phosphorylation

Dual specificity tyrosine-phosphorylation-regulated kinase 3, also known as Regulatory erythroid kinase, REDK and DYRK3, is a nucleus protein which belongs to theprotein kinase superfamily, CMGC Ser Thr protein kinase family and MNB DYRK subfamily. DYRKs are an emerging family of dual-specificity kinases that play key roles in cell proliferation, survival, and development. DYRK3 contains oneprotein kinase domain. Isoform 1 and isoform 2 of DYRK3 are highly expressed in testis and in hematopoietic tissue such as fetal liver, and bone marrow. Isoform 2 of DYRK3 is the predominant form in testis. Isoform 1 of DYRK3 is the predominant form in fetal liver and bone marrow. Isoform 1 and isoform 2 are present at low levels in heart, pancreas, lymph node, and thymus. DYRK3 is a negative regulator of EPO-dependent erythropoiesis. It may place an upper limit on red cell production during stress erythropoiesis. DYRK3 inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells. It may also act by regulating CREB CRE signaling. DYRK3 proved to effectively inhibit NFAT (nuclear factor of activated T cells) transcriptional response pathways and to co-immunoprecipitate with NFATc3. DYRK3 attenuates (and possibly apportions) red cell production selectively during anemia.

The IL12 receptor complex, formed by IL12RB1 and IL12RB2, mediates the type I immune responses of various types of lymphocytes. Its ligand, IL12, is a heterodimeric cytokine composed of IL-12p35 and IL-12p40 subunits that are linked via disulfide bonds. Ligation of IL-12 to its receptor involves the binding of IL-12p35 to IL12RB1 and IL-12p40 to IL12RB2. This will result in the activation of tyrosine kinase 2 (TYK2), which is associated with the IL12RB1 chain and Janus kinase 2 (JAK2), which is associated with the IL12RB2 chain. Activated TYK2 and JAK2 direct the phosphorylation of STAT4. IL12RB1 is present on all lymphocytes, while the expression of IL12RB2 is tightly regulated. It has shown that the expression of IL12RB2 is limited to Th2 cells. IL12RB2 subunit plays an important role in Th1 cell differentiation, since its absence leads to an abortive Th1 differentiation that has dysfunctional production of Th1 effector molecules.

EphA8, also known as Hek3 and Eek, is a 120 kDa glycosylated member of the Eph family of transmembrane receptor tyrosine kinases. The A and B classes of Eph proteins are distinguished by Ephrin ligand binding preference but have a common structural organization. Eph-Ephrin interactions are widely involved in the regulation of cell migration, tissue morphogenesis, and cancer progression. Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system plays also a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth.

Activin proteins that belong to the transforming growth factor-beta (TGF-β) superfamily, exert their biological actions by binding to heteromeric receptor complexes of type I and type II serine threonine kinase receptors. On ligand binding, type I and II receptors form a stable complex, resulting in phosphorylation of type I receptors by type II receptors with constitutive kinase activity, and subsequently initiates the activation of downstream molecules including the endogenous Smads. ActRIIB, also known as ActRIIB, is a type II receptor containing an extracellular domain (ECD), a transmembrane segment, and a cytoplasmic region that includes the kinase domain. ActRIIB is a receptor for activin A, activin B and inhibin A. Multiple ActRIIB isoforms can also be generated, which bind activin isoforms with different affinities.

Interleukin 11 (IL-11) is a member of a family of human growth factors that includes human growth hormone, granulocyte colony-stimulating factor, and other growth factors. IL-11 is a thrombopoietic growth factor that directly stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induces megakaryocyte maturation resulting in increased platelet production. It also promotes the proliferation of hepatocytes in response to liver damage. Binding to its receptor formed by IL6ST and either IL11RA1 or IL11RA2, It activates a signaling cascade that promotes cell proliferation. The signaling leads to the activation of intracellular protein kinases and the phosphorylation of STAT3.

