Q99828 (CIB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	191 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May convert the inactive conformation of integrin alpha-IIb/beta3 to an active form through binding to the integrin cytoplasmic domain. Induces cell migration and spreading mediated through integrin (possibly via focal adhesion complexes). Functions as a negative regulator of stress activated MAP kinase (MAPK) signaling pathways. May play a role in regulation of apoptosis. Interacts with and up-regulates PTK2/FAK1 activity. Down regulates inositol 1,4,5-trisphosphate receptor-dependent calcium signaling. Participates in endomitotic cell cycle, a form of mitosis in which both karyokinesis and cytokinesis are interrupted and is a hallmark of megakaryocyte differentiation. Ref.14 Ref.16 Ref.18 Ref.20 Ref.21 Ref.24
Subunit structure	Monomer. Interacts with the heterodimeric integrin alpha-IIb/beta3. Interacts with the protein kinases PLK2/SNK and with the region immediately upstream of the kinase domain of DNA-PK. Interacts with PLK3; leading to inhibit PLK3 kinase activity. Interacts with PSEN2. Interacts with MYO1C By similarity. 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 TAS1R2 (via C-terminus); this interaction is independent of the myristoylation state of CIB1. Interacts with ITPR3; in a calcium dependent manner. Interacts with PTK2/FAK1. Interacts with MAP3K5; inhibiting MAP3K5 activation by phosphorylation, and its subsequent interaction with TRAF2. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.26
Subcellular location	Membrane; Lipid-anchor. Cytoplasm. Nucleus. Cell projection › filopodium. Apical cell membrane. Note: Localizes to the perinuclear region in the presence of NBR1. Colocalizes with TAS1R2 in apical regions of taste receptor cells. Ref.11 Ref.13 Ref.15 Ref.16 Ref.20
Tissue specificity	Ubiquitous. Ref.11
Sequence similarities	Contains 2 EF-hand domains.

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Cytoplasm Membrane Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Calcium Metal-binding
PTM	Lipoprotein Myristate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from mutant phenotype Ref.9. Source: HGNC cell adhesion Traceable author statement Ref.3. Source: ProtInc double-strand break repair Traceable author statement Ref.2. Source: ProtInc endomitotic cell cycle Inferred from direct assay Ref.24. Source: UniProtKB negative regulation of cell proliferation Inferred from mutant phenotype Ref.24. Source: UniProtKB positive regulation of calcineurin-NFAT signaling cascade Inferred from direct assay PubMed 20639889. Source: BHF-UCL positive regulation of establishment of protein localization to plasma membrane Inferred from genetic interaction PubMed 20639889. Source: BHF-UCL
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum Inferred from mutant phenotype Ref.9. Source: HGNC filopodium Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Inferred from mutant phenotype Ref.9. Source: HGNC sarcolemma Inferred from direct assay PubMed 20639889. Source: BHF-UCL
Molecular_function	calcium ion binding Inferred from mutant phenotype Ref.15. Source: HGNC protein anchor Inferred from genetic interaction PubMed 20639889. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 191

190

Calcium and integrin-binding protein 1

PRO_0000073531

Regions

Domain

103 – 138

36

EF-hand 1

Domain

148 – 183

36

EF-hand 2

Calcium binding

116 – 127

12

1 Ref.22

Calcium binding

161 – 172

12

2 Ref.22

Amino acid modifications

Lipidation

2

1

N-myristoyl glycine Ref.9

Natural variations

Natural variant

44

1

S → T. Ref.1 Ref.2 Ref.4
Corresponds to variant rs3210935 [ dbSNP | Ensembl ].

VAR_019565

Natural variant

106

1

I → T.
Corresponds to variant rs11551250 [ dbSNP | Ensembl ].

VAR_048636

Experimental info

Mutagenesis

115

1

F → A: Loss of binding to ITGA2B. Ref.13

Mutagenesis

127

1

D → N: Cytoplasmic localization. Ref.15

Mutagenesis

131

1

L → A or T: Loss of binding to ITGA2B. Ref.13

Mutagenesis

153

1

I → A: Loss of binding to ITGA2B. Ref.13

Mutagenesis

172

1

E → Q: Cytoplasmic localization. Ref.15

Mutagenesis

173

1

F → A: Loss of binding to ITGA2B. Ref.13

Sequence conflict

136

1

T → M in CAG33236. Ref.5

Secondary structure

1

.

