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Q99828 (CIB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calcium and integrin-binding protein 1

Short name=CIB
Alternative name(s):
Calcium- and integrin-binding protein
Short name=CIBP
Calmyrin
DNA-PKcs-interacting protein
Kinase-interacting protein
Short name=KIP
SNK-interacting protein 2-28
Short name=SIP2-28
Gene names
Name:CIB1
Synonyms:CIB, KIP, PRKDCIP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length191 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.4 Ref.14 Ref.17 Ref.20 Ref.22 Ref.23 Ref.26 Ref.27 Ref.28 Ref.33 Ref.35 Ref.36 Ref.39

Isoform 2:Plays a regulatory role in angiogenesis and tumor growth by mediating PKD/PRKD2-induced vascular endothelial growth factor A (VEGFA) secretion (Ref.4). Ref.4 Ref.14 Ref.17 Ref.20 Ref.22 Ref.23 Ref.26 Ref.27 Ref.28 Ref.33 Ref.35 Ref.36 Ref.39

Subunit structure

Monomer. Interacts with MYO1C. Interacts (via C-terminal region) with PPP3R1 and CACNA1C; the interactions increase upon cardiomyocytes hypertrophy By similarity. Interacts with the heterodimeric integrin alpha-IIb/beta3 (ITGA2B-ITGB3). Interacts with ITGA2B (via cytoplasmic domain); the interaction is direct and calcium-dependent. Interacts with the protein kinases PLK2/SNK and PRKDC (via the region immediately upstream of the kinase domain). Interacts with PLK3; the interaction inhibits PLK3 kinase activity. Interacts with PSEN2. Interacts (via C-terminus) with F8. Interacts with NBR1 (via C-terminus). Interacts with FEZ1 (via C-terminus). Interacts with UBR5 (via C-terminus); the interaction is sensitive to DNA damage, and may target CIB1 for ubiquitin-mediated degradation. Interacts with IFI6. Interacts with BCL2. Interacts with ITPR3; the interaction occurs in a calcium-dependent manner. Interacts with PTK2/FAK1. Interacts with MAP3K5; the interaction inhibits MAP3K5 activation by phosphorylation, and its subsequent interaction with TRAF2. Isoform 2 interacts with PRKD2 (via N-terminal AP-rich region), PTK2/FAK1 and PAK1. Interacts with TAS1R2 (via C-terminus); the interaction is independent of the myristoylation state of CIB1. Interacts (via C-terminal region) with STMN2 (via the N-terminal region); the interaction is direct, occurs in a calcium-dependent manner and attenuates the STMN2-induced neurite outgrowth inhibition. Interacts with SPHK1, the interaction occurs in a calcium-dependent manner. Interacts with ITGA2B (via C-terminal cytoplasmic tail); the interaction occurs upon platelet aggregation and is stabilized/increased in a calcium and magnesium-dependent manner. Interacts with PAK1 (via N-terminal region); the interaction is direct and occurs in a calcium-dependent manner. Interacts with RAC3 (via C-terminal region); the interaction induces their association with the cytoskeleton upon alpha-IIb/beta3 integrin-mediated adhesion. Interacts with ITGA5 and ITGAV. Ref.1 Ref.2 Ref.4 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.32 Ref.33 Ref.34 Ref.36 Ref.37 Ref.38 Ref.41 Ref.43 Ref.44

Subcellular location

Membrane; Lipid-anchor. Cell membranesarcolemma. Cell membrane. Apical cell membrane. Cell projectionruffle membrane. Cell projectionfilopodium tip. Cell projectiongrowth cone. Cell projectionlamellipodium. Cytoplasm. Cytoplasmcytoskeleton. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Cytoplasmperinuclear region. Nucleus. Note: Colocalized with PPP3R1 at the cell membrane of cardiomyocytes in the hypertrophic heart By similarity. Colocalized with NBR1 to the perinuclear region. Colocalizes with TAS1R2 in apical regions of taste receptor cells. Colocalized with RAC3 in the perinuclear area and at the cell periphery. Colocalized with PAK1 within membrane ruffles during cell spreading upon readhesion to fibronectin. Redistributed to the cytoskeleton upon platelet aggregation. Translocates from the cytosol to the plasma membrane in a calcium-dependent manner. Colocalized with STMN2 in the cell body, neurites and growth cones of neurons. Colocalized with STMN2 to the leading edge of lamellipodia. Colocalized with PLK3 at centrosomes in ductal breast carcinoma cells. Ref.4 Ref.10 Ref.13 Ref.14 Ref.16 Ref.19 Ref.20 Ref.26 Ref.27 Ref.30 Ref.31 Ref.32 Ref.33 Ref.35

Isoform 2: Cytoplasmperinuclear region. Golgi apparatustrans-Golgi network Ref.4 Ref.10 Ref.13 Ref.14 Ref.16 Ref.19 Ref.20 Ref.26 Ref.27 Ref.30 Ref.31 Ref.32 Ref.33 Ref.35.

