SOX9_MOUSE
ID SOX9_MOUSE Reviewed; 507 AA.
AC Q04887; Q8C7L2; Q91ZK2; Q99KQ0;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Transcription factor SOX-9 {ECO:0000305};
DE Short=mSox9 {ECO:0000303|PubMed:26527273};
GN Name=Sox9 {ECO:0000303|Ref.1, ECO:0000312|MGI:MGI:98371}; Synonyms=Sox-9;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129;
RA Lee H.-H.;
RT "The gene expression of Sox9 in mouse genital ridges.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Hippocampus, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 113-168.
RX PubMed=8441686; DOI=10.1093/nar/21.3.744;
RA Wright E.M., Snopek B., Koopman P.;
RT "Seven new members of the Sox gene family expressed during mouse
RT development.";
RL Nucleic Acids Res. 21:744-744(1993).
RN [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=7704017; DOI=10.1038/ng0195-15;
RA Wright E., Hargrave M.R., Christiansen J., Cooper L., Kun J., Evans T.,
RA Gangadharan U., Greenfield A., Koopman P.;
RT "The Sry-related gene Sox9 is expressed during chondrogenesis in mouse
RT embryos.";
RL Nat. Genet. 9:15-20(1995).
RN [6]
RP FUNCTION, DNA-BINDING, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=9119111; DOI=10.1006/dbio.1996.8487;
RA Ng L.J., Wheatley S., Muscat G.E., Conway-Campbell J., Bowles J.,
RA Wright E., Bell D.M., Tam P.P., Cheah K.S., Koopman P.;
RT "SOX9 binds DNA, activates transcription, and coexpresses with type II
RT collagen during chondrogenesis in the mouse.";
RL Dev. Biol. 183:108-121(1997).
RN [7]
RP FUNCTION.
RX PubMed=10319868; DOI=10.1038/8792;
RA Bi W., Deng J.M., Zhang Z., Behringer R.R., de Crombrugghe B.;
RT "Sox9 is required for cartilage formation.";
RL Nat. Genet. 22:85-89(1999).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-64 AND SER-211, AND
RP MUTAGENESIS OF SER-64 AND SER-211.
RX PubMed=10805756; DOI=10.1128/mcb.20.11.4149-4158.2000;
RA Huang W., Zhou X., Lefebvre V., de Crombrugghe B.;
RT "Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A enhances
RT SOX9's ability to transactivate a Col2a1 chondrocyte-specific enhancer.";
RL Mol. Cell. Biol. 20:4149-4158(2000).
RN [9]
RP PHOSPHORYLATION AT SER-64 AND SER-211, AND MUTAGENESIS OF SER-64 AND
RP SER-211.
RX PubMed=11120880; DOI=10.1073/pnas.98.1.160;
RA Huang W., Chung U.I., Kronenberg H.M., de Crombrugghe B.;
RT "The chondrogenic transcription factor Sox9 is a target of signaling by the
RT parathyroid hormone-related peptide in the growth plate of endochondral
RT bones.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:160-165(2001).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11371614; DOI=10.1073/pnas.111092198;
RA Bi W., Huang W., Whitworth D.J., Deng J.M., Zhang Z., Behringer R.R.,
RA de Crombrugghe B.;
RT "Haploinsufficiency of Sox9 results in defective cartilage primordia and
RT premature skeletal mineralization.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:6698-6703(2001).
RN [11]
RP DISRUPTION PHENOTYPE.
RX PubMed=11857796; DOI=10.1002/gene.10050;
RA Kist R., Schrewe H., Balling R., Scherer G.;
RT "Conditional inactivation of Sox9: a mouse model for campomelic
RT dysplasia.";
RL Genesis 32:121-123(2002).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12414734; DOI=10.1101/gad.1017802;
RA Akiyama H., Chaboissier M.C., Martin J.F., Schedl A., de Crombrugghe B.;
RT "The transcription factor Sox9 has essential roles in successive steps of
RT the chondrocyte differentiation pathway and is required for expression of
RT Sox5 and Sox6.";
RL Genes Dev. 16:2813-2828(2002).
RN [13]
RP FUNCTION.
RX PubMed=15529345; DOI=10.1002/art.20611;
RA Ikeda T., Kamekura S., Mabuchi A., Kou I., Seki S., Takato T., Nakamura K.,
RA Kawaguchi H., Ikegawa S., Chung U.I.;
RT "The combination of SOX5, SOX6, and SOX9 (the SOX trio) provides signals
RT sufficient for induction of permanent cartilage.";
RL Arthritis Rheum. 50:3561-3573(2004).
RN [14]
RP FUNCTION, AND INTERACTION WITH CTNNB1.
RX PubMed=15132997; DOI=10.1101/gad.1171104;
RA Akiyama H., Lyons J.P., Mori-Akiyama Y., Yang X., Zhang R., Zhang Z.,
RA Deng J.M., Taketo M.M., Nakamura T., Behringer R.R., McCrea P.D.,
RA de Crombrugghe B.;
RT "Interactions between Sox9 and beta-catenin control chondrocyte
RT differentiation.";
RL Genes Dev. 18:1072-1087(2004).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION AT LYS-396, AND MUTAGENESIS
RP OF LYS-396.
