P48434 · SOX9_CHICK
- ProteinTranscription factor SOX-9
- GeneSOX9
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids494 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Transcription factor that plays a key role in chondrocytes differentiation and skeletal development (PubMed:10340758, PubMed:9858536).
Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis, including COL2A1 (PubMed:10340758, PubMed:9858536).
Plays a central role in successive steps of chondrocyte differentiation. 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 similarity).
Also required for chondrocyte hypertrophy, both indirectly, by keeping the lineage fate of chondrocytes, and directly, by remaining present in upper hypertrophic cells (By similarity).
Low lipid levels are the main nutritional determinant for chondrogenic commitment of skeletal progenitor cells: when lipids levels are low, FOXO transcription factors promote expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity).
In addition to cartilage development, also acts as a regulator of proliferation and differentiation in epithelial stem/progenitor cells (By similarity).
In response to bone morphogenetic protein stimulus, phosphorylation is induced and then sumoylation, allowing cooperation with SNAI2 to trigger neural crest delamination (PubMed:23382206).
Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis, including COL2A1 (PubMed:10340758, PubMed:9858536).
Plays a central role in successive steps of chondrocyte differentiation. 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 similarity).
Also required for chondrocyte hypertrophy, both indirectly, by keeping the lineage fate of chondrocytes, and directly, by remaining present in upper hypertrophic cells (By similarity).
Low lipid levels are the main nutritional determinant for chondrogenic commitment of skeletal progenitor cells: when lipids levels are low, FOXO transcription factors promote expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity).
In addition to cartilage development, also acts as a regulator of proliferation and differentiation in epithelial stem/progenitor cells (By similarity).
In response to bone morphogenetic protein stimulus, phosphorylation is induced and then sumoylation, allowing cooperation with SNAI2 to trigger neural crest delamination (PubMed:23382206).
Features
Showing features for dna binding.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
DNA binding | 105-173 | HMG box | ||||
Sequence: VKRPMNAFMVWAQAARRKLADQYPHLHNAELSKTLGKLWRLLNESEKRPFVEEAERLRVQHKKDHPDYK |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTranscription factor SOX-9
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Archelosauria > Archosauria > Dinosauria > Saurischia > Theropoda > Coelurosauria > Aves > Neognathae > Galloanserae > Galliformes > Phasianidae > Phasianinae > Gallus
Accessions
- Primary accessionP48434
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 61 | Decreases cooperating with SNAI2 to trigger neural crest delamination; when associated with R-254 and R-376. | ||||
Sequence: K → R | ||||||
Mutagenesis | 64 | Abolishes sumoylation; when associated with A-181. Abolishes phosphorylation; when associated with A-181. Reduces ability to associate with UBE2I; when associated with A-181. Prevents trunk neural crest delamination; when associated with A-181. Prevents cooperating with SNAI2 to trigger neural crest delamination; when associated with A-181. Abolishes interaction with SNAI2; when associated with A-181. | ||||
Sequence: S → A | ||||||