Tissue specificity

Detected in platelets and in cell lines of megakaryocytic and erythrocytic lineages. Both isoform 1 and isoform 2 are detected in various cancer cell lines, with isoform 2 being the predominant form (at protein level). Ubiquitously expressed. Ref.1 Ref.2 Ref.4 Ref.10 Ref.13

Induction

Up-regulated during breast cancer progression.

Domain

The EF-hands may also bind magnesium ions in the presence of high Mg2+ levels and low Ca2+ levels.

Post-translational modification

Phosphorylation of isoform 2 at Ser-78 by PRKD2 increases its ability to stimulate tumor angiogenesis Probable.

Miscellaneous

The binding of either calcium or magnesium significantly increases the structural stability of the protein in comparison to apo-CIB (calcium- and magnesium-free form) (Ref.18).

Sequence similarities

Contains 2 EF-hand domains.

Ontologies

Keywords
   Biological processAngiogenesis
Apoptosis
Cell adhesion
Cell cycle
Cell division
Differentiation
Spermatogenesis
   Cellular componentCell membrane
Cell projection
Cytoplasm
Cytoskeleton
Golgi apparatus
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandCalcium
Magnesium
Metal-binding
   PTMLipoprotein
Myristate
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

apoptotic process

Inferred from mutant phenotype Ref.11. Source: HGNC

cell adhesion

Traceable author statement Ref.1. Source: ProtInc

cell division

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to DNA damage stimulus

Inferred from direct assay Ref.15. Source: HGNC

cellular response to growth factor stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to nerve growth factor stimulus

Inferred from direct assay Ref.32. Source: UniProtKB

cellular response to tumor necrosis factor

Inferred from mutant phenotype Ref.30. Source: UniProtKB

cytoplasmic microtubule organization

Inferred from mutant phenotype Ref.33. Source: UniProtKB

double-strand break repair

Traceable author statement Ref.2. Source: ProtInc

endomitotic cell cycle

Inferred from direct assay Ref.36. Source: UniProtKB

extrinsic apoptotic signaling pathway

Traceable author statement Ref.28. Source: BHF-UCL

negative regulation of apoptotic process

Inferred from mutant phenotype Ref.30. Source: UniProtKB

negative regulation of cell proliferation

Inferred from mutant phenotype Ref.36. Source: UniProtKB

negative regulation of megakaryocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of microtubule depolymerization

Inferred from direct assay Ref.32. Source: UniProtKB

negative regulation of neuron projection development

Inferred from direct assay Ref.32. Source: UniProtKB

negative regulation of protein kinase B signaling

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

platelet formation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype Ref.30. Source: UniProtKB

positive regulation of calcineurin-NFAT signaling cascade

Inferred from direct assay Ref.31. Source: BHF-UCL

positive regulation of cell adhesion mediated by integrin

Inferred from direct assay Ref.14. Source: UniProtKB

positive regulation of cell growth

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell migration involved in sprouting angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell-matrix adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of establishment of protein localization to plasma membrane

Inferred from genetic interaction Ref.31. Source: BHF-UCL

positive regulation of gene expression involved in extracellular matrix organization

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of male germ cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of metalloenzyme activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein targeting to membrane

Inferred from mutant phenotype Ref.30. Source: UniProtKB

positive regulation of substrate adhesion-dependent cell spreading

Inferred from direct assay Ref.14. Source: UniProtKB

regulation of cell division

Inferred from mutant phenotype Ref.33. Source: UniProtKB

regulation of cell proliferation

Inferred from mutant phenotype Ref.33. Source: UniProtKB

response to ischemia

Inferred from sequence or structural similarity. Source: UniProtKB

spermatid development

Inferred from sequence or structural similarity. Source: UniProtKB

thrombopoietin-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

apical plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell periphery

Inferred from direct assay Ref.14Ref.33. Source: UniProtKB

centrosome

Inferred from direct assay Ref.33. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.14Ref.30Ref.32. Source: UniProtKB