RX PubMed=15694126; DOI=10.1016/j.matbio.2004.10.002;
RA Akiyama H., Kamitani T., Yang X., Kandyil R., Bridgewater L.C., Fellous M.,
RA Mori-Akiyama Y., de Crombrugghe B.;
RT "The transcription factor Sox9 is degraded by the ubiquitin-proteasome
RT system and stabilized by a mutation in a ubiquitin-target site.";
RL Matrix Biol. 23:499-505(2005).
RN [16]
RP TISSUE SPECIFICITY.
RX PubMed=16203988; DOI=10.1073/pnas.0504750102;
RA Akiyama H., Kim J.E., Nakashima K., Balmes G., Iwai N., Deng J.M.,
RA Zhang Z., Martin J.F., Behringer R.R., Nakamura T., de Crombrugghe B.;
RT "Osteo-chondroprogenitor cells are derived from Sox9 expressing
RT precursors.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:14665-14670(2005).
RN [17]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=17525254; DOI=10.2353/ajpath.2007.060899;
RA Sumi E., Iehara N., Akiyama H., Matsubara T., Mima A., Kanamori H.,
RA Fukatsu A., Salant D.J., Kita T., Arai H., Doi T.;
RT "SRY-related HMG box 9 regulates the expression of Col4a2 through
RT transactivating its enhancer element in mesangial cells.";
RL Am. J. Pathol. 170:1854-1864(2007).
RN [18]
RP FUNCTION.
RX PubMed=18415932; DOI=10.1387/ijdb.072490gh;
RA Hargus G., Kist R., Kramer J., Gerstel D., Neitz A., Scherer G.,
RA Rohwedel J.;
RT "Loss of Sox9 function results in defective chondrocyte differentiation of
RT mouse embryonic stem cells in vitro.";
RL Int. J. Dev. Biol. 52:323-332(2008).
RN [19]
RP FUNCTION, INTERACTION WITH ZNF219, AND SUBCELLULAR LOCATION.
RX PubMed=20940257; DOI=10.1242/jcs.071373;
RA Takigawa Y., Hata K., Muramatsu S., Amano K., Ono K., Wakabayashi M.,
RA Matsuda A., Takada K., Nishimura R., Yoneda T.;
RT "The transcription factor Znf219 regulates chondrocyte differentiation by
RT assembling a transcription factory with Sox9.";
RL J. Cell Sci. 123:3780-3788(2010).
RN [20]
RP FUNCTION.
RX PubMed=21367821; DOI=10.1242/dev.057802;
RA Ikegami D., Akiyama H., Suzuki A., Nakamura T., Nakano T., Yoshikawa H.,
RA Tsumaki N.;
RT "Sox9 sustains chondrocyte survival and hypertrophy in part through Pik3ca-
RT Akt pathways.";
RL Development 138:1507-1519(2011).
RN [21]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21212101; DOI=10.1093/hmg/ddq558;
RA Reginensi A., Clarkson M., Neirijnck Y., Lu B., Ohyama T., Groves A.K.,
RA Sock E., Wegner M., Costantini F., Chaboissier M.C., Schedl A.;
RT "SOX9 controls epithelial branching by activating RET effector genes during
RT kidney development.";
RL Hum. Mol. Genet. 20:1143-1153(2011).
RN [22]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22421045; DOI=10.1016/j.devcel.2011.12.024;
RA Dy P., Wang W., Bhattaram P., Wang Q., Wang L., Ballock R.T., Lefebvre V.;
RT "Sox9 directs hypertrophic maturation and blocks osteoblast differentiation
RT of growth plate chondrocytes.";
RL Dev. Cell 22:597-609(2012).
RN [23]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=24191021; DOI=10.1073/pnas.1311847110;
RA Rockich B.E., Hrycaj S.M., Shih H.P., Nagy M.S., Ferguson M.A., Kopp J.L.,
RA Sander M., Wellik D.M., Spence J.R.;
RT "Sox9 plays multiple roles in the lung epithelium during branching
RT morphogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E4456-E4464(2013).
RN [24]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=25229425; DOI=10.1371/journal.pone.0107577;
RA Oh C.D., Lu Y., Liang S., Mori-Akiyama Y., Chen D., de Crombrugghe B.,
RA Yasuda H.;
RT "SOX9 regulates multiple genes in chondrocytes, including genes encoding
RT ECM proteins, ECM modification enzymes, receptors, and transporters.";
RL PLoS ONE 9:e107577-e107577(2014).
RN [25]
RP FUNCTION, DNA-BINDING, AND SUBUNIT.
RX PubMed=26146088; DOI=10.1016/j.celrep.2015.06.013;
RA Ohba S., He X., Hojo H., McMahon A.P.;
RT "Distinct transcriptional programs underlie Sox9 regulation of the
RT mammalian chondrocyte.";
RL Cell Rep. 12:229-243(2015).
RN [26]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=26150426; DOI=10.1093/nar/gkv688;
RA Liu C.F., Lefebvre V.;
RT "The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through
RT super-enhancers to drive chondrogenesis.";
RL Nucleic Acids Res. 43:8183-8203(2015).
