Sox9
entrez
20682
canonical
uniprot
Q04887
canonical
ensembl
ENSMUSG00000000567
resolver
ensp
ENSMUSP00000000579
resolver
enst
ENSMUST00000000579
resolver
genesymbol
Sox9
resolver
genesymbol_syn
Sox-9
resolver
uniprot
Q8C7L2
resolver
uniprot
Q91ZK2
resolver
uniprot
Q99KQ0
resolver
uniprot_entry
SOX9_MOUSE
resolver
uniprot_sec
Q8C7L2
resolver
uniprot_sec
Q91ZK2
resolver
uniprot_sec
Q99KQ0
resolver
amino_acid_sequence
MNLLDPFMKMTDEQEKGLSGAPSPTMSEDSAGSPCPSGSGSDTENTRPQENTFPKGEPDLKKESEEDKFPVCIREAVSQVLKGYDWTLVPMPVRVNGSSKNKPHVKRPMNAFMVWAQAARRKLADQYPHLHNAELSKTLGKLWRLLNESEKRPFVEEAERLRVQHKKDHPDYKYQPRRRKSVKNGQAEAEEATEQTHISPNAIFKALQADSPHSSSGMSEVHSPGEHSGQSQGPPTPPTTPKTDVQAGKVDLKREGRPLAEGGRQPPIDFRDVDIGELSSDVISNIETFDVNEFDQYLPPNGHPGVPATHGQVTYTGSYGISSTAPTPATAGHVWMSKQQAPPPPPQQPPQAPQAPQAPPQQQAPPQQPQAPQQQQAHTLTTLSSEPGQSQRTHIKTEQLSPSHYSEQQQHSPQQISYSPFNLPHYSPSYPPITRSQYDYADHQNSGSYYSHAAGQGSGLYSTFTYMNPAQRPMYTPIADTSGVPSIPQTHSPQHWEQPVYTQLTRP
uniprot
proteins
function
FUNCTION: Transcription factor that plays a key role in chondrocytes differentiation and skeletal development (PubMed:10319868, PubMed:11371614, PubMed:12414734, PubMed:15132997, PubMed:18415932, PubMed:20940257, PubMed:28263186). 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:10805756, PubMed:12414734, PubMed:15694126, PubMed:17525254, PubMed:26146088, PubMed:26150426, PubMed:26910618, PubMed:28263186, PubMed:9119111). Also binds to some promoter regions (PubMed:20940257). Plays a central role in successive steps of chondrocyte differentiation (PubMed:11371614, PubMed:12414734, PubMed:22421045). Absolutely required for precartilaginous condensation, the first step in chondrogenesis during which skeletal progenitors differentiate into prechondrocytes (PubMed:11371614, PubMed:12414734). Together with SOX5 and SOX6, required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes, the second step in chondrogenesis (PubMed:11371614, PubMed:12414734, PubMed:15529345). 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 (PubMed:22421045, PubMed:31121357). 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 (PubMed:21367821, PubMed:22421045). 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 (PubMed:32103177). Mechanistically, helps, but is not required, to remove epigenetic signatures of transcriptional repression and deposit active promoter and enhancer marks at chondrocyte-specific genes (PubMed:30021842). Acts in cooperation with the Hedgehog pathway-dependent GLI (GLI1 and GLI3) transcription factors (PubMed:29659575). 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 (PubMed:24191021). Controls epithelial branching during kidney development (PubMed:21212101). {ECO:0000269|PubMed:10319868, ECO:0000269|PubMed:10805756, ECO:0000269|PubMed:11371614, ECO:0000269|PubMed:12414734, ECO:0000269|PubMed:15132997, ECO:0000269|PubMed:15529345, ECO:0000269|PubMed:15694126, ECO:0000269|PubMed:17525254, ECO:0000269|PubMed:18415932, ECO:0000269|PubMed:20940257, ECO:0000269|PubMed:21212101, ECO:0000269|PubMed:21367821, ECO:0000269|PubMed:22421045, ECO:0000269|PubMed:24191021, ECO:0000269|PubMed:26146088, ECO:0000269|PubMed:26150426, ECO:0000269|PubMed:26910618, ECO:0000269|PubMed:28263186, ECO:0000269|PubMed:29659575, ECO:0000269|PubMed:30021842, ECO:0000269|PubMed:31121357, ECO:0000269|PubMed:32103177, ECO:0000269|PubMed:9119111}.
uniprot
proteins
mass_dalton
56077
uniprot
proteins
mutagenesis
MUTAGEN 64; /note="S->A: Abolished phosphorylation by PKA, leading to decreased ability to activate transcription of target genes; does not affect subcellular localization; when associated with A-211."; /evidence="ECO:0000269|PubMed:10805756, ECO:0000269|PubMed:11120880"; MUTAGEN 211; /note="S->A: Abolished phosphorylation by PKA, leading to decreased ability to activate transcription of target genes; does not affect subcellular localization; when associated with A-64."; /evidence="ECO:0000269|PubMed:10805756, ECO:0000269|PubMed:11120880"; MUTAGEN 396; /note="K->A: Increased stability."; /evidence="ECO:0000269|PubMed:15694126
uniprot
proteins
post_translational_modification
PTM: Acetylated; acetylation impairs nuclear localization and ability to transactivate expression of target genes (PubMed:26910618). Deacetylated by SIRT1 (PubMed:26910618). {ECO:0000269|PubMed:26910618}.; PTM: Phosphorylation at Ser-64 and Ser-211 by PKA increases transcriptional activity and may help delay chondrocyte maturation downstream of PTHLH/PTHrP signaling (PubMed:10805756, PubMed:11120880). Phosphorylation at either Ser-64 or Ser-211 is required for sumoylation, but phosphorylation is not dependent on sumoylation (PubMed:29644115). Phosphorylated on tyrosine residues; tyrosine dephosphorylation by PTPN11/SHP2 blocks SOX9 phosphorylation by PKA and subsequent SUMOylation (PubMed:29644115). {ECO:0000269|PubMed:10805756, ECO:0000269|PubMed:11120880, ECO:0000269|PubMed:29644115}.; PTM: Sumoylated; phosphorylation at either Ser-64 or Ser-211 is required for sumoylation (PubMed:29644115). Sumoylation is induced by BMP signaling pathway (PubMed:29644115). {ECO:0000269|PubMed:29644115}.; PTM: Ubiquitinated; ubiquitination leads to proteasomal degradation and is negatively regulated by DDRGK1. {ECO:0000305|PubMed:15694126}.
uniprot
proteins
pubmed
10319868
uniprot
proteins
pubmed
10805756
uniprot
proteins
pubmed
11120880
uniprot
proteins
pubmed
11371614
uniprot
proteins
pubmed
11857796
uniprot
proteins
pubmed
12414734
uniprot
proteins
pubmed
15132997
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15529345
uniprot
proteins
pubmed
15694126
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16203988
uniprot
proteins
pubmed
17525254
uniprot
proteins
pubmed
18415932
uniprot
proteins
pubmed
20940257
uniprot
proteins
pubmed
21212101
uniprot
proteins
pubmed
21367821
uniprot
proteins
pubmed
22421045
uniprot
proteins
pubmed
22510880
uniprot
proteins
pubmed
24191021
uniprot
proteins
pubmed
25229425
uniprot
proteins
pubmed
26146088
uniprot
proteins
pubmed
26150426
uniprot
proteins
pubmed
26527273
uniprot
proteins
pubmed
26910618
uniprot
proteins
pubmed
28263186
uniprot
proteins
pubmed
29644115
uniprot
proteins
pubmed
29659575
uniprot
proteins
pubmed
30021842
uniprot
proteins
pubmed
31121357
uniprot
proteins
pubmed
31382142
uniprot
proteins
pubmed
32103177
uniprot
proteins
pubmed
7704017
uniprot
proteins
pubmed
8441686
uniprot
proteins
pubmed
9119111
uniprot
proteins
sequence_length
507
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00267, ECO:0000269|PubMed:10805756, ECO:0000269|PubMed:15694126, ECO:0000269|PubMed:20940257, ECO:0000269|PubMed:21212101, ECO:0000269|PubMed:26910618}.
uniprot
proteins