endoplasmic reticulum

Inferred from mutant phenotype Ref.11. Source: HGNC

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 20458337PubMed 23376485. Source: UniProt

filopodium tip

Inferred from direct assay Ref.33. Source: UniProtKB

growth cone

Inferred from direct assay Ref.32. Source: UniProtKB

lamellipodium

Inferred from direct assay Ref.32. Source: UniProtKB

membrane

Inferred from direct assay Ref.11. Source: HGNC

neuron projection

Inferred from direct assay Ref.32. Source: UniProtKB

neuronal cell body

Inferred from direct assay Ref.32. Source: UniProtKB

nucleoplasm

Inferred from mutant phenotype Ref.11. Source: HGNC

nucleus

Inferred from direct assay Ref.14. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.14. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.30. Source: UniProtKB

ruffle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

sarcolemma

Inferred from direct assay Ref.31. Source: BHF-UCL

   Molecular_functionRas GTPase binding

Inferred from physical interaction Ref.14. Source: UniProtKB

calcium ion binding

Inferred from mutant phenotype Ref.19. Source: HGNC

protein anchor

Inferred from genetic interaction Ref.31. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.30Ref.33Ref.32Ref.36Ref.38. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

WASLO004017EBI-372594,EBI-957615

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q99828-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q99828-2)

Also known as: CIB1a;

The sequence of this isoform differs from the canonical sequence as follows:
     29-29: L → LSVYVVLAPHLVDNEQQARSGNEHTGRPIAENTDSSPLSTR

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 191190Calcium and integrin-binding protein 1
PRO_0000073531

Regions

Domain103 – 13836EF-hand 1
Domain148 – 18336EF-hand 2
Calcium binding116 – 127121 Ref.1 Ref.18 Ref.24 Ref.29
Calcium binding161 – 172122 Ref.1 Ref.18 Ref.24 Ref.29

Amino acid modifications

Modified residue781Phosphoserine; by PKD/PRKD2; in isoform 2 Ref.4
Lipidation21N-myristoyl glycine Ref.11

Natural variations

Alternative sequence291L → LSVYVVLAPHLVDNEQQARS GNEHTGRPIAENTDSSPLST R in isoform 2.
VSP_053740
Natural variant441S → T. Ref.2 Ref.3 Ref.5
Corresponds to variant rs3210935 [ dbSNP | Ensembl ].
VAR_019565
Natural variant1061I → T.
Corresponds to variant rs11551250 [ dbSNP | Ensembl ].
VAR_048636

Experimental info

Mutagenesis21G → A: Inhibits translocation to the plasma membrane. Show increased apoptosis after TNF stimulation. Ref.30
Mutagenesis781S → A: Loss of phosphorylation by PKD/PRKD2; in isoform 2. Ref.4
Mutagenesis781S → E: Phosphomimetic; promotes tumor growth by an indirect mechanism; in isoform 2. Ref.4
Mutagenesis114 – 1174IFDF → AAAA: Loss of binding to ITGAV. Ref.38
Mutagenesis1151F → A: Loss of binding to ITGA2B. Ref.16
Mutagenesis1271D → N: Cytoplasmic localization. Ref.19
Mutagenesis1311L → A or T: Loss of binding to ITGA2B. Ref.16
Mutagenesis152 – 1532LI → AA: Loss of binding to ITGA2B. Ref.16
Mutagenesis1531I → A: Loss of binding to ITGA2B. Ref.16
Mutagenesis1671T → A: No effect on phosphorylation by PKD/PRKD2; in isoform 2. Ref.4
Mutagenesis1721E → Q: Cytoplasmic localization. Ref.19
Mutagenesis1731F → A: Loss of binding to ITGA2B. Ref.16 Ref.26 Ref.38
Mutagenesis1731F → A: Loss of binding to ITGA2B. Does not inhibit interaction with PAK1. Ref.16 Ref.26 Ref.38
Sequence conflict1361T → M in CAG33236. Ref.6
Sequence conflict1711S → F in AEZ06077. Ref.4

Secondary structure

....................................... 191
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 20, 2007. Version 4.
Checksum: 9AA19A0DE7AA1E05

FASTA19121,703
        10         20         30         40         50         60 
MGGSGSRLSK ELLAEYQDLT FLTKQEILLA HRRFCELLPQ EQRSVESSLR AQVPFEQILS 

        70         80         90        100        110        120 
LPELKANPFK ERICRVFSTS PAKDSLSFED FLDLLSVFSD TATPDIKSHY AFRIFDFDDD 

       130        140        150        160        170        180 
GTLNREDLSR LVNCLTGEGE DTRLSASEMK QLIDNILEES DIDRDGTINL SEFQHVISRS 

       190 
PDFASSFKIV L 

« Hide

Isoform 2 (CIB1a) [UniParc].

