act 2

Monokine with inflammatory and chemokinetic properties.

Human protein N-terminal glutamine amidohydrolase (WDYHV1) is an enzyme that in humans is encoded by the WDYHV1 gene, belongs to the NTAQ1 family.WDYHV1 mediates the side-chain deamidation of N-terminal glutamine residues to glutamate, which is an important step in N-end rule pathway of protein degradation. Conversion of the resulting N-terminal glutamine to glutamate renders the protein susceptible to arginylation, polyubiquitination and degradation as specified by the N-end rule. However,it does not act on substrates with internal or C-terminal glutamine andnon-glutamine residues in any position. With the exception of proline, all tested second-position residues on substrate peptides do not greatly influence the activity. In contrast, a proline at position 2, virtually abolishes deamidation of N-terminal glutamine.

Signaling lymphocyte activation molecule (SLAM), is a self-ligand glycoprotein which exists not only found on the surface of activated and memory T cells, but also on the surface of activated B cells, dendritic cells, and macrophages. SLAM consists of a extracellular domain (ECD) with two Ig-like domains,transmembrane segment, and cytoplasmic domain with three immunoreceptor tyrosine switch motifs (ITSM). SLAM is thought to play an important role in adhesion between T cells and APCs and has been shown to act as a coreceptor in TCR-dependent responses. SLAM, together with CD46, is one of the two receptors for measles virus. SLAM is a cell surface receptor that, like the B cell receptor, CD40, and CD95, can transmit positive or negative signals. SLAM can associate with the SH2-containing inositol phosphatase (SHIP), the SH2-containing protein tyrosine phosphatase (SHP-2), and the adaptor protein SH2 domain protein 1A. It’s upregulated on activated B cells and CD4+ and CD8+ T cells, but downregulated on Th2 polarized cells. Also, it can Inhibits antigen receptor-mediated production of IFN-gamma, but not IL-2, in CD4- CD8- T-cells.

Acyl-Protein Thioesterase 1 (APT-1) is lysophospholipase that belongs to the AB hydrolase 2 family. Lysophospholipases are enzymes that act on biological membranes to regulate the multifunctional lysophospholipids. APT-1 performs on biological membranes to regulate the multifunctional lysophospholipids. It hydrolyzes lysophosphatidylcholine in both monomeric and micellar forms. It hydrolyzes fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS; in addition, it also has depalmitoylating activity and low lysophospholipase activity.

SLAMF6 (signaling lymphocyte activation molecule 6) (Ly108 in mice, NTB-A or SF2000 in humans) is a homophilic receptor belonging to the superfamily immunoglobulin (Ig) domain-containing molecules. It is known to be widely and exclusively expressed on hematopoietic cells. The SLAMF6 intracellular portion is characterized by two ITSMs that act as binding sites for adaptor molecules such as SAP and EAT-2. SLAMF6 Protein, Human, Recombinant (His & Avi) is expressed in HEK293 mammalian cells with C-His-Avi tag. The predicted molecular weight is 26 kDa and the accession number is Q96DU3-1.

SLAMF6 (signaling lymphocyte activation molecule 6) (Ly108 in mice, NTB-A or SF2000 in humans) is a homophilic receptor belonging to the superfamily immunoglobulin (Ig) domain-containing molecules. It is known to be widely and exclusively expressed on hematopoietic cells. The SLAMF6 intracellular portion is characterized by two ITSMs that act as binding sites for adaptor molecules such as SAP and EAT-2. SLAMF6 Protein, Mouse, Recombinant (aa 31-239, His) is expressed in HEK293 mammalian cells with C-His tag. The predicted molecular weight is 24.03 kDa and the accession number is Q9ET39-1.

