Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Calcium and integrin-binding protein 1

Gene

Cib1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.5 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi116 – 1271PROSITE-ProRule annotationAdd BLAST12
Calcium bindingi161 – 1722PROSITE-ProRule annotationAdd BLAST12

GO - Molecular functioni

  • calcium-dependent protein kinase inhibitor activity Source: MGI
  • calcium ion binding Source: HGNC
  • ion channel binding Source: BHF-UCL
  • protein anchor Source: BHF-UCL
  • protein serine/threonine kinase inhibitor activity Source: MGI
  • Ras GTPase binding Source: MGI

GO - Biological processi

  • angiogenesis Source: UniProtKB-KW
  • apoptotic process Source: HGNC
  • cell adhesion Source: UniProtKB-KW
  • cell division Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: HGNC
  • cellular response to growth factor stimulus Source: UniProtKB
  • cellular response to nerve growth factor stimulus Source: UniProtKB
  • cellular response to tumor necrosis factor Source: UniProtKB
  • cytoplasmic microtubule organization Source: UniProtKB
  • endomitotic cell cycle Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of megakaryocyte differentiation Source: UniProtKB
  • negative regulation of microtubule depolymerization Source: UniProtKB
  • negative regulation of neuron projection development Source: UniProtKB
  • negative regulation of protein kinase B signaling Source: UniProtKB
  • negative regulation of protein phosphorylation Source: UniProtKB
  • platelet formation Source: UniProtKB
  • positive regulation of calcineurin-NFAT signaling cascade Source: BHF-UCL
  • positive regulation of catalytic activity Source: UniProtKB
  • positive regulation of cell adhesion mediated by integrin Source: UniProtKB
  • positive regulation of cell growth Source: UniProtKB
  • positive regulation of cell-matrix adhesion Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of cell migration involved in sprouting angiogenesis Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of establishment of protein localization to plasma membrane Source: BHF-UCL
  • positive regulation of male germ cell proliferation Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of protein phosphorylation Source: UniProtKB
  • positive regulation of protein serine/threonine kinase activity Source: UniProtKB
  • positive regulation of protein targeting to membrane Source: UniProtKB
  • positive regulation of substrate adhesion-dependent cell spreading Source: UniProtKB
  • regulation of cell division Source: UniProtKB
  • regulation of cell proliferation Source: UniProtKB
  • response to ischemia Source: UniProtKB
  • spermatid development Source: UniProtKB
  • thrombopoietin-mediated signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Angiogenesis, Apoptosis, Cell adhesion, Cell cycle, Cell division, Differentiation, Spermatogenesis

Keywords - Ligandi

Calcium, Magnesium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium and integrin-binding protein 1
Short name:
CIB
Alternative name(s):
Calmyrin
DNA-PKcs-interacting protein
Kinase-interacting protein
Short name:
KIP
Gene namesi
Name:Cib1
Synonyms:Cib, Kip, Prkdcip
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1344418. Cib1.

Subcellular locationi

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB-SubCell
  • axon Source: Ensembl
  • cell periphery Source: UniProtKB
  • centrosome Source: UniProtKB
  • cytoplasm Source: BHF-UCL
  • dendrite Source: Ensembl
  • endoplasmic reticulum Source: HGNC
  • extracellular exosome Source: MGI
  • filopodium tip Source: UniProtKB
  • growth cone Source: UniProtKB
  • lamellipodium Source: UniProtKB
  • membrane Source: HGNC
  • neuronal cell body Source: UniProtKB
  • neuron projection Source: UniProtKB
  • nucleoplasm Source: HGNC
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • ruffle membrane Source: UniProtKB-SubCell
  • sarcolemma Source: BHF-UCL
  • vesicle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice grow normally and are healthy; other family members (CIB2, CIB3 and CIB4) may probably compensate for CIB1 loss (PubMed:18989529). Males are sterile: spermatogenic cells can complete both mitotic and meiotic divisions, but postmeiotic spermatids do not develop normally and sperm is not produced (PubMed:16982698). Display increased bone marrow megakaryocytes and circulating platelets (PubMed:22128142). Mice display tail bleeding time increase, impaired thrombus formation and angiogenesis defect after ischemia (PubMed:19691476). Show compromised tumor growth (PubMed:20804551).5 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000735322 – 191Calcium and integrin-binding protein 1Add BLAST190

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Modified residuei78PhosphoserineBy similarity1

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

EPDiQ9Z0F4.
MaxQBiQ9Z0F4.
PaxDbiQ9Z0F4.
PeptideAtlasiQ9Z0F4.
PRIDEiQ9Z0F4.

PTM databases

PhosphoSitePlusiQ9Z0F4.

Expressioni

Tissue specificityi

Expressed in testis. Expressed in cardiac myocytes and endothelial cells. Expressed strongly in Sertoli cells, weakly in pachytene spermatocytes, round spermatids and condensing spermatids (at protein level). Ubiquitous.3 Publications

Developmental stagei

Expressed in the heart at 16 dpc (at protein level).1 Publication

Inductioni

Up-regulated upon cardiomyocytes hypertrophy (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000030538.
CleanExiMM_CIB1.
ExpressionAtlasiQ9Z0F4. baseline and differential.
GenevisibleiQ9Z0F4. MM.