Mutagenesis | 64 | Sumoylation; when associated with D-181. Initiates trunk neural crest delamination; when associated with D-181. Allows cooperating with SNAI2 to trigger neural crest delamination; when associated with D-181. Allows interaction with SNAI2; when associated with D-181. | ||||
Sequence: S → D | ||||||
Mutagenesis | 181 | Abolishes sumoylation; when associated with A-64. Abolishes phosphorylation; when associated with A-64. Reduces ability to associate with UBE2I; when associated with A-64. Prevents trunk neural crest delamination; when associated with A-64. Prevents cooperating with SNAI2 to trigger neural crest delamination; when associated with A-64. Abolishes interaction with SNAI2; when associated with A-64. | ||||
Sequence: S → A | ||||||
Mutagenesis | 181 | Sumoylation; when associated with D-64. Initiates trunk neural crest delamination; when associated with D-64. Allows cooperating with SNAI2 to trigger neural crest delamination; when associated with D-64. Allows interaction with SNAI2; when associated with D-64. | ||||
Sequence: S → D | ||||||
Mutagenesis | 254 | Decreases cooperating with SNAI2 to trigger neural crest delamination; when associated with R-61 and R-376. | ||||
Sequence: K → R | ||||||
Mutagenesis | 376 | Decreases cooperating with SNAI2 to trigger neural crest delamination; when associated with R-61 and R-254. | ||||
Sequence: K → R | ||||||
Mutagenesis | 376 | Not sumoylated. | ||||
Sequence: K → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 31 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000048745 | 1-494 | Transcription factor SOX-9 | |||
Sequence: MNLLDPFMKMTEEQDKCISDAPSPTMSDDSAGSPCPSGSGSDTENTRPQENTFPKGDPDLKKESDEDKFPVCIREAVSQVLKGYDWTLVPMPVRVNGSSKNKPHVKRPMNAFMVWAQAARRKLADQYPHLHNAELSKTLGKLWRLLNESEKRPFVEEAERLRVQHKKDHPDYKYQPRRRKSVKNGQSEQEEGSEQTHISPNAIFKALQADSPQSSSSISEVHSPGEHSGQSQGPPTPPTTPKTDAQQPGKQDLKREGRPLAEGGRQPPHIDFRDVDIGELSSDVISNIETFDVNEFDQYLPPNGHPGVPATHGQVTTYSGTYGISSSASSPAGAGHAWMAKQQPQPPQPPAQPPAQHTLPALSGEQGPAQQRPHIKTEQLSPSHYSEQQQHSPQQQQQQQQQLGYGSFNLQHYGSSYPPITRSQYDYTEHQNSGSYYSHAAGQSGGLYSTFTYMNPTQRPMYTPIADTSGVPSIPQTHSPQHWEQPVYTQLTRP | ||||||
Modified residue | 64 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 181 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 376 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K |
Post-translational modification
Phosphorylated at Ser-181 in the developing neural tube. Phosphorylation at either Ser-64 or Ser-181 is required for sumoylation, but phosphorylation is not dependent on sumoylation. Sumoylation is enhanced by PKA. Phosphorylation is required for interaction with SNAI2 to trigger neural crest delamination and for an efficient trunk neural crest delamination, whereas sumoylation plays a less significant role. Phosphorylation and sumoylation are induced by BMP signaling pathway.
Sumoylated at Lys-376; phosphorylation at either Ser-64 or Ser-181 is required for sumoylation. Sumoylation is induced by BMP signaling pathway.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
By BMP2 during chondrogenesis.
Developmental stage
Found in chondrogenic regions in the branchial arches, somites and limb buds at 22 dpc. At 28 dpc detected in the limbs, developing scapula, prevertebrae and ribs. Found in condensing mesenchyme of the forelimb at 25 dpc. Expressed in the condensing mesenchyme at the distal tips of the developing hindlimbs at 26 dpc.
Gene expression databases
Interaction
Subunit
Interacts with SNAI2; triggers neural crest delamination in a phosphorylation dependent manner. Interacts with UBE2I.
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-66 | Disordered | ||||
Sequence: MNLLDPFMKMTEEQDKCISDAPSPTMSDDSAGSPCPSGSGSDTENTRPQENTFPKGDPDLKKESDE | ||||||
Compositional bias | 18-52 | Polar residues | ||||
Sequence: ISDAPSPTMSDDSAGSPCPSGSGSDTENTRPQENT | ||||||
Region | 63-103 | Dimerization (DIM) | ||||
Sequence: ESDEDKFPVCIREAVSQVLKGYDWTLVPMPVRVNGSSKNKP | ||||||
Region | 63-103 | PQA | ||||
Sequence: ESDEDKFPVCIREAVSQVLKGYDWTLVPMPVRVNGSSKNKP | ||||||
Compositional bias | 159-187 | Basic and acidic residues | ||||
Sequence: ERLRVQHKKDHPDYKYQPRRRKSVKNGQS | ||||||
Region | 159-275 | Disordered | ||||
Sequence: ERLRVQHKKDHPDYKYQPRRRKSVKNGQSEQEEGSEQTHISPNAIFKALQADSPQSSSSISEVHSPGEHSGQSQGPPTPPTTPKTDAQQPGKQDLKREGRPLAEGGRQPPHIDFRDV | ||||||
Compositional bias | 188-233 | Polar residues | ||||
Sequence: EQEEGSEQTHISPNAIFKALQADSPQSSSSISEVHSPGEHSGQSQG | ||||||
Region | 224-309 | Transactivation domain (TAM) | ||||
Sequence: PGEHSGQSQGPPTPPTTPKTDAQQPGKQDLKREGRPLAEGGRQPPHIDFRDVDIGELSSDVISNIETFDVNEFDQYLPPNGHPGVP | ||||||
Compositional bias | 248-275 | Basic and acidic residues | ||||
Sequence: PGKQDLKREGRPLAEGGRQPPHIDFRDV | ||||||
Motif | 277-286 | 9aaTAD 1 | ||||
Sequence: IGELSSDVIS | ||||||
Motif | 292-300 | 9aaTAD 2 | ||||
Sequence: DVNEFDQYL | ||||||
Region | 326-402 | Disordered | ||||
Sequence: SSASSPAGAGHAWMAKQQPQPPQPPAQPPAQHTLPALSGEQGPAQQRPHIKTEQLSPSHYSEQQQHSPQQQQQQQQQ | ||||||
Compositional bias | 370-402 | Polar residues | ||||
Sequence: QQRPHIKTEQLSPSHYSEQQQHSPQQQQQQQQQ | ||||||
Region | 372-494 | Transactivation domain (TAC) | ||||
Sequence: RPHIKTEQLSPSHYSEQQQHSPQQQQQQQQQLGYGSFNLQHYGSSYPPITRSQYDYTEHQNSGSYYSHAAGQSGGLYSTFTYMNPTQRPMYTPIADTSGVPSIPQTHSPQHWEQPVYTQLTRP | ||||||
Motif | 445-453 | 9aaTAD 3 | ||||
Sequence: GGLYSTFTY | ||||||
Region | 462-494 | Disordered | ||||
Sequence: YTPIADTSGVPSIPQTHSPQHWEQPVYTQLTRP |
Domain
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length494
- Mass (Da)54,848
- Last updated2014-07-09 v3
- ChecksumA3926313CA954E32
Sequence caution
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 17-20 | in Ref. 1; AAB09663 | ||||
Sequence: CISD → GLSG | ||||||
Compositional bias | 18-52 | Polar residues | ||||
Sequence: ISDAPSPTMSDDSAGSPCPSGSGSDTENTRPQENT | ||||||
Compositional bias | 159-187 | Basic and acidic residues | ||||
Sequence: ERLRVQHKKDHPDYKYQPRRRKSVKNGQS | ||||||
Sequence conflict | 181 | in Ref. 1; AAB09663 | ||||
Sequence: S → T | ||||||
Compositional bias | 188-233 | Polar residues | ||||
Sequence: EQEEGSEQTHISPNAIFKALQADSPQSSSSISEVHSPGEHSGQSQG | ||||||
Compositional bias | 248-275 | Basic and acidic residues | ||||
Sequence: PGKQDLKREGRPLAEGGRQPPHIDFRDV | ||||||
Compositional bias | 370-402 | Polar residues | ||||
Sequence: QQRPHIKTEQLSPSHYSEQQQHSPQQQQQQQQQ | ||||||
Sequence conflict | 385 | in Ref. 1; AAB09663 | ||||
Sequence: Y → N | ||||||
Sequence conflict | 415 | in Ref. 1; AAB09663 | ||||
Sequence: S → F | ||||||
Sequence conflict | 424 | in Ref. 1; AAB09663 | ||||
Sequence: Q → E | ||||||
Sequence conflict | 446 | in Ref. 1; AAB09663 | ||||
Sequence: G → S | ||||||
Sequence conflict | 473 | in Ref. 1; AAB09663 | ||||
Sequence: S → T |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U12533 EMBL· GenBank· DDBJ | AAB09663.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AB012236 EMBL· GenBank· DDBJ | BAA25296.1 EMBL· GenBank· DDBJ | mRNA | ||
AADN03007462 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |