calmodulin

Calmodulin (CaM) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the binding of Ca2+ is required for the activation of Calmodulin. Once bound to Ca2+, Calmodulin acts as part of a calcium signal transduction pathway by modifying its interactions with various target proteins such as kinases or phosphatases. Calmodulin is a small, highly conserved protein that is 148 amino acids long. The protein has two approximately symmetrical globular domains each containing a pair of EF-hand motifs (the N- and C-domain) separated by a flexible linker region for a total of four Ca2+ binding sites. Calmodulin mediates many crucial processes such as inflammation, metabolism, apoptosis, smooth muscle contraction, intracellular movement, short-term and long-term memory, and the immune response. Calmodulin is expressed in many cell types and can have different subcellular locations, including the cytoplasm, within organelles, or associated with the plasma or organelle membranes, but it is always found intracellularly.

CDPK1 Protein, Toxoplasma gondii, Recombinant (His) is expressed in E. coli expression system with N-10xHis tag. The predicted molecular weight is 63.3 kDa and the accession number is Q9BJF5.

PDE1C belongs to the cyclic nucleotide phosphodiesterase family, PDE1 subfamily. Phosphodiesterases (PDEs) are a family of related phosphohydrolyases that selectively catalyze the hydrolysis of 3' cyclic phosphate bonds in adenosine and or guanine 3',5' cyclic monophosphate (cAMP and or cGMP). They regulate the cellular levels, localization and duration of action of these second messengers by controlling the rate of their degradation. PDEs are expressed ubiquitously, with each subtype having a specific tissue distribution. These enzymes are involved in many signal transduction pathways and their functions include vascular smooth muscle proliferation and contraction, cardiac contractility, platelet aggregation, hormone secretion, immune cell activation, and they are involved in learning and memory. PDE1C has a high affinity for both cAMP and cGMP. It is expressed in several tissues, including brain and heart. As a cyclic nucleotide phosphodiesterase, PDE1C has a dual-specificity for the second messengers cAMP and cGMP.

CAMKIV Protein, Mouse, Recombinant (His & GST) is expressed in Baculovirus insect cells with His and GST tag. The predicted molecular weight is 80.4 kDa and the accession number is P08414.

CAMKIV Protein, Mouse, Recombinant is expressed in Baculovirus insect cells. The predicted molecular weight is 52.7 kDa and the accession number is P08414.

CAMK2D Protein, Human, Recombinant (His) is expressed in E. coli expression system with C-6xHis tag. The predicted molecular weight is 63.1 kDa and the accession number is Q13557.

Calmodulin 2, also known as CALM2, is a calmodulin. Calmodulin 2 mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). It is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Calmodulin 2 gene may be a genetic determinant of hip osteoarthritis (OA). OA is a degenerative disease characterized by gradual loss of articular cartilage and is a leading cause of disability in elderly populations. CALM2 was most abundantly expressed in articular chondrocytes and OA cartilage.

Ca2+ calmodulin-dependent protein kinase2A (CAMK2A) belongs to the serine threonine protein kinase family and, together with other 28 different isoforms, belongs to the Ca2+ calmodulin-dependent protein kinase subfamily. CaM kinase Ⅱ is thought to be an important mediator of learning and memory and is also necessary for Ca2+homeostasis and reuptake in cardiomyocytes chloride transport in epithelia, positive T-cell selection, and CD8 T-cell activation. CAMKIIA is one of the major forms of CAMKII. It has been found to play a critical role in sustaining activation of CAMKII at the postsynaptic density. Studies have found that knockout mice without CAMKIIA demonstrate a low frequency of LTP. Additionally, these mice do not form persistent, stable place cells in the hippocampus.

CAMK1D Protein, Human, Recombinant (GST) is expressed in Baculovirus insect cells with GST tag. The predicted molecular weight is 69 kDa and the accession number is Q8IU85-1.

CAMKI Protein, Human, Recombinant is expressed in E. coli expression system. The predicted molecular weight is 41.5 kDa and the accession number is B0YIY3.

CAMKIV Protein, Human, Recombinant (GST) is expressed in Baculovirus insect cells with GST tag. The predicted molecular weight is 79 kDa and the accession number is Q16566.

CASK Protein, Human, Recombinant (His & GST) is expressed in Baculovirus insect cells with His and GST tag. The predicted molecular weight is 130 kDa and the accession number is O14936-4.