Functions as key mediator in apoptosis and inflammation. Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner. Involved in activation of the mitochondrial apoptotic pathway, promotes caspase-8-dependent proteolytic maturation of BID independently of FADD in certain cell types and also mediates mitochondrial translocation of BAX and activates BAX-dependent apoptosis coupled to activation of caspase-9, -2 and -3. Involved in macrophage pyroptosis, a caspase-1-dependent inflammatory form of cell death and is the major constituent of the ASC pyroptosome which forms upon potassium depletion and rapidly recruits and activates caspase-1. In innate immune response believed to act as an integral adapter in the assembly of the inflammasome which activates caspase-1 leading to processing and secretion of proinflammatory cytokines. The function as activating adapter in different types of inflammasomes is mediated by the pyrin and CARD domains and their homotypic interactions. Required for recruitment of caspase-1 to inflammasomes containing certain pattern recognition receptors, such as NLRP2, NLRP3, AIM2 and probably IFI16. In the NLRP1 and NLRC4 inflammasomes seems not be required but facilitates the processing of procaspase-1. In cooperation with NOD2 involved in an inflammasome activated by bacterial muramyl dipeptide leading to caspase-1 activation. May be involved in DDX58-triggered proinflammatory responses and inflammasome activation. In collaboration with AIM2 which detects cytosolic double-stranded DNA may also be involved in a caspase-1-independent cell death that involves caspase-8. In adaptive immunity may be involved in maturation of dendritic cells to stimulate T-cell immunity and in cytoskeletal rearrangements coupled to chemotaxis and antigen uptake may be involved in post-transcriptional regulation of the guanine nucleotide exchange factor DOCK2; the latter function is proposed to involve the nuclear form. Also involved in transcriptional activation of cytokines and chemokines independent of the inflammasome; this function may involve AP-1, NF-kappa-B, MAPK and caspase-8 signaling pathways. For regulation of NF-kappa-B activating and inhibiting functions have been reported. Modulates NF-kappa-B induction at the level of the IKK complex by inhibiting kinase activity of CHUK and IKBK. Proposed to compete with RIPK2 for association with CASP1 thereby down-regulating CASP1-mediated RIPK2-dependent NF-kappa-B activation and activating interleukin-1 beta processing. Modulates host resistance to DNA virus infection, probably by inducing the cleavage of and inactivating CGAS in presence of cytoplasmic double-stranded DNA.

Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids. Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids with preference for phosphatidylcholines and phosphatidylglycerols over phosphatidylethanolamines. Preferentially releases sn-2 omega-6 and omega-3 polyunsaturated fatty acyl (PUFA) chains over saturated fatty acyls. Contributes to phospholipid remodeling of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles. Hydrolyzes LDL phospholipids releasing unsaturated fatty acids that regulate macrophage differentiation toward foam cells. Efficiently hydrolyzes and inactivates PAF, a potent lipid mediator present in oxidized LDL. May act in an autocrine and paracrine manner. Secreted by lung epithelium, targets membrane phospholipids of infiltrating eosinophils, releasing arachidonate and boosting eicosanoid and cysteinyl leukotriene synthesis involved in airway inflammatory response. Secreted by gut epithelium, hydrolyzes dietary and biliary phosphatidylcholines in the gastrointestinal lumen, thereby regulating adipogenesis and body weight. Plays a stem cell regulator role in colon epithelium. Within intracellular compartment, mediates Paneth-like cell differentiation and its stem cell supporting functions by inhibiting Wnt signaling pathway in intestinal stem cell (ISC). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates the Wnt signaling pathway in ISCs and tissue regeneration. May participate in hair follicle morphogenesis by regulating phosphatidylethanolamines metabolism at the outermost epithelial layer and facilitating melanin synthesis. By generating lysophosphatidylcholines (LPCs) at sperm acrosome controls sperm cell capacitation, acrosome reaction and overall fertility. May promote neurite outgrowth in neuron fibers involved in nociception. Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Cleaves sn-2 fatty acyl chains of phosphatidylglycerols and phosphatidylethanolamines, which are major components of membrane phospholipids in bacteria. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane. In pulmonary epithelium, may contribute to host defense response against adenoviral infection. Prevents adenovirus entry into host cells by hydrolyzing host cell plasma membrane, releasing C16:0 LPCs that inhibit virus-mediated membrane fusion and viral infection. Likely prevents adenoviral entry into the endosomes of host cells. May play a role in maturation and activation of innate immune cells including macrophages, group 2 innate lymphoid cells and mast cells.