SLAM Family Member 6 (SLAMF6) is a 60 kD single-pass type I membrane protein that belongs to the SLAM subgroup of the CD2 family. Human SLAMF6 NTB-A contains a 205 amino acid extracellular domain (ECD) with one Ig-like V-set and one Ig-like C2-set domain, a 21 amino acid transmembrane segment and an 84 amino acid cytoplasmic domain, with two immunoreceptor tyrosine-based switch motifs. SLAMF6 is a homodimer. SLAMF6 can interact with PTN6 and, upon phosphorylation, with PTN11 and SH2D1A SAP. Phosphorylation-dependent NTB-A association with SAP is required for full production of IFN-γ by NK cells and independent of EAT-2 binding. It Triggers cytolytic activity only in natural killer cells (NK) expressing high surface densities of natural cytotoxicity receptors. On B cells, NTB-A modulates immunoglobulin class switching and the balance between tolerance and autoimmunity.

Signal Transducer and Activator of Transcription 5b (STAT5B) is a member of the STAT family of transcription factors. They are responsible for an array of cellular activities including regulating growth, survival, differentiation, motility, and the immune response. STAT5B mediates the signal transduction triggered by various cell ligands, such as IL2, IL4, CSF1, and different growth hormones. It has been shown to be involved in diverse biological processes, such as TCR signaling, apoptosis, adult mammary gland development, and sexual dimorphism of liver gene expression. Signal transduction and activator of transcription 5 (STAT5) is a member of the Jak STAT signal transduction pathway and is activated by a variety of cytokines (IL22, IL6). STAT5 has two isoforms (A and B) that share 93% amino acid identity and bind the DNA consensus site TTCN3GAA. STAT5 mediates cytokine signaling by acting as a signal transducer in the cytoplasm and, upon phosphorylation, translocates to the nucleus and activates transcription of specific genes. STAT5 is involved in a wide array of biological processes ranging from regulating apoptosis to adult mammary gland proliferation, differentiation and survival.

Visinin-Like Protein 1 (VILIP) is a a member of the Visinin Recoverin subfamily of neuronal calcium sensor proteins. VILIP is strongly expressed in the Granule Cells of the Cerebellum where it associates with membranes in a Calcium-dependent manner and modulates intracellular signaling pathways of the central nervous system by directly or indirectly regulating the activity of Adenylyl Cyclase. It has been shown that VILIP regulates the inhibition of rhodopsin phosphorylation in a Calcium-dependent manner in vitro.

Peroxiredoxin-4 (PRDX4) is a member of the AhpC TSA family. PRDX4 is a cytoplasmic protein and contains one thioredoxin domain. PRDX4 exists in homodimer or heterodimer with PRDX1. PRDX4 reduces hydrogen peroxide and alkyl hydroperoxides to water and alcohol with the use of reducing equivalents derived from thiol-containing donor molecules. In addition, PRDX4 is probably involved in redox regulation of the cell, regulating the activation of NF-kappa-B in the cytosol by a modulation of I-kappa-B-alpha phosphorylation.

Semaphorin-4A (SEMA4A) belongs to the semaphorin family which contains a Ig-like C2-type domain, a PSI domain and a Sema domain. SEMA4A is expressed from day 10 in the embryo, and low levels are found between days 10-12. SEMA4A is a cell surface receptor for PLXNB1, PLXNB2, PLXNB3 and PLXND1 that plays an important role in cell-cell signaling. It plays a role in priming antigen-specific T-cells, promotes differentiation of Th1 T-helper cells, and thereby contributes to adaptive immunity. SEMA4A promotes phosphorylation of TIMD2, inhibits angiogenesis, and promotes axon growth cone collapse, Inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons.

ErbB2, also called Neu and Her2 (human epidermal growth factor receptor 2), is a type I membrane glycoprotein that is a member of the ErbB family of tyrosine kinase receptors. ErbB family members serve as receptors for the epidermal growth factor (EGF) family of growth factors.Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane.

Phosphorylation of dTMP to form dTDP in both de novo and salvage pathways of dTTP synthesis. Thymidylate kinase Protein, Bacillus anthracis, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 27.8 kDa and the accession number is C3LJ02.

