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UniProtKB - Q99828 (CIB1_HUMAN)

Protein

Calcium and integrin-binding protein 1

Gene

CIB1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.
Isoform 2: Plays a regulatory role in angiogenesis and tumor growth by mediating PKD/PRKD2-induced vascular endothelial growth factor A (VEGFA) secretion.1 Publication

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).1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi116 – 1271Add BLAST12
Calcium bindingi161 – 1722Add BLAST12

GO - Molecular functioni

  • calcium-dependent protein kinase inhibitor activity Source: CACAO
  • calcium ion binding Source: HGNC
  • ion channel binding Source: Ensembl
  • protein C-terminus binding Source: Ensembl
  • protein kinase binding Source: Ensembl
  • protein membrane anchor Source: BHF-UCL
  • protein serine/threonine kinase inhibitor activity Source: CACAO
  • Ras GTPase binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Biological processAngiogenesis, Apoptosis, Cell adhesion, Cell cycle, Cell division, Differentiation, Spermatogenesis
LigandCalcium, Magnesium, Metal-binding

Enzyme and pathway databases

SIGNORiQ99828

Names & Taxonomyi

Protein namesi
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 namesi
Name:CIB1
Synonyms:CIB, KIP, PRKDCIP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000185043.10
HGNCiHGNC:16920 CIB1
MIMi602293 gene
neXtProtiNX_Q99828

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2G → A: Inhibits translocation to the plasma membrane. Show increased apoptosis after TNF stimulation. 1 Publication1
Mutagenesisi78S → A: Loss of phosphorylation by PKD/PRKD2; in isoform 2. 1 Publication1
Mutagenesisi78S → E: Phosphomimetic; promotes tumor growth by an indirect mechanism; in isoform 2. 1 Publication1
Mutagenesisi114 – 117IFDF → AAAA: Loss of binding to ITGAV. 1 Publication4
Mutagenesisi115F → A: Loss of binding to ITGA2B. 1 Publication1
Mutagenesisi127D → N: Cytoplasmic localization. 1 Publication1
Mutagenesisi131L → A or T: Loss of binding to ITGA2B. 1 Publication1
Mutagenesisi152 – 153LI → AA: Loss of binding to ITGA2B. 1 Publication2
Mutagenesisi153I → A: Loss of binding to ITGA2B. 1 Publication1
Mutagenesisi167T → A: No effect on phosphorylation by PKD/PRKD2; in isoform 2. 1 Publication1
Mutagenesisi172E → Q: Cytoplasmic localization. 1 Publication1
Mutagenesisi173F → A: Loss of binding to ITGA2B. 3 Publications1
Mutagenesisi173F → A: Loss of binding to ITGA2B. Does not inhibit interaction with PAK1. 3 Publications1

Organism-specific databases

DisGeNETi10519
OpenTargetsiENSG00000185043
PharmGKBiPA38423

Polymorphism and mutation databases

BioMutaiCIB1
DMDMi134047806

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00000735312 – 191Calcium and integrin-binding protein 1Add BLAST190

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1
Isoform 2 (identifier: Q99828-2)
Modified residuei118Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylation of isoform 2 at Ser-118 by PRKD2 increases its ability to stimulate tumor angiogenesis.1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

EPDiQ99828
MaxQBiQ99828
PaxDbiQ99828
PeptideAtlasiQ99828
PRIDEiQ99828
ProteomicsDBi78493

PTM databases

iPTMnetiQ99828
PhosphoSitePlusiQ99828

Expressioni

Tissue specificityi

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.5 Publications

Inductioni

Up-regulated during breast cancer progression.

Gene expression databases

BgeeiENSG00000185043 Expressed in 222 organ(s), highest expression level in bronchial epithelial cell
CleanExiHS_CIB1
ExpressionAtlasiQ99828 baseline and differential
GenevisibleiQ99828 HS

Organism-specific databases

HPAiCAB012991
HPA042413
HPA048825

Interactioni

Subunit structurei

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; the interaction is direct (PubMed:15685448). Interacts with BCL2 (PubMed:15685448). 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.By similarity32 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi115774, 24 interactors
CORUMiQ99828
DIPiDIP-31260N
IntActiQ99828, 33 interactors
MINTiQ99828
STRINGi9606.ENSP00000333873

Structurei

Secondary structure

1191
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ99828
SMRiQ99828
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99828

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.

