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Details on Person UniProt:P48436 SOX9
| Class:Id | ReferenceGeneProduct:64870 |
|---|---|
| _chainChangeLog | chain:1-509 added on Fri February 6 2015 |
| _displayName | UniProt:P48436 SOX9 |
| _timestamp | 2024-11-03 20:07:49 |
| chain | chain:1-509 |
| checksum | 9289CFBB8D6631A2 |
| comment | FUNCTION 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).SUBUNIT Homodimer; homodimerization is required for activity (By similarity). Interacts (via C-terminus) with ZNF219; forming a complex that binds to the COL2A1 promoter and activates COL2A1 expression (By similarity). Interacts with DDRGK1 (PubMed:28263186). Interacts with EP300/p300 (PubMed:12732631). Interacts with beta-catenin (CTNNB1); inhibiting CTNNB1 activity by competing with the binding sites of TCF/LEF within CTNNB1 (By similarity).INTERACTION The transactivation domains TAM and TAC (for transactivation domain in the middle and at the C-terminus, respectively) are required to contact transcriptional coactivators and basal transcriptional machinery components and thereby induce gene transactivation.DOMAIN The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.DOMAIN The PQA region (for proline, glutamine and alanine-rich) helps stabilize SOX9 and facilitates transactivation (PubMed:31194875). It lacks intrinsic transactivation capability (PubMed:31194875).PTM Acetylated; acetylation impairs nuclear localization and ability to transactivate expression of target genes. Deacetylated by SIRT1.PTM 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.PTM Ubiquitinated; ubiquitination leads to proteasomal degradation and is negatively regulated by DDRGK1.PTM Sumoylated; phosphorylation at either Ser-64 or Ser-211 is required for sumoylation. Sumoylation is induced by BMP signaling pathway.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry. |
| description | recommendedName: fullName evidence="26"Transcription factor SOX-9 |
| geneName | SOX9 |
| identifier | P48436 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Activator Differentiation Disease variant DNA-binding Isopeptide bond Nucleus Phosphoprotein Proteomics identification Reference proteome Transcription Transcription regulation Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | SOX9 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8996281] ENSEMBL:ENSG00000125398 SOX9 [Homo sapiens] |
| secondaryIdentifier | SOX9_HUMAN Q53Y80 |
| sequenceLength | 509 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:3214954] SOX9 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:3215004] SUMO1-K61,253,398-SOX9 [nucleoplasm] [Homo sapiens] |
| (referenceSequence) | [GroupModifiedResidue:3214941] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 61 [GroupModifiedResidue:3214976] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 253 [GroupModifiedResidue:3215005] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 398 |
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No pathways have been reviewed or authored by UniProt:P48436 SOX9 (64870)