Binds and activates TIE2 receptor by inducing its tyrosine phosphorylation. Implicated in endothelial developmental processes later and distinct from that of VEGF. Appears to play a crucial role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme. Mediates blood vessel maturation stability. It may play an important role in the heart early development. Angiopoietin-1 Protein, Canine, Recombinant (HEK293, His) is expressed in HEK293 mammalian cells with C-6xHis tag. The predicted molecular weight is 58.8 kDa and the accession number is Q60FC1.

Diacylglycerol kinase that converts diacylglycerol DAG into phosphatidic acid phosphatidate PA and regulates the respective levels of these two bioactive lipids. Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes. Also plays an important role in the biosynthesis of complex lipids (Probable). Can also phosphorylate 1-alkyl-2-acylglycerol in vitro as efficiently as diacylglycerol provided it contains an arachidonoyl group. Also involved in the production of alkyl-lysophosphatidic acid, another bioactive lipid, through the phosphorylation of 1-alkyl-2-acetyl glycerol.

Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines. HNRNPM Protein, Human, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 93.4 kDa and the accession number is P52272.

Lectin that specifically recognizes microbial carbohydrate chains in a calcium-dependent manner. Binds to microbial glycans that contain a terminal acyclic 1,2-diol moiety, including beta-linked D-galactofuranose (beta-Galf), D-phosphoglycerol-modified glycans, D-glycero-D-talo-oct-2-ulosonic acid (KO) and 3-deoxy-D-manno-oct-2-ulosonic acid (KDO). Binds to glycans from Gram-positive and Gram-negative bacteria, including K.pneumoniae, S.pneumoniae, Y.pestis, P.mirabilis and P.vulgaris. Does not bind human glycans. Probably plays a role in the defense system against microorganisms (Probable). May function as adipokine that has no effect on basal glucose uptake but enhances insulin-stimulated glucose uptake in adipocytes. Increases AKT phosphorylation in the absence and presence of insulin. May interact with lactoferrin LTF and increase its uptake, and may thereby play a role in iron absorption.

Probable regulator of the Hippo SWH (Sav Wts Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo SWH (Sav Wts Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP DCAF1 E3 ubiquitin-protein ligase complex.

Acts as a coactivator of transcriptional activity. Required to increase TGFB1 Smad-mediated transactivation. Acts through SMAD2, SMAD3 and SMAD4 to increase transcriptional activity. Increases phosphorylation of SMAD2 and SMAD3 on their C-terminal SSXS motif, possibly through recruitment of TGFBR1. Promotes the nuclear accumulation of SMAD2, SMAD3 and SMAD4 proteins. Binds to poly(A) RNA. RBPMS Protein, Human, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 28.8 kDa and the accession number is Q93062.

GTP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of GTP and thus represents the only step of substrate-level phosphorylation in the TCA. The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit. SUCLG2 Protein, Human, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 56.3 kDa and the accession number is Q96I99.

Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.

Acts as a ligand for the urokinase plasminogen activator surface receptor. Plays a role in angiogenesis by inducing endothelial cell migration and the formation of vascular network (cords). Involved in cellular migration and adhesion. Increases the phosphorylation levels of FAK. Interacts with and increases the mitogenic activity of HGF. Promotes synapse formation. Required for ultrasonic vocalizations. SRPX2 Protein, Mouse, Recombinant (His & Myc & SUMO) is expressed in E. coli expression system with N-10xHis-SUMO and C-Myc tag. The predicted molecular weight is 70.5 kDa and the accession number is Q8R054.

Plays an important role in regulating cell division and growth by reversible phosphorylation signaling. May play important roles in regulating cellular metabolism and signaling pathways, which could mediate the growth and development of the cell. Plays a role in establishing and maintaining infection.

Receptor for chemoattractant adipokine chemerin RARRES2 suggesting a role for this receptor in the regulation of inflammation and energy homesotasis. Signals mainly via beta-arrestin pathway. Binding of RARRES2 activates weakly G proteins, calcium mobilization and MAPK1 MAPK3 (ERK1 2) phosphorylation too. Acts also as a receptor for TAFA1, mediates its effects on neuronal stem-cell proliferation and differentiation via the activation of ROCK ERK and ROCK STAT3 signaling pathway.