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0034 Eukaryota
COG5126 LUCA
GeneTreeiENSGT00860000133737
HOVERGENiHBG107344
InParanoidiQ99828
KOiK17259
OMAiQDGDCTF
OrthoDBiEOG091G0OJZ
PhylomeDBiQ99828
TreeFamiTF313865

Family and domain databases

CDDicd00051 EFh, 1 hit
InterProiView protein in InterPro
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
PfamiView protein in Pfam
PF13499 EF-hand_7, 1 hit
SMARTiView protein in SMART
SM00054 EFh, 2 hits
SUPFAMiSSF47473 SSF47473, 1 hit
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 2 hits
PS50222 EF_HAND_2, 2 hits

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q99828-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MGGSGSRLSK ELLAEYQDLT FLTKQEILLA HRRFCELLPQ EQRSVESSLR 
        60         70         80         90        100
AQVPFEQILS LPELKANPFK ERICRVFSTS PAKDSLSFED FLDLLSVFSD 
       110        120        130        140        150
TATPDIKSHY AFRIFDFDDD GTLNREDLSR LVNCLTGEGE DTRLSASEMK 
       160        170        180        190 
QLIDNILEES DIDRDGTINL SEFQHVISRS PDFASSFKIV L
Length:191
Mass (Da):21,703
Last modified:March 20, 2007 - v4
Checksum:i9AA19A0DE7AA1E05
GO
Isoform 2 (identifier: Q99828-2) [UniParc]FASTAAdd to basket
Also known as: CIB1a

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

Show »
Length:231
Mass (Da):26,032
Checksum:i0D38C53F1478119E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti136T → M in CAG33236 (Ref. 6) Curated1
Sequence conflicti171S → F in AEZ06077 (PubMed:23503467).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01956544S → T3 PublicationsCorresponds to variant dbSNP:rs3210935Ensembl.1
Natural variantiVAR_048636106I → T. Corresponds to variant dbSNP:rs11551250Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05374029L → LSVYVVLAPHLVDNEQQARS GNEHTGRPIAENTDSSPLST R in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS10360.1 [Q99828-1]
CCDS73781.1 [Q99828-2]
RefSeqiNP_001264693.1, NM_001277764.1 [Q99828-2]
NP_006375.2, NM_006384.3 [Q99828-1]
UniGeneiHs.715556

Genome annotation databases

EnsembliENST00000328649; ENSP00000333873; ENSG00000185043 [Q99828-1]
ENST00000612800; ENSP00000479860; ENSG00000185043 [Q99828-2]
GeneIDi10519
KEGGihsa:10519
UCSCiuc002bpb.5 human [Q99828-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS10360.1 [Q99828-1]
CCDS73781.1 [Q99828-2]
RefSeqiNP_001264693.1, NM_001277764.1 [Q99828-2]
NP_006375.2, NM_006384.3 [Q99828-1]
UniGeneiHs.715556

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ99828
SMRiQ99828
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115774, 24 interactors
CORUMiQ99828
DIPiDIP-31260N
IntActiQ99828, 33 interactors
MINTiQ99828
STRINGi9606.ENSP00000333873

PTM databases

iPTMnetiQ99828
PhosphoSitePlusiQ99828

Polymorphism and mutation databases

BioMutaiCIB1
DMDMi134047806

Proteomic databases

EPDiQ99828
MaxQBiQ99828
PaxDbiQ99828
PeptideAtlasiQ99828
PRIDEiQ99828
ProteomicsDBi78493

Protocols and materials databases

DNASUi10519
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000328649; ENSP00000333873; ENSG00000185043 [Q99828-1]
ENST00000612800; ENSP00000479860; ENSG00000185043 [Q99828-2]
GeneIDi10519
KEGGihsa:10519
UCSCiuc002bpb.5 human [Q99828-1]

Organism-specific databases

CTDi10519
DisGeNETi10519
EuPathDBiHostDB:ENSG00000185043.10
GeneCardsiCIB1
H-InvDBiHIX0012576
HGNCiHGNC:16920 CIB1
HPAiCAB012991
HPA042413
HPA048825
MIMi602293 gene
neXtProtiNX_Q99828
OpenTargetsiENSG00000185043
PharmGKBiPA38423
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0034 Eukaryota
COG5126 LUCA
GeneTreeiENSGT00860000133737
HOVERGENiHBG107344
InParanoidiQ99828
KOiK17259
OMAiQDGDCTF
OrthoDBiEOG091G0OJZ
PhylomeDBiQ99828
TreeFamiTF313865

Enzyme and pathway databases

SIGNORiQ99828

Miscellaneous databases

ChiTaRSiCIB1 human
EvolutionaryTraceiQ99828
GeneWikiiCIB1
GenomeRNAii10519
PROiPR:Q99828
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185043 Expressed in 222 organ(s), highest expression level in bronchial epithelial cell
CleanExiHS_CIB1
ExpressionAtlasiQ99828 baseline and differential
GenevisibleiQ99828 HS

Family and domain databases

CDDicd00051 EFh, 1 hit
InterProiView protein in InterPro
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
PfamiView protein in Pfam
PF13499 EF-hand_7, 1 hit
SMARTiView protein in SMART
SM00054 EFh, 2 hits
SUPFAMiSSF47473 SSF47473, 1 hit
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 2 hits
PS50222 EF_HAND_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiCIB1_HUMAN
AccessioniPrimary (citable) accession number: Q99828
Secondary accession number(s): B5BU40
, H6WJF3, O00693, O00735, Q6IB49, Q96J54, Q99971
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 20, 2007
Last modified: October 10, 2018
This is version 181 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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