DCX (doublecortin, N-GST chimera)contains 2 doublecortin domains and belongs to the doublecortin family. It is highly expressed in neuronal cells of fetal brain, but not expressed in other fetal tissues. In the adult, it is highly expressed in the brain frontal lobe, but very low expression in other regions of brain, and not detected in heart, placenta, lung, liver, skeletal muscles, kidney and pancreas. DCX is a microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. It may act by competing with the putative neuronal protein kinase DCAMKL1 in binding to a target protein. DCX may in that way participate in a signaling pathway that is crucial for neuronal interaction before and during migration, possibly as part of a calcium ion-dependent signal transduction pathway. It may be part with LIS-1 of a overlapping, but distinct, signaling pathways that promote neuronal migration. Defects in DCX are the cause of lissencephaly X-linked type 1 and subcortical band heterotopia X-linked.

DPY30 domain containing 2 belongs to the dpy-30 family. Dumpy-30 family members act as determinants of male fertility and interaction partners of metal-responsive transcription factor 1 (MTF-1) in Drosophila. MTF-1 plays a key role in transition metal detoxification and homeostasis. It binds to metal response elements (MREs). Two candidate dMTF-1 interactors are related to the small regulatory protein Dumpy-30 (Dpy-30) of the worm C. elegans. Dpy-30 is the founding member of a protein family involved in chromatin modifications, notably histone methylation. Mutants affect mating type in yeast and male mating in C. elegans. As part of the MLL1 MLL complex, DPY30 domain containing 2 is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. DPY30 domain containing 2 may also play an indirect or direct role in endosomal transport.

HDAC4 (histone deacetylase 4), belongs to class II of the histone deacetylase AcuC APhA family. Histone Deacetylases (HDACs) are a group of enzymes closely related to sirtuins. They catalyze the removal of acetyl groups from lysine residues in histones and non-histone proteins, resulting in transcriptional repression. In general, they do not act autonomously but as components of large multiprotein complexes, such as pRb-E2F and mSin3A, that mediate important transcription regulatory pathways. There are three classes of HDACs; classes 1, 2, and 4, which are closely related to Zn2+-dependent enzymes. HDACs are ubiquitously expressed and they can exist in the nucleus or cytosol. Their subcellular localization is affected by protein-protein interactions and by the class to which they belong. HDACs have a role in cell growth arrest, differentiation, and death and this has led to substantial interest in HDAC inhibitors as possible antineoplastic agents. HDAC4 possesses histone deacetylase activity and represses transcription when tethered to a promoter. It does not bind DNA directly but through transcription factors MEF2C and MEF2D. HDAC4 seems to interact in a multiprotein complex with RbAp48 and HDAC3.

Mitogen-activated protein kinase 8 (MAPK8), also known as JNK1, is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. The protein kinases JNK1 has been found to serve as critical molecular links between obesity, metabolic inflammation, and disorders of glucose homeostasis. It is critically involved in the promotion of diet-induced obesity, metabolic inflammation, and beta-cell dysfunction. The selective deficiency of JNK1 in the murine nervous system is sufficient to suppress diet-induced obesity. Genetic analysis indicates that the effects of JNK1 can be separated from the effects of JNK1 on obesity. JNK1 is a potential pharmacological target for the development of drugs that might be useful for the treatment of metabolic syndrome, and type 2 diabetes. Furthermore, JNK1 plays a major role in hypoxic cellular damage. JNK1 protein might be an attractive target for anti-hypoxic therapy in increasing resistance to many pathological conditions and diseases, leading to the oxygen deficit.

