the transcriptome into an in
RT vitro-expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP MYRISTOYLATION AT GLY-2, AND INTERACTION WITH PSEN2.
RX PubMed=10366599; DOI=10.1083/jcb.145.6.1277;
RA Stabler S.M., Ostrowski L.L., Janicki S.M., Monteiro M.J.;
RT "A myristoylated calcium-binding protein that preferentially interacts
RT with the Alzheimer's disease presenilin 2 protein.";
RL J. Cell Biol. 145:1277-1292(1999).
RN [10]
RP INTERACTION WITH F8.
RX PubMed=11323029; DOI=10.1016/S0049-3848(01)00229-8;
RA Fang X., Chen C., Wang Q., Gu J., Chi C.;
RT "The interaction of the calcium- and integrin-binding protein (CIBP)
RT with the coagulation factor VIII.";
RL Thromb. Res. 102:177-185(2001).
RN [11]
RP INTERACTION WITH NBR1 AND FEZ1, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11856312; DOI=10.1046/j.0014-2956.2001.02681.x;
RA Whitehouse C., Chambers J., Howe K., Cobourne M., Sharpe P.,
RA Solomon E.;
RT "NBR1 interacts with fasciculation and elongation protein zeta-1
RT (FEZ1) and calcium and integrin binding protein (CIB) and shows
RT developmentally restricted expression in the neural tube.";
RL Eur. J. Biochem. 269:538-545(2002).
RN [12]
RP INTERACTION WITH UBR5.
RX PubMed=12011095; DOI=10.1074/jbc.M203527200;
RA Henderson M.J., Russell A.J., Hird S., Munoz M., Clancy J.L.,
RA Lehrbach G.M., Calanni S.T., Jans D.A., Sutherland R.L., Watts C.K.;
RT "EDD, the human hyperplastic discs protein, has a role in progesterone
RT receptor coactivation and potential involvement in DNA damage
RT response.";
RL J. Biol. Chem. 277:26468-26478(2002).
RN [13]
RP INTERACTION WITH ITGA2B, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP PHE-115; LEU-131; ILE-153 AND PHE-173.
RX PubMed=12023286; DOI=10.1074/jbc.M202983200;
RA Barry W.T., Boudignon-Proudhon C., Shock D.D., McFadden A.,
RA Weiss J.M., Sondek J., Parise L.V.;
RT "Molecular basis of CIB binding to the integrin alpha IIb cytoplasmic
RT domain.";
RL J. Biol. Chem. 277:28877-28883(2002).
RN [14]
RP FUNCTION.
RX PubMed=12714504; DOI=10.1182/blood-2003-02-0591;
RA Naik U.P., Naik M.U.;
RT "Association of CIB with GPIIb/IIIa during outside-in signaling is
RT required for platelet spreading on fibrinogen.";
RL Blood 102:1355-1362(2003).
RN [15]
RP SUBCELLULAR LOCATION, INTERACTION WITH PSEN2, AND MUTAGENESIS OF
RP ASP-127 AND GLU-172.
RX PubMed=15475008; DOI=10.1016/j.yexcr.2004.07.020;
RA Zhu J., Stabler S.M., Ames J.B., Baskakov I., Monteiro M.J.;
RT "Calcium binding sequences in calmyrin regulates interaction with
RT presenilin-2.";
RL Exp. Cell Res. 300:440-454(2004).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PTK2/FAK1.
RX PubMed=12881299; DOI=10.1182/blood-2003-05-1703;
RA Naik M.U., Naik U.P.;
RT "Calcium-and integrin-binding protein regulates focal adhesion kinase
RT activity during platelet spreading on immobilized fibrinogen.";
RL Blood 102:3629-3636(2003).
RN [17]
RP SUBUNIT.
RX PubMed=15933764;
RA Sobczak A., Blazejczyk M., Piszczek G., Zhao G., Kuznicki J.,
RA Wojda U.;
RT "Calcium-binding calmyrin forms stable covalent dimers in vitro, but
RT in vivo is found in monomeric form.";
RL Acta Biochim. Pol. 52:469-476(2005).