RN [27]
RP ACETYLATION, DEACETYLATION, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=26910618; DOI=10.1111/acel.12456;
RA Bar Oz M., Kumar A., Elayyan J., Reich E., Binyamin M., Kandel L.,
RA Liebergall M., Steinmeyer J., Lefebvre V., Dvir-Ginzberg M.;
RT "Acetylation reduces SOX9 nuclear entry and ACAN gene transactivation in
RT human chondrocytes.";
RL Aging Cell 15:499-508(2016).
RN [28]
RP FUNCTION.
RX PubMed=28263186; DOI=10.1172/jci90193;
RA Egunsola A.T., Bae Y., Jiang M.M., Liu D.S., Chen-Evenson Y., Bertin T.,
RA Chen S., Lu J.T., Nevarez L., Magal N., Raas-Rothschild A., Swindell E.C.,
RA Cohn D.H., Gibbs R.A., Campeau P.M., Shohat M., Lee B.H.;
RT "Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepimetaphyseal
RT dysplasia.";
RL J. Clin. Invest. 127:1475-1484(2017).
RN [29]
RP PHOSPHORYLATION, DEPHOSPHORYLATION, AND SUMOYLATION.
RX PubMed=29644115; DOI=10.1038/s41413-018-0013-z;
RA Zuo C., Wang L., Kamalesh R.M., Bowen M.E., Moore D.C., Dooner M.S.,
RA Reginato A.M., Wu Q., Schorl C., Song Y., Warman M.L., Neel B.G.,
RA Ehrlich M.G., Yang W.;
RT "SHP2 regulates skeletal cell fate by modifying SOX9 expression and
RT transcriptional activity.";
RL Bone Res. 6:12-12(2018).
RN [30]
RP FUNCTION.
RX PubMed=30021842; DOI=10.1242/dev.164459;
RA Liu C.F., Angelozzi M., Haseeb A., Lefebvre V.;
RT "SOX9 is dispensable for the initiation of epigenetic remodeling and the
RT activation of marker genes at the onset of chondrogenesis.";
RL Development 145:0-0(2018).
RN [31]
RP FUNCTION.
RX PubMed=29659575; DOI=10.1371/journal.pgen.1007346;
RA Tan Z., Niu B., Tsang K.Y., Melhado I.G., Ohba S., He X., Huang Y.,
RA Wang C., McMahon A.P., Jauch R., Chan D., Zhang M.Q., Cheah K.S.E.;
RT "Synergistic co-regulation and competition by a SOX9-GLI-FOXA phasic
RT transcriptional network coordinate chondrocyte differentiation
RT transitions.";
RL PLoS Genet. 14:e1007346-e1007346(2018).
RN [32]
RP FUNCTION.
RX PubMed=31121357; DOI=10.1016/j.bone.2019.05.027;
RA Lui J.C., Yue S., Lee A., Kikani B., Temnycky A., Barnes K.M., Baron J.;
RT "Persistent Sox9 expression in hypertrophic chondrocytes suppresses
RT transdifferentiation into osteoblasts.";
RL Bone 125:169-177(2019).
RN [33]
RP REVIEW.
RX PubMed=31382142; DOI=10.1016/j.ceb.2019.07.008;
RA Lefebvre V., Angelozzi M., Haseeb A.;
RT "SOX9 in cartilage development and disease.";
RL Curr. Opin. Cell Biol. 61:39-47(2019).
RN [34]
RP FUNCTION, AND INDUCTION.
RX PubMed=32103177; DOI=10.1038/s41586-020-2050-1;
RA van Gastel N., Stegen S., Eelen G., Schoors S., Carlier A., Daniels V.W.,
RA Baryawno N., Przybylski D., Depypere M., Stiers P.J., Lambrechts D.,
RA Van Looveren R., Torrekens S., Sharda A., Agostinis P., Lambrechts D.,
RA Maes F., Swinnen J.V., Geris L., Van Oosterwyck H., Thienpont B.,
RA Carmeliet P., Scadden D.T., Carmeliet G.;
RT "Lipid availability determines fate of skeletal progenitor cells via
RT SOX9.";
RL Nature 579:111-117(2020).
RN [35] {ECO:0007744|PDB:4S2Q}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 103-178.
RX PubMed=26527273; DOI=10.1107/s2053230x1501969x;
RA Vivekanandan S., Moovarkumudalvan B., Lescar J., Kolatkar P.R.;
RT "Crystallization and X-ray diffraction analysis of the HMG domain of the
RT chondrogenesis master regulator Sox9 in complex with a ChIP-Seq-identified
RT DNA element.";
RL Acta Crystallogr. F Struct. Biol. Commun. 71:1437-1441(2015).
CC -!- FUNCTION: Transcription factor that plays a key role in chondrocytes
CC differentiation and skeletal development (PubMed:10319868,
CC PubMed:11371614, PubMed:12414734, PubMed:15132997, PubMed:18415932,
CC PubMed:20940257, PubMed:28263186). Specifically binds the 5'-ACAAAG-3'
CC DNA motif present in enhancers and super-enhancers and promotes
CC expression of genes important for chondrogenesis, including cartilage
CC matrix protein-coding genes COL2A1, COL4A2, COL9A1, COL11A2 and ACAN,
CC SOX5 and SOX6 (PubMed:9119111, PubMed:10805756, PubMed:12414734,
CC PubMed:15694126, PubMed:17525254, PubMed:26146088, PubMed:26150426,
CC PubMed:26910618, PubMed:28263186). Also binds to some promoter regions
CC (PubMed:20940257). Plays a central role in successive steps of
CC chondrocyte differentiation (PubMed:11371614, PubMed:12414734,
CC PubMed:22421045). Absolutely required for precartilaginous
CC condensation, the first step in chondrogenesis during which skeletal
CC progenitors differentiate into prechondrocytes (PubMed:11371614,
CC PubMed:12414734). Together with SOX5 and SOX6, required for overt
CC chondrogenesis when condensed prechondrocytes differentiate into early
CC stage chondrocytes, the second step in chondrogenesis (PubMed:11371614,
CC PubMed:12414734, PubMed:15529345). Later, required to direct
CC hypertrophic maturation and block osteoblast differentiation of growth
CC plate chondrocytes: maintains chondrocyte columnar proliferation,
CC delays prehypertrophy and then prevents osteoblastic differentiation of
CC chondrocytes by lowering beta-catenin (CTNNB1) signaling and RUNX2
CC expression (PubMed:22421045, PubMed:31121357). Also required for
CC chondrocyte hypertrophy, both indirectly, by keeping the lineage fate
CC of chondrocytes, and directly, by remaining present in upper
CC hypertrophic cells and transactivating COL10A1 along with MEF2C
CC (PubMed:21367821, PubMed:22421045). Low lipid levels are the main
CC nutritional determinant for chondrogenic commitment of skeletal
CC progenitor cells: when lipids levels are low, FOXO (FOXO1 and FOXO3)
CC transcription factors promote expression of SOX9, which induces
CC chondrogenic commitment and suppresses fatty acid oxidation
CC (PubMed:32103177). Mechanistically, helps, but is not required, to
CC remove epigenetic signatures of transcriptional repression and deposit
CC active promoter and enhancer marks at chondrocyte-specific genes
CC (PubMed:30021842). Acts in cooperation with the Hedgehog pathway-
CC dependent GLI (GLI1 and GLI3) transcription factors (PubMed:29659575).
CC In addition to cartilage development, also acts as a regulator of
CC proliferation and differentiation in epithelial stem/progenitor cells:
CC involved in the lung epithelium during branching morphogenesis, by
CC balancing proliferation and differentiation and regulating the
CC extracellular matrix (PubMed:24191021). Controls epithelial branching
CC during kidney development (PubMed:21212101).
CC {ECO:0000269|PubMed:10319868, ECO:0000269|PubMed:10805756,
CC ECO:0000269|PubMed:11371614, ECO:0000269|PubMed:12414734,
CC ECO:0000269|PubMed:15132997, ECO:0000269|PubMed:15529345,
CC ECO:0000269|PubMed:15694126, ECO:0000269|PubMed:17525254,
CC ECO:0000269|PubMed:18415932, ECO:0000269|PubMed:20940257,
CC ECO:0000269|PubMed:21212101, ECO:0000269|PubMed:21367821,
CC ECO:0000269|PubMed:22421045, ECO:0000269|PubMed:24191021,
CC ECO:0000269|PubMed:26146088, ECO:0000269|PubMed:26150426,
CC ECO:0000269|PubMed:26910618, ECO:0000269|PubMed:28263186,
CC ECO:0000269|PubMed:29659575, ECO:0000269|PubMed:30021842,
CC ECO:0000269|PubMed:31121357, ECO:0000269|PubMed:32103177,
CC ECO:0000269|PubMed:9119111}.
CC -!- SUBUNIT: Homodimer; homodimerization is required for activity
CC (PubMed:26146088). Interacts (via C-terminus) with ZNF219; forming a
CC complex that binds to the COL2A1 promoter and activates COL2A1
CC expression (PubMed:20940257). Interacts with DDRGK1 (By similarity).
CC Interacts with EP300/p300 (By similarity). Interacts with beta-catenin
CC (CTNNB1); inhibiting CTNNB1 activity by competing with the binding
CC sites of TCF/LEF within CTNNB1 (PubMed:15132997).
CC {ECO:0000250|UniProtKB:P48436, ECO:0000269|PubMed:15132997,
CC ECO:0000269|PubMed:20940257, ECO:0000269|PubMed:26146088}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00267,
CC ECO:0000269|PubMed:10805756, ECO:0000269|PubMed:15694126,
CC ECO:0000269|PubMed:20940257, ECO:0000269|PubMed:21212101,
CC ECO:0000269|PubMed:26910618}.
CC -!- TISSUE SPECIFICITY: Expressed in progenitor cells in various organs,
CC including chondroprogenitors, osteoprogenitors and preadipocytes, but
CC is not expressed in most differentiated cell types such as osteoblasts
CC and adipocytes, with the exception of chondrocytes (PubMed:16203988).
CC Highly expressed in developing chondrogenic tissues (PubMed:9119111).
CC Also expressed in some non-chondrogenic tissues such as notochord, otic
CC vesicle and neural tube (PubMed:9119111). {ECO:0000269|PubMed:16203988,
CC ECO:0000269|PubMed:9119111}.
CC -!- DEVELOPMENTAL STAGE: Predominantly expressed in mesenchymal
CC condensations throughout the embryo before and during the deposition of
CC cartilage (PubMed:7704017). Expressed in multipotent skeletogenic cells
CC (PubMed:9119111). Continues to be expressed during chondrocyte lineage
CC progression, except in terminally differentiating growth plate
CC chondrocytes (PubMed:9119111). Also expressed in some non-chondrogenic
CC tissues such as notochord, otic vesicle and neural tube
CC (PubMed:9119111). In the developing lung, expressed at the distal tips
CC of the branching epithelium as branching occurs and is down-regulated
CC starting at embryonic day (E)16.5, at the onset of terminal
CC differentiation of type 1 and type 2 alveolar cells (PubMed:24191021).
CC {ECO:0000269|PubMed:24191021, ECO:0000269|PubMed:7704017,
CC ECO:0000269|PubMed:9119111}.
CC -!- INDUCTION: Upon lipid starvation conditions, expression is activated by
CC FOXO (FOXO1 and FOXO3). {ECO:0000269|PubMed:32103177}.
CC -!- DOMAIN: The transactivation domains TAM and TAC (for transactivation
CC domain in the middle and at the C-terminus, respectively) are required
CC to contact transcriptional coactivators and basal transcriptional
CC machinery components and thereby induce gene transactivation.
CC {ECO:0000250|UniProtKB:P48436}.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000250|UniProtKB:P48436}.
CC -!- DOMAIN: The PQA region (for proline, glutamine and alanine-rich) helps
CC stabilize SOX9 and facilitates transactivation. It lacks intrinsic
CC transactivation capability. {ECO:0000250|UniProtKB:P48436}.
CC -!- PTM: Acetylated; acetylation impairs nuclear localization and ability
CC to transactivate expression of target genes (PubMed:26910618).
CC Deacetylated by SIRT1 (PubMed:26910618). {ECO:0000269|PubMed:26910618}.
CC -!- PTM: Phosphorylation at Ser-64 and Ser-211 by PKA increases
CC transcriptional activity and may help delay chondrocyte maturation
CC downstream of PTHLH/PTHrP signaling (PubMed:10805756, PubMed:11120880).
CC Phosphorylation at either Ser-64 or Ser-211 is required for
CC sumoylation, but phosphorylation is not dependent on sumoylation
CC (PubMed:29644115). Phosphorylated on tyrosine residues; tyrosine
CC dephosphorylation by PTPN11/SHP2 blocks SOX9 phosphorylation by PKA and
CC subsequent SUMOylation (PubMed:29644115). {ECO:0000269|PubMed:10805756,
CC ECO:0000269|PubMed:11120880, ECO:0000269|PubMed:29644115}.
CC -!- PTM: Sumoylated; phosphorylation at either Ser-64 or Ser-211 is
CC required for sumoylation (PubMed:29644115). Sumoylation is induced by
CC BMP signaling pathway (PubMed:29644115). {ECO:0000269|PubMed:29644115}.
CC -!- PTM: Ubiquitinated; ubiquitination leads to proteasomal degradation and
CC is negatively regulated by DDRGK1. {ECO:0000305|PubMed:15694126}.
CC -!- DISRUPTION PHENOTYPE: Perinatal lethality, with cleft palate, as well
CC as hypoplasia and bending of many skeletal structures derived from
CC cartilage precursors (PubMed:11371614). Heterozygous mice die shortly
CC after birth and display skeletal malformations caused by impaired
CC precartilaginous condensations (PubMed:11371614). In embryonic day 12.5
CC dpc heterozygotes embryos, skeletal elements are smaller
CC (PubMed:11371614, PubMed:11857796). In 14.5 dpc heterozygous embryos,
CC bending of radius, ulna and tibia cartilages is already prominent
CC (PubMed:11371614). Premature mineralization is observed in many bones,
CC including vertebrae and some craniofacial bones in 18.5 dpc
CC heterozygous embryos (PubMed:11371614). Conditional deletion in
CC undifferentiated mesenchymal cells of limb buds before mesenchymal
CC condensations results in a complete absence of both cartilage and bone,
CC while markers for the different axes of limb development show a normal
CC pattern of expression (PubMed:12414734). Conditional deletion in
CC undifferentiated mesenchymal cells of limb buds after chondrogenic
CC mesenchymal condensations causes a severe generalized chondrodysplasia,
CC in which most prechondrocytes are arrested as condensed mesenchymal
CC cells and do not undergo overt differentiation into chondrocytes
CC (PubMed:12414734). Conditional deletion in differentiated growth plate
CC chondrocytes results in severe dwarfism caused by shortened columnar
CC zones in growth plates, leading to an absence of chondrocyte
CC enlargement (PubMed:22421045). Conditional deletion in epithelial cells
CC leads to severe branching defects in the lung (PubMed:24191021).
CC {ECO:0000269|PubMed:11371614, ECO:0000269|PubMed:11857796,
CC ECO:0000269|PubMed:12414734, ECO:0000269|PubMed:22421045,
CC ECO:0000269|PubMed:24191021}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF421878; AAL16093.1; -; mRNA.
DR EMBL; AK030187; BAC26830.1; -; mRNA.
DR EMBL; AK049986; BAC34018.1; -; mRNA.
DR EMBL; BC004064; AAH04064.1; -; mRNA.
DR EMBL; BC023796; AAH23796.1; -; mRNA.
DR EMBL; BC023808; AAH23808.1; -; mRNA.
DR EMBL; BC023953; AAH23953.1; -; mRNA.
DR EMBL; BC024958; AAH24958.1; -; mRNA.
DR EMBL; BC034264; AAH34264.1; -; mRNA.
DR EMBL; Z18958; CAA79483.1; -; mRNA.
DR CCDS; CCDS25595.1; -.
DR PIR; S30243; S30243.
DR PIR; S52469; S52469.
DR RefSeq; NP_035578.3; NM_011448.4.
DR PDB; 4S2Q; X-ray; 2.70 A; D=103-178.
DR PDBsum; 4S2Q; -.
DR AlphaFoldDB; Q04887; -.
DR SMR; Q04887; -.
DR BioGRID; 203413; 8.
DR IntAct; Q04887; 1.
DR STRING; 10090.ENSMUSP00000000579; -.
DR iPTMnet; Q04887; -.
DR PhosphoSitePlus; Q04887; -.
DR MaxQB; Q04887; -.
DR PaxDb; Q04887; -.
DR PeptideAtlas; Q04887; -.
DR PRIDE; Q04887; -.
DR ProteomicsDB; 261484; -.
DR Antibodypedia; 915; 926 antibodies from 41 providers.
DR DNASU; 20682; -.
DR Ensembl; ENSMUST00000000579; ENSMUSP00000000579; ENSMUSG00000000567.
DR GeneID; 20682; -.
DR KEGG; mmu:20682; -.
DR UCSC; uc007med.2; mouse.
DR CTD; 6662; -.
DR MGI; MGI:98371; Sox9.
DR VEuPathDB; HostDB:ENSMUSG00000000567; -.
DR eggNOG; KOG0527; Eukaryota.
DR GeneTree; ENSGT00940000158269; -.
DR HOGENOM; CLU_031800_0_0_1; -.
DR InParanoid; Q04887; -.
DR OMA; QSSNSYY; -.
DR OrthoDB; 782373at2759; -.
DR PhylomeDB; Q04887; -.
DR TreeFam; TF351735; -.
DR Reactome; R-MMU-3769402; Deactivation of the beta-catenin transactivating complex.
DR Reactome; R-MMU-8878166; Transcriptional regulation by RUNX2.
DR BioGRID-ORCS; 20682; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Sox9; mouse.
DR PRO; PR:Q04887; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q04887; protein.
DR Bgee; ENSMUSG00000000567; Expressed in digit and 432 other tissues.
DR Genevisible; Q04887; MM.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0008013; F:beta-catenin binding; IDA:UniProtKB.
DR GO; GO:0043425; F:bHLH transcription factor binding; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0097157; F:pre-mRNA intronic binding; IDA:MGI.
DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0097065; P:anterior head development; IMP:MGI.
DR GO; GO:0003180; P:aortic valve morphogenesis; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0060018; P:astrocyte fate commitment; IGI:MGI.
DR GO; GO:0030282; P:bone mineralization; IMP:MGI.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IEP:UniProtKB.
DR GO; GO:0060532; P:bronchus cartilage development; IMP:MGI.
DR GO; GO:0019933; P:cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:MGI.
DR GO; GO:0001502; P:cartilage condensation; IMP:MGI.
DR GO; GO:0051216; P:cartilage development; IDA:UniProtKB.
DR GO; GO:0045165; P:cell fate commitment; IGI:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0061323; P:cell proliferation involved in heart morphogenesis; IMP:MGI.
DR GO; GO:0098609; P:cell-cell adhesion; IMP:MGI.
DR GO; GO:0071773; P:cellular response to BMP stimulus; ISS:UniProtKB.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0071504; P:cellular response to heparin; IDA:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IDA:UniProtKB.
DR GO; GO:0071300; P:cellular response to retinoic acid; IDA:MGI.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; IEP:UniProtKB.
DR GO; GO:0002063; P:chondrocyte development; IMP:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IDA:UniProtKB.
DR GO; GO:0003413; P:chondrocyte differentiation involved in endochondral bone morphogenesis; ISS:UniProtKB.
DR GO; GO:0003415; P:chondrocyte hypertrophy; IMP:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB.
DR GO; GO:0090103; P:cochlea morphogenesis; IMP:MGI.
DR GO; GO:0007010; P:cytoskeleton organization; IMP:MGI.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; IMP:MGI.
DR GO; GO:0060350; P:endochondral bone morphogenesis; IMP:MGI.
DR GO; GO:0031018; P:endocrine pancreas development; IMP:MGI.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI.
DR GO; GO:0060517; P:epithelial cell proliferation involved in prostatic bud elongation; IMP:MGI.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; IMP:MGI.
DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IMP:MGI.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0085029; P:extracellular matrix assembly; IMP:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0002067; P:glandular epithelial cell differentiation; IMP:MGI.
DR GO; GO:0021780; P:glial cell fate specification; IMP:MGI.
DR GO; GO:0003430; P:growth plate cartilage chondrocyte growth; IMP:UniProtKB.
DR GO; GO:0001942; P:hair follicle development; IMP:MGI.
DR GO; GO:0070384; P:Harderian gland development; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0003170; P:heart valve development; IMP:UniProtKB.
DR GO; GO:0003188; P:heart valve formation; IMP:MGI.
DR GO; GO:0003179; P:heart valve morphogenesis; IMP:MGI.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IMP:MGI.
DR GO; GO:0060575; P:intestinal epithelial cell differentiation; IMP:MGI.
DR GO; GO:0060729; P:intestinal epithelial structure maintenance; IMP:MGI.
DR GO; GO:0035622; P:intrahepatic bile duct development; IMP:MGI.
DR GO; GO:0032808; P:lacrimal gland development; IMP:MGI.
DR GO; GO:0060174; P:limb bud formation; IEP:UniProtKB.
DR GO; GO:0060487; P:lung epithelial cell differentiation; IMP:MGI.
DR GO; GO:0061145; P:lung smooth muscle development; IMP:MGI.
DR GO; GO:0019100; P:male germ-line sex determination; IMP:MGI.
DR GO; GO:0008584; P:male gonad development; IMP:MGI.
DR GO; GO:0030238; P:male sex determination; IGI:MGI.
DR GO; GO:0030879; P:mammary gland development; IEP:UniProtKB.
DR GO; GO:0097152; P:mesenchymal cell apoptotic process; IMP:MGI.
DR GO; GO:0010463; P:mesenchymal cell proliferation; IMP:MGI.
DR GO; GO:0072289; P:metanephric nephron tubule formation; IGI:MGI.
DR GO; GO:0072170; P:metanephric tubule development; IEP:UniProtKB.
DR GO; GO:0061138; P:morphogenesis of a branching epithelium; IMP:MGI.
DR GO; GO:0002009; P:morphogenesis of an epithelium; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:1904864; P:negative regulation of beta-catenin-TCF complex assembly; IMP:UniProtKB.
DR GO; GO:0070168; P:negative regulation of biomineral tissue development; IMP:UniProtKB.
DR GO; GO:0030502; P:negative regulation of bone mineralization; IMP:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IMP:MGI.
DR GO; GO:0030857; P:negative regulation of epithelial cell differentiation; IMP:MGI.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0046322; P:negative regulation of fatty acid oxidation; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:MGI.
DR GO; GO:0002683; P:negative regulation of immune system process; IMP:UniProtKB.
DR GO; GO:2001054; P:negative regulation of mesenchymal cell apoptotic process; IMP:MGI.
DR GO; GO:1902894; P:negative regulation of miRNA transcription; ISO:MGI.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IDA:MGI.
DR GO; GO:0030279; P:negative regulation of ossification; IMP:UniProtKB.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IDA:UniProtKB.
DR GO; GO:0046533; P:negative regulation of photoreceptor cell differentiation; IGI:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0014032; P:neural crest cell development; IMP:MGI.
DR GO; GO:0014036; P:neural crest cell fate specification; ISS:UniProtKB.
DR GO; GO:0048665; P:neuron fate specification; IMP:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:MGI.
DR GO; GO:0030903; P:notochord development; IEP:UniProtKB.
DR GO; GO:0006334; P:nucleosome assembly; ISS:UniProtKB.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IMP:MGI.
DR GO; GO:0001503; P:ossification; IEP:UniProtKB.
DR GO; GO:0071599; P:otic vesicle development; IEP:UniProtKB.
DR GO; GO:0030916; P:otic vesicle formation; IMP:MGI.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; IMP:UniProtKB.
DR GO; GO:0061036; P:positive regulation of cartilage development; IDA:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI.
DR GO; GO:2000138; P:positive regulation of cell proliferation involved in heart morphogenesis; IMP:MGI.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IDA:UniProtKB.
DR GO; GO:1902732; P:positive regulation of chondrocyte proliferation; ISO:MGI.
DR GO; GO:0030858; P:positive regulation of epithelial cell differentiation; IMP:MGI.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IMP:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:UniProtKB.
DR GO; GO:1901203; P:positive regulation of extracellular matrix assembly; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:MGI.
DR GO; GO:0090184; P:positive regulation of kidney development; IGI:UniProtKB.
DR GO; GO:2000020; P:positive regulation of male gonad development; ISS:UniProtKB.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IMP:MGI.
DR GO; GO:2000741; P:positive regulation of mesenchymal stem cell differentiation; ISS:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IMP:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:MGI.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030850; P:prostate gland development; IEP:UniProtKB.
DR GO; GO:0060512; P:prostate gland morphogenesis; IMP:MGI.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0034504; P:protein localization to nucleus; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0065003; P:protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:0061046; P:regulation of branching involved in lung morphogenesis; IMP:MGI.
DR GO; GO:0030155; P:regulation of cell adhesion; IMP:MGI.
DR GO; GO:0010564; P:regulation of cell cycle process; ISS:UniProtKB.
DR GO; GO:0045595; P:regulation of cell differentiation; IMP:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0060784; P:regulation of cell proliferation involved in tissue homeostasis; IMP:MGI.
DR GO; GO:2000794; P:regulation of epithelial cell proliferation involved in lung morphogenesis; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:MGI.
DR GO; GO:0072034; P:renal vesicle induction; IMP:UniProtKB.
DR GO; GO:0070542; P:response to fatty acid; IDA:UniProtKB.
DR GO; GO:0060041; P:retina development in camera-type eye; IGI:MGI.
DR GO; GO:0060221; P:retinal rod cell differentiation; IGI:MGI.
DR GO; GO:0060009; P:Sertoli cell development; IGI:MGI.
DR GO; GO:0060008; P:Sertoli cell differentiation; IMP:MGI.
DR GO; GO:0007165; P:signal transduction; IMP:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; ISS:UniProtKB.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IMP:MGI.
DR GO; GO:0007283; P:spermatogenesis; IGI:MGI.
DR GO; GO:0072089; P:stem cell proliferation; IMP:MGI.
DR GO; GO:0001894; P:tissue homeostasis; IMP:UniProtKB.
DR GO; GO:0060534; P:trachea cartilage development; IMP:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0060509; P:type I pneumocyte differentiation; IMP:MGI.
DR GO; GO:0072189; P:ureter development; IGI:MGI.
DR GO; GO:0072197; P:ureter morphogenesis; IGI:MGI.
DR GO; GO:0072193; P:ureter smooth muscle cell differentiation; IMP:MGI.
DR GO; GO:0072190; P:ureter urothelium development; IEP:UniProtKB.
DR Gene3D; 1.10.30.10; -; 1.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR029548; SOX-9.
DR InterPro; IPR022151; Sox_N.
DR PANTHER; PTHR45803:SF1; PTHR45803:SF1; 1.
DR Pfam; PF00505; HMG_box; 1.
DR Pfam; PF12444; Sox_N; 1.
DR SMART; SM00398; HMG; 1.
DR SUPFAM; SSF47095; SSF47095; 1.
DR PROSITE; PS50118; HMG_BOX_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Differentiation; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..507
FT /note="Transcription factor SOX-9"
FT /id="PRO_0000048741"
FT DNA_BIND 105..173
FT /note="HMG box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 1..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 63..103
FT /note="Dimerization (DIM)"
FT /evidence="ECO:0000250|UniProtKB:P48436"
FT REGION 63..103
FT /note="PQA"
FT /evidence="ECO:0000250|UniProtKB:P48436"
FT REGION 160..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 224..307
FT /note="Transactivation domain (TAM)"
FT /evidence="ECO:0000250|UniProtKB:P48436"
FT REGION 335..429
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 392..507
FT /note="Transactivation domain (TAC)"
FT /evidence="ECO:0000250|UniProtKB:P48436"
FT REGION 477..507
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 275..284
FT /note="9aaTAD 1"
FT /evidence="ECO:0000250|UniProtKB:P48436"
FT MOTIF 290..298
FT /note="9aaTAD 2"
FT /evidence="ECO:0000250|UniProtKB:P48436"
FT MOTIF 458..466
FT /note="9aaTAD 3"
FT /evidence="ECO:0000250|UniProtKB:P48436"
FT COMPBIAS 18..52
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 160..187
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 188..233
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 339..367
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..429
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 482..507
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 64
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:10805756"
FT MOD_RES 211
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:10805756"
FT CROSSLNK 396
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:15694126"
FT MUTAGEN 64
FT /note="S->A: Abolished phosphorylation by PKA, leading to
FT deacreased ability to activate transcription of target
FT genes; does not affect subcellular localization; when
FT associated with A-211."
FT /evidence="ECO:0000269|PubMed:10805756,
FT ECO:0000269|PubMed:11120880"
FT MUTAGEN 211
FT /note="S->A: Abolished phosphorylation by PKA, leading to
FT deacreased ability to activate transcription of target
FT genes; does not affect subcellular localization; when
FT associated with A-64."
FT /evidence="ECO:0000269|PubMed:10805756,
FT ECO:0000269|PubMed:11120880"
FT MUTAGEN 396
FT /note="K->A: Increased stability."
FT /evidence="ECO:0000269|PubMed:15694126"
FT CONFLICT 62
FT /note="K -> R (in Ref. 2; BAC34018)"
FT /evidence="ECO:0000305"
FT HELIX 111..126
FT /evidence="ECO:0007829|PDB:4S2Q"
FT HELIX 132..144
FT /evidence="ECO:0007829|PDB:4S2Q"
FT HELIX 148..168
FT /evidence="ECO:0007829|PDB:4S2Q"
SQ SEQUENCE 507 AA; 56077 MW; 01FC3B54FF329BDA CRC64;
MNLLDPFMKM TDEQEKGLSG APSPTMSEDS AGSPCPSGSG SDTENTRPQE NTFPKGEPDL
KKESEEDKFP VCIREAVSQV LKGYDWTLVP MPVRVNGSSK NKPHVKRPMN AFMVWAQAAR
RKLADQYPHL HNAELSKTLG KLWRLLNESE KRPFVEEAER LRVQHKKDHP DYKYQPRRRK
SVKNGQAEAE EATEQTHISP NAIFKALQAD SPHSSSGMSE VHSPGEHSGQ SQGPPTPPTT
PKTDVQAGKV DLKREGRPLA EGGRQPPIDF RDVDIGELSS DVISNIETFD VNEFDQYLPP
NGHPGVPATH GQVTYTGSYG ISSTAPTPAT AGHVWMSKQQ APPPPPQQPP QAPQAPQAPP
QQQAPPQQPQ APQQQQAHTL TTLSSEPGQS QRTHIKTEQL SPSHYSEQQQ HSPQQISYSP
FNLPHYSPSY PPITRSQYDY ADHQNSGSYY SHAAGQGSGL YSTFTYMNPA QRPMYTPIAD
TSGVPSIPQT HSPQHWEQPV YTQLTRP
