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Nfatc1 | Nuclear factor of activated T-cells, cytoplasmic 1; Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 or IL-4 gene transcription. Also controls gene expression in embryonic cardiac cells. Could regulate not only the activation and proliferation but also the differentiation and programmed death of T- lymphocytes as well as lymphoid and non-lymphoid cells (By similarity). Required for osteoclastogenesis and regulates many genes important for osteoclast differentiation and function. (939 aa) | ||||
Ccl2 | C-C motif chemokine 2; Acts as a ligand for C-C chemokine receptor CCR2 (By similarity). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobilization of intracellular calcium ions (By similarity). Exhibits a chemotactic activity for monocytes and basophils but not neutrophils or eosinophils (By similarity). Plays an important role in mediating peripheral nerve injury-induced neuropathic pain. Increases NMDA-mediated synaptic transmission in both dopamine D1 and D2 receptor-containing neurons, which may be caused by MAPK/ERK-dependent phospho [...] (148 aa) | ||||
Ern1 | Serine/threonine-protein kinase/endoribonuclease IRE1; Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR). In unstressed cells, the endoplasmic reticulum luminal domain is maintained in its inactive monomeric state by binding to the endoplasmic reticulum chaperone HSPA5/BiP. Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP, allowing the luminal domain to homodimerize, promoting autophosphorylation of the kinase domain and subsequent activation of the endor [...] (977 aa) | ||||
Akt1 | RAC-alpha serine/threonine-protein kinase; AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the [...] (480 aa) | ||||
Nqo1 | NAD(P)H dehydrogenase [quinone] 1; The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis. (274 aa) | ||||
Ikbkg | NF-kappa-B essential modulator; Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. Also considered to be a mediator for TAX activation of NF- kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires [...] (430 aa) | ||||
Traf6 | TNF receptor-associated factor 6; E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, IRAK1, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation (By similarity). Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter p [...] (530 aa) | ||||
Eif2ak4 | eIF-2-alpha kinase GCN2; Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2- alpha/EIF2S1) on 'Ser-52' in response to low amino acid availability. Plays a role as an activator of the integrated stress response (ISR) required for adapatation to amino acid starvation. Converts phosphorylated eIF-2- alpha/EIF2S1 either to a competitive inhibitor of the translation initiation factor eIF-2B, leading to a global protein synthesis repression, and thus to a reduced overall utilization of amino acids, or to a transl [...] (1648 aa) | ||||
Hmox1 | Heme oxygenase 1; Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed. Exhibits cytoprotective effects since excess of free heme sensitizes cells to undergo apoptosis. (289 aa) | ||||
Pth1r | Parathyroid hormone/parathyroid hormone-related peptide receptor; Receptor for parathyroid hormone and for parathyroid hormone- related peptide. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatidylinositol-calcium second messenger system. (591 aa) | ||||
Sod2 | Superoxide dismutase [Mn], mitochondrial; Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems; Belongs to the iron/manganese superoxide dismutase family. (222 aa) | ||||
Dnajb9 | DnaJ homolog subfamily B member 9; Co-chaperone for Hsp70 protein HSPA5/BiP that acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (By similarity). J domain-containing co-chaperones stimulate the ATPase activity of Hsp70 proteins and are required for efficient substrate recognition by Hsp70 proteins. In the unstressed endoplasmic reticulum, interacts with the luminal region of ERN1/IRE1 and selectively recruits HSPA5/BiP: HSPA5/BiP disrupts the dimerization of the active ERN1/IRE1 luminal region, thereby inactivating ERN1/IRE1 (By similarity). Also invol [...] (222 aa) | ||||
Atf6b | Processed cyclic AMP-dependent transcription factor ATF-6 beta; Transcriptional factor that acts in the unfolded protein response (UPR) pathway by activating UPR target genes induced during ER stress. Binds DNA on the 5'-CCAC[GA]-3' half of the ER stress response element (ERSE) (5'-CCAATN(9)CCAC[GA]-3') when NF-Y is bound to ERSE (By similarity); Belongs to the bZIP family. ATF subfamily. (706 aa) | ||||
