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| Sox9 | Transcription factor SOX-9; Transcriptional regulator that plays a role in chondrocytes differentiation and skeletal development. Binds to the COL2A1 promoter and activates COL2A1 expression, as part of a complex with ZNF219. (507 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) | ||||
| Mmp13 | Collagenase 3; Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CCN2. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bon [...] (472 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) | ||||
| Pfn1 | Profilin-1; Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR (By similarity). (140 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) | ||||
| 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) | ||||
| Fgf18 | Fibroblast growth factor 18; Plays an important role in the regulation of cell proliferation, cell differentiation and cell migration. Required for normal ossification and bone development. Stimulates hepatic and intestinal proliferation (By similarity). (207 aa) | ||||
| Ror2 | Tyrosine-protein kinase transmembrane receptor ROR2; Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes. It seems to be required for cartilage and growth plate development. Phosphorylates YWHAB, leading to induction of osteogenesis and bone formation. In contrast, has also been shown to have very little tyrosine kinase activity in vitro. May act as a receptor for wnt ligand WNT5A which may result in the inhibition of WNT3A-mediated signaling (By similarity). (944 aa) | ||||
| Pitx1 | Pituitary homeobox 1; Sequence-specific transcription factor that binds gene promoters and activates their transcription. May play a role in the development of anterior structures, and in particular, the brain and facies and in specifying the identity or structure of hindlimb. Can independently activate and synergize with PIT-1 on pituitary-specific target gene promoters, thus may subserve functions in generating both precursor and specific cell phenotypes in the anterior pituitary gland and in several other organs. Can activate pituitary transcription of the proopiomelanocortin gene. (315 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) | ||||
| Vdr | Vitamin D3 receptor; Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells (By similarity). Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR (By similarity). The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes (By similarity). Plays a central role in calcium homeostasis (By similarity). (422 aa) | ||||
| Ifitm5 | Interferon-induced transmembrane protein 5; Required for normal bone mineralization. (134 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) | ||||
| Fgf21 | Fibroblast growth factor 21; Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity probably requires the presence of KLB; Belongs to the heparin-binding growth factors family. (210 aa) | ||||
| Rgs10 | Regulator of G-protein signaling 10; Regulates G protein-coupled receptor signaling cascades, including signaling downstream of the muscarinic acetylcholine receptor CHRM2. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Modulates the activity of potassium channels that are activated in response to CHRM2 signaling. Activity on GNAZ is inhibited by palmitoylation of the G-protein. (181 aa) | ||||
| Smad3 | Mothers against decapentaplegic homolog 3; Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP- 1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and m [...] (425 aa) | ||||
| Wnt4 | Protein Wnt-4; Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Plays an important role in the embryonic development of the urogenital tract and the lung. Required for normal mesenchyme to epithelium transition during embryonic kidney development. Required for the formation of early epithelial renal vesicles during kidney development. Required for normal formation of the Mullerian duct in females, and normal levels of oocytes in the ovaries. Required for normal down- regulation of 3 beta-hydroxysteroid dehydrogenase in the ovary. Required for norma [...] (351 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) | ||||
| Pbxip1 | Pre-B-cell leukemia transcription factor-interacting protein 1; Regulator of pre-B-cell leukemia transcription factors (BPXs) function. Inhibits the binding of PBX1-HOX complex to DNA and blocks the transcriptional activity of E2A-PBX1. Tethers estrogen receptor- alpha (ESR1) to microtubules and allows them to influence estrogen receptors-alpha signaling (By similarity). (727 aa) | ||||
| Mitf | Microphthalmia-associated transcription factor; Transcription factor that regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR). Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1). Plays a critical role in the differentiation of various cell types, such as neural crest-derived melanocyt [...] (526 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) | ||||
| Flnb | Filamin-B; Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton (By similarity). Belongs to the filamin family. (2602 aa) | ||||
| Foxc1 | Forkhead box protein C1; DNA-binding transcriptional factor that plays a role in a broad range of cellular and developmental processes such as eye, bones, cardiovascular, kidney and skin development. Acts either as a transcriptional activator or repressor. Binds to the consensus binding site 5'-[G/C][A/T]AAA[T/C]AA[A/C]-3' in promoter of target genes. Upon DNA-binding, promotes DNA bending. Acts as a transcriptional coactivator. Stimulates Indian hedgehog (Ihh)-induced target gene expression mediated by the transcription factor GLI2, and hence regulates endochondral ossification. Acts [...] (553 aa) | ||||
| Cdc42 | Cell division control protein 42 homolog; Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In its active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Regulates cell migration (By similarity). In neurons, plays a role in the extension and maintenance of the formation of filopodia, thin and actin-rich surface projections. Req [...] (191 aa) | ||||
| Gli2 | Zinc finger protein GLI2; Functions as transcription regulator in the hedgehog (Hh) pathway. Functions as transcriptional activator. May also function as transcriptional repressor. Requires STK36 for full transcriptional activator activity. Binds to the DNA sequence 5'-GAACCACCCA-3' which is part of the TRE-2S regulatory element (By similarity). Is involved in the smoothened (SHH) signaling pathway. Required for normal skeleton development. Belongs to the GLI C2H2-type zinc-finger protein family. (1544 aa) | ||||
| Riox1 | Ribosomal oxygenase 1; Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase Also catalyzes the hydroxylation of 60S ribosomal protein L8 on 'His-216'. Acts as a regulator of osteoblast differentiation via its interaction with SP7/OSX by demethylating H3K4me and H3K36me, thereby inhibiting SP7/OSX-mediated promoter activation. May also play a role in ribosome biogenesis and in the replication or remodeling of certain heterochromatic region. Participates in MYC-induced transcriptional activation (By similarity). Specifically demethylates 'Lys- [...] (603 aa) | ||||
| Npr3 | Atrial natriuretic peptide receptor 3; Receptor for the natriuretic peptide hormones, binding with similar affinities atrial natriuretic peptide NPPA/ANP, brain natriuretic peptide NPPB/BNP, and C-type natriuretic peptide NPPC/CNP. May function as a clearance receptor for NPPA, NPPB and NPPC, regulating their local concentrations and effects. May regulate diuresis, blood pressure and skeletal development. Does not have guanylate cyclase activity. (536 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) | ||||
| Smpd3 | Sphingomyelin phosphodiesterase 3; Catalyzes the hydrolysis of sphingomyelin to form ceramide and phosphocholine. Ceramide mediates numerous cellular functions, such as apoptosis and growth arrest, and is capable of regulating these 2 cellular events independently. Also hydrolyzes sphingosylphosphocholine. Regulates the cell cycle by acting as a growth suppressor in confluent cells. Acts as a regulator of postnatal development and participates in bone and dentin mineralization. Overexpression enhances cell death, suggesting that it may be involved in apoptosis control. Belongs to the n [...] (655 aa) | ||||
| Tg | Thyroglobulin; Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (By similarity). The synthesis of T3 and T4 involves iodination of selected tyrosine residues of TG/thyroglobulin followed by their oxidative coupling (By similarity). Following TG re-internalization and lysosomal-mediated proteolysis, T3 and T4 are released from the polypeptide backbone leading to their secretion into the bloodstream (Probable). (2766 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) | ||||
| Phex | Phosphate-regulating neutral endopeptidase PHEX; Peptidase that cleaves SIBLING (small integrin-binding ligand, N-linked glycoprotein)-derived ASARM peptides, thus regulating their biological activity (By similarity). Cleaves ASARM peptides between Ser and Glu or Asp residues (By similarity). Regulates osteogenic cell differentiation and bone mineralization through the cleavage of the MEPE-derived ASARM peptide. Promotes dentin mineralization and renal phosphate reabsorption by cleaving DMP1- and MEPE-derived ASARM peptides. Inhibits the cleavage of MEPE by CTSB/cathepsin B thus preven [...] (749 aa) | ||||
| Ltbp3 | Latent-transforming growth factor beta-binding protein 3; Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space. Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta. (1253 aa) | ||||
| Adamts10 | A disintegrin and metalloproteinase with thrombospondin motifs 10; Metalloprotease that participate in microfibrils assembly. Microfibrils are extracellular matrix components occurring independently or along with elastin in the formation of elastic tissues (By similarity). (1104 aa) | ||||
| Mmp14 | Matrix metalloproteinase-14; Endopeptidase that degrades various components of the extracellular matrix such as collagen. Activates progelatinase A. Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal connective tissues during development. May be involved in actin cytoskeleton reorganization by cleaving PTK7 (By similarity). Acts as a positive regulator of cell growth and migration via activation of MMP15. Involved in the formation of the fibrovascular tissues (By similarity). Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiogenesis (By si [...] (582 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) | ||||
| Col10a1 | Collagen alpha-1(X) chain; Type X collagen is a product of hypertrophic chondrocytes and has been localized to presumptive mineralization zones of hyaline cartilage. (680 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) | ||||
| Csf1r | Macrophage colony-stimulating factor 1 receptor; Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and 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 in response to IL34 and CSF1, 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 regulat [...] (977 aa) | ||||
| Tcirg1 | V-type proton ATPase subunit a; Essential component of the vacuolar proton pump (V-ATPase), a multimeric enzyme that catalyzes the translocation of protons across the membranes. Required for assembly and activity of the V-ATPase. (834 aa) | ||||
| 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) | ||||
| Hspg2 | Basement membrane-specific heparan sulfate proteoglycan core protein; Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development (By similarity). The LG3 peptide has anti-angiogenic propert [...] (4383 aa) | ||||
| Fgfr3 | Fibroblast growth factor receptor 3; Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Required for normal development of the inner ear. Ph [...] (801 aa) | ||||
| Asap1 | Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1; May function as a signal transduction protein involved in the differentiation of fibroblasts into adipocytes and possibly other cell types. Plays a role in ciliogenesis (By similarity). Posseses phosphatidylinositol 4,5-bisphosphate-dependent GTPase-activating protein activity for ARF1 (ADP ribosylation factor 1) and ARF5 and a lesser activity towards ARF6. May coordinate membrane trafficking with cell growth or actin cytoskeleton remodeling by binding to both SRC and PIP2. (1147 aa) | ||||
| Acp5 | Tartrate-resistant acid phosphatase type 5; May play a role in the process of bone resorption. The osteoclastic trap acts on nucleotide tri- and diphosphates with higher affinity, compared with other substrates. (327 aa) | ||||