SOX9

The protein encoded by this gene recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins. It acts during chondrocyte differentiation and, with steroidogenic factor 1, regulates transcription of the anti-Muellerian hormone (AMH) gene. Deficiencies lead to the skeletal malformation syndrome campomelic dysplasia, frequently with sex reversal. [provided by RefSeq, Jul 2008]

SOX9

Transcription factor that plays a key role in chondrocytes differentiation and skeletal development (PubMed:24038782).
Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis, including cartilage matrix protein-coding genes COL2A1, COL4A2, COL9A1, COL11A2 and ACAN, SOX5 and SOX6 (PubMed:8640233).
Also binds to some promoter regions (By similarity).
Plays a central role in successive steps of chondrocyte differentiation (By similarity).
Absolutely required for precartilaginous condensation, the first step in chondrogenesis during which skeletal progenitors differentiate into prechondrocytes (By similarity).
Together with SOX5 and SOX6, required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes, the second step in chondrogenesis (By similarity).
Later, required to direct hypertrophic maturation and block osteoblast differentiation of growth plate chondrocytes: maintains chondrocyte columnar proliferation, delays prehypertrophy and then prevents osteoblastic differentiation of chondrocytes by lowering beta-catenin (CTNNB1) signaling and RUNX2 expression (By similarity).
Also required for chondrocyte hypertrophy, both indirectly, by keeping the lineage fate of chondrocytes, and directly, by remaining present in upper hypertrophic cells and transactivating COL10A1 along with MEF2C (By similarity).
Low lipid levels are the main nutritional determinant for chondrogenic commitment of skeletal progenitor cells: when lipids levels are low, FOXO (FOXO1 and FOXO3) transcription factors promote expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity).
Mechanistically, helps, but is not required, to remove epigenetic signatures of transcriptional repression and deposit active promoter and enhancer marks at chondrocyte-specific genes (By similarity).
Acts in cooperation with the Hedgehog pathway-dependent GLI (GLI1 and GLI3) transcription factors (By similarity).
In addition to cartilage development, also acts as a regulator of proliferation and differentiation in epithelial stem/progenitor cells: involved in the lung epithelium during branching morphogenesis, by balancing proliferation and differentiation and regulating the extracellular matrix (By similarity).
Controls epithelial branching during kidney development (By similarity).

Biological Process anterior head developmentIEA:Ensembl
Biological Process aortic valve morphogenesisManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process astrocyte fate commitmentIEA:Ensembl
Biological Process bone mineralizationIEA:Ensembl
Biological Process branching involved in ureteric bud morphogenesisIEA:Ensembl
Biological Process bronchus cartilage developmentIEA:Ensembl
Biological Process cAMP-mediated signalingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process canonical Wnt signaling pathwayIEA:Ensembl
Biological Process cartilage condensationISS:UniProtKB
Biological Process cartilage developmentISS:UniProtKB
Biological Process cell fate specificationISS:UniProtKB
Biological Process cell proliferation involved in heart morphogenesisIEA:Ensembl
Biological Process cell-cell adhesionIEA:Ensembl
Biological Process cellular response to BMP stimulusISS:UniProtKB
Biological Process cellular response to epidermal growth factor stimulusBy SimilarityISS:UniProtKB
Biological Process cellular response to heparinBy SimilarityISS:UniProtKB
Biological Process cellular response to interleukin-1Manual Assertion Based On ExperimentIEP:UniProtKB
Biological Process cellular response to mechanical stimulusBy SimilarityISS:UniProtKB
Biological Process cellular response to retinoic acidManual Assertion Based On ExperimentIEP:UniProtKB
Biological Process cellular response to transforming growth factor beta stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process chondrocyte differentiationISS:UniProtKB
Biological Process chondrocyte differentiation involved in endochondral bone morphogenesisManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process chondrocyte hypertrophyISS:UniProtKB
Biological Process chromatin remodelingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process cochlea morphogenesisISS:UniProtKB
Biological Process cytoskeleton organizationIEA:Ensembl
Biological Process endocardial cushion morphogenesisISS:UniProtKB
Biological Process endocrine pancreas developmentIEA:Ensembl
Biological Process epidermal growth factor receptor signaling pathwayBy SimilarityISS:UniProtKB
Biological Process epithelial cell proliferation involved in prostatic bud elongationISS:UniProtKB
Biological Process epithelial to mesenchymal transitionISS:UniProtKB
Biological Process epithelial tube branching involved in lung morphogenesisIEA:Ensembl
Biological Process ERK1 and ERK2 cascadeBy SimilarityISS:UniProtKB
Biological Process extracellular matrix assemblyIEA:Ensembl
Biological Process glandular epithelial cell differentiationIEA:Ensembl
Biological Process glial cell fate specificationIEA:Ensembl
Biological Process growth plate cartilage chondrocyte growthISS:UniProtKB
Biological Process hair follicle developmentISS:UniProtKB
Biological Process Harderian gland developmentIEA:Ensembl
Biological Process heart developmentManual Assertion Based On ExperimentIBA:GO_Central
Biological Process heart valve developmentISS:UniProtKB
Biological Process heart valve formationIEA:Ensembl
Biological Process heart valve morphogenesisISS:UniProtKB
Biological Process intestinal epithelial cell differentiationIEA:Ensembl
Biological Process intestinal epithelial structure maintenanceISS:UniProtKB
Biological Process intrahepatic bile duct developmentIEA:Ensembl
Biological Process lacrimal gland developmentIEA:Ensembl
Biological Process limb bud formationIEA:Ensembl
Biological Process lung smooth muscle developmentIEA:Ensembl
Biological Process male germ-line sex determinationISS:UniProtKB
Biological Process male gonad developmentManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process mammary gland developmentIEA:Ensembl
Biological Process mesenchymal cell apoptotic processIEA:Ensembl
Biological Process mesenchymal cell proliferationIEA:Ensembl
Biological Process metanephric nephron tubule formationISS:UniProtKB
Biological Process morphogenesis of a branching epitheliumISS:UniProtKB
Biological Process morphogenesis of an epitheliumManual Assertion Based On ExperimentIBA:GO_Central
Biological Process negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of beta-catenin-TCF complex assemblyIEA:Ensembl
Biological Process negative regulation of biomineral tissue developmentManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of bone mineralizationIEA:Ensembl
Biological Process negative regulation of canonical Wnt signaling pathwayISS:UniProtKB
Biological Process negative regulation of chondrocyte differentiationISS:UniProtKB
Biological Process negative regulation of DNA-templated transcriptionManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of epithelial cell differentiationIEA:Ensembl
Biological Process negative regulation of epithelial cell proliferationISS:UniProtKB
Biological Process negative regulation of fatty acid oxidationISS:UniProtKB
Biological Process negative regulation of gene expressionIEA:Ensembl
Biological Process negative regulation of immune system processISS:UniProtKB
Biological Process negative regulation of mesenchymal cell apoptotic processIEA:Ensembl
Biological Process negative regulation of miRNA transcriptionManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of myoblast differentiationISS:UniProtKB
Biological Process negative regulation of ossificationManual Assertion Based On ExperimentIDA:CACAO
Biological Process negative regulation of osteoblast differentiationISS:UniProtKB
Biological Process negative regulation of photoreceptor cell differentiationISS:UniProtKB
Biological Process negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:CACAO
Biological Process neural crest cell developmentIEA:Ensembl
Biological Process neural crest cell fate specificationISS:UniProtKB
Biological Process neuron fate specificationIEA:Ensembl
Biological Process Notch signaling pathwayIEA:Ensembl
Biological Process notochord developmentIEA:Ensembl
Biological Process nucleosome assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process oligodendrocyte differentiationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process otic vesicle formationISS:UniProtKB
Biological Process positive regulation of branching involved in ureteric bud morphogenesisISS:UniProtKB
Biological Process positive regulation of cartilage developmentManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of cell proliferation involved in heart morphogenesisIEA:Ensembl
Biological Process positive regulation of chondrocyte differentiationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of chondrocyte proliferationManual Assertion Based On ExperimentIDA:CACAO
Biological Process positive regulation of DNA-templated transcriptionManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of epithelial cell differentiationISS:UniProtKB
Biological Process positive regulation of epithelial cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of epithelial cell proliferationManual Assertion Based On ExperimentIEP:UniProtKB
Biological Process positive regulation of extracellular matrix assemblyIEA:Ensembl
Biological Process positive regulation of gene expressionManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of kidney developmentISS:UniProtKB
Biological Process positive regulation of male gonad developmentManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of mesenchymal cell proliferationISS:UniProtKB
Biological Process positive regulation of mesenchymal stem cell differentiationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of phosphatidylinositol 3-kinase signalingISS:UniProtKB
Biological Process positive regulation of protein catabolic processIEA:Ensembl
Biological Process positive regulation of protein phosphorylationISS:UniProtKB
Biological Process positive regulation of stem cell proliferationIEA:Ensembl
Biological Process positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process prostate gland developmentManual Assertion Based On ExperimentIEP:UniProtKB
Biological Process protein kinase B signalingIEA:Ensembl
Biological Process protein localization to nucleusIEA:Ensembl
Biological Process protein phosphorylationIEA:Ensembl
Biological Process protein-containing complex assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of apoptotic processISS:UniProtKB
Biological Process regulation of branching involved in lung morphogenesisIEA:Ensembl
Biological Process regulation of cell adhesionIEA:Ensembl
Biological Process regulation of cell cycle processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of cell population proliferationISS:UniProtKB
Biological Process regulation of cell proliferation involved in tissue homeostasisISS:UniProtKB
Biological Process regulation of epithelial cell proliferation involved in lung morphogenesisIEA:Ensembl
Biological Process regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Biological Process renal vesicle inductionISS:UniProtKB
Biological Process response to fatty acidISS:UniProtKB
Biological Process response to organic cyclic compoundIEA:Ensembl
Biological Process retina development in camera-type eyeISS:UniProtKB
Biological Process retinal rod cell differentiationISS:UniProtKB
Biological Process Sertoli cell developmentIEA:Ensembl
Biological Process Sertoli cell differentiationISS:UniProtKB
Biological Process signal transductionISS:UniProtKB
Biological Process skeletal system developmentManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process somatic stem cell population maintenanceISS:UniProtKB
Biological Process spermatogenesisISS:UniProtKB
Biological Process stem cell proliferationIEA:Ensembl
Biological Process tissue homeostasisISS:UniProtKB
Biological Process trachea cartilage developmentIEA:Ensembl
Biological Process transcription by RNA polymerase IIIEA:Ensembl
Biological Process type I pneumocyte differentiationIEA:Ensembl
Biological Process ureter morphogenesisIEA:Ensembl
Biological Process ureter smooth muscle cell differentiationIEA:Ensembl
Biological Process ureter urothelium developmentIEA:Ensembl

Nucleus

Campomelic dysplasia (CMD1):
A rare, often lethal, osteochondrodysplasia characterized by congenital bowing and angulation of long bones. Other skeletal defects include unusually small scapula, deformed pelvis and spine, and a missing pair of ribs. Craniofacial and ear defects are common. Most patients die soon after birth due to respiratory distress which has been attributed to hypoplasia of the tracheobronchial cartilage and small thoracic cage. Up to two-thirds of affected XY individuals have genital defects or may develop as phenotypic females.
46,XX sex reversal 2 (SRXX2):
A condition in which male gonads develop in a genetic female (female to male sex reversal).
46,XY sex reversal 10 (SRXY10):
A disorder of sex development. Affected individuals have a 46,XY karyotype, show gonadal dysgenesis with streak gonads, look like normal females at birth, do not develop secondary sexual characteristics at puberty and do not menstruate.

Acetylated; acetylation impairs nuclear localization and ability to transactivate expression of target genes. Deacetylated by SIRT1.
Phosphorylation at Ser-64 and Ser-211 by PKA increases transcriptional activity and may help delay chondrocyte maturation downstream of PTHLH/PTHrP signaling. Phosphorylation at either Ser-64 or Ser-211 is required for sumoylation, but phosphorylation is not dependent on sumoylation. Phosphorylated on tyrosine residues; tyrosine dephosphorylation by PTPN11/SHP2 blocks SOX9 phosphorylation by PKA and subsequent SUMOylation.
Ubiquitinated; ubiquitination leads to proteasomal degradation and is negatively regulated by DDRGK1.
Sumoylated; phosphorylation at either Ser-64 or Ser-211 is required for sumoylation. Sumoylation is induced by BMP signaling pathway.