ATP1B4 is a member of the X(+) potassium ATPases subunit beta family. It is highly expressed in skeletal muscle and at a lower level in heart. ATP1B4 gene can be found in all vertebrate genomes sequenced to date. However, this gene has undergone a change in function in placental mammals compared to other species. Specifically, in fish, avian, and amphibian species, this gene encodes plasma membrane-bound beta-subunits of Na, K-ATPase. In placental mammals, the encoded protein interacts with the nuclear transcriptional coregulator SKIP and may be involved in the regulation of TGF-beta signaling. ATP1B4 may act as a transcriptional coregulator during muscle development through its interaction with SNW1. Na+, K+-ATPase is an important regulator of intracellular electrolyte levels in most mammalian cells. It is a Mg2+-dependent transport pump responsible for maintaining the low intracellular Na+:K+ ratio that is essential for cell homeostasis and physiological function. It catalyzes the active uptake of K+ and extrusion of Na+ at the expense of hydrolyzing ATP with a stoichiometry of 3 Na+ for 2 K+. ATP1B4 has lost its ancestral function as a Na,K-ATPase beta-subunit.

72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the MMP2 gene.It belongs to the matrix metalloproteinase (MMP) family. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade components of the extracellular matrix (ECM) and play essential roles in various physiological processes such as morphogenesis, differentiation, angiogenesis and tissue remodeling, as well as pathological processes including inflammation, arthritis, cardiovascular diseases, pulmonary diseases and tumor invasion. MMP-2 is ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, atherosclerotic plaque rupture, as well as degrading extracellular matrix proteins. MMP-2 can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. MMP-2 cleaves KISS at a Gly-|-Leu bond and appears to have a role in myocardial cell death pathways.

SMAD Family Member 4 (SMAD4) is a cytoplasmic protein that belongs to the Dwarfin SMAD family. SMAD4 contains one MH1 (MAD homology 1) domain and one MH2 (MAD homology 2) domain. It is the component of the heterotrimeric SMAD2 SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. SMAD4 promotes binding of the SMAD2 SMAD4 FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. SMAD4 may act as a tumor suppressor. It positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. Mutations or deletions in SMAD4 have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome.

GFER is a hepatotrophic growth factor and flavin-linked sulfhydryl oxidase which belongs to the Erv1 ALR family of proteins. GFER is widely expressed in various human tissues. They are two isoforms of this protein. Isoform 1 could regenerate the redox-active disulfide bonds in CHCHD4 MIA40, a chaperone essential for disulfide bond formation and protein folding in the mitochondrial intermembrane space. The reduced form of CHCHD4 MIA40 forms a transient intermolecular disulfide bridge with GFER ERV1, resulting in regeneration of the essential disulfide bonds in CHCHD4 MIA40, while GFER ERV1 becomes re-oxidized by donating electrons to cytochrome c or molecular oxygen. Isoform 2 may act as an autocrine hepatotrophic growth factor promoting liver regeneration. GFER could also induce the expression of S-adenosylmethionine decarboxyl-ase and ornithine decarboxylases (ODC). S-adenosylmethionine decarboxyl-ase and ornithine decarboxylases play an important role in the synthesis of polyamines.

Metalloproteinase inhibitor 4 is an enzyme that in humans is encoded by the TIMP4 gene, belongs to the protease inhibitor I35 (TIMP) family. The protein complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9.

Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses. Regulates transcription of IFN and IFN-inducible genes, host response to viral and bacterial infections, regulation of many genes expressed during hematopoiesis, inflammation, immune responses and cell proliferation and differentiation, regulation of the cell cycle and induction of growth arrest and programmed cell death following DNA damage. Stimulates both innate and acquired immune responses through the activation of specific target genes and can act as a transcriptional activator and repressor regulating target genes by binding to an interferon-stimulated response element (ISRE) in their promoters. Competes with the transcriptional repressor ZBED2 for binding to a common consensus sequence in gene promoters. Its target genes for transcriptional activation activity include: genes involved in anti-viral response, such as IFN-alpha beta, DDX58 RIG-I, TNFSF10 TRAIL, ZBP1, OAS1 2, PIAS1 GBP, EIF2AK2 PKR and RSAD2 viperin; antibacterial response, such as NOS2 INOS; anti-proliferative response, such as p53 TP53, LOX and CDKN1A; apoptosis, such as BBC3 PUMA, CASP1, CASP7 and CASP8; immune response, such as IL7, IL12A B and IL15, PTGS2 COX2 and CYBB; DNA damage responses and DNA repair, such as POLQ POLH; MHC class I expression, such as TAP1, PSMB9 LMP2, PSME1 PA28A, PSME2 PA28B and B2M and MHC class II expression, such as CIITA; metabolic enzymes, such as ACOD1 IRG1. Represses genes involved in anti-proliferative response, such as BIRC5 survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and TLR4. Stimulates p53 TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53 TP53. Plays an important role in immune response directly affecting NK maturation and activity, macrophage production of IL12, Th1 development and maturation of CD8+ T-cells. Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development. Acts as a tumor suppressor and plays a role not only in antagonism of tumor cell growth but also in stimulating an immune response against tumor cells.

Acts as an inhibitory receptor for myeloid cells and mast cells. Positively regulates the phagocytosis of apoptotic cells (efferocytosis) via phosphatidylserine (PS) recognition; recognizes and binds PS as a ligand which is expressed on the surface of apoptotic cells. Plays an important role in the maintenance of immune homeostasis, by promoting macrophage-mediated efferocytosis and by inhibiting dendritic cell-mediated efferocytosis. Negatively regulates Fc epsilon receptor-dependent mast cell activation and allergic responses via binding to ceramide and sphingomyelin which act as ligands. May act as a coreceptor for interleukin 4 (IL-4). Associates with and regulates IL-4 receptor alpha-mediated responses by augmenting IL-4- and IL-13-induced signaling. Negatively regulates the Toll-like receptor (TLR) signaling mediated by MYD88 and TRIF through activation of PTPN6 SHP-1 and PTPN11 SHP-2. Inhibits osteoclast formation. Induces macrophage cell death upon engagement.

Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3 MST2 and STK4 MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1 2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1 TAZ. Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization. Plays a key role in controlling cell proliferation in response to cell contact. Phosphorylation of YAP1 by LATS1 2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage-independent growth, and epithelial mesenchymal transition (EMT) induction. Suppresses ciliogenesis via acting as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1. In conjunction with WWTR1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation.; Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3).; Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3).

ROBO2 belongs to the ROBO family. Members of the ROBO family are a group of highly conserved transmembrane glycoproteins that make up a small subgroup of the immunoglobulin (Ig) superfamily. They are best known for their roles as receptors for the Slit family of repellent axon guidance cues. In structure, ROBOs are characterized by five C2-type Ig-like repeats, three fibronectin type III domains, a transmembrane region, and an intracellular domain with three (ROBO3) or four (ROBO1, 2) CC (conserved cytoplasmic) motifs. ROBO2 is a receptor for SLIT2, and probably SLIT1, which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development. ROBO2 also abrogates SLIT-ROBO signaling in vitro.

Angiopoietin-like protein 1 (ANGPTL1) has been reported to suppress migration and invasion in lung and breast cancer, acting as a novel tumor suppressor candidate. Downregulation of tumor suppressor signaling plays an important role in the pathogenesis of hepatocellular carcinoma (HCC).The downregulation of the angiopoietin-like protein ANGPTL1 is associated with vascular invasion, tumor thrombus, metastasis, and poor prognosis in HCC. Ectopic expression of ANGPTL1 in HCC cells effectively decreased their in vitro and in vivotumorigenicity, cell motility, and angiogenesis. shRNA-mediated depletion of ANGPTL1 exerted opposing effects. ANGPTL1 promoted apoptosis via inhibition of the STAT3 Bcl-2-mediated antiapoptotic pathway and decreased cell migration and invasion via downregulation of transcription factors SNAIL and SLUG. Furthermore, ANGPTL1 inhibited angiogenesis by attenuating ERK and AKT signaling and interacted with integrin α1β1 receptor to suppress the downstream FAK Src-JAK-STAT3 signaling pathway. Taken together, these results suggest ANGPTL1 as a prognostic biomarker and novel therapeutic agent in HCC. ANGPTL1 expression was down-regulated in CRC tissues and inversely correlated with poor survival. ANGPTL1 repressed migration and invasion of CRC cells, and microRNA-138 was involved in this process. Angiopoietin-like protein 1 (ANGPTL1) has been shown to act as a tumor suppressor by inhibiting angiogenesis, cancer invasion, and metastasis.

Casein kinase I gamma 2 isoform (CSNK1G2), a member of the large casein kinase I (CKI) subfamily, protein kinase superfamily. It may affect the development of brain, and associate with vesicular trafficking and neurotransmitter releasing from small synaptic vesicles. The CKI family includes several other isoforms (alpha, beta, gamma, and delta). Dishevelled (Dsh), another positive component of the Wnt pathway, becomes phosphorylated in response to Wnt signals. All the CKI isoforms, with the exception of gamma, increase the phosphorylation of Dsh in vivo. Casein kinase 1 gamma (CK1gamma, or CSNK1G) is associated with the cell membrane and binds to LRP. CK1gamma was found to be needed for Wnt signaling through Wnt receptor LRP. CSNK1G2 inhibits Smad3-mediated TGF-beta responses including induction of target genes and cell growth arrest, and this inhibition is dependent on CSNK1G2 kinase activity. The overexpression of CSNK1G2 in human cancers, may act as an oncoprotein during tumorigenesis. In addition, as an MTA1s-binding protein, CSNK1G2 could further potentiate the estrogen receptor (ER) corepressive function of MTA1s.

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.

Granulocyte colony-stimulating factor (G-CSF) is a growth factor and an essential cytokine which belongs to the IL-6 superfamily. Granulocyte macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. G-CSF binding to its receptor G-CSF-R which belongs to the cytokine receptor type I family depends on the interaction of alpha-helical motifs of the former and two fibronectin type III as well as an immunoglobulin-like domain of the latter. G-CSF is a cytokine that have been demonstrated to improve cardiac function and perfusion in myocardial infarction. And it was initially evaluated as a stem cell mobilizer and erythropoietin as a cytoprotective agent.

Retinoic acid receptor responder protein 2(RARRES2) is a secreted protein that in humans is encoded by the RARRES2 gene. It is highly expressed in skin, also found in pancreas, liver, spleen, prostate, ovary, small intestine and colon. It is a chemoattractant protein that acts as a ligand for the G protein-coupled receptor CMKLR1. RARRES2 is secreted in an inactive form as prochemerin and is activated through cleavage of the C-terminus by inflammatory and coagulation serine proteases. It is thought to act as a cell surface receptor, found to stimulate chemotaxis of dendritic cells and macrophages to the site of inflammation. RARRES2 is inhibited in psoriatic lesions,it is activated by tazarotene in skin rafts and in the epidermis of psoriatic lesions.

Low-Density Lipoprotein Receptor-Related Protein 12 (LRP12) belongs to the LDLR family. LRP12 is a type I transmembrane protein annd widely expressed in heart, skeletal muscle, brain, lung, placenta and pancreas. LRP12 contains 2 CUB domain and 5 LDL-receptor class A domain. LRP12 has been shown to interact with GNB2L1, ZFYVE9 and ITGB1BP3. LRP12 is a receptor probably, which may be involved in the internalization of lipophilic molecules and or signal transduction. In addition, LRP12 may act as a tumor suppressor.

Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin specifically blocks mammalian neuronal nAChR of the alpha-7 CHRNA7, alpha-3-beta-2 CHRNA3-CHRNB2 and alpha-4-beta-2 CHRNA4-CHRNB2 subtypes. VxXXA and VxXXB inhibit alpha-7 CHRNA7 and alpha-3-beta-2 CHRNA3-CHRNB2 nAChR more efficiently than VxXXC. VxXXB is the most effective at inhibiting alpha-4-beta-2 CHRNA4-CHRNB2 nAChR, followed by VxXXC and VxXXA. VxXIIC Protein, Conus vexillum, Recombinant (His & Myc & SUMO) is expressed in E. coli expression system with N-10xHis-SUMO and C-Myc tag. The predicted molecular weight is 25.3 kDa and the accession number is P0C1W7.

Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. May form part of a tissue-specific acute response to remodeling stimuli. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MMP-14 and MMP-15.

Alpha-2-glycoprotein, also known as AZGP1, belongs to the MHC class I family. It can be detected in body fluids such as serum, sweat, and seminal and breast cyst fluids. It has been shown that alpha-2-glycoprotein can stimulate lipolysis by adipocytes in vivo and in vitro. Thus it is believed that alpha-2-glycoprotein plays an important role in the regulation of body weight, and age-dependent changes in genetically influenced obesity, and it also regulates melanin production by normal and malignant melanocytes. Alpha-2-glycoprotein is produced by both white and brown fat adipocytes and may act in a local autocrine fashion in the reduction of adiposity in cachexia.

SLAMF6 (signaling lymphocyte activation molecule 6) (Ly108 in mice, NTB-A or SF2000 in humans) is a homophilic receptor belonging to the superfamily immunoglobulin (Ig) domain-containing molecules. It is known to be widely and exclusively expressed on hematopoietic cells. The SLAMF6 intracellular portion is characterized by two ITSMs that act as binding sites for adaptor molecules such as SAP and EAT-2. SLAMF6 Protein, Cynomolgus, Recombinant (His) is expressed in HEK293 mammalian cells with C-His tag. The predicted molecular weight is 23.98 kDa and the accession number is G7NWD4.

Pleckstrin Homology-Like Domain Family A Member 2 (PHLDA2) is a peripheral membrane protein that belongs to the PHLDA2 family. PHLDA2 is expressed in the placenta and adult prostate gland. In the placenta, it is present in all cells of the villous cytotrophoblast. PHLDA2 plays a role in regulating placenta growth. PHLDA2 may act via its PH domain that competes with other PH domain-containing proteins, thereby preventing their binding to membrane lipids.

Glutathione S-transferase Mu 2, also known as GST class-mu 2, GSTM2-2, and GSTM2, is a cytoplasm protein that belongs to the GST superfamily and Mu family. GSTM2 GST4 contains one GST C-terminal domain and one GST N-terminal domain. The glutathione S-transferases (GSTs) are a multigene family of enzymes largely involved in the detoxification of chemicals. Eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta, and zeta. Butyrate, an important luminal component produced from the fermentation of dietary fibers, is an efficient inducer of GSTs and especially of GSTM2. Butyrate may act chemoprotective by increasing detoxification capabilities in the colon mucosa.

Glycosyl transferase 25 domain 2 (GLT25D2) is a glucosyltransferase enzyme expressed only at low levels in the nervous system. Glycosyltransferases are enzymes that act as a catalyst for the transfer of a monosaccharide unit from an activated nucleotide sugar (also known as the glycosyl donor ) to a glycosyl acceptor molecule, usually an alcohol. Glycosyl transferases transfer glycosyl groups onto their substrate. Localization partially defines their function. Glt25D2 enzyme showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL which contains a collagen domain.