Calcium calmodulin-dependent protein kinase II beta (CAMK2B) is a member of the serine threonine protein kinase family and to the Ca(2+) calmodulin-dependent protein kinase subfamily. CaMKII is an important player in prostate cancer cells ability to escape apoptosis under androgen ablation and facilitate the progression of prostate cancer cells to an androgen independent state. As a multifunctional protein kinase, the loss of activity may play a critical role in initiating the changes leading to ischemia-induced cell death. CaMKII are found to be important for the functions of immune cells. CaMKII can be activated by TLR ligands, and in turn promotes both myeloid differentiating factor 88 and Toll IL-1 receptor domain-containing adaptor protein-inducing IFN-beta-dependent inflammatory responses by directly activating TAK1 and IRF3. CAMKII has four subunit isoforms (alpha, beta, gamma, delta). It is possible that distinct isoforms of this chain have different cellular localizations and interact differently with calmodulin. The alpha- and beta-isoforms have narrow distributions restricted mainly to neuronal tissues, but the gamma- and delta-isoforms are ubiquitously expressed within neuronal and non-neuronal tissues. CAMK2B is important for controlling the direction of plasticity at the parallel fiber-Purkinje cell synapse. CaMK2 is involved in neuronal survival through the reorganization of the neuroarchitecture and that the regulation of this role is controlled at the level of gene expression. Because CaMK2B influences the expression of many neuroreceptors and influences neural outgrowth and pruning, its altered expression in the cerebral cortex in schizophrenia or depression may contribute to schizophrenia and depression.

Calcium Calmodulin-Dependent Protein Kinase Type 1 (CAMK1) belongs to the protein kinase superfamily, CAMK Ser Thr protein kinase family, and CaMK subfamily. CAMK1 contains one protein kinase domain and widely expressed. CAMK1 is phosphorylated by CaMKK1 and CaMKK2 on Thr-177. CAMK1 regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization, and neurite outgrowth. CAMK1 plays a role in K+ and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex.

Calmodulin-like protein 5, also known as Calmodulin-like skin protein, CALML5 and CLSP, is a protein which contains fourEF-hand domains. CALML5 CLSP is particularly abundant in the epidermis where its expression is directly related to keratinocyte differentiation.The expression is very low in lung. CALML5 CLSP binds calcium. It may be involved in terminal differentiation of keratinocytes. Coxsackievirus and adenovirus receptor (CAR) is a member of the immunoglobulin (Ig) superfamily and a component of epithelial tight junction. CAR functions as a primary receptor for coxsackievirus B and adenovirus (Ad) infection. CALML5 CLSP is closely related to CAR. The structure and dynamics of human calmodulin-like skin protein CALML5 CLSP have been characterized by NMR spectroscopy. The mobility of CALML5 CLSP has been found to be different for the N-terminal and C-terminal domains. The N-terminal domain is characterized by four stable helices, which experience large fluctuations. This is shown to be due to mutations in the hydrophobic core. The overall N-terminal domain behavior is similar both in the full-length protein and in the isolated domain.

CASK Protein, Human, Recombinant is expressed in Baculovirus insect cells. The predicted molecular weight is 102.1 kDa and the accession number is O14936-4.

Potent and specific inhibitor of CaM-kinase II (CAMK2). CAMK2N1 Protein, Human, Recombinant (His & Trx) is expressed in E. coli expression system with N-6xHis-Trx tag. The predicted molecular weight is 25.6 kDa and the accession number is Q7Z7J9.

PDE1C Protein, Rat, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 92.6 kDa and the accession number is Q63421.

Calcium calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B, also known as Cam-PDE 1B and PDE1B, is a cytoplasm protein that belongs to the cyclic nucleotide phosphodiesterase family and PDE1 subfamily. Phosphodiesterase-1A (PDE1A), Phosphodiesterase-1B (PDE1B), Phosphodiesterase-4B (PDE4B), and Phosphodiesterase-4A (PDE4A) are important regulators of signal transduction in striatum due to their catalysis of cyclic AMP and cyclic GMP. PDE1B is highly expressed in the striatum. It binds two divalent metal cations per subunit. Site one of PDE1B may preferentially bind zinc ions, while site two of PDE1B has a preference for magnesium and or manganese ions. PDE1B is a cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. It has a preference for cGMP as a substrate.

Calmodulin-like protein 3 (CALML3) is similar to that of authentic calmodulin and may actually compete with calmodulin by binding, with different affinity, to cellular substrates. Calmodulin-like protein 3 (CALML3) is a tumor-sensitive protein specifically expressed in normal epithelial cells but downregulated in tumorigenesis. Downregulation of the protein is an early event in breast cancer development. One of the most pressing questions raised by the discovery of CLP CALML3 is that of its potential targets. Although it is 85% identical to human calmodulin, the distinct properties of CLP suggest that it has specific targets or targets that only partially overlap with those of calmodulin. Research has identified the unconventional myosin-10 (Myo10) as a specific target of CALML3. The discovery of Myo10 as a specific target of CALML3 is highly significant and suggests multiple lines of further research such as investigations of the Ca2+ regulation of Myo10 and the role of the loss of CLP in epithelial differentiation, adhesion, and cancer. Cells expressing CALML3 displayed a striking increase in the number and length of myosin-10-positive filopodia and showed increased mobility in a wound healing assay.