Dentin matrix acidic phosphoprotein (DMP1) is an extracellular matrix protein and a member of the small integrin binding ligand N-linked glycoprotein family. This protein, which is critical for proper mineralization of bone and dentin, is present in diverse cells of bone and tooth tissues. DMP1 contains a large number of acidic domains, multiple phosphorylation sites, a functional arg-gly-asp cell attachment sequence, and a DNA binding domain. In undifferentiated osteoblasts it is primarily a nuclear protein that regulates the expression of osteoblast-specific genes. During osteoblast maturation, DMP1 becomes phosphorylated and is exported to the extracellular matrix, where it orchestrates mineralized matrix formation. Mutations in DMP1 are known to cause autosomal recessive hypophosphatemia, a disease that manifests as rickets and osteomalacia. DMP1 may have a dual function during osteoblast differentiation. In the nucleus of undifferentiated osteoblasts, unphosphorylated form acts as a transcriptional component for activation of osteoblast-specific genes like osteocalcin. During the osteoblast to osteocyte transition phase it is phosphorylated and exported into the extracellular matrix, where it regulates nucleation of hydroxyapatite.

The three fibronectin leucine-rich repeat transmembrane (FLRT) proteins contain 10 leucine-rich repeats (LRR), a type III fibronectin (FN) domain, followed by the transmembrane region, and a short cytoplasmic tail. FLRT1 is expressed in kidney and brain, which is a target for tyrosine phosphorylation mediated by FGFR1 and implicates a non-receptor Src family kinase (SFK). All FLRTs can interact with FGFR1 and FLRTs can be induced by the activation of FGF signalling by FGF-2. The phosphorylation state of FLRT1, which is itself FGFR1 dependent, may play a critical role in the potentiation of FGFR1 signalling and may also depend on a SFK-dependent phosphorylation mechanism acting via the FGFR. This is consistent with an 'in vivo' role for FLRT1 regulation of FGF signalling via SFKs. Furthermore, the phosphorylation-dependent futile cycle mechanism controlling FGFR1 signalling is concurrently crucial for regulation of FLRT1-mediated neurite outgrowth. FLRT1, FLRT2 and FLRT3 are members of the fibronectin leucine rich transmembrane protein (FLRT) family. They may function in cell adhesion and or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. FLRT3 shares 55% amino acid sequence identity with FLRT1.

PHPT1, also known as 14 kDa phosphohistidine phosphatase, phosphohistidine phosphatase 1, protein janus-A homolog, PHP14, is a cytoplasm protein which belongs to the janus family. PHPT1 PHP14 is expressed abundantly in heart and skeletal muscle. Phosphatases are a diverse group of enzymes that regulate numerous cellular processes. Much of what is known relates to the tyrosine, threonine, and serine phosphatases, whereas the histidine phosphatases have not been studied as much. Protein histidine phosphorylation exists widely in vertebrates, and it plays important roles in signal transduction and other cellular functions. Protein histidine phosphorylation accounts for about 6% of the total protein phosphorylation in eukaryotic cells. The knowledge about eukaryotic PHPT (protein histidine phosphatase) is still very limited. To date, only one vertebrate PHPT has been discovered, and two crystal structures of human PHPT1 have been solved. PHPT1 PHP14 can dephosphorylate a variety of proteins (e.g. ATP-citrate lyase and the beta-subunit of G proteins). A putative active site has been identified by its electrostatic character, ion binding, and conserved protein residues.

Integrin-linked kinase-associated serine threonine phosphatase 2C, also known as ILKAP, is a cytoplasm protein that belongs to the PP2C family. ILKAP contains one PP2C-like domain. ILKAP is widely expressed. Highest levels expressed in striated muscle. Much lower levels are evident in various smooth muscle tissues. ILKAP may play a role in the regulation of cell cycle progression via dephosphorylation of its substrates whose appropriate phosphorylation states might be crucial for cell proliferation. ILKAP selectively associates with integrin-linked kinase (ILK), to modulate cell adhesion and growth factor signaling. ILKAP inhibits the ILK-GSK3B signaling axis and may play an important role in inhibiting oncogenic transformation. Integrin-linked kinase ( ILK ) plays key roles in a variety of cell functions, including cell proliferation, adhesion, and migration. Within the cell, ILK localizes to multiple sites, including the cytoplasm, focal adhesion complexes that mediate cell adhesion to extracellular substrates, as well as cell-cell junctions in epidermal keratinocytes. Nuclear ILK can be rapidly exported into the cytoplasm through a CRM1-dependent pathway, and its export is enhanced by the type 2C protein phosphatase ILKAP. Nuclear localization of ILK in epidermal keratinocytes is associated with increased DNA synthesis, which is sensitive to inhibition by ILKAP.

Ubiquitin-conjugating enzyme E2 A (also known as HHR6A or UBE2A), encoded by human DNA repair genes HHR6A, belongs to the ubiquitin-conjugating enzymes (E2 enzymes) family and is likely to be involved in postreplication repair and induced mutagenesis. UBE2A is described as a CDK2 substrate. It is the human homologue of the product of the Saccharomyces cerevisiae RAD6 UBC2 gene, a member of the family of ubiquitin-conjugating enzymes. In vivo, HHR6A phosphorylation peaks during the G2 M phase of cell cycle transition, with a concomitant increase in histone H2B ubiquitylation. Mutation of Ser120 to threonine or alanine abolished UBE2A activity, while mutation to aspartate to mimic phosphorylated serine increased UBE2A activity 3-fold. A mutation of UBE2A is considered as the cause of a novel X-linked mental retardation (XLMR) syndrome that affects three males in a two-generation family.

Annexin A6, also known as ANXA6 or ANXAⅥ, belongs to a family of Ca2+-dependent membrane and phospholipid binding proteins. Members of this family have been implicated in membrane-related events along exocytotic and endocytotic pathways. Annexin 6 is phosphorylated in vivo associated with cell growth. Annexin 6 was not phosphorylated in quiescent cells, but was phosphorylated on serine and to a lesser extent threonine, several hours following cell stimulation. Experiment has revealed the presence of annexin A6 on the cell surface of variety cells as putative receptors and or binding proteins for chondroitin sulfate proteoglycans, helping cells to bind with this extracellular matrix glycosaminoglycan chondroitin sulfate which is related to the cell-substratum adhesion. A post-tranlational modification other than direct protein phosphorylation may influence the activity of annexin6 and provide evidence linking cell growth with regulation of annexin 6 function.

Ribonucleoside reductase subunit M2B, also known as RRM2B or p53R2, is an enzyme belonging to the iron-dependent ribonucleotide reductase (RNR) enzyme family which is essential for DNA synthesis. Ribonucleotide reductase (RNR) is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides and plays a critical role in regulating the total rate of DNA synthesis so that DNA to cell mass is maintained at a constant ratio during cell division and DNA repair. RRM2B is a phosphorylated protein. It is hypothesized that RRM2B activity can be regulated at the posttranslational level in response to DNA damage. RRM2B has previously been shown to be essential for the maintenance of mtDNA copy number and its candidacy for tumor suppression has been evaluated in several mutational analyses of different cancer types. However, the contribution of RRM2B to the DNA damage response has been questioned because its transcriptional induction upon DNA damage is not rapid enough for prompt DNA repair. Instead, ATM-mediated phosphorylation has been suggested to regulate the DNA repair activity of RRM2B posttranslationally. Besides, a defect in RRM2B can induce a mild muscle disease of adult onset through disturbance of mitochondrial homeostasis but that this defect does not appear to be oncogenic.

PRC1 (protein regulator of cytokinesis 1) is a key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. It is essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. PRC1 is required for KIF14 localization to the central spindle and midbody. It is also required to recruit PLK1 to the spindle. PRC1 stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle. It is a homodimer and interacts with the C-terminal Rho-GAP domain and the basic region of RACGAP1. The interaction with RACGAP1 inhibits its GAP activity towards CDC42 in vitro, which may be required for maintaining normal spindle morphology. PRC1 also interacts separately via its N-terminal region with the C-terminus of CENPE, KIF4A and KIF23 during late mitosis. It interacts with KIF14, IF20A and PLK1.

UBASH3B contains a ubiquitin associated domain at the N-terminus, an SH3 domain, and a C-terminal domain with similarities to the catalytic motif of phosphoglycerate mutase. UBASH3B was found to inhibit endocytosis of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor. UBASH3B interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases. It promotes accumulation of activated target receptors, such as T-cell receptors and EGFR, on the cell surface. UBASH3B exhibits tyrosine phosphatase activity toward several substrates including EGFR, FAK, SYK, and ZAP7. Down-regulates proteins that are dually modified by both protein tyrosine phosphorylation and ubiquitination.

The histone chaperone anti-silencing factor 1a (ASF1a) interacts with MDC1 and is recruited to sites of DSBs to facilitate the interaction of phospho-ATM with MDC1 and phosphorylation of MDC1, which are required for the recruitment of RNF8 RNF168 histone ubiquitin ligases. Thus, ASF1a deficiency reduces histone ubiquitination at DSBs, decreasing the recruitment of 53BP1, and decreases NHEJ, rendering cells more sensitive to DSBs. This role of ASF1a in DSB repair cannot be provided by the closely related ASF1b and does not require its histone chaperone activity. Homozygous deletion of ASF1A is seen in 10%-15% of certain cancers, suggesting that loss of NHEJ may be selected in some malignancies and that the deletion can be used as a molecular biomarker for cancers susceptible to radiotherapy or to DSB-inducing chemotherapy. Anti-silencing function 1 (ASF1) is a histone H3-H4 chaperone involved in DNA replication and repair, and transcriptional regulation. Here, we identify ASF1B, the mammalian paralog to ASF1, as a proliferation-inducing histone chaperone in human β-cells. Overexpression of ASF1B led to distinct transcriptional signatures consistent with increased cellular proliferation and reduced cellular death.

Tribbles homolog 3, also known as Neuronal cell death-inducible putative kinase, p65-interacting inhibitor of NF-kappa-B, SINK and TRIB3, is a Nucleus protein that belongs to the protein kinase superfamily and CAMK Ser Thr protein kinase family and Tribbles subfamily. Highest expression Of TRIB3 is in liver, pancreas, peripheral blood leukocytes and bone marrow. It is also highly expressed in a number of primary lung, colon and breast tumors. TRIB3 is expressed in spleen, thymus, and prostate and is undetectable in other examined tissues, including testis, ovary, small intestine, colon, leukocyte, heart, brain, placenta, lung, skeletal muscle, and kidney. TRIB3 disrupts insulin signaling by binding directly to Akt kinases and blocking their activation. TRIB3 may bind directly to and mask the 'Thr-38' phosphorylation site in AKT1. It binds to ATF4 and inhibits its transcriptional activation activity. TRIB3 interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity. It interacts with MAPK kinases and regulates activation of MAP kinases. It may play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells. TRIB3 does not display kinase activity.

Serine threonine-protein kinase SRPK1, also known as SFRS protein kinase 1, Serine arginine-rich protein-specific kinase 1, SR-protein-specific kinase 1 and SRPK1, is a cytoplasm and nucleus protein that belongs to the protein kinase superfamily and CMGC Ser Thr protein kinase family. Isoform 2 of SRPK1 is predominantly expressed in the testis but is also present at lower levels in heart, ovary, small intestine, liver, kidney, pancreas and skeletal muscle. Isoform 1 of SRPK1 is only seen in the testis, at lower levels than isoform 2. SRPK1 hyperphosphorylates RS domain-containing proteins such as SFRS1, SFRS2 and ZRSR2 on serine residues during metaphase but at lower levels during interphase. SRPK1 plays a central role in the regulatory network for splicing, controlling the intranuclear distribution of splicing factors in interphase cells and the reorganization of nuclear speckles during mitosis. SRPK1 locks onto SFRS1 to form a stable complex and processively phosphorylates the RS domain. SRPK1 appears to mediate HBV core protein phosphorylation which is a prerequisite for pregenomic RNA encapsidation into viral capsids.

PS6K, also known as RPS6KB1, is a serine threonine-protein kinase. It belongs to the RSK (ribosomal s6 kinase) family. Members of this family function in signal transduction. PS6K is an isoform of p70 ribosomal S6 kinase (S6K). S6K can be activated by mitogenic stimuli such as growth factors, insulin and cytokines. It phosphorylates the ribosomal protein S6. PS6K also phosphorylates other proteins such as elF4B, eEF2K and SKAR. It is a crucial effector of mTOR(rapamycin) signaling. PS6K is dissociated from the EIF3 complex and activated upon mitogenic stimulation, phosphorylation by the mammalian target of mTOR complex 1 (mTORC1). Its active form then phosphorylates and activates several substrates in the preinitiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. PS6K also functions in cell proliferation, cell growth and cell cycle progression.

FGF (fibroblast growth factor) signalling is known to be required for many aspects of mesoderm formation and patterning during Xenopus development and has been implicated in regulating genes required for the specification of both blood and skeletal muscle lineages. Fibroblast growth factor 4 (FGF4) signaling induces differentiation from embryonic stem cells (ESCs) via the phosphorylation of downstream molecules such as mitogen-activated protein kinase extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1 2 (ERK1 2). Fibroblast Growth Factor 4 (FGF-4) could not only increase the proliferation of bone marrow mesenchymal stem cells (BMSCs), but also induce BMSCs into hepatocyte-like cells in vitro. FGF4 transduced BMSCs contributed to liver regeneration might by the transplanted microenvironment. The FGF4-bFGF BMSCs thus can enhance the survival of the transplanted cells, diminish myocardial fibrosis, promote myocardial angiogenesis, and improve cardiac functions.

NFKBIB (NFKB Inhibitor Beta) is a Protein Coding gene. The protein encoded by this gene belongs to the NF-kappa-B inhibitor family, which inhibits NF-kappa-B by complexing with and trapping it in the cytoplasm. Phosphorylation of serine residues on these proteins by kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation of the NF-kappa-B, which translocates to the nucleus to function as a transcription factor. NF-kappaB regulation involves the inhibitor protein NFKBIB, which form complexes with NF-kappaB to sequester it in the cytoplasm. Overexpression of NFKBIB protein in IAV infected cells led to lower levels of IAV. MiR-20a could promote activation of the NFkappaB pathway and downstream targets Livin and Survivin by targeting NFKBIB, which potentially contributed to GC chemoresistance.

Synapse-associated protein 1 (SYAP1), also known as PRO3113 and BSTA, belongs to the synapse-associated BSD domain family, featuring three α-helices and two conserved tryptophan and phenylalanine residues located at the C-terminus. Expressed near neuronal Golgi and synaptic regions of cerebellar Purkinje cells, SYAP1 has been linked to intact sensorimotor control and general vesicular trafficking in neurons. SYAP1-deficient mice display impaired locomotor activity. In cultured adipocytes, SYAP1 facilitates mTORC2-mediated phosphorylation of protein kinase Akt1 and adipocyte differentiation. Chromosomal band Xp22.2 houses the human SYAP1 gene, a region associated with developmental delay and autism spectrum disorder. SYAP 1 may be a target for future cancer therapies as it was induced by tamoxifen in breast cancer cells sensitive to tamoxifen growth inhibition.

Viral mimic of eIF-2-alpha that acts as a pseudosubstrate for EIF2AK2 PKR kinase. Inhibits therefore eIF-2-alpha phosphorylation by host EIF2AK2 PKR kinase and prevents protein synthesis shutoff. Vaccinia virus (strain Western Reserve) K3 Protein (His) is expressed in yeast with N-6xHis tag. The predicted molecular weight is 12.6 kDa and the accession number is P18378.

Tousled-like kinase 1 (or protein kinase ubiquitous, PKU-beta TLK1) is a serine threonine protein kinase that is implicated in chromatin remodeling, DNA replication and mitosis. TLK1 has a function important for proper chromosome segregation and maintenance of diploid cells at mitosis in mammalian cells that could be mediated by reduced phosphorylation of histone H3 and condensation of chromosomes, although other explanations to the phenotype are possible.