Interactioni

Subunit structurei

Monomer. 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 TAS1R2 (via C-terminus); the interaction is independent of the myristoylation state of CIB1. 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. 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 (By similarity). Interacts with MYO1C. Interacts with ITGA2B (via C-terminal cytoplasmic tail region). Interacts (via C-terminal region) with PPP3R1 isoform 1 and isoform 2; the interactions increase upon cardiomyocytes hypertrophy. Interacts with CACNA1C; the interaction increases upon cardiomyocytes hypertrophy.By similarity3 Publications

GO - Molecular functioni

  • ion channel binding Source: BHF-UCL
  • protein anchor Source: BHF-UCL
  • Ras GTPase binding Source: MGI

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000070901.

Structurei

3D structure databases

ProteinModelPortaliQ9Z0F4.
SMRiQ9Z0F4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini103 – 138EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini148 – 183EF-hand 2PROSITE-ProRule annotationAdd BLAST36

Domaini

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

Sequence similaritiesi

Contains 2 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0034. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00860000133737.
HOGENOMiHOG000233019.
HOVERGENiHBG107344.
InParanoidiQ9Z0F4.
KOiK17259.
OMAiILQYPEL.
OrthoDBiEOG091G0OJZ.
PhylomeDBiQ9Z0F4.
TreeFamiTF313865.

Family and domain databases

CDDicd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 2 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9Z0F4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGGSGSRLSK ELLAEYQDLT FLTKQEILLA HRRFCELLPP EQRTVEESLH
60 70 80 90 100
TRVSFEQILS LPELKANPFK ERICMVFSTS PTRDSLSFED FLDLLSVFSD
110 120 130 140 150
TATPDIKSHY AFRIFDFDDD GTLDREDLSQ LVNCLTGEGE DTRLSASEMK
160 170 180 190
QLIDNILEES DIDRDGTINL SEFQHVISRS PDFASSFKIV L
Length:191
Mass (Da):21,763
Last modified:January 23, 2007 - v3
Checksum:iC85B603A19F9D9AC
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB006463 mRNA. Translation: BAA74429.1.
AB017361 Genomic DNA. Translation: BAA36165.1.
AF173010 mRNA. Translation: AAG38960.1.
AK010345 mRNA. Translation: BAB26868.1.
AK027915 mRNA. Translation: BAC25663.1.
AK152805 mRNA. Translation: BAE31510.1.
AK165472 mRNA. Translation: BAE38209.1.
BC003714 mRNA. Translation: AAH03714.1.
BC054385 mRNA. Translation: AAH54385.1.
CCDSiCCDS21392.1.
RefSeqiNP_001278204.1. NM_001291275.1.
NP_001278205.1. NM_001291276.1.
NP_036000.1. NM_011870.5.
UniGeneiMm.30217.

Genome annotation databases

EnsembliENSMUST00000065163; ENSMUSP00000070901; ENSMUSG00000030538.
GeneIDi23991.
KEGGimmu:23991.
UCSCiuc009hzs.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB006463 mRNA. Translation: BAA74429.1.
AB017361 Genomic DNA. Translation: BAA36165.1.
AF173010 mRNA. Translation: AAG38960.1.
AK010345 mRNA. Translation: BAB26868.1.
AK027915 mRNA. Translation: BAC25663.1.
AK152805 mRNA. Translation: BAE31510.1.
AK165472 mRNA. Translation: BAE38209.1.
BC003714 mRNA. Translation: AAH03714.1.
BC054385 mRNA. Translation: AAH54385.1.
CCDSiCCDS21392.1.
RefSeqiNP_001278204.1. NM_001291275.1.
NP_001278205.1. NM_001291276.1.
NP_036000.1. NM_011870.5.
UniGeneiMm.30217.

3D structure databases

ProteinModelPortaliQ9Z0F4.
SMRiQ9Z0F4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000070901.

PTM databases

PhosphoSitePlusiQ9Z0F4.

Proteomic databases

EPDiQ9Z0F4.
MaxQBiQ9Z0F4.
PaxDbiQ9Z0F4.
PeptideAtlasiQ9Z0F4.
PRIDEiQ9Z0F4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000065163; ENSMUSP00000070901; ENSMUSG00000030538.
GeneIDi23991.
KEGGimmu:23991.
UCSCiuc009hzs.2. mouse.

Organism-specific databases

CTDi10519.
MGIiMGI:1344418. Cib1.

Phylogenomic databases

eggNOGiKOG0034. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00860000133737.
HOGENOMiHOG000233019.
HOVERGENiHBG107344.
InParanoidiQ9Z0F4.
KOiK17259.
OMAiILQYPEL.
OrthoDBiEOG091G0OJZ.
PhylomeDBiQ9Z0F4.
TreeFamiTF313865.

Miscellaneous databases

PROiQ9Z0F4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030538.
CleanExiMM_CIB1.
ExpressionAtlasiQ9Z0F4. baseline and differential.
GenevisibleiQ9Z0F4. MM.

Family and domain databases

CDDicd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 2 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCIB1_MOUSE
AccessioniPrimary (citable) accession number: Q9Z0F4
Secondary accession number(s): Q3TN80
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 142 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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).By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.