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191

Helix Strand Turn

Details...

Helix

14 – 16

3

Turn

18 – 20

3

Helix

24 – 35

12

Helix

40 – 42

3

Helix

45 – 50

6

Helix

55 – 59

5

Helix

62 – 65

4

Helix

70 – 77

8

Beta strand

81 – 86

6

Helix

88 – 98

11

Helix

104 – 115

12

Beta strand

120 – 123

4

Helix

125 – 135

11

Beta strand

137 – 139

3

Beta strand

145 – 147

3

Helix

149 – 160

12

Beta strand

165 – 168

4

Helix

170 – 179

10

Helix

181 – 190

10

Sequences

	Sequence		Length	Mass (Da)
	Q99828 [UniParc]. Last modified March 20, 2007. Version 4. Checksum: 9AA19A0DE7AA1E05	FASTA	191	21,703
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"SNK, a Ser/Thr protein kinase, associated proteins." Yuan O. Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-44.
[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], VARIANT THR-44.
[3]	"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]. Tissue: Fetal liver.
[4]	"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.
[5]	"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].
[6]	"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. , 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].
[7]	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. , 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].
[8]	"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]. Tissue: Cervix.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.
[18]	"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.
[19]	"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.
[20]	"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.
[21]	"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.
[22]	"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.
[23]	"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.
[24]	"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.
[25]	"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.
[26]	"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.
[27]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U83236 mRNA. Translation: AAB39758.1.
U85611 mRNA. Translation: AAB53387.1.
U82226 mRNA. Translation: AAC51106.1.
AB021866 Genomic DNA. Translation: BAA36281.1.
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.

IPI

IPI00018451.

RefSeq

NP_006375.2. NM_006384.3.

UniGene

Hs.715556.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DGU	NMR	-	A	9-191	[»]
1DGV	NMR	-	A	9-191	[»]
1XO5	X-ray	1.99	A/B	9-191	[»]
1Y1A	X-ray	2.30	A/B	9-191	[»]
2L4H	NMR	-	A	1-191	[»]
2L4I	NMR	-	A	1-191	[»]
2LM5	NMR	-	A	1-191	[»]

ProteinModelPortal

Q99828.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31260N.

IntAct

Q99828. 11 interactions.

MINT

MINT-95290.

STRING

9606.ENSP00000333873.

PTM databases

PhosphoSite

Q99828.

Polymorphism databases

DMDM

134047806.

Proteomic databases

PaxDb

Q99828.

PRIDE

Q99828.

Protocols and materials databases

DNASU

10519.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000328649; ENSP00000333873; ENSG00000185043.

GeneID

10519.

KEGG

hsa:10519.

UCSC

uc002bpb.4. human.

Organism-specific databases

CTD

10519.

GeneCards

GC15M090773.

H-InvDB

HIX0012576.

HGNC

HGNC:16920. CIB1.

HPA

CAB012991.

MIM

602293. gene.

neXtProt

NX_Q99828.

PharmGKB

PA38423.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG257993.

HOVERGEN

HBG107344.

InParanoid

Q99828.

OMA

CELLPPE.

OrthoDB

EOG45B1GQ.

PhylomeDB

Q99828.

Gene expression databases

Bgee

Q99828.

CleanEx

HS_CIB1.

Genevestigator

Q99828.

GermOnline

ENSG00000185043. Homo sapiens.

Family and domain databases

Gene3D

1.10.238.10. 1 hit.

InterPro

IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]

Pfam

PF13499. EF_hand_5. 1 hit.
[Graphical view]

SMART

SM00054. EFh. 2 hits.
[Graphical view]

PROSITE

PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

CIB1. human.

EvolutionaryTrace

Q99828.

GenomeRNAi

10519.

NextBio

39892.

SOURCE

Search...

Entry information

Entry name

CIB1_HUMAN

Accession

Primary (citable) accession number: Q99828
Secondary accession number(s): B5BU40 , O00693, O00735, Q6IB49, Q96J54, Q99971

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	March 20, 2007
Last modified:	May 1, 2013
This is version 130 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.