InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CIB1

Summary

InnateDB Protein

IDBP-29932.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CIB1

Protein Name

calcium and integrin binding 1 (calmyrin)

Synonyms

CIB; CIBP; KIP1; PRKDCIP; SIP2-28;

Species

Homo sapiens

Ensembl Protein

ENSP00000333873

InnateDB Gene

IDBG-29930 (CIB1)

Protein Structure

UniProt Annotation

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.Isoform 2: Plays a regulatory role in angiogenesis and tumor growth by mediating PKD/PRKD2-induced vascular endothelial growth factor A (VEGFA) secretion. {ECO:0000269PubMed:23503467}.

Subcellular Localization

Membrane; Lipid-anchor. Cell membrane, sarcolemma. Cell membrane. Apical cell membrane. Cell projection, ruffle membrane. Cell projection, filopodium tip. Cell projection, growth cone. Cell projection, lamellipodium. Cytoplasm. Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, perinuclear 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. {ECO:0000250}.Isoform 2: Cytoplasm, perinuclear region {ECO:0000269PubMed:23503467}. Golgi apparatus, trans-Golgi network {ECO:0000269PubMed:23503467}.

Disease Associations

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. {ECO:0000269PubMed:10477286, ECO:0000269PubMed:11856312, ECO:0000269PubMed:23503467, ECO:0000269PubMed:9030514, ECO:0000269PubMed:9372844}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 35 experimentally validated interaction(s) in this database.

Experimentally validated
Total	35 [view]
Protein-Protein	31 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0017016	Ras GTPase binding
GO:0043495	protein anchor

Biological Process

GO:0001525	angiogenesis
GO:0001933	negative regulation of protein phosphorylation
GO:0001934	positive regulation of protein phosphorylation
GO:0001954	positive regulation of cell-matrix adhesion
GO:0002931	response to ischemia
GO:0006302	double-strand break repair
GO:0006915	apoptotic process
GO:0006974	cellular response to DNA damage stimulus
GO:0007026	negative regulation of microtubule depolymerization
GO:0007113	endomitotic cell cycle
GO:0007155	cell adhesion
GO:0007286	spermatid development
GO:0008284	positive regulation of cell proliferation
GO:0008285	negative regulation of cell proliferation
GO:0010977	negative regulation of neuron projection development
GO:0030220	platelet formation
GO:0030307	positive regulation of cell growth
GO:0030335	positive regulation of cell migration
GO:0031122	cytoplasmic microtubule organization
GO:0033630	positive regulation of cell adhesion mediated by integrin
GO:0038163	thrombopoietin-mediated signaling pathway
GO:0042127	regulation of cell proliferation
GO:0043066	negative regulation of apoptotic process
GO:0045653	negative regulation of megakaryocyte differentiation
GO:0048554	positive regulation of metalloenzyme activity
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051301	cell division
GO:0051302	regulation of cell division
GO:0051898	negative regulation of protein kinase B signaling
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0070886	positive regulation of calcineurin-NFAT signaling cascade
GO:0071356	cellular response to tumor necrosis factor
GO:0071363	cellular response to growth factor stimulus
GO:0071902	positive regulation of protein serine/threonine kinase activity
GO:0090004	positive regulation of establishment of protein localization to plasma membrane
GO:0090050	positive regulation of cell migration involved in sprouting angiogenesis
GO:0090314	positive regulation of protein targeting to membrane
GO:0097191	extrinsic apoptotic signaling pathway
GO:1900026	positive regulation of substrate adhesion-dependent cell spreading
GO:1901313	positive regulation of gene expression involved in extracellular matrix organization
GO:1990090	cellular response to nerve growth factor stimulus
GO:2000256	positive regulation of male germ cell proliferation

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005783	endoplasmic reticulum
GO:0005794	Golgi apparatus
GO:0005813	centrosome
GO:0005886	plasma membrane
GO:0016020	membrane
GO:0016324	apical plasma membrane
GO:0030027	lamellipodium
GO:0030426	growth cone
GO:0032433	filopodium tip
GO:0032587	ruffle membrane
GO:0042383	sarcolemma
GO:0043005	neuron projection
GO:0043025	neuronal cell body
GO:0048471	perinuclear region of cytoplasm
GO:0070062	extracellular vesicular exosome
GO:0071944	cell periphery