PFK1, also known as PFKM, is a regulatory glycolytic enzyme. PFK1 converts fructose 6-phosphate and ATP into fructose 1,6-bisphosphate (through PFK-1), fructose 2,6-bisphosphate (through PFK-2) and ADP. It is a muscle-type isozyme. There are three phosphofructokinase isozymes in humans: muscle, liver and platelet. These isozymes function as subunits of the mammalian tetramer phosphofructokinase, which catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate. Mutations in PFK1 gene have been related to glycogen storage disease type VII, also identified as Tarui disease.

CARKL, also known as SHPK, is a nonprotein kinase of glucose metabolism. CARKL has weak homology to several carbohydrate kinases, a class of proteins involved in the phosphorylation of sugars as they enter a cell, inhibiting return across the cell membrane. CARKL catalyzes an orphan reaction in the pentose phosphate pathway, refocusing cellular metabolism to a high-redox state upon physiological or artificial downregulation. CARKL-dependent metabolic reprogramming is required for proper M1- and M2-like macrophage polarization and uncover a rate-limiting requirement for appropriate glucose flux in macrophage polarization.

G protein-coupled receptor kinase 6, also known as G protein-coupled receptor kinase GRK6, GRK6, and GPRK6, is a lipid-anchor protein that belongs to the protein kinase superfamily, AGC Ser Thr protein kinase family, and GPRK subfamily. GRK6 GPRK6 contains one AGC-kinase C-terminal domain, one protein kinase domain, and one RGS domain. This protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. Several transcript variants encoding different isoforms have been described. GRK6 GPRK6 is widely expressed. GRK6 GPRK6 silencing causes suppression of signal transducer and activator of transcription 3 (STAT3) phosphorylation associated with a reduction in MCL1 levels and phosphorylation, illustrating a potent mechanism for the cytotoxicity of GRK6 inhibition in multiple myeloma (MM) tumor cells. GRK6 also appears to be involved in responses to morphine. Inhibition of GRK6 represents a uniquely targeted novel therapeutic strategy in human multiple myeloma.

Serine threonine-protein kinase D2, also known as PRKD2 and PKD2, is a cytoplasm and membrane protein that belongs to the protein kinase superfamily, CAMK Ser Thr protein kinase family and PKD subfamily. PRKD2 PKD2 is widely expressed. It contains one PH domain, two phorbol-ester DAG-type zinc fingers and one protein kinase domain. PRKD2 PKD2 is activated by DAG and phorbol esters. Phorbol-ester DAG-type domains bind DAG, mediating translocation to membranes. Autophosphorylation of Ser-71 and phosphorylation of Ser-76 by PKC relieves auto-inhibition by the PH domain. PRKD2 PKD2 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. Involved in resistance to oxidative stress.

Protein Phosphatase 1 Regulatory Subunit 1A (PPP1R1A) is an inhibitor of protein-phosphatase 1. PPP1R1A is a cellular regulator of eIF2 alpha phosphorylation. In hormonal control of glycogen metabolism, IPP-1 protein plays important function. Hormones can elevate intracellular cAMP level and elevate IPP-1 activity. PPP1R1A activation caused cAMP increase , cAMP control over proteins that are not directly phosphorylated by PKA following a rise in intracellular calcium. IPP-1 is inactivated by calcineurin (PP2B). Multiple domains in IPP-1 target cellular PP1 complexes.

Activin Receptor Type-2A is a protein that in humans is encoded by the ACVR2A gene. ACVR2A is an activin type 2 receptor. This gene encodes activin A type II receptor. Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I (I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine threonine specificity. Type I receptors are essential for signaling; and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in phosphorylation of type I receptors by type II receptors. Type II receptors are considered to be constitutively active kinases.

Interferon‑alpha beta receptor 1 (IFN‑ alpha beta R1), also known as IFNAR1, are present in all tissues and even on the surface of most IFN-resistant cells. Isoform 1, isoform 2 and isoform 3 are expressed in the IFN-alpha sensitive myeloma cell line U266B1. Isoform 2 and isoform 3 are expressed in the IFN-alpha resistant myeloma cell line U266R. Isoform 1 is not expressed in IFN-alpha resistant myeloma cell line U266R. It interacts with STAT1 and STAT2, the interaction requires its phosphorylation at Tyr-466. It also interacts with FBXW11, the substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex.