SOX9_CANLF
ID SOX9_CANLF Reviewed; 513 AA.
AC Q7YRJ7;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 25-MAY-2022, entry version 106.
DE RecName: Full=Transcription factor SOX-9 {ECO:0000305};
GN Name=SOX9;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12840810; DOI=10.1002/mrd.10317;
RA Meyers-Wallen V.N.;
RT "Sry and Sox9 expression during canine gonadal sex determination assayed by
RT quantitative reverse transcription-polymerase chain reaction.";
RL Mol. Reprod. Dev. 65:373-381(2003).
CC -!- FUNCTION: Transcription factor that plays a key role in chondrocytes
CC differentiation and skeletal development. Specifically binds the 5'-
CC ACAAAG-3' DNA motif present in enhancers and super-enhancers and
CC promotes expression of genes important for chondrogenesis, including
CC cartilage matrix protein-coding genes COL2A1, COL4A2, COL9A1, COL11A2
CC and ACAN, SOX5 and SOX6. Also binds to some promoter regions. Plays a
CC central role in successive steps of chondrocyte differentiation.
CC Absolutely required for precartilaginous condensation, the first step
CC in chondrogenesis during which skeletal progenitors differentiate into
CC prechondrocytes. Together with SOX5 and SOX6, required for overt
CC chondrogenesis when condensed prechondrocytes differentiate into early
CC stage chondrocytes, the second step in chondrogenesis. Later, required
CC to direct hypertrophic maturation and block osteoblast differentiation
CC of growth plate chondrocytes: maintains chondrocyte columnar
CC proliferation, delays prehypertrophy and then prevents osteoblastic
CC differentiation of chondrocytes by lowering beta-catenin (CTNNB1)
CC signaling and RUNX2 expression. Also required for chondrocyte
CC hypertrophy, both indirectly, by keeping the lineage fate of
CC chondrocytes, and directly, by remaining present in upper hypertrophic
CC cells and transactivating COL10A1 along with MEF2C. Low lipid levels
CC are the main nutritional determinant for chondrogenic commitment of
CC skeletal progenitor cells: when lipids levels are low, FOXO (FOXO1 and
CC FOXO3) transcription factors promote expression of SOX9, which induces
CC chondrogenic commitment and suppresses fatty acid oxidation.
CC Mechanistically, helps, but is not required, to remove epigenetic
CC signatures of transcriptional repression and deposit active promoter
CC and enhancer marks at chondrocyte-specific genes. Acts in cooperation
CC with the Hedgehog pathway-dependent GLI (GLI1 and GLI3) transcription
CC factors. In addition to cartilage development, also acts as a regulator
CC of proliferation and differentiation in epithelial stem/progenitor
CC cells: involved in the lung epithelium during branching morphogenesis,
CC by balancing proliferation and differentiation and regulating the
CC extracellular matrix. Controls epithelial branching during kidney
CC development. {ECO:0000250|UniProtKB:Q04887}.
CC -!- SUBUNIT: Homodimer; homodimerization is required for activity.
CC Interacts (via C-terminus) with ZNF219; forming a complex that binds to
CC the COL2A1 promoter and activates COL2A1 expression (By similarity).
CC Interacts with DDRGK1. Interacts with EP300/p300 (By similarity).
CC Interacts with beta-catenin (CTNNB1); inhibiting CTNNB1 activity by
CC competing with the binding sites of TCF/LEF within CTNNB1 (By
CC similarity). {ECO:0000250|UniProtKB:P48436,
CC ECO:0000250|UniProtKB:Q04887}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q04887,
CC ECO:0000255|PROSITE-ProRule:PRU00267}.
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. Deacetylated by SIRT1.
CC {ECO:0000250|UniProtKB:Q04887}.
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. Phosphorylation at either Ser-64
CC or Ser-211 is required for sumoylation, but phosphorylation is not
CC dependent on sumoylation. Phosphorylated on tyrosine residues; tyrosine
CC dephosphorylation by PTPN11/SHP2 blocks SOX9 phosphorylation by PKA and
CC subsequent SUMOylation. {ECO:0000250|UniProtKB:Q04887}.
CC -!- PTM: Sumoylated; phosphorylation at either Ser-64 or Ser-211 is
CC required for sumoylation. Sumoylation is induced by BMP signaling
CC pathway. {ECO:0000250|UniProtKB:Q04887}.
CC -!- PTM: Ubiquitinated; ubiquitination leads to proteasomal degradation and
CC is negatively regulated by DDRGK1. {ECO:0000250|UniProtKB:Q04887}.
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DR EMBL; AY237827; AAP69840.1; -; mRNA.
DR RefSeq; NP_001002978.1; NM_001002978.1.
DR AlphaFoldDB; Q7YRJ7; -.
DR SMR; Q7YRJ7; -.
DR STRING; 9612.ENSCAFP00000006510; -.
DR GeneID; 403464; -.
DR KEGG; cfa:403464; -.
DR CTD; 6662; -.
DR eggNOG; KOG0527; Eukaryota.
DR InParanoid; Q7YRJ7; -.
DR OrthoDB; 782373at2759; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0019933; P:cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:0001502; P:cartilage condensation; ISS:UniProtKB.
DR GO; GO:0051216; P:cartilage development; ISS:UniProtKB.
DR GO; GO:0001708; P:cell fate specification; ISS:UniProtKB.
DR GO; GO:0071773; P:cellular response to BMP stimulus; ISS:UniProtKB.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0071504; P:cellular response to heparin; ISS:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISS:UniProtKB.
DR GO; GO:0002062; P:chondrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0003413; P:chondrocyte differentiation involved in endochondral bone morphogenesis; ISS:UniProtKB.
DR GO; GO:0003415; P:chondrocyte hypertrophy; ISS:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB.
DR GO; GO:0090103; P:cochlea morphogenesis; ISS:UniProtKB.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0060517; P:epithelial cell proliferation involved in prostatic bud elongation; ISS:UniProtKB.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0003430; P:growth plate cartilage chondrocyte growth; ISS:UniProtKB.
DR GO; GO:0001942; P:hair follicle development; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; IBA:GO_Central.
DR GO; GO:0003170; P:heart valve development; ISS:UniProtKB.
DR GO; GO:0003179; P:heart valve morphogenesis; ISS:UniProtKB.
DR GO; GO:0060729; P:intestinal epithelial structure maintenance; ISS:UniProtKB.
DR GO; GO:0019100; P:male germ-line sex determination; ISS:UniProtKB.
DR GO; GO:0072289; P:metanephric nephron tubule formation; ISS:UniProtKB.
DR GO; GO:0061138; P:morphogenesis of a branching epithelium; ISS:UniProtKB.
DR GO; GO:0002009; P:morphogenesis of an epithelium; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0070168; P:negative regulation of biomineral tissue development; ISS:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0046322; P:negative regulation of fatty acid oxidation; ISS:UniProtKB.
DR GO; GO:0002683; P:negative regulation of immune system process; ISS:UniProtKB.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; ISS:UniProtKB.
DR GO; GO:0030279; P:negative regulation of ossification; ISS:UniProtKB.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0046533; P:negative regulation of photoreceptor cell differentiation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0014036; P:neural crest cell fate specification; ISS:UniProtKB.
DR GO; GO:0006334; P:nucleosome assembly; ISS:UniProtKB.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IBA:GO_Central.
DR GO; GO:0030916; P:otic vesicle formation; ISS:UniProtKB.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0030858; P:positive regulation of epithelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISS:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0090184; P:positive regulation of kidney development; ISS: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; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0061035; P:regulation of cartilage development; ISS:UniProtKB.
DR GO; GO:0010564; P:regulation of cell cycle process; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0060784; P:regulation of cell proliferation involved in tissue homeostasis; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0072034; P:renal vesicle induction; ISS:UniProtKB.
DR GO; GO:0070542; P:response to fatty acid; ISS:UniProtKB.
DR GO; GO:0060041; P:retina development in camera-type eye; ISS:UniProtKB.
DR GO; GO:0060221; P:retinal rod cell differentiation; ISS:UniProtKB.
DR GO; GO:0060008; P:Sertoli cell differentiation; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; ISS:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; ISS:UniProtKB.
DR GO; GO:0035019; P:somatic stem cell population maintenance; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0001894; P:tissue homeostasis; ISS: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 2: Evidence at transcript level;
KW Acetylation; Activator; Differentiation; DNA-binding; Isopeptide bond;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..513
FT /note="Transcription factor SOX-9"
FT /id="PRO_0000048738"
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..273
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 334..447
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 398..513
FT /note="Transactivation domain (TAC)"
FT /evidence="ECO:0000250|UniProtKB:P48436"
FT REGION 483..513
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 464..472
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..382
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 383..428
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 488..513
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 64
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04887"
FT MOD_RES 211
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04887"
FT CROSSLNK 402
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q04887"
SQ SEQUENCE 513 AA; 56562 MW; CEF5BDEF15DA27E0 CRC64;
MNLLDPFMKM TDEQEKGLSG APSPTMSEDS AGSPCPSGSG SDTENTRPQE NTFPKGEPDL
KKESEEDKFP VCIREAVSQV LKGYDWTLVP MPVRVNGSSK NKPHVKRPMN AFMVWAQAAR
RKLADQYPHL HNAELSKTLG KLWRLLNESE KRPFVEEAER LRVQHKKDHP DYKYQPRRRK
SVKNGQAEAE EATEQTHISP NAIFKRLQAD SPHSSSGMNE VHSPGKHSGQ SQGPPTPPTT
PKTDVQPGKA DLKREGRPLP EGGRQPPIDF RDVDIGELSS DVISNIETFD VNEFDQYLPP
NGHPGVPATH GQVTYTGSYG ISSTAATPAG AGHVWMSKQQ APPPPPPPPQ QSPQAPPQPP
QAPPQAPQAP PQPQPAPPQP QAAHTLTPLS SEPGQAQRTH IKTEQLSPSH YSEQQQHSPQ
QIAYSPFSLP HYSPSYPPIT RSQYDYTDHQ NSGSYYSHAA GQGSSLYSTF TYMNPAQRPM
YTPIADTSGV PSIPQTHSPQ HWEQPVYTQL TRP
