CIB1

This gene encodes a member of the EF-hand domain-containing calcium-binding superfamily. The encoded protein interacts with many other proteins, including the platelet integrin alpha-IIb-beta-3, DNA-dependent protein kinase, presenilin-2, focal adhesion kinase, p21 activated kinase, and protein kinase D. The encoded protein may be involved in cell survival and proliferation, and is associated with several disease states including cancer and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]

Calcium And Integrin Binding 1

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.

(Microbial infection) Involved in keratinocyte-intrinsic immunity to human beta-papillomaviruses (HPVs).

Angiogenesis Source: UniProtKB-KW
Apoptotic process Source: HGNC-UCL
Cell adhesion Source: ProtInc
Cell division Source: UniProtKB-KW
Cellular response to DNA damage stimulus Source: HGNC-UCL
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
Double-strand break repair Source: ProtInc
Endomitotic cell cycle Source: UniProtKB
Extrinsic apoptotic signaling pathway Source: BHF-UCL
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of cell population 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 population proliferation Source: UniProtKB
Positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
Positive regulation of male germ cell proliferation Source: UniProtKB
Positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
Positive regulation of protein localization to plasma membrane Source: BHF-UCL
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 population proliferation Source: UniProtKB
Response to ischemia Source: UniProtKB
Spermatid development Source: UniProtKB
Thrombopoietin-mediated signaling pathway Source: UniProtKB

Cytoplasm; Cytoskeleton; Centrosome; Nucleus; Sarcolemma; Cell membrane; Apical cell membrane; Ruffle membrane; Membrane; Filopodium tip; Growth cone; Lamellipodium; Perinuclear region; Neuron projection; Perikaryon. 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 PLK3 at centrosomes in ductal breast carcinoma cells.
Isoform 2: Trans-Golgi network; Perinuclear region

Epidermodysplasia verruciformis 3 (EV3):
A form of epidermodysplasia verruciformis, a rare genodermatosis associated with a high risk of skin carcinoma that results from an abnormal susceptibility to infection by specific human papillomaviruses, including the oncogenic HPV5. Infection leads to the early development of disseminated flat wart-like and pityriasis versicolor-like skin lesions. Cutaneous Bowen's carcinomas in situ and invasive squamous cell carcinomas develop in about half of the patients, mainly on sun-exposed skin areas. EV3 inheritance is autosomal recessive.

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