P48434 · SOX9_CHICK

  • Protein
    Transcription factor SOX-9
  • Gene
    SOX9
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Features

Showing features for dna binding.

TypeIDPosition(s)Description
DNA binding105-173HMG box

GO annotations

AspectTerm
Cellular Componentnucleoplasm
Cellular Componentnucleus
Cellular Componenttranscription regulator complex
Molecular Functionbeta-catenin binding
Molecular Functionchromatin binding
Molecular Functioncis-regulatory region sequence-specific DNA binding
Molecular FunctionDNA-binding transcription activator activity, RNA polymerase II-specific
Molecular FunctionDNA-binding transcription factor activity, RNA polymerase II-specific
Molecular Functionpre-mRNA intronic binding
Molecular Functionprotein kinase A catalytic subunit binding
Molecular FunctionRNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular Functionubiquitin-like protein conjugating enzyme binding
Biological Processanterior head development
Biological Processaortic valve morphogenesis
Biological Processastrocyte fate commitment
Biological Processbone mineralization
Biological Processbranching involved in ureteric bud morphogenesis
Biological Processbronchus cartilage development
Biological ProcesscAMP-mediated signaling
Biological Processcanonical Wnt signaling pathway
Biological Processcartilage condensation
Biological Processcell proliferation involved in heart morphogenesis
Biological Processcell-cell adhesion
Biological Processcellular response to BMP stimulus
Biological Processcellular response to epidermal growth factor stimulus
Biological Processcellular response to heparin
Biological Processcellular response to interleukin-1
Biological Processcellular response to mechanical stimulus
Biological Processcellular response to retinoic acid
Biological Processcellular response to transforming growth factor beta stimulus
Biological Processchondrocyte differentiation
Biological Processcochlea morphogenesis
Biological Processcytoskeleton organization
Biological ProcessDNA-templated transcription
Biological Processembryonic digestive tract development
Biological Processendocardial cushion morphogenesis
Biological Processendocrine pancreas development
Biological Processepidermal growth factor receptor signaling pathway
Biological Processepithelial cell proliferation involved in prostatic bud elongation
Biological Processepithelial tube branching involved in lung morphogenesis
Biological ProcessERK1 and ERK2 cascade
Biological Processextracellular matrix assembly
Biological Processglandular epithelial cell differentiation
Biological Processglial cell fate specification
Biological Processgrowth plate cartilage chondrocyte growth
Biological ProcessHarderian gland development
Biological Processheart development
Biological Processheart valve development
Biological Processheart valve formation
Biological Processhomeostasis of number of cells within a tissue
Biological Processintestinal epithelial cell differentiation
Biological Processintestinal epithelial structure maintenance
Biological Processintrahepatic bile duct development
Biological Processlacrimal gland development
Biological Processlimb bud formation
Biological Processlung smooth muscle development
Biological Processmale germ-line sex determination
Biological Processmale gonad development
Biological Processmesenchymal cell apoptotic process
Biological Processmesenchymal cell proliferation
Biological Processmetanephric nephron tubule formation
Biological Processmorphogenesis of an epithelium
Biological Processnegative regulation of beta-catenin-TCF complex assembly
Biological Processnegative regulation of bone development
Biological Processnegative regulation of bone mineralization
Biological Processnegative regulation of canonical Wnt signaling pathway
Biological Processnegative regulation of chondrocyte differentiation
Biological Processnegative regulation of epithelial cell differentiation
Biological Processnegative regulation of epithelial cell proliferation
Biological Processnegative regulation of fatty acid oxidation
Biological Processnegative regulation of gene expression
Biological Processnegative regulation of immune system process
Biological Processnegative regulation of mesenchymal cell apoptotic process
Biological Processnegative regulation of miRNA transcription
Biological Processnegative regulation of myoblast differentiation
Biological Processnegative regulation of osteoblast differentiation
Biological Processnegative regulation of photoreceptor cell differentiation
Biological Processnegative regulation of transcription by RNA polymerase II
Biological Processneural crest cell delamination
Biological Processneural crest cell fate specification
Biological Processneural crest cell migration
Biological Processneuron fate specification
Biological ProcessNotch signaling pathway
Biological Processnotochord development
Biological Processnucleosome assembly
Biological Processoligodendrocyte differentiation
Biological Processotic vesicle formation
Biological Processphosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processpositive regulation of branching involved in ureteric bud morphogenesis
Biological Processpositive regulation of cartilage condensation
Biological Processpositive regulation of cell proliferation involved in heart morphogenesis
Biological Processpositive regulation of chondrocyte differentiation
Biological Processpositive regulation of chondrocyte proliferation
Biological Processpositive regulation of collagen biosynthetic process
Biological Processpositive regulation of epithelial cell differentiation
Biological Processpositive regulation of epithelial cell migration
Biological Processpositive regulation of epithelial cell proliferation
Biological Processpositive regulation of extracellular matrix assembly
Biological Processpositive regulation of gene expression
Biological Processpositive regulation of male gonad development
Biological Processpositive regulation of mesenchymal cell proliferation
Biological Processpositive regulation of mesenchymal stem cell differentiation
Biological Processpositive regulation of neural crest formation
Biological Processpositive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processpositive regulation of protein catabolic process
Biological Processpositive regulation of protein phosphorylation
Biological Processpositive regulation of stem cell proliferation
Biological Processprotein localization to nucleus
Biological Processregulation of branching involved in lung morphogenesis
Biological Processregulation of cartilage development
Biological Processregulation of cell cycle process
Biological Processregulation of cell proliferation involved in tissue homeostasis
Biological Processregulation of epithelial cell proliferation involved in lung morphogenesis
Biological Processrenal vesicle induction
Biological Processresponse to fatty acid
Biological Processretinal rod cell differentiation
Biological ProcessSertoli cell development
Biological Processsomatic stem cell population maintenance
Biological Processspermatogenesis
Biological Processstem cell proliferation
Biological Processtrachea cartilage development
Biological Processtranscription by RNA polymerase II
Biological Processtransdifferentiation
Biological Processtype I pneumocyte differentiation
Biological Processureter morphogenesis
Biological Processureter smooth muscle cell differentiation
Biological Processureter urothelium development

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Transcription factor SOX-9

Gene names

    • Name
      SOX9

Organism names

  • Taxonomic identifier
  • Strain
    • Red jungle fowl
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Archelosauria > Archosauria > Dinosauria > Saurischia > Theropoda > Coelurosauria > Aves > Neognathae > Galloanserae > Galliformes > Phasianidae > Phasianinae > Gallus

Accessions

  • Primary accession
    P48434
  • Secondary accessions
    • F1P307
    • O73668

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis61Decreases cooperating with SNAI2 to trigger neural crest delamination; when associated with R-254 and R-376.
Mutagenesis64Abolishes 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.
Mutagenesis64Sumoylation; 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.
Mutagenesis181Abolishes 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.
Mutagenesis181Sumoylation; 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.
Mutagenesis254Decreases cooperating with SNAI2 to trigger neural crest delamination; when associated with R-61 and R-376.
Mutagenesis376Decreases cooperating with SNAI2 to trigger neural crest delamination; when associated with R-61 and R-254.
Mutagenesis376Not sumoylated.

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.

Go to variant viewer

PTM/Processing

Features

Showing features for chain, modified residue, cross-link.

TypeIDPosition(s)Description
ChainPRO_00000487451-494Transcription factor SOX-9
Modified residue64Phosphoserine
Modified residue181Phosphoserine
Cross-link376Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

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

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.

TypeIDPosition(s)Description
Region1-66Disordered
Compositional bias18-52Polar residues
Region63-103Dimerization (DIM)
Region63-103PQA
Compositional bias159-187Basic and acidic residues
Region159-275Disordered
Compositional bias188-233Polar residues
Region224-309Transactivation domain (TAM)
Compositional bias248-275Basic and acidic residues
Motif277-2869aaTAD 1
Motif292-3009aaTAD 2
Region326-402Disordered
Compositional bias370-402Polar residues
Region372-494Transactivation domain (TAC)
Motif445-4539aaTAD 3
Region462-494Disordered

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 status
    Complete
  • Length
    494
  • Mass (Da)
    54,848
  • Last updated
    2014-07-09 v3
  • Checksum
    A3926313CA954E32
MNLLDPFMKMTEEQDKCISDAPSPTMSDDSAGSPCPSGSGSDTENTRPQENTFPKGDPDLKKESDEDKFPVCIREAVSQVLKGYDWTLVPMPVRVNGSSKNKPHVKRPMNAFMVWAQAARRKLADQYPHLHNAELSKTLGKLWRLLNESEKRPFVEEAERLRVQHKKDHPDYKYQPRRRKSVKNGQSEQEEGSEQTHISPNAIFKALQADSPQSSSSISEVHSPGEHSGQSQGPPTPPTTPKTDAQQPGKQDLKREGRPLAEGGRQPPHIDFRDVDIGELSSDVISNIETFDVNEFDQYLPPNGHPGVPATHGQVTTYSGTYGISSSASSPAGAGHAWMAKQQPQPPQPPAQPPAQHTLPALSGEQGPAQQRPHIKTEQLSPSHYSEQQQHSPQQQQQQQQQLGYGSFNLQHYGSSYPPITRSQYDYTEHQNSGSYYSHAAGQSGGLYSTFTYMNPTQRPMYTPIADTSGVPSIPQTHSPQHWEQPVYTQLTRP

Sequence caution

The sequence AAB09663.1 differs from that shown. Reason: Frameshift

Features

Showing features for sequence conflict, compositional bias.

TypeIDPosition(s)Description
Sequence conflict17-20in Ref. 1; AAB09663
Compositional bias18-52Polar residues
Compositional bias159-187Basic and acidic residues
Sequence conflict181in Ref. 1; AAB09663
Compositional bias188-233Polar residues
Compositional bias248-275Basic and acidic residues
Compositional bias370-402Polar residues
Sequence conflict385in Ref. 1; AAB09663
Sequence conflict415in Ref. 1; AAB09663
Sequence conflict424in Ref. 1; AAB09663
Sequence conflict446in Ref. 1; AAB09663
Sequence conflict473in Ref. 1; AAB09663

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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.

Genome annotation databases

Similar Proteins

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