Checksum: 0D38C53F1478119E
Show »

FASTA23126,032

References

« Hide 'large scale' references
[1]"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. 272:4651-4654(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH ITGA2B, TISSUE SPECIFICITY, CALCIUM-BINDING.
Tissue: Fetal liver.
[2]"Interaction between DNA-dependent protein kinase and a novel protein, KIP."
Wu X., Lieber M.R.
Mutat. Res. 385:13-20(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH PRKDC, TISSUE SPECIFICITY, VARIANT THR-44.
[3]"Genomic structure of mouse and human genes for DNA-PKcs interacting protein (KIP)."
Hattori A., Seki N., Hayashi A., Kozuma S., Saito T.
DNA Seq. 10:415-418(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-44.
[4]"A novel splice variant of calcium and integrin-binding protein 1 mediates protein kinase D2-stimulated tumour growth by regulating angiogenesis."
Armacki M., Joodi G., Nimmagadda S.C., de Kimpe L., Pusapati G.V., Vandoninck S., Van Lint J., Illing A., Seufferlein T.
Oncogene 33:1167-1180(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORM 2), INTERACTION WITH PRKD2; PTK2 AND PAK1, SUBCELLULAR LOCATION (ISOFORM 2), TISSUE SPECIFICITY, PHOSPHORYLATION AT SER-78, MUTAGENESIS OF SER-78 AND THR-167.
Tissue: Brain.
[5]"SNK, a Ser/Thr protein kinase, associated proteins."
Yuan O.
Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-44.
[6]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]"Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
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. expand/collapse author list , 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.
Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Cervix.
[10]"Calcium-dependent properties of CIB binding to the integrin alphaIIb cytoplasmic domain and translocation to the platelet cytoskeleton."
Shock D.D., Naik U.P., Brittain J.E., Alahari S.K., Sondek J., Parise L.V.
Biochem. J. 342:729-735(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ITGA2B, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[11]"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. 145:1277-1292(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: MYRISTOYLATION AT GLY-2, INTERACTION WITH PSEN2.
[12]"The interaction of the calcium- and integrin-binding protein (CIBP) with the coagulation factor VIII."
Fang X., Chen C., Wang Q., Gu J., Chi C.
Thromb. Res. 102:177-185(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH F8.
[13]"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. 269:538-545(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NBR1 AND FEZ1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[14]"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. 277:8321-8328(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RAC3, SUBCELLULAR LOCATION.
[15]"EDD, the human hyperplastic discs protein, has a role in progesterone receptor coactivation and potential involvement in DNA damage response."
Henderson M.J., Russell A.J., Hird S., Munoz M., Clancy J.L., Lehrbach G.M., Calanni S.T., Jans D.A., Sutherland R.L., Watts C.K.
J. Biol. Chem. 277:26468-26478(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBR5.
[16]"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. 277:28877-28883(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ITGA2B, SUBCELLULAR LOCATION, MUTAGENESIS OF PHE-115; LEU-131; ILE-153 AND PHE-173.
[17]"Association of CIB with GPIIb/IIIa during outside-in signaling is required for platelet spreading on fibrinogen."
Naik U.P., Naik M.U.
Blood 102:1355-1362(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[18]"Metal ion binding properties and conformational states of calcium- and integrin-binding protein."
Yamniuk A.P., Nguyen L.T., Hoang T.T., Vogel H.J.
Biochemistry 43:2558-2568(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ITGA2B, CALCIUM-BINDING, MAGNESIUM-BINDING.
[19]"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. 300:440-454(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PSEN2, MUTAGENESIS OF ASP-127 AND GLU-172.
[20]"Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen."
Naik M.U., Naik U.P.
Blood 102:3629-3636(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PTK2/FAK1.
[21]"Calcium-binding calmyrin forms stable covalent dimers in vitro, but in vivo is found in monomeric form."
Sobczak A., Blazejczyk M., Piszczek G., Zhao G., Kuznicki J., Wojda U.
Acta Biochim. Pol. 52:469-476(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[22]"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."
Tahara E. Jr., Tahara H., Kanno M., Naka K., Takeda Y., Matsuzaki T., Yamazaki R., Ishihara H., Yasui W., Barrett J.C., Ide T., Tahara E.
Cancer Immunol. Immunother. 54:729-740(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH IFI6 AND BCL2.
[23]"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. 170:465-476(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PAK1.
[24]"Calcium- and magnesium-dependent interactions between calcium- and integrin-binding protein and the integrin alphaIIb cytoplasmic domain."
Yamniuk A.P., Vogel H.J.
Protein Sci. 14:1429-1437(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ITGA2B, CALCIUM-BINDING, MAGNESIUM-BINDING.
[25]"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. 281:20825-20833(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ITPR3.
[26]"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. 172:169-175(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PAK1, SUBCELLULAR LOCATION, MUTAGENESIS OF PHE-173.
[27]"Sweet taste receptor interacting protein CIB1 is a general inhibitor of InsP3-dependent Ca2+ release in vivo."
Hennigs J.K., Burhenne N., Staehler F., Winnig M., Walter B., Meyerhof W., Schmale H.
J. Neurochem. 106:2249-2262(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TAS1R2, SUBCELLULAR LOCATION.
[28]"CIB1 functions as a Ca(2+)-sensitive modulator of stress-induced signaling by targeting ASK1."
Yoon K.W., Cho J.H., Lee J.K., Kang Y.H., Chae J.S., Kim Y.M., Kim J., Kim E.K., Kim S.E., Baik J.H., Naik U.P., Cho S.G., Choi E.J.
Proc. Natl. Acad. Sci. U.S.A. 106:17389-17394(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAP3K5.
[29]"Auxiliary Ca2+ binding sites can influence the structure of CIB1."
Yamniuk A.P., Anderson K.L., Fraser M.E., Vogel H.J.
Protein Sci. 18:1128-1134(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, CALCIUM-BINDING.
[30]"Translocation of sphingosine kinase 1 to the plasma membrane is mediated by calcium- and integrin-binding protein 1."
Jarman K.E., Moretti P.A., Zebol J.R., Pitson S.M.
J. Biol. Chem. 285:483-492(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SPHK1, SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-2.
[31]"CIB1 is a regulator of pathological cardiac hypertrophy."
Heineke J., Auger-Messier M., Correll R.N., Xu J., Benard M.J., Yuan W., Drexler H., Parise L.V., Molkentin J.D.
Nat. Med. 16:872-879(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[32]"Calmyrin1 binds to SCG10 protein (stathmin2) to modulate neurite outgrowth."
Sobczak A., Debowska K., Blazejczyk M., Kreutz M.R., Kuznicki J., Wojda U.
Biochim. Biophys. Acta 1813:1025-1037(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STMN2, SUBCELLULAR LOCATION.
[33]"Calcium- and integrin-binding protein 1 regulates microtubule organization and centrosome segregation through polo like kinase 3 during cell cycle progression."
Naik M.U., Naik U.P.
Int. J. Biochem. Cell Biol. 43:120-129(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PLK3, SUBCELLULAR LOCATION (ISOFORM 1).
[34]"Calcium-dependent inhibition of polo-like kinase 3 activity by CIB1 in breast cancer cells."
Naik M.U., Pham N.T., Beebe K., Dai W., Naik U.P.
Int. J. Cancer 128:587-596(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PLK3.
[35]"Contra-regulation of calcium- and integrin-binding protein 1-induced cell migration on fibronectin by PAK1 and MAP kinase signaling."
Naik M.U., Naik U.P.
J. Cell. Biochem. 112:3289-3299(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION (ISOFORM 1).
[36]"Calcium- and integrin-binding protein 1 regulates endomitosis and its interaction with Polo-like kinase 3 is enhanced in endomitotic Dami cells."
Kostyak J.C., Naik U.P.
PLoS ONE 6:E14513-E14513(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PLK3.
[37]"Biophysical and structural studies of the human calcium- and integrin-binding protein family: understanding their functional similarities and differences."
Huang H., Bogstie J.N., Vogel H.J.
Biochem. Cell Biol. 90:646-656(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ITGA2B.
[38]"Identification of novel integrin binding partners for calcium and integrin binding protein 1 (CIB1): structural and thermodynamic basis of CIB1 promiscuity."
Freeman T.C. Jr., Black J.L., Bray H.G., Dagliyan O., Wu Y.I., Tripathy A., Dokholyan N.V., Leisner T.M., Parise L.V.
Biochemistry 52:7082-7090(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ITGA5 AND ITGAV, MUTAGENESIS OF 114-ILE--PHE-117; 152-LEU-ILE-153 AND PHE-173.
[39]"CIB1 prevents nuclear GAPDH accumulation and non-apoptotic tumor cell death via AKT and ERK signaling."
Leisner T.M., Moran C., Holly S.P., Parise L.V.
Oncogene 32:4017-4027(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[40]"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."
Hwang P.M., Vogel H.J.
J. Mol. Recognit. 13:83-92(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 9-191.
[41]"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. 280:8407-8415(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 9-191 IN COMPLEX WITH CALCIUM IONS, SUBUNIT.
[42]"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. 14:1214-1221(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 9-191.
[43]"Solution structures of Ca2+-CIB1 and Mg2+-CIB1 and their interactions with the platelet integrin alphaIIb cytoplasmic domain."
Huang H., Ishida H., Yamniuk A.P., Vogel H.J.
J. Biol. Chem. 286:17181-17192(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-191 IN COMPLEXES WITH CALCIUM IONS AND MAGNESIUM ION, INTERACTION WITH ITGA2B.
[44]"Structural basis for the activation of platelet integrin alphaIIbbeta3 by calcium- and integrin-binding protein 1."
Huang H., Vogel H.J.
J. Am. Chem. Soc. 134:3864-3872(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-191 IN COMPLEX WITH ITGA2B PEPTIDE AND CALCIUM IONS, INTERACTION WITH ITGA2B.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U82226 mRNA. Translation: AAC51106.1.
U85611 mRNA. Translation: AAB53387.1.
AB021866 Genomic DNA. Translation: BAA36281.1.
JQ246073 mRNA. Translation: AEZ06077.1.
U83236 mRNA. Translation: AAB39758.1.
CR456955 mRNA. Translation: CAG33236.1.
AB451276 mRNA. Translation: BAG70090.1.
AB451406 mRNA. Translation: BAG70220.1.
CH471101 Genomic DNA. Translation: EAX02090.1.
BC000846 mRNA. Translation: AAH00846.1.
CCDSCCDS10360.1.
RefSeqNP_001264693.1. NM_001277764.1. [Q99828-2]
NP_006375.2. NM_006384.3. [Q99828-1]
UniGeneHs.715556.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DGUNMR-A9-191[»]
1DGVNMR-A9-191[»]
1XO5X-ray1.99A/B9-191[»]
1Y1AX-ray2.30A/B9-191[»]
2L4HNMR-A1-191[»]
2L4INMR-A1-191[»]
2LM5NMR-A1-191[»]
ProteinModelPortalQ99828.
SMRQ99828. Positions 9-191.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115774. 18 interactions.
DIPDIP-31260N.
IntActQ99828. 15 interactions.
MINTMINT-95290.
STRING9606.ENSP00000333873.

