SOX9
entrez
6662
canonical
uniprot
P48436
canonical
ensembl
ENSG00000125398
resolver
ensp
ENSP00000245479
resolver
enst
ENST00000245479
resolver
genesymbol
SOX9
resolver
hgnc
HGNC:11204
resolver
uniprot
Q53Y80
resolver
uniprot_entry
SOX9_HUMAN
resolver
uniprot_sec
Q53Y80
resolver
amino_acid_sequence
MNLLDPFMKMTDEQEKGLSGAPSPTMSEDSAGSPCPSGSGSDTENTRPQENTFPKGEPDLKKESEEDKFPVCIREAVSQVLKGYDWTLVPMPVRVNGSSKNKPHVKRPMNAFMVWAQAARRKLADQYPHLHNAELSKTLGKLWRLLNESEKRPFVEEAERLRVQHKKDHPDYKYQPRRRKSVKNGQAEAEEATEQTHISPNAIFKALQADSPHSSSGMSEVHSPGEHSGQSQGPPTPPTTPKTDVQPGKADLKREGRPLPEGGRQPPIDFRDVDIGELSSDVISNIETFDVNEFDQYLPPNGHPGVPATHGQVTYTGSYGISSTAATPASAGHVWMSKQQAPPPPPQQPPQAPPAPQAPPQPQAAPPQQPAAPPQQPQAHTLTTLSSEPGQSQRTHIKTEQLSPSHYSEQQQHSPQQIAYSPFNLPHYSPSYPPITRSQYDYTDHQNSSSYYSHAAGQGTGLYSTFTYMNPAQRPMYTPIADTSGVPSIPQTHSPQHWEQPVYTQLTRP
uniprot
proteins
disease_involvement
DISEASE: Campomelic dysplasia (CMD1) [MIM:114290]: 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. {ECO:0000269|PubMed:10446171, ECO:0000269|PubMed:10951468, ECO:0000269|PubMed:11323423, ECO:0000269|PubMed:11754051, ECO:0000269|PubMed:12783851, ECO:0000269|PubMed:19033726, ECO:0000269|PubMed:19921652, ECO:0000269|PubMed:20513132, ECO:0000269|PubMed:24038782, ECO:0000269|PubMed:7485151, ECO:0000269|PubMed:7990924, ECO:0000269|PubMed:8001137, ECO:0000269|PubMed:9002675, ECO:0000269|PubMed:9452059}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 46,XX sex reversal 2 (SRXX2) [MIM:278850]: A condition in which male gonads develop in a genetic female (female to male sex reversal). {ECO:0000269|PubMed:21208124}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 46,XY sex reversal 10 (SRXY10) [MIM:616425]: 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. {ECO:0000269|PubMed:25604083}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q04887, ECO:0000269|PubMed:24038782, ECO:0000269|PubMed:8640233}.
uniprot
proteins
mass_dalton
56137
uniprot
proteins
mutagenesis
MUTAGEN 278; /note="L->S: Impaired ability to activate transcription in vitro."; /evidence="ECO:0000269|PubMed:31194875"; MUTAGEN 282; /note="V->D: Impaired ability to activate transcription in vitro."; /evidence="ECO:0000269|PubMed:31194875"; MUTAGEN 290; /note="D->A: Impaired ability to activate transcription in vitro."; /evidence="ECO:0000269|PubMed:31194875"; MUTAGEN 293; /note="E->M,T: Impaired ability to activate transcription in vitro."; /evidence="ECO:0000269|PubMed:31194875"; MUTAGEN 294; /note="F->L: Does not affect ability to activate transcription in vitro."; /evidence="ECO:0000269|PubMed:31194875"; MUTAGEN 294; /note="F->S,A: Impaired ability to activate transcription in vitro."; /evidence="ECO:0000269|PubMed:31194875"; MUTAGEN 296; /note="Q->R: Impaired, but not abolished, ability to activate transcription in vitro."; /evidence="ECO:0000269|PubMed:31194875"; MUTAGEN 297; /note="Y->L,S,D,F: Impaired ability to activate transcription in vitro."; /evidence="ECO:0000269|PubMed:31194875"; MUTAGEN 298; /note="L->D: Impaired ability to activate transcription in vitro."; /evidence="ECO:0000269|PubMed:31194875
uniprot
proteins
post_translational_modification
PTM: Acetylated; acetylation impairs nuclear localization and ability to transactivate expression of target genes. Deacetylated by SIRT1. {ECO:0000250|UniProtKB:Q04887}.; 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. {ECO:0000250|UniProtKB:Q04887}.; PTM: Ubiquitinated; ubiquitination leads to proteasomal degradation and is negatively regulated by DDRGK1. {ECO:0000269|PubMed:28263186}.; PTM: Sumoylated; phosphorylation at either Ser-64 or Ser-211 is required for sumoylation. Sumoylation is induced by BMP signaling pathway. {ECO:0000250|UniProtKB:Q04887}.
uniprot
proteins
pubmed
10446171
uniprot
proteins
pubmed
10951468
uniprot
proteins
pubmed
11323423
uniprot
proteins
pubmed
11754051
uniprot
proteins
pubmed
12732631
uniprot
proteins
pubmed
12783851
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
19033726
uniprot
proteins
pubmed
19921652
uniprot
proteins
pubmed
20513132
uniprot
proteins
pubmed
21208124
uniprot
proteins
pubmed
24038782
uniprot
proteins
pubmed
25604083
uniprot
proteins
pubmed
28263186
uniprot
proteins
pubmed
31194875
uniprot
proteins
pubmed
31382142
uniprot
proteins
pubmed
34342803
uniprot
proteins
pubmed
7485151
uniprot
proteins
pubmed
7990924
uniprot
proteins
pubmed
8001137
uniprot
proteins
pubmed
8640233
uniprot
proteins
pubmed
9002675
uniprot
proteins
pubmed
9143916
uniprot
proteins
pubmed
9452059
uniprot
proteins
sequence_length
509
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00267, ECO:0000269|PubMed:8640233}.
uniprot
proteins