BioPAX pathway converted from "Beta-catenin binds SOX proteins" in the Reactome database.LEFT-TO-RIGHTBeta-catenin binds SOX proteinsSOX protein family members are the transcription factors that regulate many different development processes and also control homeostasis in adult tissues. SOX proteins can be either transcriptional activators or repressors depending on the cellular context and their associated interacting proteins (Kormish et al. 2010). There are over twenty SOX proteins encoded in mammalian genome of which many of these can physically interact with beta-catenin and TCF (T-cell factor) transcription factors and modulate the Wnt signaling. Evidences suggest that SOX proteins have widespread role in modulating Wnt signaling in development and disease. In most cases SOX proteins repress WNT transcriptional responses, however some SOX proteins appear to enhance WNT-regulated gene expression. The precise mechanism by which SOX proteins regulate beta-catenin/TCF activity are still unclear. Differential recruitment of transcriptional co-activators or co-repressors is one mechanism by which SOX factors can either enhance or repress Wnt-target gene transcription. Another mechanism by which some SOX proteins repress Wnt signaling is by promoting proteosome-mediated beta-catenin degradation (Kormish et al. 2010). <br>Human SRY binds beta-catenin through a N-terminal domain (Bernard et al. 2008), SOX6 interacts via a centrally located leucine zipper (LZ/Q) element (Iguchi et al. 2007), and mammalian SOX7, SOX9 and SOX17 all bind beta-catenin via their C-terminal regions (Zorn et al., 1999; Takash et al., 2001; Akiyama et al., 2004; Sinner et al., 2007, Kormish et al. 2010). SRY and SOX9 function in part by suppressing canonical Wnt signaling by promoting beta-catenin phosphorylation in the nucleus (Topol et al. 2009). SOX9 and SRY are involved in the regulation of mammalian sex determination and mutation in human SRY and SOX9 results in sex reversal, with female development in XY individuals (Bernard et al. 2008). SOX2 binds beta-catenin and promotes cell proliferation by transcriptionally activating the Wnt target Cyclin D1 gene in breast cancer cells (Chen et al., 2008), whereas SOX6 represses Cyclin D1 transcription in pancreatic cells (Iguchi et al., 2007). SOX7 and SOX17 reduce cyclin-D1 expression and repress proliferation by stimulating beta-catenin degradation (Sinner et al. 2007, Zhang et al. 2008, 2009).Authored: Garapati, P V, 2014-10-08Reviewed: Zorn, Aaron M, Harley, Vincent, 2015-02-11Edited: Garapati, P V, 2014-10-08CTNNB1Catenin beta-1CTNB1_HUMANReactome DB_ID: 3451168nucleoplasmGENE ONTOLOGYGO:0005654UniProt:P35222 CTNNB1CTNNB1CTNNBOK/SW-cl.35PRO2286FUNCTION Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (By similarity). Acts as a negative regulator of centrosome cohesion (PubMed:18086858). Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization (PubMed:21262353). Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (PubMed:18957423). Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML (PubMed:22155184). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity).SUBUNIT Two separate complex-associated pools are found in the cytoplasm. The majority is present as component of an E-cadherin:catenin adhesion complex composed of at least E-cadherin/CDH1 and beta-catenin/CTNNB1, and possibly alpha-catenin/CTNNA1; the complex is located to adherens junctions. The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex. Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1. Another cytoplasmic pool is part of a large complex containing AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. Wnt-dependent activation of DVL antagonizes the action of GSK3B. When GSK3B activity is inhibited the complex dissociates, CTNNB1 is dephosphorylated and is no longer targeted for destruction. The stabilized protein translocates to the nucleus, where it binds TCF/LEF-1 family members, TBP, BCL9, BCL9L and possibly also RUVBL1 and CHD8. Binds CTNNBIP and EP300. CTNNB1 forms a ternary complex with LEF1 and EP300 that is disrupted by CTNNBIP1 binding. Interacts with TAX1BP3 (via the PDZ domain); this interaction inhibits the transcriptional activity of CTNNB1. Interacts with AJAP1, BAIAP1, CARM1, CTNNA3, CXADR and PCDH11Y. Binds SLC9A3R1. Interacts with GLIS2 and MUC1. Interacts with SLC30A9. Interacts with XIRP1. Interacts directly with AXIN1; the interaction is regulated by CDK2 phosphorylation of AXIN1. Interacts with SCRIB. Interacts with RAPGEF2. Interacts with PTPRU (via the cytoplasmic juxtamembrane domain). Interacts with EMD. Interacts with TNIK and TCF7L2. Interacts with SESTD1 and TRPC4. Interacts with CAV1. Interacts with TRPV4. The TRPV4 and CTNNB1 complex can interact with CDH1. Interacts with VCL. Interacts with PTPRJ. Interacts with PKT7 and CDK2. Interacts with FAT1 (via the cytoplasmic domain). Interacts with NANOS1 and NDRG2. Interacts with isoform 1 of NEK2. Interacts with both isoform 1 and isoform 2 of CDK5. Interacts with PTK6. Interacts with SOX7; this interaction may lead to proteasomal degradation of active CTNNB1 and thus inhibition of Wnt/beta-catenin-stimulated transcription. Identified in a complex with HINT1 and MITF. Interacts with FHIT. The CTNNB1 and TCF7L2/TCF4 complex interacts with PML (isoform PML-4). Interacts with FERMT2. Identified in a complex with TCF7L2/TCF4 and FERMT2 (PubMed:29739711, PubMed:22699938). Interacts with RORA. May interact with P-cadherin/CDH3. Interacts with RNF220 (PubMed:25266658). Interacts with CTNND2 (PubMed:25807484). Interacts (via the C-terminal region) with CBY1 (PubMed:12712206, PubMed:16424001). The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at 'Ser-9') (PubMed:25169422). Interacts with DLG5 (By similarity). Interacts with FAM53B; promoting translocation to the nucleus (PubMed:25183871). Interacts with TMEM170B (PubMed:29367600). Interacts with AHI1 (PubMed:21623382). Interacts with GID8 (PubMed:28829046). Component of an cadherin:catenin adhesion complex composed of at least of CDH26, beta-catenin/CTNNB1, alpha-catenin/CTNNA1 and p120 catenin/CTNND1 (PubMed:28051089). Forms a complex comprising APPL1, RUVBL2, APPL2, HDAC1 and HDAC2 (PubMed:19433865). Interacts with IRF2BPL; mediates the ubiquitination and degradation of CTNNB1 (PubMed:29374064). Interacts with AMFR (By similarity). Interacts with LMBR1L (PubMed:31073040). Interacts with SOX30; prevents interaction of CTNNB1 with TCF7L2/TCF4 and leads to inhibition of Wnt signaling (PubMed:29739711). Interacts with SOX9; inhibiting CTNNB1 activity by competing with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity).SUBUNIT (Microbial infection) Interacts with herpes virus 8 protein vPK; this interaction inhibits the Wnt signaling pathway.TISSUE SPECIFICITY Expressed in several hair follicle cell types: basal and peripheral matrix cells, and cells of the outer and inner root sheaths. Expressed in colon. Present in cortical neurons (at protein level). Expressed in breast cancer tissues (at protein level) (PubMed:29367600).PTM Phosphorylation at Ser-552 by AMPK promotes stabilizion of the protein, enhancing TCF/LEF-mediated transcription (By similarity). Phosphorylation by GSK3B requires prior phosphorylation of Ser-45 by another kinase. Phosphorylation proceeds then from Thr-41 to Ser-37 and Ser-33. Phosphorylated by NEK2. EGF stimulates tyrosine phosphorylation. Phosphorylation on Tyr-654 decreases CDH1 binding and enhances TBP binding. Phosphorylated on Ser-33 and Ser-37 by HIPK2 and GSK3B, this phosphorylation triggers proteasomal degradation (PubMed:25169422). Phosphorylation on Ser-191 and Ser-246 by CDK5. Phosphorylation by CDK2 regulates insulin internalization. Phosphorylation by PTK6 at Tyr-64, Tyr-142, Tyr-331 and/or Tyr-333 with the predominant site at Tyr-64 is not essential for inhibition of transcriptional activity.PTM Ubiquitinated by the SCF(BTRC) E3 ligase complex when phosphorylated by GSK3B, leading to its degradation (PubMed:12077367). Ubiquitinated by a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X, leading to its subsequent proteasomal degradation (PubMed:11389839, PubMed:11389840, PubMed:20307497). Ubiquitinated and degraded following interaction with SOX9 (By similarity).PTM S-nitrosylation at Cys-619 within adherens junctions promotes VEGF-induced, NO-dependent endothelial cell permeability by disrupting interaction with E-cadherin, thus mediating disassembly adherens junctions.PTM O-glycosylation at Ser-23 decreases nuclear localization and transcriptional activity, and increases localization to the plasma membrane and interaction with E-cadherin CDH1.PTM Deacetylated at Lys-49 by SIRT1.DISEASE Activating mutations in CTNNB1 have oncogenic activity resulting in tumor development. Somatic mutations are found in various tumor types, including colon cancers, ovarian and prostate carcinomas, hepatoblastoma (HB), hepatocellular carcinoma (HCC). HBs are malignant embryonal tumors mainly affecting young children in the first three years of life.DISEASE A chromosomal aberration involving CTNNB1 is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(3;8)(p21;q12) with PLAG1.SIMILARITY Belongs to the beta-catenin family.Homo sapiensNCBI Taxonomy9606UniProtP352221EQUAL781EQUALReactome Database ID Release 753451168Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3451168ReactomeR-HSA-34511681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3451168.1Reactomehttp://www.reactome.orgConverted from EntitySet in Reactomebeta-catenin binding SOX proteinsSRY,SOX2,SOX3,SOX4,SOX6,SOX7,SOX9,SOX17Reactome DB_ID: 5626912SRYSex-determining region Y proteinSRY_HUMANReactome DB_ID: 5627706UniProt:Q05066 SRYSRYTDFFUNCTION Transcriptional regulator that controls a genetic switch in male development. It is necessary and sufficient for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells (By similarity). In male adult brain involved in the maintenance of motor functions of dopaminergic neurons (By similarity). Involved in different aspects of gene regulation including promoter activation or repression (By similarity). Promotes DNA bending. SRY HMG box recognizes DNA by partial intercalation in the minor groove. Also involved in pre-mRNA splicing. Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3'.SUBUNIT Interacts with CALM, EP300, HDAC3, KPNB1, ZNF208 isoform KRAB-O, PARP1, SLC9A3R2 and WT1. The interaction with EP300 modulates its DNA-binding activity. The interaction with KPNB1 is sensitive to dissociation by Ran in the GTP-bound form (By similarity). Interaction with PARP1 impaired its DNA-binding activity (By similarity).DOMAIN DNA binding and bending properties of the HMG domains of human and mouse SRY differ form each other. Human SRY shows more extensive minor groove contacts with DNA and a lower specificity of sequence recognition than mouse SRY.PTM Phosphorylated on serine residues by PKA. Phosphorylation by PKA enhances its DNA-binding activity and stimulates transcription repression.PTM Acetylation of Lys-136 contributes to its nuclear localization and enhances its interaction with KPNB1. Deacetylated by HDAC3.PTM Poly-ADP-ribosylated by PARP1. ADP-ribosylation reduces its DNA-binding activity.DISEASE A 45,X chromosomal aberration involving SRY is found in Turner syndrome, a disease characterized by gonadal dysgenesis with short stature, 'streak gonads', variable abnormalities such as webbing of the neck, cubitus valgus, cardiac defects, low posterior hair line. The phenotype is female.SIMILARITY Belongs to the SRY family.UniProtQ050661EQUAL204EQUALReactome Database ID Release 755627706Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5627706ReactomeR-HSA-56277061Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5627706.1SOX2Transcription factor SOX-2SOX2_HUMANReactome DB_ID: 452271UniProt:P48431 SOX2SOX2FUNCTION Transcription factor that forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (By similarity). Binds to the proximal enhancer region of NANOG (By similarity). Critical for early embryogenesis and for embryonic stem cell pluripotency (PubMed:18035408). Downstream SRRT target that mediates the promotion of neural stem cell self-renewal (By similarity). Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation (By similarity). May function as a switch in neuronal development (By similarity).SUBUNIT Interacts with ZSCAN10 (By similarity). Interacts with SOX3 and FGFR1 (By similarity). Interacts with GLIS1 (PubMed:21654807). Interacts with POU5F1; binds synergistically with POU5F1 to DNA (By similarity).PTM Sumoylation inhibits binding on DNA and negatively regulates the FGF4 transactivation.BIOTECHNOLOGY POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four Yamanaka factors. When combined, these factors are sufficient to reprogram differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes.UniProtP484311EQUAL317EQUALReactome Database ID Release 75452271Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=452271ReactomeR-HSA-4522711Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-452271.1SOX3Transcription factor SOX-3SOX3_HUMANReactome DB_ID: 5625835UniProt:P41225 SOX3SOX3FUNCTION Transcription factor required during the formation of the hypothalamo-pituitary axis. May function as a switch in neuronal development. Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation. Required also within the pharyngeal epithelia for craniofacial morphogenesis. Controls a genetic switch in male development. Is necessary for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells (By similarity).SUBUNIT Interacts with SOX2 and FGFR1.CAUTION Was originally termed SOX-9.UniProtP412251EQUAL446EQUALReactome Database ID Release 755625835Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5625835ReactomeR-HSA-56258351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5625835.1SOX4Transcription factor SOX-4SOX4_HUMANReactome DB_ID: 5625832UniProt:Q06945 SOX4SOX4FUNCTION Transcriptional activator that binds with high affinity to the T-cell enhancer motif 5'-AACAAAG-3' motif (PubMed:30661772). Required for IL17A-producing Vgamma2-positive gamma-delta T-cell maturation and development, via binding to regulator loci of RORC to modulate expression (By similarity).SUBUNIT Interacts with UBE2I.TISSUE SPECIFICITY Testis, brain, and heart.UniProtQ069451EQUAL474EQUALReactome Database ID Release 755625832Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5625832ReactomeR-HSA-56258321Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5625832.1SOX6Transcription factor SOX-6SOX6_HUMANReactome DB_ID: 3246093UniProt:P35712 SOX6SOX6FUNCTION Transcription factor that plays a key role in several developmental processes, including neurogenesis, chondrocytes differentiation and cartilage formation. Specifically binds the 5'-AACAAT-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis. Required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes: SOX5 and SOX6 cooperatively bind with SOX9 on active enhancers and super-enhancers associated with cartilage-specific genes, and thereby potentiate SOX9's ability to transactivate. Not involved in precartilaginous condensation, the first step in chondrogenesis, during which skeletal progenitors differentiate into prechondrocytes. Together with SOX5, required to form and maintain a pool of highly proliferating chondroblasts between epiphyses and metaphyses, to form columnar chondroblasts, delay chondrocyte prehypertrophy but promote hypertrophy, and to delay terminal differentiation of chondrocytes on contact with ossification fronts. Binds to the proximal promoter region of the myelin protein MPZ gene, and is thereby involved in the differentiation of oligodendroglia in the developing spinal tube. Binds to the gene promoter of MBP and acts as a transcriptional repressor.SUBUNIT Interacts with DAZAP2 (By similarity). May interact with CENPK (By similarity).TISSUE SPECIFICITY Expressed in a wide variety of tissues, most abundantly in skeletal muscle.PTM Sumoylation inhibits the transcriptional activity.UniProtP357121EQUAL828EQUALReactome Database ID Release 753246093Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3246093ReactomeR-HSA-32460931Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3246093.1SOX7Transcription factor SOX-7SOX7_HUMANReactome DB_ID: 5627712UniProt:Q9BT81 SOX7SOX7FUNCTION Binds to and activates the CDH5 promoter, hence plays a role in the transcriptional regulation of genes expressed in the hemogenic endothelium and blocks further differentiation into blood precursors (By similarity). May be required for the survival of both hematopoietic and endothelial precursors during specification (By similarity). Competes with GATA4 for binding and activation of the FGF3 promoter (By similarity). Represses Wnt/beta-catenin-stimulated transcription, probably by targeting CTNNB1 to proteasomal degradation. Binds the DNA sequence 5'-AACAAT-3'.SUBUNIT Interacts with CTNNB1/beta-catenin; this interaction may lead to the proteasomal degradation of active CTNNB1 and thus inhibition of Wnt/beta-catenin-stimulated transcription.TISSUE SPECIFICITY Widely expressed in adult and fetal tissues. Present both in mesenchymal and epithelial cells in some adult tissues, including colon. Tends to be down-regulated in prostate adenocarcinomas and colorectal tumors due to promoter hypermethylation.DEVELOPMENTAL STAGE In 8 week-old embryo, expressed in brain, tongue, heart, liver, lung and vertebrae.UniProtQ9BT811EQUAL388EQUALReactome Database ID Release 755627712Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5627712ReactomeR-HSA-56277121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5627712.1SOX9Transcription factor SOX-9SOX9_HUMANReactome DB_ID: 3214954UniProt:P48436 SOX9SOX9FUNCTION 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).SUBUNIT Homodimer; homodimerization is required for activity (By similarity). Interacts (via C-terminus) with ZNF219; forming a complex that binds to the COL2A1 promoter and activates COL2A1 expression (By similarity). Interacts with DDRGK1 (PubMed:28263186). Interacts with EP300/p300 (PubMed:12732631). Interacts with beta-catenin (CTNNB1); inhibiting CTNNB1 activity by competing with the binding sites of TCF/LEF within CTNNB1 (By similarity).DOMAIN The transactivation domains TAM and TAC (for transactivation domain in the middle and at the C-terminus, respectively) are required to contact transcriptional coactivators and basal transcriptional machinery components and thereby induce gene transactivation.DOMAIN The PQA region (for proline, glutamine and alanine-rich) helps stabilizing SOX9 and facilitates transactivation (PubMed:31194875). It lacks intrinsic transactivation capability (PubMed:31194875).PTM Acetylated; acetylation impairs nuclear localization and ability to transactivate expression of target genes. Deacetylated by SIRT1.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.PTM Ubiquitinated; ubiquitination leads to proteasomal degradation and is negatively regulated by DDRGK1.PTM Sumoylated; phosphorylation at either Ser-64 or Ser-211 is required for sumoylation. Sumoylation is induced by BMP signaling pathway.UniProtP484361EQUAL509EQUALReactome Database ID Release 753214954Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3214954ReactomeR-HSA-32149541Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3214954.1SOX17Transcription factor SOX-17SOX17_HUMANReactome DB_ID: 5625834UniProt:Q9H6I2 SOX17SOX17FUNCTION Acts as transcription regulator that binds target promoter DNA and bends the DNA. Binds to the sequences 5'-AACAAT-'3 or 5'-AACAAAG-3'. Modulates transcriptional regulation via WNT3A. Inhibits Wnt signaling. Promotes degradation of activated CTNNB1. Plays a key role in the regulation of embryonic development. Required for normal development of the definitive gut endoderm. Required for normal looping of the embryonic heart tube. Plays an important role in embryonic and postnatal vascular development, including development of arteries. Plays an important role in postnatal angiogenesis, where it is functionally redundant with SOX18. Required for the generation and maintenance of fetal hematopoietic stem cells, and for fetal hematopoiesis. Probable transcriptional activator in the premeiotic germ cells.SUBUNIT Interacts with CTNNB1, LEF1 and TCF4.TISSUE SPECIFICITY Expressed in adult heart, lung, spleen, testis, ovary, placenta, fetal lung, and kidney. In normal gastrointestinal tract, it is preferentially expressed in esophagus, stomach and small intestine than in colon and rectum.UniProtQ9H6I21EQUAL414EQUALReactome Database ID Release 755625834Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5625834ReactomeR-HSA-56258341Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5625834.1Reactome Database ID Release 755626912Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5626912ReactomeR-HSA-56269121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5626912.1CTNNB1:SRY,SOX2,SOX3,SOX4,SOX6,SOX7,SOX9,SOX17Reactome DB_ID: 562691511Reactome Database ID Release 755626915Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5626915ReactomeR-HSA-56269151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5626915.1Reactome Database ID Release 755626938Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5626938ReactomeR-HSA-56269382Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5626938.215132997Pubmed2004Interactions between Sox9 and beta-catenin control chondrocyte differentiationAkiyama, HaruhikoLyons, Jon PMori-Akiyama, YukoYang, XiaohongZhang, RenZhang, ZhaopingDeng, Jian MinTaketo, Makoto MNakamura, TakashiBehringer, Richard RMcCrea, Pierre Dde Crombrugghe, BenoitGenes Dev. 18:1072-8719631281Pubmed2010All purpose Sox: The many roles of Sox proteins in gene expressionWegner, MichaelInt. J. Biochem. Cell Biol. 42:381-9019854293Pubmed2010Acquisition of SOX transcription factor specificity through protein-protein interaction, modulation of Wnt signalling and post-translational modificationBernard, PascalHarley, Vincent RInt. J. Biochem. Cell Biol. 42:400-1017875931Pubmed2007Sox17 and Sox4 differentially regulate beta-catenin/T-cell factor activity and proliferation of colon carcinoma cellsSinner, DéboraKordich, Jennifer JSpence, Jason ROpoka, RobertRankin, ScottLin, Suh-Chin JJonatan, DivaZorn, Aaron MWells, James MMol. Cell. Biol. 27:7802-1517698607Pubmed2007Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epitheliumBastide, PaulineDarido, CharbelPannequin, JulieKist, RalfRobine, SylvieMarty-Double, ChristianeBibeau, FrédéricScherer, GerdJoubert, DominiqueHollande, FrédéricBlache, PhilippeJay, PhilippeJ. 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