PTM databases

PhosphoSiteQ99828.

Polymorphism databases

DMDM134047806.

Proteomic databases

MaxQBQ99828.
PaxDbQ99828.
PRIDEQ99828.

Protocols and materials databases

DNASU10519.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000328649; ENSP00000333873; ENSG00000185043.
GeneID10519.
KEGGhsa:10519.
UCSCuc002bpb.4. human. [Q99828-1]

Organism-specific databases

CTD10519.
GeneCardsGC15M090773.
H-InvDBHIX0012576.
HGNCHGNC:16920. CIB1.
HPACAB012991.
HPA048825.
MIM602293. gene.
neXtProtNX_Q99828.
PharmGKBPA38423.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG257993.
HOVERGENHBG107344.
InParanoidQ99828.
KOK17259.
OMAYKRFSEL.
OrthoDBEOG7KM5V7.
PhylomeDBQ99828.
TreeFamTF313865.

Gene expression databases

BgeeQ99828.
CleanExHS_CIB1.
GenevestigatorQ99828.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamPF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTSM00054. EFh. 2 hits.
[Graphical view]
PROSITEPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCIB1. human.
EvolutionaryTraceQ99828.
GeneWikiCIB1.
GenomeRNAi10519.
NextBio35528000.
PROQ99828.
SOURCESearch...

Entry information

Entry nameCIB1_HUMAN
AccessionPrimary (citable) accession number: Q99828
Secondary accession number(s): B5BU40 expand/collapse secondary AC list , H6WJF3, O00693, O00735, Q6IB49, Q96J54, Q99971
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 20, 2007
Last modified: July 9, 2014
This is version 141 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM