Gene: SOX9

Basic information

Tag Content
Uniprot ID P48436; Q53Y80;
Entrez ID 6662
Genbank protein ID CAA86598.1; AAH07951.1; AAP35521.1; AAH56420.1; EAW89102.1; AAB32870.1;
Genbank nucleotide ID NM_000346.3
Ensembl protein ID ENSP00000245479
Ensembl nucleotide ID ENSG00000125398
Gene name Transcription factor SOX-9
Gene symbol SOX9
Organism Homo sapiens
NCBI taxa ID 9606
Cleft type
Developmental stage
Data sources Manually collected
Reference 23826492
Functional description 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).
Sequence
MNLLDPFMKM TDEQEKGLSG APSPTMSEDS AGSPCPSGSG SDTENTRPQE NTFPKGEPDL 60
KKESEEDKFP VCIREAVSQV LKGYDWTLVP MPVRVNGSSK NKPHVKRPMN AFMVWAQAAR 120
RKLADQYPHL HNAELSKTLG KLWRLLNESE KRPFVEEAER LRVQHKKDHP DYKYQPRRRK 180
SVKNGQAEAE EATEQTHISP NAIFKALQAD SPHSSSGMSE VHSPGEHSGQ SQGPPTPPTT 240
PKTDVQPGKA DLKREGRPLP EGGRQPPIDF RDVDIGELSS DVISNIETFD VNEFDQYLPP 300
NGHPGVPATH GQVTYTGSYG ISSTAATPAS AGHVWMSKQQ APPPPPQQPP QAPPAPQAPP 360
QPQAAPPQQP AAPPQQPQAH TLTTLSSEPG QSQRTHIKTE QLSPSHYSEQ QQHSPQQIAY 420
SPFNLPHYSP SYPPITRSQY DYTDHQNSSS YYSHAAGQGT GLYSTFTYMN PAQRPMYTPI 480
ADTSGVPSIP QTHSPQHWEQ PVYTQLTRP 509

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Gene expression information

Gene expression in different tissues (GTEx V7)

  

Gene expression in different tissues (ENCODE)

  

Protein structural annotations

3D structure in PDB database


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Protein disorder information

Orthologous information

Relation Gene symbol Entrez ID UniProt ID Cleft type Developmental stage Species Evidence Details
1:1 orthologSOX9106503295A0A452FKA9Capra hircusPredictionMore>>
1:1 orthologSOX96662P48436Homo sapiensPublicationMore>>
1:1 orthologSox920682Q04887CPOE14.5Mus musculusPublicationMore>>
1:1 orthologSOX9H2QDR6Pan troglodytesPredictionMore>>
1:1 orthologSOX9396840F1RV30Sus scrofaPredictionMore>>
1:1 orthologSox9140586F1LYL9Rattus norvegicusPredictionMore>>
1:1 orthologsox9a60641Q9DFH2Danio rerioPredictionMore>>

Other genetic variants/mutations

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Disease or phenotype associated information

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Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO ID GO Term Evidence
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA bindingIDA
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specificISA
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specificISM
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specificIDA
GO:0000987 cis-regulatory region sequence-specific DNA bindingISS
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specificIDA
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specificIBA
GO:0003682 chromatin bindingIDA
GO:0003700 DNA-binding transcription factor activityIDA
GO:0003700 DNA-binding transcription factor activityIMP
GO:0005515 protein bindingIPI
GO:0008013 beta-catenin bindingIEA
GO:0034236 protein kinase A catalytic subunit bindingIPI
GO:0035326 cis-regulatory region bindingIDA
GO:0043425 bHLH transcription factor bindingIEA
GO:0097157 pre-mRNA intronic bindingIEA