Ctsk | Cathepsin K; Thiol protease involved in osteoclastic bone resorption. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation (By similarity). Involved in the release of thyroid hormone thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the thyroid follicle lumen ; Belongs to the peptidase C1 family. (329 aa) | ||||
Ncf1 | Neutrophil cytosol factor 1; NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production). (404 aa) | ||||
Mmp9 | Matrix metalloproteinase-9; Could play a role in bone osteoclastic resorption. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments (By similarity). Belongs to the peptidase M10A family. (730 aa) | ||||
Map2k3 | Dual specificity mitogen-activated protein kinase kinase 3; Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. (347 aa) | ||||
Calm3 | Calmodulin-1; Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Mediates calcium- dependent inactivation of CACNA1C. Positively regulates calcium- activated potassium channel activity of KCNN2. (149 aa) | ||||
Hif1a | Hypoxia-inducible factor 1-alpha; Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT; heterodimer binds to core DNA sequenc [...] (836 aa) | ||||
Fos | Proto-oncogene c-Fos; Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex, at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling (By similarity). Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation. In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and [...] (380 aa) | ||||
Traf3 | TNF receptor-associated factor 3; Regulates pathways leading to the activation of NF-kappa-B and MAP kinases, and plays a central role in the regulation of B-cell survival. Part of signaling pathways leading to the production of cytokines and interferon. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Plays a role in the regulation of antiviral responses. Is an essential constituent of several E3 ubiquitin-protein ligase complexes. May have E3 ubiquitin-protein ligase activity and promote 'Lys-63'- linked ubiquitination of [...] (567 aa) | ||||
Tnfsf11 | Tumor necrosis factor ligand superfamily member 11, membrane form; Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy (By similarity). Induces osteoclastogenesis by activating multiple signali [...] (316 aa) | ||||
Dcstamp | Dendritic cell-specific transmembrane protein; Probable cell surface receptor that plays several roles in cellular fusion, cell differentiation, bone and immune homeostasis. Plays a role in TNFSF11-mediated osteoclastogenesis. Cooperates with OCSTAMP in modulating cell-cell fusion in both osteoclasts and foreign body giant cells (FBGCs). Participates in osteoclast bone resorption. Involved in inducing the expression of tartrate-resistant acid phosphatase in osteoclast precursors. Plays a role in haematopoietic stem cell differentiation of bone marrow cells toward the myeloid lineage. I [...] (470 aa) | ||||
Eif2ak2 | Interferon-induced, double-stranded RNA-activated protein kinase; IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including west nile virus (WNV), sindbis virus (SV), foot-and-mouth virus (FMDV), semliki Forest virus (SFV) and lymphocytic choriomeningitis virus (LCMV). Inhibits viral replication via phosphorylation of the a [...] (515 aa) | ||||
Tnf | Tumor necrosis factor, membrane form; Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation (By similarity). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces [...] (235 aa) | ||||
Rela | Transcription factor p65; NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain- containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kap [...] (549 aa) | ||||
Chuk | Inhibitor of nuclear factor kappa-B kinase subunit alpha; Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into t [...] (745 aa) | ||||
Ddit3 | DNA damage-inducible transcript 3 protein; Multifunctional transcription factor in ER stress response. Plays an essential role in the response to a wide variety of cell stresses and induces cell cycle arrest and apoptosis in response to ER stress. Plays a dual role both as an inhibitor of CCAAT/enhancer- binding protein (C/EBP) function and as an activator of other genes. Acts as a dominant-negative regulator of C/EBP-induced transcription: dimerizes with members of the C/EBP family, impairs their association with C/EBP binding sites in the promoter regions, and inhibits the expression [...] (168 aa) | ||||
Il6 | Interleukin-6; Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Involved in lymphocyte and monocyte differentiation. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance. It induces myeloma and plasm [...] (211 aa) | ||||
Tnfrsf11a | Tumor necrosis factor receptor superfamily member 11A; Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL- mediated osteoclastogenesis. Involved in the regulation of interactions between T-cells and dendritic cells. (625 aa) | ||||
Atf6 | Processed cyclic AMP-dependent transcription factor ATF-6 alpha; Transmembrane glycoprotein of the endoplasmic reticulum that functions as a transcription activator and initiates the unfolded protein response (UPR) during endoplasmic reticulum stress. Cleaved upon ER stress, the N-terminal processed cyclic AMP-dependent transcription factor ATF-6 alpha translocates to the nucleus where it activates transcription of genes involved in the UPR. Binds DNA on the 5'-CCAC[GA]-3'half of the ER stress response element (ERSE) (5'-CCAAT- N(9)-CCAC[GA]-3') and of ERSE II (5'-ATTGG-N-CCACG-3'). Bi [...] (656 aa) | ||||
Hspa5 | Endoplasmic reticulum chaperone BiP; Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen. Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate. Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (By similarity). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimeriz [...] (655 aa) | ||||
Creb3l1 | Processed cyclic AMP-responsive element-binding protein 3-like protein 1; Transcription factor involved in unfolded protein response (UPR). Binds the DNA consensus sequence 5'-GTGXGCXGC-3' (By similarity). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain [...] (520 aa) | ||||
Il1b | Interleukin-1 beta; Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B- cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T- helper 1 (Th1) cells; Belongs to the IL-1 family. (269 aa) | ||||
Creb3l4 | Processed cyclic AMP-responsive element-binding protein 3-like protein 4; Transcriptional activator that may play a role in the unfolded protein response of the testis. Proposed to be involved in spermiogenesis. May be involved in regulating the maturation of sperm head nuclei. Alternatively proposed to be a paternally delivered transcription factor that may function in early zygotic gene activation. Increases the binding of CREM isoform Tau with CRE. The CREM isoform Tau-CREB3L4 heterodimer functions through CRE but not through UPRE and may recruit HIRA to CRE to regulate histone exchange. (370 aa) | ||||
Nfkb1 | Nuclear factor NF-kappa-B p105 subunit; NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain- containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dime [...] (971 aa) | ||||
Atp6v0d2 | V-type proton ATPase subunit d 2; Subunit of the integral membrane V0 complex of vacuolar ATPase. Vacuolar ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells, thus providing most of the energy required for transport processes in the vacuolar system (By similarity). May play a role in coupling of proton transport and ATP hydrolysis. Regulator of osteoclast fusion and bone formation. Belongs to the V-ATPase V0D/AC39 subunit family. (350 aa) | ||||
Itpr1 | Inositol 1,4,5-trisphosphate receptor type 1; Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5- trisphosphate. Involved in the regulation of epithelial secretion of electrolytes and fluid through the interaction with AHCYL1. Plays a role in ER stress-induced apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CaM kinase II, eventually leading to the activation of downstream apoptosis pathways. (2749 aa) | ||||
Tnfrsf1a | Tumor necrosis factor receptor superfamily member 1A; Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis (By similarity). (454 aa) | ||||
Tyrobp | TYRO protein tyrosine kinase-binding protein; Adapter protein which non-covalently associates with activating receptors found on the surface of a variety of immune cells to mediate signaling and cell activation following ligand binding by the receptors. TYROBP is tyrosine- phosphorylated in the ITAM domain following ligand binding by the associated receptors which leads to activation of additional tyrosine kinases and subsequent cell activation. Also has an inhibitory role in some cells. Non-covalently associates with activating receptors of the CD300 family to mediate cell activation [...] (114 aa) | ||||
Ern2 | Serine/threonine-protein kinase/endoribonuclease IRE2; Role in expression of the DDIT3 transcription factor, required for the unfolded-protein response, growth arrest and apoptosis. Has no effect on 28S ribosomal RNA cleavage, unlike the corresponding human protein. (911 aa) | ||||
Il2rg | Cytokine receptor common subunit gamma; Common subunit for the receptors for a variety of interleukins. Probably in association with IL15RA, involved in the stimulation of neutrophil phagocytosis by IL15 (By similarity). (369 aa) | ||||
Ikbkb | Inhibitor of nuclear factor kappa-B kinase subunit beta; Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is transloca [...] (757 aa) | ||||
Eif2ak3 | Eukaryotic translation initiation factor 2-alpha kinase 3; Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2- alpha/EIF2S1) on 'Ser-52' during the unfolded protein response (UPR) and in response to low amino acid availability. Converts phosphorylated eIF-2-alpha/EIF2S1 either in a global protein synthesis inhibitor, leading to a reduced overall utilization of amino acids, or to a translation initiation activator of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated [...] (1114 aa) | ||||
Calml4 | Calmodulin-like protein 4. (153 aa) | ||||
Zc3h12a | Endoribonuclease ZC3H12A; Endoribonuclease involved in various biological functions such as cellular inflammatory response and immune homeostasis, glial differentiation of neuroprogenitor cells, cell death of cardiomyocytes, adipogenesis and angiogenesis. Functions as an endoribonuclease involved in mRNA decay. Modulates the inflammatory response by promoting the degradation of a set of translationally active cytokine-induced inflammation-related mRNAs, such as IL6 and IL12B, during the early phase of inflammation. Prevents aberrant T-cell-mediated immune reaction by degradation of mul [...] (596 aa) | ||||
Itpr3 | Inositol 1,4,5-trisphosphate receptor type 3; Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. (2670 aa) | ||||
Map2k4 | Dual specificity mitogen-activated protein kinase kinase 4; Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylati [...] (397 aa) | ||||
Oscar | Osteoclast-associated immunoglobulin-like receptor; Regulator of osteoclastogenesis which plays an important bone-specific function in osteoclast differentiation. Belongs to the leukocyte receptor complex/polymeric immunogobulin receptor (PIR/LRC) family. (271 aa) | ||||
Arl6ip5 | PRA1 family protein 3; Regulates intracellular concentrations of taurine and glutamate (By similarity). Negatively modulates SLC1A1/EAAC1 glutamate transport activity by decreasing its affinity for glutamate in a PKC activity-dependent manner. May be involved in membrane traffic (By similarity). (188 aa) | ||||
Calm4 | Calmodulin-4; Implicated in the early stage of ectopic ossification. (148 aa) | ||||
Itpr2 | Inositol 1,4,5-trisphosphate receptor type 2; Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. This release is regulated by cAMP both dependently and independently of PKA. (2701 aa) | ||||
Pthlh | Parathyroid hormone-related protein; Neuroendocrine peptide which is a critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport. Regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Required for skeletal homeostasis. Promotes mammary mesenchyme differentiation and bud outgrowth by modulating mesenchymal cell responsiveness to BMPs. Upregulates BMPR1A expression in the mammary mesenchyme and this increases the sensitivity o [...] (175 aa) | ||||
Pdia6 | Protein disulfide-isomerase A6; May function as a chaperone that inhibits aggregation of misfolded proteins. Negatively regulates the unfolded protein response (UPR) through binding to UPR sensors such as ERN1, which in turn inactivates ERN1 signaling (By similarity). May also regulate the UPR via the EIF2AK3 UPR sensor (By similarity). Plays a role in platelet aggregation and activation by agonists such as convulxin, collagen and thrombin (By similarity). Belongs to the protein disulfide isomerase family. (445 aa) | ||||
Xbp1 | X-box-binding protein 1, cytoplasmic form; Functions as a transcription factor during endoplasmic reticulum stress by regulating the unfolded protein response (UPR). Required for cardiac myogenesis and hepatogenesis during embryonic development and the development of secretory tissues such as exocrine pancreas and salivary gland. Involved in differentiation of B lymphocytes to plasma cells and production of immunoglobulins. Modulates the cellular response to ER stress in a PIK3R-dependent manner. Binds to the cis-acting X box present in the promoter regions of major histocompatibility [...] (267 aa) | ||||
Pik3r1 | Phosphatidylinositol 3-kinase regulatory subunit alpha; Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity). Modulates the cellular response to ER stress by promoting nucle [...] (724 aa) | ||||
Junb | Transcription factor jun-B; Transcription factor involved in regulating gene activity following the primary growth factor response. Binds to the DNA sequence 5'-TGA[CG]TCA-3'; Belongs to the bZIP family. Jun subfamily. (344 aa) | ||||
Nfatc2 | Nuclear factor of activated T-cells, cytoplasmic 2; Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway. (927 aa) | ||||
Calml3 | Calmodulin-like protein 3; May function as a specific light chain of unconventional myosin-10 (MYO10), also enhances MYO10 translation, possibly by acting as a chaperone for the emerging MYO10 heavy chain protein. May compete with calmodulin by binding, with different affinities, to cellular substrates (By similarity). (149 aa) | ||||
Tnfrsf11b | Tumor necrosis factor receptor superfamily member 11B; Acts as decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostasis seems to depend on the local ratio between TNFSF11 and TNFRSF11B. May also play a role in preventing arterial calcification. May act as decoy receptor for TNFSF10/TRAIL and protect against apoptosis. TNFSF10/TRAIL binding blocks the inhibition of osteoclastogenesis. (401 aa) | ||||
Pth | Parathyroid hormone; PTH elevates calcium level by dissolving the salts in bone and preventing their renal excretion; Belongs to the parathyroid hormone family. (115 aa) | ||||
Fcer1g | High affinity immunoglobulin epsilon receptor subunit gamma; Adapter protein containing an immunoreceptor tyrosine-based activation motif (ITAM) that transduces activation signals from various immunoreceptors. As a component of the high-affinity immunoglobulin E (IgE) receptor, mediates allergic inflammatory signaling in mast cells. As a constitutive component of interleukin-3 receptor complex, selectively mediates interleukin 4/IL4 production by basophils, priming T-cells toward effector T-helper 2 subset. Associates with pattern recognition receptors CLEC4D and CLEC4E to form a funct [...] (86 aa) | ||||
Traf5 | TNF receptor-associated factor 5; Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. Mediates activation of NF-kappa-B and probably JNK. Seems to be involved in apoptosis. Plays a role in mediating activation of NF- kappa-B by EIF2AK2/PKR. (552 aa) | ||||
Edem1 | ER degradation-enhancing alpha-mannosidase-like protein 1; Extracts misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle. It is directly involved in endoplasmic reticulum-associated degradation (ERAD) and targets misfolded glycoproteins for degradation in an N-glycan- independent manner, probably by forming a complex with SEL1L. It has low mannosidase activity, catalyzing mannose trimming from Man8GlcNAc2 to Man7GlcNAc2. (652 aa) | ||||
Src | Neuronal proto-oncogene tyrosine-protein kinase Src; Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redun [...] (541 aa) | ||||
Relb | Transcription factor RelB; NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishab [...] (558 aa) | ||||
Eif2ak1 | Eukaryotic translation initiation factor 2-alpha kinase 1; Inhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. Exerts its function through the phosphorylation of EIF2S1 at 'Ser-48' and 'Ser- 51', thus preventing its recycling. Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell. Thanks to this unique heme-se [...] (619 aa) | ||||
Rac1 | Ras-related C3 botulinum toxin substrate 1; Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity [...] (211 aa) | ||||
Nfe2l2 | Nuclear factor erythroid 2-related factor 2; Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reactive electrophiles. In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex. In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, hetero [...] (597 aa) | ||||
Rel | Proto-oncogene c-Rel; Proto-oncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferen [...] (588 aa) | ||||
Creb3 | Processed cyclic AMP-responsive element-binding protein 3; Endoplasmic reticulum (ER)-bound sequence-specific transcription factor that directly binds DNA and activates transcription. Plays a role in the unfolded protein response (UPR), promoting cell survival versus ER stress-induced apoptotic cell death. Also involved in cell proliferation, migration and differentiation, tumor suppression and inflammatory gene expression. Acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration. Associates with chromatin to the HERPUD1 promoter. Also induce [...] (379 aa) | ||||
Jun | Transcription factor AP-1; Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. Involved in activated KRAS-mediated transcriptional activation of USP28 (By similarity). Binds to the USP28 promoter (By similarity). (334 aa) | ||||
Maf | Transcription factor Maf; Acts as a transcriptional activator or repressor. When overexpressed, represses anti-oxidant response element (ARE)-mediated transcription. Involved either as an oncogene or as a tumor suppressor, depending on the cell context. Binds to the ARE sites of detoxifying enzyme gene promoters (By similarity). Involved in embryonic lens fiber cell development. Recruits the transcriptional coactivators CREBBP and/or EP300 to crystallin promoters leading to up-regulation of crystallin gene during lens fiber cell differentiation. Activates the expression of IL4 in T hel [...] (370 aa) | ||||
Atf4 | Cyclic AMP-dependent transcription factor ATF-4; Transcriptional activator. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer. Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production. Regulates the induction of DDIT3/CHOP and asparagine synthetase (ASNS) in response to ER stress. In concert with DDIT3/CHOP, activates the transcription [...] (349 aa) | ||||
Nfkb2 | Nuclear factor NF-kappa-B p100 subunit; NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain- containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the indi [...] (899 aa) | ||||
Traf2 | TNF receptor-associated factor 2; Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin-protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels [...] (508 aa) | ||||
Pik3c3 | Phosphatidylinositol 3-kinase catalytic subunit type 3; Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2. Involved in the transport of lysosomal enzyme precursors to lysosomes. Requ [...] (887 aa) | ||||
Sirt1 | NAD-dependent protein deacetylase sirtuin-1; NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolism, apoptosis and autophagy. Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression (By similarity). Deacetylates a broad range of transcription factors and coregulators, thereby regulating ta [...] (737 aa) | ||||
Creb3l3 | Processed cyclic AMP-responsive element-binding protein 3-like protein 3; Transcription factor that may act during endoplasmic reticulum stress by activating unfolded protein response target genes. Activated in response to cAMP stimulation. Binds to the cAMP response element (CRE). Activates transcription through box-B element (By similarity). Activates transcription through CRE. Seems to function synergistically with ATF6. In acute inflammatory response, may activate expression of acute phase response (APR) genes. May be involved in growth suppression; Belongs to the bZIP family. ATF [...] (479 aa) | ||||
Syk | Tyrosine-protein kinase SYK; Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can a [...] (629 aa) | ||||
Traf1 | TNF receptor-associated factor 1; Adapter molecule that regulates the activation of NF-kappa-B and JNK. Plays a role in the regulation of cell survival and apoptosis. The heterotrimer formed by TRAF1 and TRAF2 is part of a E3 ubiquitin- protein ligase complex that promotes ubiquitination of target proteins, such as MAP3K14. The TRAF1/TRAF2 complex recruits the antiapoptotic E3 protein-ubiquitin ligases BIRC2 and BIRC3 to TNFRSF1B/TNFR2 (By similarity). (409 aa) | ||||
Keap1 | Kelch-like ECH-associated protein 1; Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination. KEAP1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes. In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine [...] (624 aa) | ||||
Canx | Calnexin; Calcium-binding protein that interacts with newly synthesized glycoproteins in the endoplasmic reticulum. It may act in assisting protein assembly and/or in the retention within the ER of unassembled protein subunits. It seems to play a major role in the quality control apparatus of the ER by the retention of incorrectly folded proteins. Associated with partial T-cell antigen receptor complexes that escape the ER of immature thymocytes, it may function as a signaling complex regulating thymocyte maturation. Additionally it may play a role in receptor-mediated endocytosis at t [...] (591 aa) | ||||
Calm5 | Skin calmodulin-related protein 2. (140 aa) | ||||
Dnah8 | Dynein heavy chain 8, axonemal; Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Involved in sperm motility; implicated in sperm flagellar assembly. (4731 aa) |