NTPDase 2, also known as ENTPD2, belongs to the ecto-nucleoside triphosphate diphosphohydrolase family (E-NTPDase). Members of E-NTPDase family are nucleotidases able to hydrolyze 5′-nucleoside tri- and or diphosphates; the main role of these enzymes is the termination of purinergic signaling. NTPDases are ubiquitous and were previously shown in other parasites including the trypanosomatides of genus Leishmania and in T. brucei. NTPase activity would act as a timer and is crucial to T. gondii infection. In L. pneumophila it was demonstrated that an E-NTPDase, similar to CD39, is essential for intracellular bacterial multiplication. NTPDase 2 is an integral membrane protein. In the nervous system, it could hydrolyze ATP and other nucleotides to regulate purinergic neurotransmission. Alternative splicing of NTPDase 2 gene results in multiple transcript variants.

BMF(Bcl2 modifying factor) belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. BMF contains a single BCL2 homology domain 3 (BH3), and has been shown to bind BCL2 proteins and function as an apoptotic activator. BMF is found to be sequestered to myosin V motors by its association with dynein light chain 2, which may be important for sensing intracellular damage and triggering apoptosis. Alternatively spliced transcript variants encoding different isoforms have been identified.

BCL2L11, also known as Bim, belongs to the BCL-2 protein family. Members of this family form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. BCL2L11 contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family, including BCL2, BCL2L1 BCL-X(L), and MCL1, and to act as an apoptotic activator. BCL2L11 gene functions as an essential initiator of apoptosis in thymocyte-negative selection.

CCL4 Protein, Human, Recombinant (His) is expressed in yeast with His tag. The predicted molecular weight is 9.2 kDa and the accession number is P13236.

PAK3 is a member of PAK proteins, a family of serine threonine p21-activating kinases, serve as effectors of small Rho GTPases Cdc42 and RAC and have been implicated in a wide range of biological activities. There are six mammalian PAKs which can be divided into two groups: group I PAKs (PAK1-3) and group II PAKs (PAK4-6). Although the two PAK groups are architecturally similar there are differences in their mode of regulation suggesting their cellular functions are likely to be different. Group I p21-activated kinases (PAK1 2 3) is demonstrated as ERK3 ERK4 activation loop kinases. It has been shown that group I PAKs phosphorylate ERK3 and ERK4 on Ser-189 and Ser-186, respectively, both in vitro and in vivo, and that expression of activated Rac1 augments this response. Besides regulation enzymatic activation of ERK3 ERK4, PAKs can also play roles in downstream activation of MAP kinase-activated protein kinase 5 (MK5) in vivo. Thus, the group I PAKs act as upstream activators of ERK3 and ERK4 and unravel a novel PAK-ERK3 ERK4-MK5 signaling pathway. In clinical, PAK has been proposed as a potential therapeutic target in schwannomas.

Serine threonine-protein kinase 1, also known as Lymphocyte-oriented kinase, STK1 and LOK, belongs to the protein kinase superfamily, STE Ser Thr protein kinase family and STE2 subfamily. Protein kinases constitute a large superfamily of enzymes with key regulatory functions in nearly all signal transmission processes of eukaryotic cells. The Ste2 family of serine threonine kinases plays an important role in numerous cellular functions such as growth, apoptosis, and morphogenesis. STK1 is similar to several known polo-like kinase kinases. It can associate with and phosphorylate polo-like kinase 1, and overexpression of a kinase-dead version of the protein interferes with normal cell cycle progression. STK1 can also negatively regulate interleukin 2 expression in T-cells via the mitogen activated protein kinase kinase 1 pathway. Stk1 can associate with Plk1 in cells and furthermore can phosphorylate Plk1. It can also act on substrates such as myelin basic protein and histone 2A on serine and threonine residues.

Macrophage Colony-Stimulating Factors (m-csf) are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and themonocytes-macrophages. CSF-1 promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. It also plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone development. CSF-1 is required for normal male and female fertility and promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration. it also plays a role in lipoprotein clearance.