GO:Biological Process

GO ID GO Term Evidence
GO:0000122 negative regulation of transcription by RNA polymerase IIIBA
GO:0000122 negative regulation of transcription by RNA polymerase IIIDA
GO:0001501 skeletal system developmentIMP
GO:0001502 cartilage condensationISS
GO:0001503 ossificationIEA
GO:0001658 branching involved in ureteric bud morphogenesisIEA
GO:0001708 cell fate specificationISS
GO:0001837 epithelial to mesenchymal transitionISS
GO:0001894 tissue homeostasisISS
GO:0001934 positive regulation of protein phosphorylationISS
GO:0001942 hair follicle developmentISS
GO:0002009 morphogenesis of an epitheliumIBA
GO:0002053 positive regulation of mesenchymal cell proliferationISS
GO:0002062 chondrocyte differentiationISS
GO:0002062 chondrocyte differentiationIBA
GO:0002683 negative regulation of immune system processISS
GO:0003170 heart valve developmentISS
GO:0003179 heart valve morphogenesisISS
GO:0003180 aortic valve morphogenesisIDA
GO:0003188 heart valve formationIEA
GO:0003203 endocardial cushion morphogenesisISS
GO:0003413 chondrocyte differentiation involved in endochondral bone morphogenesisIMP
GO:0003415 chondrocyte hypertrophyISS
GO:0006334 nucleosome assemblyIDA
GO:0006338 chromatin remodelingIDA
GO:0006367 transcription initiation from RNA polymerase II promoterTAS
GO:0007010 cytoskeleton organizationIEA
GO:0007165 signal transductionISS
GO:0007173 epidermal growth factor receptor signaling pathwayISS
GO:0007219 Notch signaling pathwayIEA
GO:0007283 spermatogenesisISS
GO:0007417 central nervous system developmentIBA
GO:0007507 heart developmentIBA
GO:0008284 positive regulation of cell population proliferationIMP
GO:0008584 male gonad developmentIEP
GO:0008584 male gonad developmentIMP
GO:0010564 regulation of cell cycle processIMP
GO:0010628 positive regulation of gene expressionIDA
GO:0010634 positive regulation of epithelial cell migrationIMP
GO:0014032 neural crest cell developmentIEA
GO:0014036 neural crest cell fate specificationISS
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signalingISS
GO:0019100 male germ-line sex determinationISS
GO:0019933 cAMP-mediated signalingIDA
GO:0030155 regulation of cell adhesionIEA
GO:0030198 extracellular matrix organizationIEA
GO:0030279 negative regulation of ossificationISS
GO:0030279 negative regulation of ossificationIDA
GO:0030502 negative regulation of bone mineralizationIEA
GO:0030850 prostate gland developmentIEP
GO:0030857 negative regulation of epithelial cell differentiationIEA
GO:0030858 positive regulation of epithelial cell differentiationISS
GO:0030879 mammary gland developmentIEA
GO:0030903 notochord developmentIEA
GO:0030916 otic vesicle formationISS
GO:0031018 endocrine pancreas developmentIEA
GO:0032331 negative regulation of chondrocyte differentiationISS
GO:0032332 positive regulation of chondrocyte differentiationIMP
GO:0032332 positive regulation of chondrocyte differentiationIDA
GO:0032332 positive regulation of chondrocyte differentiationIBA
GO:0032808 lacrimal gland developmentIEA
GO:0034504 protein localization to nucleusIEA
GO:0035019 somatic stem cell population maintenanceISS
GO:0035622 intrahepatic bile duct developmentIEA
GO:0042127 regulation of cell population proliferationISS
GO:0042981 regulation of apoptotic processISS
GO:0043066 negative regulation of apoptotic processISS
GO:0043066 negative regulation of apoptotic processIMP
GO:0043491 protein kinase B signalingIEA
GO:0045662 negative regulation of myoblast differentiationISS
GO:0045732 positive regulation of protein catabolic processIEA
GO:0045892 negative regulation of transcription, DNA-templatedIMP
GO:0045893 positive regulation of transcription, DNA-templatedIDA
GO:0045893 positive regulation of transcription, DNA-templatedIMP
GO:0045944 positive regulation of transcription by RNA polymerase IIIDA
GO:0045944 positive regulation of transcription by RNA polymerase IIIBA
GO:0046533 negative regulation of photoreceptor cell differentiationISS
GO:0048709 oligodendrocyte differentiationIBA
GO:0050679 positive regulation of epithelial cell proliferationISS
GO:0050679 positive regulation of epithelial cell proliferationIEP
GO:0050680 negative regulation of epithelial cell proliferationISS
GO:0051216 cartilage developmentISS
GO:0060008 Sertoli cell differentiationISS
GO:0060009 Sertoli cell developmentIEA
GO:0060018 astrocyte fate commitmentIEA
GO:0060041 retina development in camera-type eyeISS
GO:0060174 limb bud formationIEA
GO:0060221 retinal rod cell differentiationISS
GO:0060441 epithelial tube branching involved in lung morphogenesisIEA
GO:0060487 lung epithelial cell differentiationIEA
GO:0060517 epithelial cell proliferation involved in prostatic bud elongationISS
GO:0060532 bronchus cartilage developmentIEA
GO:0060534 trachea cartilage developmentIEA
GO:0060729 intestinal epithelial structure maintenanceISS
GO:0060784 regulation of cell proliferation involved in tissue homeostasisISS
GO:0061036 positive regulation of cartilage developmentIDA
GO:0061046 regulation of branching involved in lung morphogenesisIEA
GO:0061138 morphogenesis of a branching epitheliumISS
GO:0061145 lung smooth muscle developmentIEA
GO:0065003 protein-containing complex assemblyIDA
GO:0070168 negative regulation of biomineral tissue developmentISS
GO:0070168 negative regulation of biomineral tissue developmentIDA
GO:0070371 ERK1 and ERK2 cascadeISS
GO:0070384 Harderian gland developmentIEA
GO:0071260 cellular response to mechanical stimulusISS
GO:0071300 cellular response to retinoic acidIEP
GO:0071347 cellular response to interleukin-1IEP
GO:0071364 cellular response to epidermal growth factor stimulusISS
GO:0071504 cellular response to heparinISS
GO:0071560 cellular response to transforming growth factor beta stimulusIDA
GO:0071773 cellular response to BMP stimulusISS
GO:0072034 renal vesicle inductionISS
GO:0072190 ureter urothelium developmentIEA
GO:0072193 ureter smooth muscle cell differentiationIEA
GO:0072197 ureter morphogenesisIEA
GO:0072289 metanephric nephron tubule formationISS
GO:0090090 negative regulation of canonical Wnt signaling pathwayISS
GO:0090103 cochlea morphogenesisISS
GO:0090184 positive regulation of kidney developmentISS
GO:0090190 positive regulation of branching involved in ureteric bud morphogenesisISS
GO:0097065 anterior head developmentIEA
GO:0098609 cell-cell adhesionIEA
GO:1901203 positive regulation of extracellular matrix assemblyIEA
GO:1902732 positive regulation of chondrocyte proliferationIDA
GO:1902894 negative regulation of pri-miRNA transcription by RNA polymerase IIIDA
GO:2000020 positive regulation of male gonad developmentIDA
GO:2000138 positive regulation of cell proliferation involved in heart morphogenesisIEA
GO:2000741 positive regulation of mesenchymal stem cell differentiationIDA
GO:2000794 regulation of epithelial cell proliferation involved in lung morphogenesisIEA
GO:2001054 negative regulation of mesenchymal cell apoptotic processIEA

GO:Cellular Component

GO ID GO Term Evidence
GO:0000790 nuclear chromatinISA
GO:0005634 nucleusISS
GO:0005634 nucleusIDA
GO:0005654 nucleoplasmIDA
GO:0005654 nucleoplasmTAS
GO:0032991 protein-containing complexIDA
GO:0044798 nuclear transcription factor complexIEA

Reactome Pathway

Reactome ID Reactome Term Evidence
R-HSA-162582 Signal TransductionTAS
R-HSA-195721 Signaling by WNTTAS
R-HSA-201681 TCF dependent signaling in response to WNTTAS
R-HSA-212436 Generic Transcription PathwayTAS
R-HSA-3769402 Deactivation of the beta-catenin transactivating complexTAS
R-HSA-73857 RNA Polymerase II TranscriptionTAS
R-HSA-74160 Gene expression (Transcription)TAS
R-HSA-8878166 Transcriptional regulation by RUNX2TAS

Drugs and compounds information

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Functional annotations

Keywords

Keyword ID Keyword Term
KW-0002 3D-structure
KW-0007 Acetylation
KW-0010 Activator
KW-0221 Differentiation
KW-0225 Disease mutation
KW-0238 DNA-binding
KW-1017 Isopeptide bond
KW-0539 Nucleus
KW-0597 Phosphoprotein
KW-1185 Reference proteome
KW-0804 Transcription
KW-0805 Transcription regulation
KW-0832 Ubl conjugation

Interpro

InterPro ID InterPro Term
IPR009071 HMG_box_dom
IPR036910 HMG_box_dom_sf
IPR029548 SOX-9
IPR022151 Sox_N

PROSITE

PROSITE ID PROSITE Term
PS50118 HMG_BOX_2

Pfam

Pfam ID Pfam Term
PF00505 HMG_box
PF12444 Sox_N

Protein-protein interaction

Protein-miRNA interaction