Calmodulin-Dependent Protein Kinase (CaM Kinase) is a kind of protein phosphorylate multiple downstream targets. Concentration of cytosolic calcium functions as a second messenger that mediates a wide range of cellular responses. Calcium binds to calcium binding proteins (calmodulin CaM) and stimulates the activity of a variety of enzymes, including CaM kinases referred to as CaM-kinases (CaMKs), such as CaMKI, CaMKII, CaMKIV and CaMKK. Calmodulin-dependent protein kinase CL3 CaMKIγ is a memberane-anchored CaMK belonging to the CaM kinase family. Its C-terminal region is uniquely modified by two sequential lipidification steps: prenylation followed by a kinase-activity-regulated palmitoylation. These modifications are essential for CaMKIγ membrane anchoring and targeting into detergent-resistant lipid microdomains in the dendrites. It has been found that CaMKIγ critically contributed to BDNF-stimulated dendritic growth. Raft insertion of CaMKIγ specifically promoted dendritogenesis of cortical neurons by acting upstream of RacGEF STEF and Rac, both present in lipid rafts. Thus, CaMKIγ may represent a key element in the Ca2+-dependent and lipid-raft-delineated switch that turns on extrinsic activity-regulated dendrite formation in developing cortical neurons.

Oncomodulin-1 (OM) is a small, calcium-binding protein and a macrophage-derived growth factor, which can promote axon regeneration in retinal ganglion cells. Oncomodulin-1 is constitutively secreted by activated macrophages in the vitreous and retina in response to inflammatory conditions that promote optic nerve regeneration. Oncomodulin-1 binds RGCs with high affinity in vitro, but only when cAMP is pharmacologically elevated or if the membrane is permeabilized allowing Oncomodulin-1 access to the cytosolic compartment. Oncomodulin-1 is a member of the superfamily of calmodulin proteins and is a high-affinity calcium ion-binding protein and contains 2 EF-hand domains. OM is found in early embryonic cells in the placenta and also in tumors. It has some calmodulin-like activity with respect to enzyme activation and growth regulation.

Phosphorylates a specific serine in the N-terminus of a myosin light chain, which leads to the formation of calmodulin MLCK signal transduction complexes which allow selective transduction of calcium signals. MLCK Protein, Chicken, Recombinant (His & Myc & SUMO) is expressed in E. coli expression system with N-10xHis-SUMO and C-Myc tag. The predicted molecular weight is 52.9 kDa and the accession number is P11799.

Thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin and tropomyosin. The interaction of calponin with actin inhibits the actomyosin Mg-ATPase activity. Calponin-2 CNN2 Protein, Human, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 49.6 kDa and the accession number is Q99439.

Cyclic AMP-dependent transcription factor ATF-1(ATF1) which contains 1 bZIP (basic-leucine zipper) domain and 1 KID (kinase-inducible) domain, belongs to the bZIP family. It influences cellular physiologic processes by regulating the expression of downstream target genes, which are related to growth, survival, and other cellular activities. ATF1 binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. It also binds to the Tax-responsive element (TRE) of HTLV-I. ATF1 mediates PKA-induced stimulation of CRE-reporter genes, represses the expression of FTH1 and other antioxidant detoxification genes, triggers cell proliferation and transformation. ATF1 is phosphorylated at serine 63 in its kinase-inducible domain by serine threonine kinases, cAMP-dependent protein kinase A, calmodulin-dependent protein kinase I II, mitogen- and stress-activated protein kinase and CDK3. Its phosphorylation enhances its transactivation and transcriptional activities, and enhances cell transformation.

Ca2+-regulated heat-stable protein of 24 kDa (CRHSP-24) is a serine phosphoprotein originally identified as a physiological substrate for the Ca2+-calmodulin regulated protein phosphatase calcineurin (PP2B). CRHSP-24 is a paralog of the brain-specific mRNA-binding protein PIPPin and was recently shown to interact with the STYX dead phosphatase protein in developing spermatids.

Has some calmodulin-like activity with respect to enzyme activation and growth regulation. Binds two calcium ions. OM Protein, Rat, Recombinant (E. coli, His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 18.0 kDa and the accession number is P02631.