RN [18]
RP FUNCTION, AND INTERACTION WITH IFI6 AND BCL2.
RX PubMed=15685448; DOI=10.1007/s00262-004-0645-2;
RA Tahara E. Jr., Tahara H., Kanno M., Naka K., Takeda Y., Matsuzaki T.,
RA Yamazaki R., Ishihara H., Yasui W., Barrett J.C., Ide T., Tahara E.;
RT "G1P3, an interferon inducible gene 6-16, is expressed in gastric
RT cancers and inhibits mitochondrial-mediated apoptosis in gastric
RT cancer cell line TMK-1 cell.";
RL Cancer Immunol. Immunother. 54:729-740(2005).
RN [19]
RP INTERACTION WITH ITPR3.
RX PubMed=16723353; DOI=10.1074/jbc.M602175200;
RA White C., Yang J., Monteiro M.J., Foskett J.K.;
RT "CIB1, a ubiquitously expressed Ca2+-binding protein ligand of the
RT InsP3 receptor Ca2+ release channel.";
RL J. Biol. Chem. 281:20825-20833(2006).
RN [20]
RP FUNCTION, INTERACTION WITH TAS1R2, AND SUBCELLULAR LOCATION.
RX PubMed=18627437; DOI=10.1111/j.1471-4159.2008.05563.x;
RA Hennigs J.K., Burhenne N., Staehler F., Winnig M., Walter B.,
RA Meyerhof W., Schmale H.;
RT "Sweet taste receptor interacting protein CIB1 is a general inhibitor
RT of InsP3-dependent Ca2+ release in vivo.";
RL J. Neurochem. 106:2249-2262(2008).
RN [21]
RP FUNCTION, AND INTERACTION WITH MAP3K5.
RX PubMed=19805025; DOI=10.1073/pnas.0812259106;
RA Yoon K.W., Cho J.H., Lee J.K., Kang Y.H., Chae J.S., Kim Y.M., Kim J.,
RA Kim E.K., Kim S.E., Baik J.H., Naik U.P., Cho S.G., Choi E.J.;
RT "CIB1 functions as a Ca(2+)-sensitive modulator of stress-induced
RT signaling by targeting ASK1.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:17389-17394(2009).
RN [22]
RP SUBUNIT, AND CALCIUM-BINDING.
RX PubMed=19388079; DOI=10.1002/pro.104;
RA Yamniuk A.P., Anderson K.L., Fraser M.E., Vogel H.J.;
RT "Auxiliary Ca2+ binding sites can influence the structure of CIB1.";
RL Protein Sci. 18:1128-1134(2009).
RN [23]
RP INTERACTION WITH PLK3.
RX PubMed=20473878; DOI=10.1002/ijc.25388;
RA Naik M.U., Pham N.T., Beebe K., Dai W., Naik U.P.;
RT "Calcium-dependent inhibition of polo-like kinase 3 activity by CIB1
RT in breast cancer cells.";
RL Int. J. Cancer 128:587-596(2011).
RN [24]
RP FUNCTION, AND INTERACTION WITH PLK3.
RX PubMed=21264284; DOI=10.1371/journal.pone.0014513;
RA Kostyak J.C., Naik U.P.;
RT "Calcium- and integrin-binding protein 1 regulates endomitosis and its
RT interaction with Polo-like kinase 3 is enhanced in endomitotic Dami
RT cells.";
RL PLoS ONE 6:E14513-E14513(2011).
RN [25]
RP STRUCTURE BY NMR OF 9-191.
RX PubMed=10822252;
RX DOI=10.1002/(SICI)1099-1352(200003/04)13:2<83::AID-JMR491>3.3.CO;2-1;
RA Hwang P.M., Vogel H.J.;
RT "Structures of the platelet calcium- and integrin-binding protein and
RT the alphaIIb-integrin cytoplasmic domain suggest a mechanism for
RT calcium-regulated recognition; homology modelling and NMR studies.";
RL J. Mol. Recognit. 13:83-92(2000).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 9-191 IN COMPLEX WITH
RP CALCIUM IONS, AND SUBUNIT.
RX PubMed=15574431; DOI=10.1074/jbc.M411515200;
RA Gentry H.R., Singer A.U., Betts L., Yang C., Ferrara J.D., Sondek J.,
RA Parise L.V.;
RT "Structural and biochemical characterization of CIB1 delineates a new
RT family of EF-hand-containing proteins.";
RL J. Biol. Chem. 280:8407-8415(2005).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 9-191.
RX PubMed=15840829; DOI=10.1110/ps.041270805;
RA Blamey C.J., Ceccarelli C., Naik U.P., Bahnson B.J.;
RT "The crystal structure of calcium- and integrin-binding protein 1:
RT insights into redox regulated functions.";
RL Protein Sci. 14:1214-1221(2005).
CC -!- FUNCTION: May convert the inactive conformation of integrin alpha-
CC IIb/beta3 to an active form through binding to the integrin
CC cytoplasmic domain. Induces cell migration and spreading mediated
CC through integrin (possibly via focal adhesion complexes).
CC Functions as a negative regulator of stress activated MAP kinase
CC (MAPK) signaling pathways. May play a role in regulation of
CC apoptosis. Interacts with and up-regulates PTK2/FAK1 activity.
CC Down regulates inositol 1,4,5-trisphosphate receptor-dependent
CC calcium signaling. Participates in endomitotic cell cycle, a form
CC of mitosis in which both karyokinesis and cytokinesis are
CC interrupted and is a hallmark of megakaryocyte differentiation.
CC -!- SUBUNIT: Monomer. Interacts with the heterodimeric integrin alpha-
CC IIb/beta3. Interacts with the protein kinases PLK2/SNK and with
CC the region immediately upstream of the kinase domain of DNA-PK.
CC Interacts with PLK3; leading to inhibit PLK3 kinase activity.
CC Interacts with PSEN2. Interacts with MYO1C (By similarity).
CC Interacts (via C-terminus) with F8. Interacts with NBR1 (via C-
CC terminus). Interacts with FEZ1 (via C-terminus). Interacts with
CC UBR5 (via C-terminus); the interaction is sensitive to DNA damage,
CC and may target CIB1 for ubiquitin-mediated degradation. Interacts
CC with IFI6. Interacts with BCL2. Interacts with TAS1R2 (via C-
CC terminus); this interaction is independent of the myristoylation
CC state of CIB1. Interacts with ITPR3; in a calcium dependent
CC manner. Interacts with PTK2/FAK1. Interacts with MAP3K5;
CC inhibiting MAP3K5 activation by phosphorylation, and its
CC subsequent interaction with TRAF2.
CC -!- INTERACTION:
CC O00401:WASL; NbExp=7; IntAct=EBI-372594, EBI-957615;
CC -!- SUBCELLULAR LOCATION: Membrane; Lipid-anchor. Cytoplasm. Nucleus.
CC Cell projection, filopodium. Apical cell membrane. Note=Localizes
CC to the perinuclear region in the presence of NBR1. Colocalizes
CC with TAS1R2 in apical regions of taste receptor cells.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SIMILARITY: Contains 2 EF-hand domains.
CC -----------------------------------------------------------------------
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DR EMBL; U83236; AAB39758.1; -; mRNA.
DR EMBL; U85611; AAB53387.1; -; mRNA.
DR EMBL; U82226; AAC51106.1; -; mRNA.
DR EMBL; AB021866; BAA36281.1; -; Genomic_DNA.
DR EMBL; CR456955; CAG33236.1; -; mRNA.
DR EMBL; AB451276; BAG70090.1; -; mRNA.
DR EMBL; AB451406; BAG70220.1; -; mRNA.
DR EMBL; CH471101; EAX02090.1; -; Genomic_DNA.
DR EMBL; BC000846; AAH00846.1; -; mRNA.
DR RefSeq; NP_006375.2; NM_006384.3.
DR UniGene; Hs.715556; -.
DR PDB; 1DGU; NMR; -; A=9-191.
DR PDB; 1DGV; NMR; -; A=9-191.
DR PDB; 1XO5; X-ray; 1.99 A; A/B=9-191.
DR PDB; 1Y1A; X-ray; 2.30 A; A/B=9-191.
DR PDB; 2L4H; NMR; -; A=1-191.
DR PDB; 2L4I; NMR; -; A=1-191.
DR PDB; 2LM5; NMR; -; A=1-191.
DR PDBsum; 1DGU; -.
DR PDBsum; 1DGV; -.
DR PDBsum; 1XO5; -.
DR PDBsum; 1Y1A; -.
DR PDBsum; 2L4H; -.
DR PDBsum; 2L4I; -.
DR PDBsum; 2LM5; -.
DR ProteinModelPortal; Q99828; -.
DR SMR; Q99828; 9-191.
DR DIP; DIP-31260N; -.
DR IntAct; Q99828; 14.
DR MINT; MINT-95290; -.
DR STRING; 9606.ENSP00000333873; -.
DR PhosphoSite; Q99828; -.
DR DMDM; 134047806; -.
DR PaxDb; Q99828; -.
DR PRIDE; Q99828; -.
DR DNASU; 10519; -.
DR Ensembl; ENST00000328649; ENSP00000333873; ENSG00000185043.
DR GeneID; 10519; -.
DR KEGG; hsa:10519; -.
DR UCSC; uc002bpb.4; human.
DR CTD; 10519; -.
DR GeneCards; GC15M090773; -.
DR H-InvDB; HIX0012576; -.
DR HGNC; HGNC:16920; CIB1.
DR HPA; CAB012991; -.
DR MIM; 602293; gene.
DR neXtProt; NX_Q99828; -.
DR PharmGKB; PA38423; -.
DR eggNOG; NOG257993; -.
DR HOVERGEN; HBG107344; -.
DR InParanoid; Q99828; -.
DR KO; K17259; -.
DR OMA; ILQYPEL; -.
DR OrthoDB; EOG7KM5V7; -.
DR PhylomeDB; Q99828; -.
DR ChiTaRS; CIB1; human.
DR EvolutionaryTrace; Q99828; -.
DR GeneWiki; CIB1; -.
DR GenomeRNAi; 10519; -.
DR NextBio; 39892; -.
DR PRO; PR:Q99828; -.
DR Bgee; Q99828; -.
DR CleanEx; HS_CIB1; -.
DR Genevestigator; Q99828; -.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IMP:HGNC.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IMP:HGNC.
DR GO; GO:0042383; C:sarcolemma; IDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IMP:HGNC.
DR GO; GO:0043495; F:protein anchor; IGI:BHF-UCL.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0006302; P:double-strand break repair; TAS:ProtInc.
DR GO; GO:0007113; P:endomitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; TAS:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; IDA:BHF-UCL.
DR GO; GO:0090004; P:positive regulation of establishment of protein localization to plasma membrane; IGI:BHF-UCL.
DR Gene3D; 1.10.238.10; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF13499; EF-hand_7; 1.
DR SMART; SM00054; EFh; 2.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell membrane; Cell projection;
KW Complete proteome; Cytoplasm; Lipoprotein; Membrane; Metal-binding;
KW Myristate; Nucleus; Polymorphism; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 191 Calcium and integrin-binding protein 1.
FT /FTId=PRO_0000073531.
FT DOMAIN 103 138 EF-hand 1.
FT DOMAIN 148 183 EF-hand 2.
FT CA_BIND 116 127 1.
FT CA_BIND 161 172 2.
FT LIPID 2 2 N-myristoyl glycine.
FT VARIANT 44 44 S -> T (in dbSNP:rs3210935).
FT /FTId=VAR_019565.
FT VARIANT 106 106 I -> T (in dbSNP:rs11551250).
FT /FTId=VAR_048636.
FT MUTAGEN 115 115 F->A: Loss of binding to ITGA2B.
FT MUTAGEN 127 127 D->N: Cytoplasmic localization.
FT MUTAGEN 131 131 L->A,T: Loss of binding to ITGA2B.
FT MUTAGEN 153 153 I->A: Loss of binding to ITGA2B.
FT MUTAGEN 172 172 E->Q: Cytoplasmic localization.
FT MUTAGEN 173 173 F->A: Loss of binding to ITGA2B.
FT CONFLICT 136 136 T -> M (in Ref. 5; CAG33236).
FT HELIX 14 16
FT TURN 18 20
FT HELIX 24 35
FT HELIX 40 42
FT HELIX 45 50
FT HELIX 55 59
FT HELIX 62 65
FT HELIX 70 77
FT STRAND 81 86
FT HELIX 88 98
FT HELIX 104 115
FT STRAND 120 123
FT HELIX 125 135
FT STRAND 137 139
FT STRAND 145 147
FT HELIX 149 160
FT STRAND 165 168
FT HELIX 170 179
FT HELIX 181 190
SQ SEQUENCE 191 AA; 21703 MW; 9AA19A0DE7AA1E05 CRC64;
MGGSGSRLSK ELLAEYQDLT FLTKQEILLA HRRFCELLPQ EQRSVESSLR AQVPFEQILS
LPELKANPFK ERICRVFSTS PAKDSLSFED FLDLLSVFSD TATPDIKSHY AFRIFDFDDD
GTLNREDLSR LVNCLTGEGE DTRLSASEMK QLIDNILEES DIDRDGTINL SEFQHVISRS
PDFASSFKIV L
//
MIM
602293
*RECORD*
*FIELD* NO
602293
*FIELD* TI
*602293 CALCIUM- AND INTEGRIN-BINDING PROTEIN 1; CIB1
;;CIB;;
KINASE-INTERACTING PROTEIN 1; KIP1;;
read moreKIP
*FIELD* TX
CLONING
Integrin-alpha-IIb-beta-3 (see 607759 and 173470), the platelet
fibrinogen receptor, is converted from an inactive conformation to an
active, high-affinity state through a mechanism that may involve the
binding of proteins to the integrin cytoplasmic domains. To identify
candidate proteins that bind to the cytoplasmic domain of alpha-IIb,
Naik et al. (1997) screened a human fetal liver cDNA library using the
yeast 2-hybrid system. They isolated a novel cDNA that encodes a
predicted hydrophilic 191-amino acid protein that they called CIB. CIB
contains 2 calcium-binding EF-hand motifs and shares 58% and 55% amino
acid sequence similarity with calcineurin B (601302) and calmodulin
(114180), respectively. Using RT-PCR and Western blot analysis, Naik et
al. (1997) detected CIB mRNA and CIB protein, respectively, in
platelets.
Gentry et al. (2005) stated that the CIB1 protein contains 10 helical
domains separated from one another by loop regions. Gel filtration and
sedimentation equilibrium analyses showed that only a small percentage
of CIB1 formed dimers, with most CIB1 remaining monomeric in the
presence or absence of Ca(2+). The calculated molecular mass of CIB1 is
21.7 kD, but the protein had an apparent molecular mass of either 26.9
or 30.6 kD, depending on the method used, most likely due to its
irregular shape.
Using Western blotting and immunohistochemistry to analyze heart Cib1
expression in vivo in mice, Heineke et al. (2010) observed high levels
at embryonic day 16, at birth, and 1 week after birth, with a
progressive reduction in expression with aging. Localization of Cib1
within cardiac myocytes shifted from a diffuse cytoplasmic pattern
before birth to the sarcolemma in the adult heart. CIB1 was also
detected at the sarcolemma in histologic sections from human hearts,
with more CIB1 at the sarcolemma in sections from hypertrophic human
hearts than control hearts.
MAPPING
By PCR analysis of human/rodent somatic cell hybrid and radiation hybrid
panels and FISH, Seki et al. (1998) mapped the KIP gene to chromosome
15q25.3-q26.1.
GENE FUNCTION
By yeast 2-hybrid analysis, Naik et al. (1997) found that CIB bound
specifically to the alpha-IIb cytoplasmic domain and did not interact
with the cytoplasmic domains of the other integrin subunits examined.
CIB specifically bound calcium in blot overlay assays. Naik et al.
(1997) demonstrated an in vitro interaction between CIB and intact
integrin alpha-IIb-beta-3 using enzyme-linked immunosorbent assays. They
suggested that CIB is a candidate regulatory molecule for integrin
alpha-IIb-beta-3.
Heineke et al. (2010) identified CIB1 in a screen for previously unknown
regulators of cardiac hypertrophy, and yeast 2-hybrid screening revealed
calcineurin B (601302) as a CIB1-interacting partner. Studies in Cib1
-/- mouse hearts showed that Cib1 anchors calcineurin to the sarcolemma
and controls its activation in coordination with the L-type Ca(2+)
channel. Immunohistochemical analysis demonstrated that Cib1 protein
amounts and membrane association were enhanced in cardiac pathologic
hypertrophy, but not in physiologic hypertrophy in mice. Consistent with
these observations, Cib1-deleted mice showed a marked reduction in
myocardial hypertrophy, fibrosis, cardiac dysfunction, and
calcineurin-NFAT (NFATC; 600489) activity after pressure overload,
whereas the degree of physiologic hypertrophy after swimming exercise
was not altered. Transgenic mice with inducible and cardiac-specific
overexpression of Cib1 showed enhanced cardiac hypertrophy in response
to pressure overload or calcineurin signaling. Mice lacking Ppp3cb
(114106) showed no enhancement in cardiac hypertrophy associated with
Cib1 overexpression. Heineke et al. (2010) concluded that CIB1 functions
as a regulator of cardiac hypertrophy through its ability to regulate
the association of calcineurin with the sarcolemma and its activation.
BIOCHEMICAL FEATURES
- Crystal Structure
Gentry et al. (2005) resolved the crystal structure of Ca(2+)-bound CIB1
to 2.0-angstrom resolution. The overall fold of CIB1 is similar to other
Ca(2+)-binding proteins containing 4 EF-hands, but the authors found
that only EF3 and EF4 of CIB1 bound Ca(2+). A large insertion within EF1
is likely responsible for its inability to bind Ca(2+). CIB1 has a
ligand-binding hydrophobic pocket, and a proline between helices H3a and
H3b causes a kink that is important for the overall structure of the
pocket.
*FIELD* RF
1. Gentry, H. R.; Singer, A. U.; Betts, L.; Yang, C.; Ferrara, J.
D.; Sondek, J.; Parise, L. V.: Structural and biochemical characterization
of CIB1 delineates a new family of EF-hand-containing proteins. J.
Biol. Chem. 280: 8407-8415, 2005.
2. Heineke, J.; Auger-Messier, M.; Correll, R. N.; Xu, J.; Benard,
M. J.; Yuan, W.; Drexler, H.; Parise, L. V.; Molkentin, J. D.: CIB1
is a regulator of pathological cardiac hypertrophy. Nature Med. 16:
872-879, 2010.
3. Naik, U. P.; Patel, P. M.; Parise, L. V.: Identification of a
novel calcium-binding protein that interacts with the integrin alpha-IIb
cytoplasmic domain. J. Biol. Chem. 272: 4651-4654, 1997.
4. Seki, N.; Hayashi, A.; Abe, M.; Araki, R.; Fujimori, A.; Fukumura,
R.; Hattori, A.; Kozuma, S.; Ohhira, M.; Hori, T.; Saito, T.: Chromosomal
assignment of the gene for human DNA-PKcs interacting protein (KIP)
on chromosome 15q25.3-q26.1 by somatic hybrid analysis and fluorescence
in situ hybridization. J. Hum. Genet. 43: 275-277, 1998.
*FIELD* CN
Marla J. F. O'Neill - updated: 10/4/2011
Patricia A. Hartz - updated: 12/8/2006
Joanna S. Amberger - updated: 12/18/2001
*FIELD* CD
Patti M. Sherman: 1/29/1998
*FIELD* ED
carol: 10/05/2011
terry: 10/4/2011
mgross: 12/12/2006
terry: 12/8/2006
ckniffin: 5/15/2003
carol: 12/19/2001
joanna: 12/18/2001
cwells: 1/22/2001
dholmes: 1/29/1998
*RECORD*
*FIELD* NO
602293
*FIELD* TI
*602293 CALCIUM- AND INTEGRIN-BINDING PROTEIN 1; CIB1
;;CIB;;
KINASE-INTERACTING PROTEIN 1; KIP1;;
read moreKIP
*FIELD* TX
CLONING
Integrin-alpha-IIb-beta-3 (see 607759 and 173470), the platelet
fibrinogen receptor, is converted from an inactive conformation to an
active, high-affinity state through a mechanism that may involve the
binding of proteins to the integrin cytoplasmic domains. To identify
candidate proteins that bind to the cytoplasmic domain of alpha-IIb,
Naik et al. (1997) screened a human fetal liver cDNA library using the
yeast 2-hybrid system. They isolated a novel cDNA that encodes a
predicted hydrophilic 191-amino acid protein that they called CIB. CIB
contains 2 calcium-binding EF-hand motifs and shares 58% and 55% amino
acid sequence similarity with calcineurin B (601302) and calmodulin
(114180), respectively. Using RT-PCR and Western blot analysis, Naik et
al. (1997) detected CIB mRNA and CIB protein, respectively, in
platelets.
Gentry et al. (2005) stated that the CIB1 protein contains 10 helical
domains separated from one another by loop regions. Gel filtration and
sedimentation equilibrium analyses showed that only a small percentage
of CIB1 formed dimers, with most CIB1 remaining monomeric in the
presence or absence of Ca(2+). The calculated molecular mass of CIB1 is
21.7 kD, but the protein had an apparent molecular mass of either 26.9
or 30.6 kD, depending on the method used, most likely due to its
irregular shape.
Using Western blotting and immunohistochemistry to analyze heart Cib1
expression in vivo in mice, Heineke et al. (2010) observed high levels
at embryonic day 16, at birth, and 1 week after birth, with a
progressive reduction in expression with aging. Localization of Cib1
within cardiac myocytes shifted from a diffuse cytoplasmic pattern
before birth to the sarcolemma in the adult heart. CIB1 was also
detected at the sarcolemma in histologic sections from human hearts,
with more CIB1 at the sarcolemma in sections from hypertrophic human
hearts than control hearts.
MAPPING
By PCR analysis of human/rodent somatic cell hybrid and radiation hybrid
panels and FISH, Seki et al. (1998) mapped the KIP gene to chromosome
15q25.3-q26.1.
GENE FUNCTION
By yeast 2-hybrid analysis, Naik et al. (1997) found that CIB bound
specifically to the alpha-IIb cytoplasmic domain and did not interact
with the cytoplasmic domains of the other integrin subunits examined.
CIB specifically bound calcium in blot overlay assays. Naik et al.
(1997) demonstrated an in vitro interaction between CIB and intact
integrin alpha-IIb-beta-3 using enzyme-linked immunosorbent assays. They
suggested that CIB is a candidate regulatory molecule for integrin
alpha-IIb-beta-3.
Heineke et al. (2010) identified CIB1 in a screen for previously unknown
regulators of cardiac hypertrophy, and yeast 2-hybrid screening revealed
calcineurin B (601302) as a CIB1-interacting partner. Studies in Cib1
-/- mouse hearts showed that Cib1 anchors calcineurin to the sarcolemma
and controls its activation in coordination with the L-type Ca(2+)
channel. Immunohistochemical analysis demonstrated that Cib1 protein
amounts and membrane association were enhanced in cardiac pathologic
hypertrophy, but not in physiologic hypertrophy in mice. Consistent with
these observations, Cib1-deleted mice showed a marked reduction in
myocardial hypertrophy, fibrosis, cardiac dysfunction, and
calcineurin-NFAT (NFATC; 600489) activity after pressure overload,
whereas the degree of physiologic hypertrophy after swimming exercise
was not altered. Transgenic mice with inducible and cardiac-specific
overexpression of Cib1 showed enhanced cardiac hypertrophy in response
to pressure overload or calcineurin signaling. Mice lacking Ppp3cb
(114106) showed no enhancement in cardiac hypertrophy associated with
Cib1 overexpression. Heineke et al. (2010) concluded that CIB1 functions
as a regulator of cardiac hypertrophy through its ability to regulate
the association of calcineurin with the sarcolemma and its activation.
BIOCHEMICAL FEATURES
- Crystal Structure
Gentry et al. (2005) resolved the crystal structure of Ca(2+)-bound CIB1
to 2.0-angstrom resolution. The overall fold of CIB1 is similar to other
Ca(2+)-binding proteins containing 4 EF-hands, but the authors found
that only EF3 and EF4 of CIB1 bound Ca(2+). A large insertion within EF1
is likely responsible for its inability to bind Ca(2+). CIB1 has a
ligand-binding hydrophobic pocket, and a proline between helices H3a and
H3b causes a kink that is important for the overall structure of the
pocket.
*FIELD* RF
1. Gentry, H. R.; Singer, A. U.; Betts, L.; Yang, C.; Ferrara, J.
D.; Sondek, J.; Parise, L. V.: Structural and biochemical characterization
of CIB1 delineates a new family of EF-hand-containing proteins. J.
Biol. Chem. 280: 8407-8415, 2005.
2. Heineke, J.; Auger-Messier, M.; Correll, R. N.; Xu, J.; Benard,
M. J.; Yuan, W.; Drexler, H.; Parise, L. V.; Molkentin, J. D.: CIB1
is a regulator of pathological cardiac hypertrophy. Nature Med. 16:
872-879, 2010.
3. Naik, U. P.; Patel, P. M.; Parise, L. V.: Identification of a
novel calcium-binding protein that interacts with the integrin alpha-IIb
cytoplasmic domain. J. Biol. Chem. 272: 4651-4654, 1997.
4. Seki, N.; Hayashi, A.; Abe, M.; Araki, R.; Fujimori, A.; Fukumura,
R.; Hattori, A.; Kozuma, S.; Ohhira, M.; Hori, T.; Saito, T.: Chromosomal
assignment of the gene for human DNA-PKcs interacting protein (KIP)
on chromosome 15q25.3-q26.1 by somatic hybrid analysis and fluorescence
in situ hybridization. J. Hum. Genet. 43: 275-277, 1998.
*FIELD* CN
Marla J. F. O'Neill - updated: 10/4/2011
Patricia A. Hartz - updated: 12/8/2006
Joanna S. Amberger - updated: 12/18/2001
*FIELD* CD
Patti M. Sherman: 1/29/1998
*FIELD* ED
carol: 10/05/2011
terry: 10/4/2011
mgross: 12/12/2006
terry: 12/8/2006
ckniffin: 5/15/2003
carol: 12/19/2001
joanna: 12/18/2001
cwells: 1/22/2001
dholmes: 1/29/1998