DegronMD - P48436(SOX9)

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}. View more >>

GO - Biological processes (BP): anterior head development [GO:0097065]; aortic valve morphogenesis [GO:0003180]; astrocyte fate commitment [GO:0060018]; branching involved in ureteric bud morphogenesis [GO:0001658]; bronchus cartilage development [GO:0060532]; cAMP-mediated signaling [GO:0019933]; cartilage condensation [GO:0001502]; cartilage development [GO:0051216]; cell-cell adhesion [GO:0098609]; cell fate specification [GO:0001708]; cellular response to BMP stimulus [GO:0071773]; cellular response to epidermal growth factor stimulus [GO:0071364]; cellular response to heparin [GO:0071504]; cellular response to interleukin-1 [GO:0071347]; cellular response to mechanical stimulus [GO:0071260]; cellular response to retinoic acid [GO:0071300]; cellular response to transforming growth factor beta stimulus [GO:0071560]; chondrocyte differentiation [GO:0002062]; chondrocyte differentiation involved in endochondral bone morphogenesis [GO:0003413]; chondrocyte hypertrophy [GO:0003415]; chromatin remodeling [GO:0006338]; cochlea morphogenesis [GO:0090103]; cytoskeleton organization [GO:0007010]; endocardial cushion morphogenesis [GO:0003203]; endocrine pancreas development [GO:0031018]; epidermal growth factor receptor signaling pathway [GO:0007173]; epithelial cell proliferation involved in prostatic bud elongation [GO:0060517]; epithelial to mesenchymal transition [GO:0001837]; epithelial tube branching involved in lung morphogenesis [GO:0060441]; ERK1 and ERK2 cascade [GO:0070371]; extracellular matrix organization [GO:0030198]; growth plate cartilage chondrocyte growth [GO:0003430]; hair follicle development [GO:0001942]; Harderian gland development [GO:0070384]; heart development [GO:0007507]; heart valve development [GO:0003170]; heart valve formation [GO:0003188]; heart valve morphogenesis [GO:0003179]; intestinal epithelial structure maintenance [GO:0060729]; intrahepatic bile duct development [GO:0035622]; lacrimal gland development [GO:0032808]; limb bud formation [GO:0060174]; lung epithelial cell differentiation [GO:0060487]; lung smooth muscle development [GO:0061145]; male germ-line sex determination [GO:0019100]; male gonad development [GO:0008584]; mammary gland development [GO:0030879]; metanephric nephron tubule formation [GO:0072289]; morphogenesis of a branching epithelium [GO:0061138]; morphogenesis of an epithelium [GO:0002009]; negative regulation of apoptotic process [GO:0043066]; negative regulation of beta-catenin-TCF complex assembly [GO:1904864]; negative regulation of biomineral tissue development [GO:0070168]; negative regulation of bone mineralization [GO:0030502]; negative regulation of canonical Wnt signaling pathway [GO:0090090]; negative regulation of chondrocyte differentiation [GO:0032331]; negative regulation of epithelial cell differentiation [GO:0030857]; negative regulation of epithelial cell proliferation [GO:0050680]; negative regulation of fatty acid oxidation [GO:0046322]; negative regulation of gene expression [GO:0010629]; negative regulation of immune system process [GO:0002683]; negative regulation of mesenchymal cell apoptotic process [GO:2001054]; negative regulation of miRNA transcription [GO:1902894]; negative regulation of myoblast differentiation [GO:0045662]; negative regulation of ossification [GO:0030279]; negative regulation of osteoblast differentiation [GO:0045668]; negative regulation of photoreceptor cell differentiation [GO:0046533]; negative regulation of transcription, DNA-templated [GO:0045892]; negative regulation of transcription by RNA polymerase II [GO:0000122]; neural crest cell development [GO:0014032]; neural crest cell fate specification [GO:0014036]; Notch signaling pathway [GO:0007219]; notochord development [GO:0030903]; nucleosome assembly [GO:0006334]; oligodendrocyte differentiation [GO:0048709]; ossification [GO:0001503]; otic vesicle formation [GO:0030916]; positive regulation of branching involved in ureteric bud morphogenesis [GO:0090190]; positive regulation of cartilage development [GO:0061036]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of cell proliferation involved in heart morphogenesis [GO:2000138]; positive regulation of chondrocyte differentiation [GO:0032332]; positive regulation of chondrocyte proliferation [GO:1902732]; positive regulation of epithelial cell differentiation [GO:0030858]; positive regulation of epithelial cell migration [GO:0010634]; positive regulation of epithelial cell proliferation [GO:0050679]; positive regulation of extracellular matrix assembly [GO:1901203]; positive regulation of gene expression [GO:0010628]; positive regulation of kidney development [GO:0090184]; positive regulation of male gonad development [GO:2000020]; positive regulation of mesenchymal cell proliferation [GO:0002053]; positive regulation of mesenchymal stem cell differentiation [GO:2000741]; positive regulation of phosphatidylinositol 3-kinase signaling [GO:0014068]; positive regulation of protein catabolic process [GO:0045732]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; prostate gland development [GO:0030850]; protein-containing complex assembly [GO:0065003]; protein kinase B signaling [GO:0043491]; protein localization to nucleus [GO:0034504]; regulation of apoptotic process [GO:0042981]; regulation of branching involved in lung morphogenesis [GO:0061046]; regulation of cell adhesion [GO:0030155]; regulation of cell cycle process [GO:0010564]; regulation of cell population proliferation [GO:0042127]; regulation of cell proliferation involved in tissue homeostasis [GO:0060784]; regulation of epithelial cell proliferation involved in lung morphogenesis [GO:2000794]; regulation of transcription by RNA polymerase II [GO:0006357]; renal vesicle induction [GO:0072034]; response to fatty acid [GO:0070542]; retina development in camera-type eye [GO:0060041]; retinal rod cell differentiation [GO:0060221]; Sertoli cell development [GO:0060009]; Sertoli cell differentiation [GO:0060008]; signal transduction [GO:0007165]; skeletal system development [GO:0001501]; somatic stem cell population maintenance [GO:0035019]; spermatogenesis [GO:0007283]; tissue homeostasis [GO:0001894]; trachea cartilage development [GO:0060534]; ureter morphogenesis [GO:0072197]; ureter smooth muscle cell differentiation [GO:0072193]; ureter urothelium development [GO:0072190] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.A481G	TCGA-35-4123	LUAD	TCGA	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.3056
p.A481G	DO26394	LUAD	ICGC	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.3056
p.P235A	TCGA-B0-5109	KIRC	TCGA	PPTPPTT	DEG_SCF_FBW7_1	234:240	Mutation altering degron motif	0.6392
p.P235A	DO18769	KIRC	ICGC	PPTPPTT	DEG_SCF_FBW7_1	234:240	Mutation altering degron motif	0.6392
p.R474C	TCGA-B5-A11Y	UCEC	TCGA	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.1111
p.R474C	DO40889	UCEC	ICGC	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.1111
p.P490L	TCGA-B5-A3FC	UCEC	TCGA	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.3056
p.P490L	DO41871	UCEC	ICGC	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.3056
p.S214P	TCGA-BP-5185	KIRC	TCGA	PHSSS	DEG_SPOP_SBC_1	212:216	Mutation altering degron motif	0.7863
p.S214P	DO20516	KIRC	ICGC	PHSSS	DEG_SPOP_SBC_1	212:216	Mutation altering degron motif	0.7863
p.R474H	TCGA-BR-8363	STAD	TCGA	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.1111
p.R474H	DO47837	STAD	ICGC	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.1111
p.S484A	TCGA-D1-A17Q	UCEC	TCGA	DTSGVPSI	DEG_COP1_1	482:489	Mutation altering degron motif	0.6477
p.S484A	DO41903	UCEC	ICGC	DTSGVPSI	DEG_COP1_1	482:489	Mutation altering degron motif	0.6477
p.S484F	TCGA-D3-A2JP	SKCM	TCGA	DTSGVPSI	DEG_COP1_1	482:489	Mutation altering degron motif	0.6871
p.S484F	DO47407	SKCM	ICGC	DTSGVPSI	DEG_COP1_1	482:489	Mutation altering degron motif	0.6871
p.G485V	TCGA-EE-A184	SKCM	TCGA	DTSGVPSI	DEG_COP1_1	482:489	Mutation altering degron motif	0.6421
p.G485V	DO47442	SKCM	ICGC	DTSGVPSI	DEG_COP1_1	482:489	Mutation altering degron motif	0.6421
p.A206V	TCGA-FI-A2D5	UCEC	TCGA	PHSSS	DEG_SPOP_SBC_1	212:216	Mutation rewiring degron network	0.1667
p.A206V	DO41331	UCEC	ICGC	PHSSS	DEG_SPOP_SBC_1	212:216	Mutation rewiring degron network	0.1667
p.S494N	TCGA-FW-A3R5	SKCM	TCGA	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.1944
p.S494N	DO37406	SKCM	ICGC	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.1944
p.Q473R	TCGA-HU-A4H3	STAD	TCGA	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.0833
p.Q473R	DO47903	STAD	ICGC	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.0833
p.H497N	TCGA-MT-A67A	HNSC	TCGA	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.1111
p.H497N	DO49048	HNSC	ICGC	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.1111
p.M218I	TCGA-XF-A9SZ	BLCA	TCGA	PHSSS	DEG_SPOP_SBC_1	212:216	Mutation rewiring degron network	0.2778
p.M218I	DO51919	BLCA	ICGC	PHSSS	DEG_SPOP_SBC_1	212:216	Mutation rewiring degron network	0.2778
p.A209V	DO6675	CLLE	ICGC	PHSSS	DEG_SPOP_SBC_1	212:216	Mutation rewiring degron network	0.25
p.G248S	DO11854	GBM	ICGC	PPTPPTT	DEG_SCF_FBW7_1	234:240	Mutation rewiring degron network	0.1111
p.G248V	DO228985	LICA	ICGC	PPTPPTT	DEG_SCF_FBW7_1	234:240	Mutation rewiring degron network	0.1111
p.G217V	DO229018	LICA	ICGC	PHSSS	DEG_SPOP_SBC_1	212:216	Mutation rewiring degron network	0.3056
p.P479H	DO32912	PACA	ICGC	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.25
p.S215F	SIDM02023	Pancreatic Carcinoma	GDSC	PHSSS	DEG_SPOP_SBC_1	212:216	Mutation altering degron motif	0.7982
p.H213Q	SIDM01165	Pancreatic Carcinoma	GDSC	PHSSS	DEG_SPOP_SBC_1	212:216	Mutation altering degron motif	0.647
p.H213Q	ACH-000155	Pancreatic Cancer	CCLE	PHSSS	DEG_SPOP_SBC_1	212:216	Mutation altering degron motif	0.647
p.H213Q	SW1990	pancreas	COSMIC	PHSSS	DEG_SPOP_SBC_1	212:216	Mutation altering degron motif	0.647
p.K249N	SIDM00151	Ovarian Carcinoma	GDSC	PPTPPTT	DEG_SCF_FBW7_1	234:240	Mutation blocking ubiquitination signal	0.5278
p.K249N	ACH-000966	Ovarian Cancer	CCLE	PPTPPTT	DEG_SCF_FBW7_1	234:240	Mutation blocking ubiquitination signal	0.5278
p.K249N	IGROV-1	ovary	COSMIC	PPTPPTT	DEG_SCF_FBW7_1	234:240	Mutation blocking ubiquitination signal	0.5278
p.Q496H	ACH-000954	Endometrial/Uterine Cancer	CCLE	DTSGVPSI	DEG_COP1_1	482:489	Mutation rewiring degron network	0.1389
p.Q246P	ACH-002118	Bone Cancer	CCLE	PPTPPTT	DEG_SCF_FBW7_1	234:240	Mutation rewiring degron network	0.1667
p.Q246P	EW-3	bone	COSMIC	PPTPPTT	DEG_SCF_FBW7_1	234:240	Mutation rewiring degron network	0.1667

DegronMD: protein-targeted degradation, mutation and drug response to degrons

SOX9

UniProt ID: P48436

Entrez ID: 6662

Protein name: Transcription factor SOX-9

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for SOX9 in