Neuromodulin, also known as Axonal membrane protein GAP-43, Growth-associated protein 43, Neural phosphoprotein B-5, pp46 and GAP43, is a cell membrane protein which belongs to theneuromodulin family. Neuromodulin GAP43 contains oneIQ domain. Neuromodulin GAP43 is associated with nerve growth. It is a major component of the motile growth cones that form the tips of elongating axons. Neuromodulin GAP43 is involved in neurite outgrowth, a crucial process for the differentiation of neurons. The sudden infant death syndrome (SIDS) is the main cause of postneonatal infant death and its cause is still unknown. Neuromodulin GAP43 is a marker of synaptic plasticity and is critical for normal development of the serotonergic innervation. Neuromodulin GAP43 is a major cortical cytoskeleton-associated and calmodulin binding protein that is widely and abundantly expressed during development, maintained in selected brain structures in the adult, and reinduced during nerve regeneration. CAP23 and GAP43 are functionally related intrinsic determinants of anatomical plasticity. These proteins function by locally promoting subplasmalemmal actin cytoskeleton accumulation.

PPP3CA, also known as protein phosphatase 2B, is a member of the PPP phosphatase family, PP-2B subfamily. It is the alpha catalytic subunit of protein phosphatase 2B (PP2B). PP2B is a holoenzyme that is comprised of a catalytic subunit associated with regulatory subunits. It is a calcium regulated enzyme that is activated by calmodulin and participates in the signaling cascades involved in development of the nervous, cardiovascular, and musculoskeletal systems. PPP3CA activates the T cells of the immune system and can be blocked by drugs. It also activates NFATc (a transcription factor) by dephosphorylating it. The activated NFATc is subsequently translocated into the nucleus, where it upregulates the expression of interleukin 2. PPP3CA interacts with CRTC2, MYOZ1, MYOZ2 and MYOZ3. It also interacts with DNM1L. The interaction dephosphorylates DNM1L and regulates its translocation to mitochondria.

Death-associated protein kinase 1, also known as DAP kinase 1, DAPK1 and DAPK, is a cytoplasm protein which belongs to theprotein kinase superfamily, CAMK Ser Thr protein kinase family and DAP kinase subfamily. DAPK1 contains tenANK repeats, onedeath domain and oneprotein kinase domain. DAPK1 is a calcium calmodulin-dependent serine threonine kinase which acts as a positive regulator of apoptosis. DAPK1 gene is a candidate tumor suppressor (TSG) and the abnormal methylation of DAPK1 gene has been found in many carcinomas. DAPK1 over-expression can induce cell apoptosis and inhibit tumor cell metastasis. DAPK1 gene over-expression could suppress PGCl3 cells malignant phenotype, inhibit PGCl3 cells growth, invasive, migration and adhesion ability, upregulate p53 gene and downregulate bcl-2 gene. Loss of activity of death-associated protein kinase 1 ( DAPK1 ) may be an independent factor affecting survival of non-small cell lung cancer patients. DAPK1 promoter methylation might play a significant role in the progression of chronic myeloid leukemia ( CML ).

Serine Threonine-Protein Phosphatase PP1-Υ Catalytic Subunit (PPP1CC) is a member of the PPP phosphatase family. It is essential for cell division, participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. PPP1CC colocalizes with SPZ1 in the nucleus, with URI1 at mitochondrion, Rapidly exchanges between the nucleolar, nucleoplasmic and cytoplasmic compartments. As a cofactor, PPP1CC binds one iron ion and one manganese ion per subunit.. In addition, PPP1CC may play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca2+ calmodulin dependent protein kinase II.

Calcium calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis.

Glutamate decarboxylase 1, also known as 67 kDa glutamic acid decarboxylase, Glutamate decarboxylase 67 kDa isoform and GAD1, is a member of thegroup II decarboxylase family. GAD1 is expressed in benign and malignant prostatic tissue and may serve as a highly prostate-specific tissue biomarker. GAD1 isoform3 is expressed in pancreatic islets, testis, adrenal cortex, and perhaps other endocrine tissues, but not in brain. Tissue-specific markers are useful for identification of tumour type in advanced cancers of unknown origin. In plants, as in most eukaryotes, glutamate decarboxylase catalyses the synthesis of GABA. Root-specific calcium calmodulin-regulated GAD1 plays a major role in GABA synthesis in plants under normal growth conditions and in response to stress. Defects in GAD1 are the cause of cerebral palsy spastic quadriplegic type 1 (CPSQ1)which is a non-progressive disorder of movement and or posture resulting from defects in the developing central nervous system. Affected individuals manifest symmetrical, non-progressive spasticity and no adverse perinatal history or obvious underlying alternative diagnosis.

Binds calmodulin in a calcium dependent manner. May function as scaffolding or signaling protein. Striatin-3 Protein, Human, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 93.2 kDa and the accession number is Q13033.

Has some calmodulin-like activity with respect to enzyme activation and growth regulation. Binds two calcium ions.

Has some calmodulin-like activity with respect to enzyme activation and growth regulation. Binds two calcium ions. OM Protein, Rat, Recombinant (His) is expressed in yeast with N-10xHis tag. The predicted molecular weight is 14.5 kDa and the accession number is P02631.

PPP3R1 belongs to the calcineurin regulatory subunit family. It is a regulatory subunit of calcineurin. Calcineurin is composed of two subunits: calcineurin A (CnA) and calcineurin B (CnB). Dephosphorylation of the nuclear factor of activated T-cells (NF-AT) by Calcineurin is essential for NF-AT activation, nuclear translocation, and early gene expression in T-cells. PPP3R1 is a Ser Thr-specific calcium and calmodulin-dependent protein phosphatase which takes a vital part in the T cell activation pathway. PPP3R1 is involved in protein dephosphorylation, NFAT protein import into nucleus (ortholog) and epithelial to mesenchymal transition (ortholog). It participates in calcineurin signaling pathway; mitogen activated protein kinase signaling pathway. PPP3R1 interacts with (+)-pilocarpine, 2,4-dinitrotoluene and ammonium chloride. It contains four EF-hand domains and four functional calcium-binding sites. PPP3R1 plays an important role in the T cell activation pathway.

CABP3, also known as CABP5, belongs to a subfamily of calcium binding proteins, which share similarity to calmodulin. Calcium binding proteins are an important component of calcium mediated cellular signal transduction. Expression of CABP3 gene is retina-specific. The mouse homolog of CABP3 has been shown to express in the inner nuclear layer of the retina, suggested its role in neuronal functioning. The specific function of CABP3 gene is unknown. Study of the transcripts and genomic structure revealed that the 5 end of this gene is complementary and reverse to that of the CABP5 gene, and the sequence beyond the overlapping region is nearly identical to that of CABP5. Thus, these two genes encode the protein products with distinct N-terminal halves but identical C-terminal halves. CABP3 inhibits calcium-dependent inactivation of L-type calcium channel and shifts voltage dependence of activation to more depolarized membrane potentials. It is also involved in the transmission of light signals.

Glycoprotein VI (GPVI) is a 63 kDa platelet megakaryocyte-specific type I transmembrane glycoprotein of the immunoglobulin superfamily that is an important collagen receptor and initiator of platelet activation, aggregation and thrombin generation. GPVI is also a secondary receptor required for platelet spreading on laminin. GPVI associates with the Fc receptor gamma -chain via charged aa in the TM domains of GPVI (arginine) and the FcR gamma (aspartic acid). Collagen binding by the GPVI Ig-like domains initiates signaling through the FcR gamma ITAM sequence. Dimerization of GPVI (2:2 with FcR gamma ) and N-glycosylation greatly enhances collagen binding. Type I and III collagens are strong thrombus-forming components in the vascular subendothelium and atherosclerotic plaques. GPVI initiates binding to fibrillar collagens under flow conditions, then activates integrin alpha 2 beta 1 which binds collagen more tightly. GPVI deficiencies cause only a mild bleeding tendency, probably because integrin alpha 2 beta 1 is able to minimally initiate collagen binding. Normal human GPVI concentration can vary widely and affect maximum thrombin generation. Engagement of GPVI by collagens or other agonists, including autoantibodies, causes calmodulin-regulated metalloproteinase cleavage of the 57 kDa ECD and depletes surface GPVI.

Endothelial Differentiation-Related Factor 1 (EDF1) is a 148 amino acid transcriptional coactivator that contains 1 HTH cro C1-type DNA-binding domain. It has been postulated that the protein functions as a bridging molecule that interconnects regulatory proteins and the basal transcriptional machinery, thereby modulating the transcription of genes involved in endothelial differentiation. When endothelial cells are induced to differentiate in vitro, EDF1 is downregulated, leading to inhibition of cell growth and cell polarization. EDF1 binds calmodulin thorough its IQ domain and regulates nitric oxide synthase activity through calmodulin sequestration in the cytoplasm. Though ubiquitously expressed, EDF1 is most abundant in adult liver, heart, adipose tissues, intestine and pancreas. In fetal tissues, EDF1 is most abundant in kidney. There are two isoforms of EDF1 that are produced as a result of alternative splicing events.

Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane.