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| | Pparg | Peroxisome proliferator-activated receptor gamma; Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut ho [...] (505 aa) |
| | Sost | Sclerostin; Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation; Belongs to the sclerostin family. (211 aa) |
| | Col1a1 | Collagen alpha-1(I) chain; Type I collagen is a member of group I collagen (fibrillar forming collagen); Belongs to the fibrillar collagen family. (1453 aa) |
| | Clec11a | C-type lectin domain family 11 member A; Promotes osteogenesis by stimulating the differentiation of mesenchymal progenitors into mature osteoblasts. Important for repair and maintenance of adult bone. (328 aa) |
| | Wwox | WW domain-containing oxidoreductase; Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. May function synergistically with p53/TP53 to control genotoxic stress-induced cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. Inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm (By similarity). May also play a role in tumor necrosis factor (TNF)-mediated cell death. Required for normal bone development. (414 aa) |
| | Prkaca | cAMP-dependent protein kinase catalytic subunit alpha; Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA and VASP. RORA is activated by phosphorylation. Required for glucose- mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the [...] (351 aa) |
| | Igf1r | Insulin-like growth factor 1 receptor alpha chain; Receptor tyrosine kinase which mediates actions of insulin- like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates ( [...] (1369 aa) |
| | Htra1 | Serine protease HTRA1; Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3 production. May also degrade proteoglycans, such as aggrecan, decorin and fibromodulin. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the range and intensity of FGF signals in the extracellular space. Regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF- binding proteins. Inhibits sign [...] (480 aa) |
| | Cav1 | Caveolin-1; May act as a scaffolding protein within caveolar membranes (By similarity). Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the recruitment of CAVIN proteins (CAVIN1/2/3/4) to the caveolae. Interacts directly with G-protein alpha subunits and can functionally regulate their activity (By similarity). Involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependen [...] (178 aa) |
| | Csf1 | Processed macrophage colony-stimulating factor 1; Cytokine that plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone development. Required for normal male a [...] (552 aa) |
| | Lrrk1 | Leucine-rich repeat serine/threonine-protein kinase 1. (2014 aa) |
| | Ager | Advanced glycosylation end product-specific receptor; Mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis and in particular as a complication of diabetes. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF-alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S1 [...] (402 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) |
| | Il10 | Interleukin-10; Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanistically, IL10 binds to its heterotetrameric receptor comprising IL10RA and IL10RB leading to JAK1 and STAT2-mediated phosphorylation of STAT3. In turn, STAT3 translocates to the nucleus where it drives expression of anti-inflammatory mediators. Targets antigen-presenting cells (APCs) such as macrophages and monocytes and inhibits their release of pro-inflammatory cytokines in [...] (178 aa) |
| | Pdk4 | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial; Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism in response to prolonge [...] (412 aa) |
| | Ccn2 | CCN family member 2; Major connective tissue mitoattractant secreted by vascular endothelial cells. Promotes proliferation and differentiation of chondrocytes (By similarity). Mediates heparin- and divalent cation- dependent cell adhesion in many cell types including fibroblasts, myofibroblasts, endothelial and epithelial cells (By similarity). Enhances fibroblast growth factor-induced DNA synthesis (By similarity). (348 aa) |
| | Il20ra | Interleukin-20 receptor subunit alpha; The IL20RA/IL20RB dimer is a receptor for IL19, IL20 and IL24. The IL20RA/IL10RB dimer is a receptor for IL26 (By similarity). (546 aa) |
| | Ifngr1 | Interferon gamma receptor 1; Associates with IFNGR2 to form a receptor for the cytokine interferon gamma (IFNG). Ligand binding stimulates activation of the JAK/STAT signaling pathway (By similarity). (477 aa) |
| | Socs2 | Suppressor of cytokine signaling 2; SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway. Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). (198 aa) |
| | Itgb3 | Integrin beta-3; Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIB/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIB/beta-3 and alpha- V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIB/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A- G-D-V in fibrinogen gamma chain. Following ac [...] (787 aa) |
| | Thrb | Thyroid hormone receptor beta; Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine; Belongs to the nuclear hormone receptor family. NR1 subfamily. (475 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) |
| | Tmem178 | Transmembrane protein 178A; Acts as a negative regulator of osteoclast differentiation in basal and inflammatory conditions by regulating TNFSF11-induced Ca (2+) fluxes, thereby controlling the induction of NFATC1. (297 aa) |
| | Dpp3 | Dipeptidyl peptidase 3; Cleaves and degrades bioactive peptides, including angiotensin, Leu-enkephalin and Met-enkephalin. Also cleaves Arg-Arg- beta-naphthylamide (in vitro); Belongs to the peptidase M49 family. (738 aa) |
| | Fam20c | Extracellular serine/threonine protein kinase FAM20C; Golgi serine/threonine protein kinase that phosphorylates secretory pathway proteins within Ser-x-Glu/pSer motifs and plays a key role in biomineralization of bones and teeth. Constitutes the main protein kinase for extracellular proteins, generating the majority of the extracellular phosphoproteome (By similarity). Mainly phosphorylates proteins within the Ser-x-Glu/pSer motif, but also displays a broader substrate specificity (By similarity). Phosphorylates casein as well as a number of proteins involved in biomineralization such [...] (579 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) |
| | Notch1 | Neurogenic locus notch homolog protein 1; Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the [...] (2531 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) |
| | Lrp4 | Low-density lipoprotein receptor-related protein 4; Mediates SOST-dependent inhibition of bone formation. Functions as a specific facilitator of SOST-mediated inhibition of Wnt signaling. Plays a key role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between motor neuron and skeletal muscle. Directly binds AGRIN and recruits it to the MUSK signaling complex. Mediates the AGRIN-induced phosphorylation of MUSK, the kinase of the complex. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the [...] (1905 aa) |
| | Rassf2 | Ras association domain-containing protein 2; Potential tumor suppressor. Acts as a KRAS-specific effector protein. May promote apoptosis and cell cycle arrest. Stabilizes STK3/MST2 by protecting it from proteasomal degradation (By similarity). (326 aa) |
| | Bmp2 | Bone morphogenetic protein 2; Induces cartilage and bone formation. Stimulates the differentiation of myoblasts into osteoblasts via the EIF2AK3- EIF2A- ATF4 pathway. BMP2 activation of EIF2AK3 stimulates phosphorylation of EIF2A which leads to increased expression of ATF4 which plays a central role in osteoblast differentiation. In addition stimulates TMEM119, which upregulates the expression of ATF4. Belongs to the TGF-beta family. (394 aa) |
| | Npy2r | Neuropeptide Y receptor type 2; Receptor for neuropeptide Y and peptide YY; Belongs to the G-protein coupled receptor 1 family. (381 aa) |
| | Lmna | Prelamin-A/C; Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics. Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation. Required for osteoblastogenesis and bone formation. A [...] (665 aa) |
| | Cisd2 | CDGSH iron-sulfur domain-containing protein 2; Regulator of autophagy that contributes to antagonize BECN1- mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca(2+) stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy (By similarity). Belongs to the CISD protein family. CISD2 subfamily. (135 aa) |
| | Akr1a1 | Aldo-keto reductase family 1 member A1; Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosaccharides and bile acids, with a preference for negatively charged substrates, such as glucuronate and succinic semialdehyde (By similarity). Plays an important role in ascorbic acid biosynthesis by catalyzing the reduction of D-glucuronic acid and D-glucurono-gamma-lactone. Functions as a detoxifiying enzyme b [...] (325 aa) |
| | Alpl | Alkaline phosphatase, tissue-nonspecific isozyme; This isozyme plays a key role in skeletal mineralization by regulating levels of diphosphate (PPi). (524 aa) |
| | Nos3 | Nitric oxide synthase, endothelial; Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. May play a significant role in normal and abnormal limb development; Belongs to the NOS family. (1202 aa) |
| | Rgs12 | Regulator of G-protein signaling 12; Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP- bound form. (1381 aa) |
| | Fosl2 | Fos-related antigen 2; Controls osteoclast survival and size. As a dimer with JUN, activates LIF transcription. Activates CEBPB transcription in PGE2- activated osteoblasts (By similarity). (326 aa) |
| | Ibsp | Bone sialoprotein 2; Binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction. Promotes Arg-Gly-Asp-dependent cell attachment (By similarity). (324 aa) |
| | Trpv5 | Transient receptor potential cation channel subfamily V member 5; Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine. Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules. The channel is activated by low internal calcium level and the current exhibits an inward rectification. A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay. Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit [...] (723 aa) |
| | Clec2d | C-type lectin domain family 2 member D; Receptor for KLRB1B that protects target cells against natural killer cell-mediated lysis. Inhibits osteoclast formation. Binds high molecular weight sulfated glycosaminoglycans. (207 aa) |
| | Mgp | Matrix Gla protein; Associates with the organic matrix of bone and cartilage. Thought to act as an inhibitor of bone formation. (104 aa) |
| | Xylt1 | Xylosyltransferase 1; Catalyzes the first step in the biosynthesis of chondroitin sulfate and dermatan sulfate proteoglycans, such as DCN. Transfers D- xylose from UDP-D-xylose to specific serine residues of the core protein. Required for normal maturation of chondrocytes during bone development, normal onset of ossification and normal embryonic and postnatal skeleton development, especially of the long bones. (953 aa) |
| | Ilk | Integrin-linked protein kinase; Receptor-proximal protein kinase regulating integrin-mediated signal transduction. May act as a mediator of inside-out integrin signaling. Focal adhesion protein part of the complex ILK-PINCH. This complex is considered to be one of the convergence points of integrin- and growth factor-signaling pathway. Could be implicated in mediating cell architecture, adhesion to integrin substrates and anchorage-dependent growth in epithelial cells. Phosphorylates beta-1 and beta-3 integrin subunit on serine and threonine residues, but also AKT1 and GSK3B. (452 aa) |
| | Slc10a7 | Sodium/bile acid cotransporter 7; Involved in teeth and skeletal development. Has an essential role in the biosynthesis and trafficking of glycosaminoglycans and glycoproteins to produce a proper functioning extracellular matrix. Required for extracellular matrix mineralization. Also involved in the regulation of cellular calcium homeostasis (By similarity). Does not show transport activity towards bile acids or steroid sulfates (including taurocholate, cholate, chenodeoxycholate, estrone-3-sulfate, dehydroepiandrosterone sulfate (DHEAS) and pregnenolone sulfate); Belongs to the bile a [...] (340 aa) |
| | Ppib | Peptidyl-prolyl cis-trans isomerase B; PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding; Belongs to the cyclophilin-type PPIase family. PPIase B subfamily. (216 aa) |
| | Cldn18 | Claudin-18; Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity; Belongs to the claudin family. (264 aa) |
| | Clcn7 | H(+)/Cl(-) exchange transporter 7; Slowly voltage-gated channel mediating the exchange of chloride ions against protons. Functions as antiporter and contributes to the acidification of the lysosome lumen. Belongs to the chloride channel (TC 2.A.49) family. ClC- 7/CLCN7 subfamily. (803 aa) |
| | Cnot3 | CCR4-NOT transcription complex subunit 3; Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. May be involved in metabolic regulation; may be involved in recruitment of the CCR4-NOT complex to deadenylation target mRNAs involved in energy metabolism. Involved in mitotic [...] (751 aa) |
| | Npffr2 | Neuropeptide FF receptor 2; Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides. Can also be activated by a variety of naturally occurring or synthetic FMRF-amide like ligands. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system (By similarity). (417 aa) |
| | Twist1 | Twist-related protein 1; Acts as a transcriptional regulator. Inhibits myogenesis by sequestrating E proteins, inhibiting trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. This interaction probably involves the basic domains of both proteins. Also represses expression of proinflammatory cytokines such as TNFA and IL1B. Regulates cranial suture patterning and fusion. Activates transcription as a heterodimer with E proteins. Regulates gene expression differentially, depending on dimer composition. Homodimers induce expression of FGFR2 and POSTN w [...] (206 aa) |
| | Atp6v1h | V-type proton ATPase subunit H; Subunit of the peripheral V1 complex of vacuolar ATPase. Subunit H activates the ATPase activity of the enzyme and couples ATPase activity to proton flow. 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. Involved in the endocytosis mediated by clathrin- coated pits, required for the formation of endosomes (By similarity). (483 aa) |
| | Itln1 | Intelectin-1a; 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 mammalian glycans. Probably plays a role in the defense system agains [...] (313 aa) |
| | Snx10 | Sorting nexin-10; Probable phosphoinositide-binding protein involved in protein sorting and membrane trafficking in endosomes. Plays a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium. Required for the localization to the cilium of V-ATPase subunit ATP6V1D and ATP6V0D1, and RAB8A. Involved in osteoclast differentiation and therefore bone resorption. (201 aa) |
| | Suco | SUN domain-containing ossification factor; Required for bone modeling during late embryogenesis. Regulates type I collagen synthesis in osteoblasts during their postnatal maturation. (1254 aa) |
| | Npy1r | Neuropeptide Y receptor type 1; Receptor for neuropeptide Y and peptide YY. (382 aa) |
| | Ano5 | Anoctamin-5; Does not exhibit calcium-activated chloride channel (CaCC) activity. (904 aa) |
| | Chsy1 | Chondroitin sulfate synthase 1; Has both beta-1,3-glucuronic acid and beta-1,4-N- acetylgalactosamine transferase activity. Transfers glucuronic acid (GlcUA) from UDP-GlcUA and N-acetylgalactosamine (GalNAc) from UDP- GalNAc to the non-reducing end of the elongating chondroitin polymer. (800 aa) |
| | Chad | Chondroadherin; Promotes attachment of chondrocytes, fibroblasts, and osteoblasts. This binding is mediated (at least for chondrocytes and fibroblasts) by the integrin alpha(2)beta(1). May play an important role in the regulation of chondrocyte growth and proliferation (By similarity); Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class IV subfamily. (358 aa) |
| | Runx3 | Runt-related transcription factor 3; Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'- TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T [...] (423 aa) |
| | Tmem64 | Transmembrane protein 64; Positively regulates TNFSF11-induced osteoclast differentiation. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with SERCA2 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca (2+) signaling cascades that promote osteoclast differentiation and activation. Negatively regulates [...] (381 aa) |
| | Irs1 | Insulin receptor substrate 1; May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity). (1231 aa) |
| | Slc39a14 | Zinc transporter ZIP14; Broad-scope metal ion transporter with a preference for zinc uptake. Also mediates cellular uptake of nontransferrin-bound iron. (489 aa) |
| | Thra | Thyroid hormone receptor alpha; Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Isoform Alpha- deltaE6 does not bind DNA, inhibits the activity of isoform Alpha-1, and stimulates myoblast differentiation. (492 aa) |
| | Casr | Extracellular calcium-sensing receptor; G-protein-coupled receptor that senses changes in the extracellular concentration of calcium ions and plays a key role in maintaining calcium homeostasis (By similarity). Senses fluctuations in the circulating calcium concentration and modulates the production of parathyroid hormone (PTH) in parathyroid glands. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system (By similarity). The G-protein-coupled receptor activity is activated by a co-agonist mechanism: aromatic amino [...] (1079 aa) |
| | Cebpb | CCAAT/enhancer-binding protein beta; Important transcription factor regulating the expression of genes involved in immune and inflammatory responses. Plays also a significant role in adipogenesis, as well as in the gluconeogenic pathway, liver regeneration, and hematopoiesis. The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Its functional capacity is governed by protein interactions and post-translational protein modifications. During early embryogenesis, plays essential and redundant functions with CEBPA. Has a promitotic effect on many cell types such as hepatocytes and adipo [...] (296 aa) |
| | Cthrc1 | Collagen triple helix repeat-containing protein 1; May act as a negative regulator of collagen matrix deposition. (245 aa) |
| | Smad1 | Mothers against decapentaplegic homolog 1; Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor- regulated SMAD (R-SMAD) (By similarity). May play a role in the initiation and maintenance of spermatogenesis. SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1 (By similarity). May act synergistically with SMAD4 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. (465 aa) |
| | Calcr | Calcitonin receptor; This is a receptor for calcitonin. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. The calcitonin receptor is thought to couple to the heterotrimeric guanosine triphosphate-binding protein that is sensitive to cholera toxin; Belongs to the G-protein coupled receptor 2 family. (533 aa) |
| | Bglap | Osteocalcin; Constitutes 1-2% of the total bone protein. It binds strongly to apatite and calcium; Belongs to the osteocalcin/matrix Gla protein family. (95 aa) |
| | Notch2 | Neurogenic locus notch homolog protein 2; Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation (By [...] (2473 aa) |
| | Slc4a2 | Anion exchange protein 2; Plasma membrane anion exchange protein of wide distribution; Belongs to the anion exchanger (TC 2.A.31) family. (1237 aa) |
| | Plcg2 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2; The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signaling (By similarity). (1265 aa) |
| | Spp1 | Osteopontin; Binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction; Belongs to the osteopontin family. (295 aa) |
| | Agtr2 | Type-2 angiotensin II receptor; Receptor for angiotensin II. Cooperates with MTUS1 to inhibit ERK2 activation and cell proliferation. (363 aa) |
| | Hfe | Hereditary hemochromatosis protein homolog; Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin. (359 aa) |
| | Naca | Nascent polypeptide-associated complex subunit alpha, muscle-specific form; Cardiac- and muscle-specific transcription factor. May act to regulate the expression of genes involved in the development of myotubes. Plays a critical role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration. Involved in the organized assembly of thick and thin filaments of myofibril sarcomeres. (2187 aa) |
| | Id1 | DNA-binding protein inhibitor ID-1; Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Implicated in regulating a variety of cellular processes, including cellular growth, senescence, differentiation, apoptosis, angiogenesis, and neoplastic transformation. Inhibits skeletal muscle and cardiac myocyte differentiation. Regulates the circadian clock by repressing the transcriptional activator activity of the C [...] (148 aa) |
| | Bglap2 | Osteocalcin-2; Constitutes 1-2% of the total bone protein. It binds strongly to apatite and calcium; Belongs to the osteocalcin/matrix Gla protein family. (95 aa) |
| | Grem1 | Gremlin-1; Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as BMP a antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH feedback loop. Down-regulates the BMP4 signaling in a dose-dependent manner. Antagonist of BMP2; inhibits BMP2-mediated differentiation of osteoblasts (in vitro) (By similarity). Acts as inhibitor of monocyte chemotaxis (By similarity). (184 aa) |
| | Nlrp3 | NACHT, LRR and PYD domains-containing protein 3; As the sensor component of the NLRP3 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP3, PYCARD and CASP1 (or possibly CASP4/CASP11). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. Activation of NLRP3 inflammasome is also required for HMGB1 secretion. The active cytokines a [...] (1033 aa) |
| | Adam17 | Disintegrin and metalloproteinase domain-containing protein 17; Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Plays a role in the proteolytic processing of ACE2 (By similarity). Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Acts as an activator of [...] (846 aa) |
| | Fbn1 | Fibrillin-1; [Fibrillin-1]: Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues. Fibrillin-1-containing microfibrils provide long-term force bearing structural support. In tissues such as the lung, blood vessels and skin, microfibrils form the periphery of the elastic fiber, acting as a scaffold for the deposition of elastin. In addition, microfibrils can occur as elastin-independent networks in tissues such as the ciliary zonule, tendon, cornea and glomerulus [...] (2873 aa) |
| | P3h1 | Prolyl 3-hydroxylase 1; Basement membrane-associated chondroitin sulfate proteoglycan (CSPG). Has prolyl 3-hydroxylase activity catalyzing the post- translational formation of 3-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens, especially types IV and V. May be involved in the secretory pathway of cells. Has growth suppressive activity in fibroblasts (By similarity). (748 aa) |
| | Cd47 | Leukocyte surface antigen CD47; Has a role in both cell adhesion by acting as an adhesion receptor for THBS1 on platelets, and in the modulation of integrins. Plays an important role in memory formation and synaptic plasticity in the hippocampus. Receptor for SIRPA, binding to which prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. Interaction with SIRPG mediates cell-cell adhesion, enhances superantigen-dependent T-cell-mediated proliferation and costimulates T-cell activation. May play a role in membrane transport and/or integ [...] (324 aa) |
| | Ebf1 | Transcription factor COE1; Transcriptional activator which recognizes variations of the palindromic sequence 5'-ATTCCCNNGGGAATT-3'. Belongs to the COE family. (592 aa) |
| | Hgs | Hepatocyte growth factor-regulated tyrosine kinase substrate; Involved in intracellular signal transduction mediated by cytokines and growth factors. When associated with STAM, it suppresses DNA signaling upon stimulation by IL-2 and GM-CSF. Could be a direct effector of PI3-kinase in vesicular pathway via early endosomes and may regulate trafficking to early and late endosomes by recruiting clathrin. May concentrate ubiquitinated receptors within clathrin- coated regions. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with STAM (E [...] (776 aa) |
| | Hivep3 | Transcription factor HIVEP3; Plays a role of transcription factor; binds to recognition signal sequences (Rss heptamer) for somatic recombination of immunoglobulin and T-cell receptor gene segments; Binds also to the kappa-B motif of gene such as S100A4, involved in cell progression and differentiation. Kappa-B motif is a gene regulatory element found in promoters and enhancers of genes involved in immunity, inflammation, and growth and that responds to viral antigens, mitogens, and cytokines. Involvement of HIVEP3 in cell growth is strengthened by the fact that its down-regulation pro [...] (2348 aa) |
| | Scube2 | Signal peptide, CUB and EGF-like domain-containing protein 2; Lipid-binding protein required for SHH long-range signaling by binding to the dually lipid-modified SHH (ShhNp) and by promoting ShhNp mobilization, solubilization and release from the cell membrane. Acts by enhancing the proteolytic processing (shedding) of the lipid-modified N- and C- terminal of ShhNp at the cell surface. Synergizes with DISP1 to cause an increase in SHH secretion. Probable cell surface coreceptor for VEGFR2 involved in VEGFR2-mediated angiogenesis. (968 aa) |
| | Spop | Speckle-type POZ protein; Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation. The cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOP has higher ubiquitin ligase activity than the complex that contains the heterodimer formed by SPOP and SPOPL (By similarity). In complex with CUL3, involved in ubiquitination and proteasomal degradation of BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. In complex with CUL3 [...] (374 aa) |
| | Nfix | Nuclear factor 1 X-type; Recognizes and binds the palindromic sequence 5'- TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication. Isoform NFIX1 acts as a transcriptional activator while isoform NFIX3 acts as a repressor; Belongs to the CTF/NF-I family. (494 aa) |
| | Runx2 | Runt-related transcription factor 2; Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis. Essential for the maturation of osteoblasts and both intramembranous and endochondral ossification. CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, osteocalcin, osteopontin, bone sialoprotein, alpha 1(I) collagen, LCK, IL-3 and GM-CSF promoters. Inhibits KAT6B-dependent transcriptional activation (By similarity). In osteoblasts, supports transc [...] (528 aa) |
| | Amer1 | APC membrane recruitment protein 1; Regulator of the canonical Wnt signaling pathway. Acts by specifically binding phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), translocating to the cell membrane and interacting with key regulators of the canonical Wnt signaling pathway, such as components of the beta-catenin destruction complex. Acts both as a positive and negative regulator of the Wnt signaling pathway, depending on the context: acts as a positive regulator by promoting LRP6 phosphorylation. Also acts as a negative regulator by acting as a scaffold protein for the beta-caten [...] (1132 aa) |
| | Sh3bp2 | SH3 domain-binding protein 2; Binds differentially to the SH3 domains of certain proteins of signal transduction pathways. Binds to phosphatidylinositols; linking the hemopoietic tyrosine kinase fes to the cytoplasmic membrane in a phosphorylation dependent mechanism (By similarity). (615 aa) |
| | Stat3 | Signal transducer and activator of transcription 3; Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (By similarity). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (By similarity). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Binds to the interleukin-6 (IL-6)- responsive elements identified in the promoters of various acute-phase protein genes (By similarity). Activated by IL31 through IL31RA (By s [...] (770 aa) |
| | Nos1 | Nitric oxide synthase, brain; Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Isoform NNOS Mu may be an effector enzyme for the dystrophin complex. (1429 aa) |
| | Abhd5 | 1-acylglycerol-3-phosphate O-acyltransferase ABHD5; Coenzyme A-dependent lysophosphatidic acid acyltransferase that catalyzes the transfert of an acyl group on a lysophosphatidic acid. Functions preferentially with 1-oleoyl- lysophosphatidic acid followed by 1-palmitoyl-lysophosphatidic acid, 1- stearoyl-lysophosphatidic acid and 1-arachidonoyl-lysophosphatidic acid as lipid acceptor. Functions preferentially with arachidonoyl-CoA followed by oleoyl-CoA as acyl group donors. Functions in phosphatidic acid biosynthesis (By similarity). May regulate the cellular storage of triacylglycero [...] (351 aa) |
| | Inpp5d | Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1; Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways (By similarity). Able also to hydrolyzes the 5-phosphate of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3) and inositol 1,3,4,5-tetrakisphosphate. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), p [...] (1191 aa) |
| | Ccr2 | C-C chemokine receptor type 2; Key functional receptor for CCL2 but can also bind CCL7 and CCL12 chemokines. Its binding with CCL2 on monocytes and macrophages mediates chemotaxis and migration induction through the activation of the PI3K cascade, the small G protein Rac and lamellipodium protrusion (By similarity). Also acts as a receptor for the beta-defensin DEFB106A/DEFB106B (By similarity). Regulates the expression of T-cell inflammatory cytokines and T-cell differentiation, promoting the differentiation of T-cells into T-helper 17 cells (Th17) during inflammation. Facilitates the [...] (373 aa) |
| | Usp34 | Ubiquitin carboxyl-terminal hydrolase 34; Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. Acts as an activator of the Wnt signaling pathway downstream of the beta-catenin destruction complex by deubiquitinating and stabilizing AXIN1 and AXIN2, leading to promote nuclear accumulation of AXIN1 and AXIN2 and positively regulate beta-catenin (CTNBB1)-mediated transcription. Recognizes and hydrolyzes the peptide bond at the C- terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precurs [...] (3582 aa) |
| | Ccdc154 | Coiled-coil domain-containing protein 154. (664 aa) |
| | Il6st | Interleukin-6 receptor subunit beta; Signal-transducing molecule. The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6ST homodimerization and formation of a high-affinity receptor complex, which activates Janus kinases. That causes phosphorylation of IL6ST tyrosine residues which in turn activates STAT3. Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism. Has a role in embryonic development. Does not bind IL6 (By similarity). Essential for [...] (917 aa) |
| | Pgr | Progesterone receptor; The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor. [Isoform B]: Transcriptional activator of several progesteron-dependent promoters in a variety of cell types. Involved in activation of SRC-dependent MAPK signaling on hormone stimulation. Belongs to the nuclear hormone receptor family. NR3 subfamily. (926 aa) |
| | Pcdh7 | Protocadherin 7. (1255 aa) |
| | Casp3 | Caspase-3 subunit p12; Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Triggers cell adhesion in sympathetic neurons through RET cleavage (By similarity). Cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytok [...] (277 aa) |
| | Inpp4b | Type II inositol 3,4-bisphosphate 4-phosphatase; Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate and inositol 3,4-bisphosphate (By similarity). Plays a role in the late stages of macropinocytosis by dephosphorylating phosphatidylinositol 3,4-bisphosphate in membrane ruffles (By similarity). Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (By similarity). (941 aa) |
| | Sbno2 | Protein strawberry notch homolog 2; Acts as a transcriptional coregulator, that can have both coactivator and corepressor functions. Inhibits the DCSTAMP-repressive activity of TAL1, hence enhancing the access of the transcription factor MITF to the DC- STAMP promoter in osteoclast. Plays a role in bone homeostasis; required as a positive regulator in TNFSF11//RANKL- mediated osteoclast fusion via a DCSTAMP-dependent pathway. May also be required in the regulation of osteoblast differentiation. Involved in the transcriptional corepression of NF-kappaB in macrophages. Plays a role as a [...] (1349 aa) |
