SOX9A_XENLA
ID SOX9A_XENLA Reviewed; 477 AA.
AC B7ZR65; B7ZR67; Q90YL1;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 49.
DE RecName: Full=Transcription factor Sox-9-A {ECO:0000305};
GN Name=sox9-a; Synonyms=sox9 {ECO:0000303|PubMed:11807034};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAK61366.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=11807034; DOI=10.1242/dev.129.2.421;
RA Spokony R.F., Aoki Y., Saint-Germain N., Magner-Fink E.,
RA Saint-Jeannet J.-P.;
RT "The transcription factor Sox9 is required for cranial neural crest
RT development in Xenopus.";
RL Development 129:421-432(2002).
RN [2] {ECO:0000312|EMBL:AAI70058.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Gastrula {ECO:0000312|EMBL:AAI70058.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12812785; DOI=10.1016/s0012-1606(03)00161-1;
RA Aoki Y., Saint-Germain N., Gyda M., Magner-Fink E., Lee Y.-H., Credidio C.,
RA Saint-Jeannet J.-P.;
RT "Sox10 regulates the development of neural crest-derived melanocytes in
RT Xenopus.";
RL Dev. Biol. 259:19-33(2003).
RN [4] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=12885557; DOI=10.1016/s0012-1606(03)00247-1;
RA Honore S.M., Aybar M.J., Mayor R.;
RT "Sox10 is required for the early development of the prospective neural
RT crest in Xenopus embryos.";
RL Dev. Biol. 260:79-96(2003).
RN [5] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=14584783;
RA Lee Y.-H., Saint-Jeannet J.-P.;
RT "Sox9, a novel pancreatic marker in Xenopus.";
RL Int. J. Dev. Biol. 47:459-462(2003).
RN [6] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15084460; DOI=10.1242/dev.01066;
RA Saint-Germain N., Lee Y.-H., Zhang Y., Sargent T.D., Saint-Jeannet J.-P.;
RT "Specification of the otic placode depends on Sox9 function in Xenopus.";
RL Development 131:1755-1763(2004).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=15464575; DOI=10.1016/j.ydbio.2004.07.036;
RA Lee Y.-H., Aoki Y., Hong C.-S., Saint-Germain N., Credidio C.,
RA Saint-Jeannet J.-P.;
RT "Early requirement of the transcriptional activator Sox9 for neural crest
RT specification in Xenopus.";
RL Dev. Biol. 275:93-103(2004).
RN [8] {ECO:0000305}
RP FUNCTION, INTERACTION WITH UBE2I AND SMO1, SUMOYLATION AT LYS-61 AND
RP LYS-365, AND MUTAGENESIS OF LYS-61 AND LYS-365.
RX PubMed=16256735; DOI=10.1016/j.devcel.2005.09.016;
RA Taylor K.M., Labonne C.;
RT "SoxE factors function equivalently during neural crest and inner ear
RT development and their activity is regulated by SUMOylation.";
RL Dev. Cell 9:593-603(2005).
RN [9] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16943273; DOI=10.1242/dev.02558;
RA O'Donnell M., Hong C.-S., Huang X., Delnicki R.J., Saint-Jeannet J.-P.;
RT "Functional analysis of Sox8 during neural crest development in Xenopus.";
RL Development 133:3817-3826(2006).
RN [10] {ECO:0000305}
RP IDENTIFICATION.
RX PubMed=18850318; DOI=10.1007/s10577-008-1257-z;
RA Uno Y., Nishida C., Yoshimoto S., Ito M., Oshima Y., Yokoyama S.,
RA Nakamura M., Matsuda Y.;
RT "Diversity in the origins of sex chromosomes in anurans inferred from
RT comparative mapping of sexual differentiation genes for three species of
RT the Raninae and Xenopodinae.";
RL Chromosome Res. 16:999-1011(2008).
CC -!- FUNCTION: Transcription factor that plays a key role in chondrocytes
CC differentiation and skeletal development (By similarity). Specifically
CC binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-
CC enhancers and promotes expression of genes important for
CC chondrogenesis, including COL2A1 (By similarity). Plays a central role
CC in successive steps of chondrocyte differentiation (By similarity).
CC Absolutely required for precartilaginous condensation, the first step
CC in chondrogenesis during which skeletal progenitors differentiate into
CC prechondrocytes (By similarity). Together with SOX5 and SOX6, required
CC for overt chondrogenesis when condensed prechondrocytes differentiate
CC into early stage chondrocytes, the second step in chondrogenesis (By
CC similarity). Later, required to direct hypertrophic maturation and
CC block osteoblast differentiation of growth plate chondrocytes:
CC maintains chondrocyte columnar proliferation, delays prehypertrophy and
CC then prevents osteoblastic differentiation of chondrocytes (By
CC similarity). Also required for chondrocyte hypertrophy, both
CC indirectly, by keeping the lineage fate of chondrocytes, and directly,
CC by remaining present in upper hypertrophic cells (By similarity). Low
CC lipid levels are the main nutritional determinant for chondrogenic
CC commitment of skeletal progenitor cells: when lipids levels are low,
CC FOXO transcription factors promote expression of SOX9, which induces
CC chondrogenic commitment and suppresses fatty acid oxidation (By
CC similarity). In addition to cartilage development, also acts as a
CC regulator of proliferation and differentiation in epithelial
CC stem/progenitor cells (By similarity). Involved in development of the
CC cranial neural crest, which is fated to form skeletal elements
CC (PubMed:11807034, PubMed:12812785, PubMed:15464575, PubMed:16256735,
CC PubMed:16943273). Also required for otic placode specification during
CC inner ear development (PubMed:15084460). {ECO:0000250|UniProtKB:Q04887,
CC ECO:0000269|PubMed:11807034, ECO:0000269|PubMed:12812785,
CC ECO:0000269|PubMed:15084460, ECO:0000269|PubMed:15464575,
CC ECO:0000269|PubMed:16256735, ECO:0000269|PubMed:16943273}.
CC -!- SUBUNIT: Interacts with the sumoylation factors ube2i/ubc9 and sumo1.
CC {ECO:0000269|PubMed:16256735}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00267,
CC ECO:0000269|PubMed:11807034}. Cytoplasm {ECO:0000250|UniProtKB:Q6F2E7}.
CC Note=Restricted to the nucleus of Sertoli-like cells in the testis, but
CC localizes to the cytoplasm of previtellogenic oocytes in the ovary
CC before being translocated into the nucleus of vitellogenic oocytes.
CC {ECO:0000250|UniProtKB:Q6F2E7, ECO:0000269|PubMed:11807034}.
CC -!- TISSUE SPECIFICITY: From mid-gastrula (stage 10.5-11), expressed in a
CC ring around the blastopore, with expression decreasing toward the
CC dorsal side. At stage 12, expression around the blastopore decreases
CC and begins to increase lateral to the neural plate in the presumptive
CC neural crest, where expression dramatically increases around stage 14.
CC Also expressed in the otic placode as early as stage 13/14. By the
CC tailbud stage expression is restricted to the otic cup and then
CC throughout the otic vesicle, with more intense staining at the dorsal-
CC most region, the prospective region of the semicircular canals and
CC endolymphatic duct. At the early tailbud stage (stage 23), expressed in
CC migrating cranial neural crest cells and in the trunk neural crest.
CC Also expressed in the genital ridges, developing eye, nasal placode and
CC prospective pineal gland. Around stage 25, expression is down-regulated
CC in the trunk neural crest but persists in the migrating cranial crest
CC cells as they populate the pharyngeal arches, otic placode, developing
CC eye, genital ridges and notochord. By stage 31, expression remains
CC strong in the pharyngeal arches. Also expressed in the pancreas; first
CC expressed at stage 25 in the pancreatic anlagen, dorsally in
CC diverticulum. As development proceeds, expression continues in
CC pancreatic tissue, being restricted to ventral and dorsal pancreatic
CC buds. {ECO:0000269|PubMed:11807034, ECO:0000269|PubMed:12812785,
CC ECO:0000269|PubMed:12885557, ECO:0000269|PubMed:14584783,
CC ECO:0000269|PubMed:15084460, ECO:0000269|PubMed:16943273}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC Expressed from mid-gastrula (around stage 10.5) and persists at least
CC through to tadpoles (stage 41). {ECO:0000269|PubMed:11807034}.
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 -!- PTM: Sumoylated. Lys-365 is the major site of sumoylation, although
CC sumoylation at Lys-61 also occurs. Sumoylation plays a key role in
CC regulating formation of the neural crest and otic placode.
CC {ECO:0000269|PubMed:16256735}.
CC -!- DISRUPTION PHENOTYPE: Loss of neural crest progenitors and an expansion
CC of the neural plate, leading to loss or reduction of neural crest-
CC derived skeletal elements later during development.
CC {ECO:0000269|PubMed:11807034}.
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DR EMBL; AY035397; AAK61366.1; -; mRNA.
DR EMBL; BC170058; AAI70058.1; -; mRNA.
DR EMBL; BC170060; AAI70060.1; -; mRNA.
DR RefSeq; NP_001084276.1; NM_001090807.1.
DR AlphaFoldDB; B7ZR65; -.
DR SMR; B7ZR65; -.
DR GeneID; 399405; -.
DR KEGG; xla:399405; -.
DR CTD; 399405; -.
DR Xenbase; XB-GENE-6253910; sox9.S.
DR OMA; QSSNSYY; -.
DR OrthoDB; 782373at2759; -.
DR Proteomes; UP000186698; Chromosome 9_10S.
DR Bgee; 399405; Expressed in internal ear and 14 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IEA:InterPro.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IPI:UniProtKB.
DR GO; GO:0051216; P:cartilage development; ISS:UniProtKB.
DR GO; GO:0002062; P:chondrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0007506; P:gonadal mesoderm development; IEA:UniProtKB-KW.
DR GO; GO:0003430; P:growth plate cartilage chondrocyte growth; ISS:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0046322; P:negative regulation of fatty acid oxidation; ISS:UniProtKB.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0014029; P:neural crest formation; IMP:UniProtKB.
DR GO; GO:0043049; P:otic placode formation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0070542; P:response to fatty acid; 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 1: Evidence at protein level;
KW Activator; Chondrogenesis; Cytoplasm; Developmental protein;
KW Differentiation; DNA-binding; Gonadal differentiation; Isopeptide bond;
KW Nucleus; Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..477
FT /note="Transcription factor Sox-9-A"
FT /id="PRO_0000377415"
FT DNA_BIND 105..173
FT /note="HMG box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 1..66
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 157..274
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 224..308
FT /note="Transactivation domain (TAM)"
FT /evidence="ECO:0000250|UniProtKB:P48436"
FT REGION 301..384
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 361..477
FT /note="Transactivation domain (TAC)"
FT /evidence="ECO:0000250|UniProtKB:P48436"
FT REGION 446..477
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 276..285
FT /note="9aaTAD 1"
FT /evidence="ECO:0000250|UniProtKB:P48436"
FT MOTIF 291..299
FT /note="9aaTAD 2"
FT /evidence="ECO:0000250|UniProtKB:P48436"
FT MOTIF 428..436
FT /note="9aaTAD 3"
FT /evidence="ECO:0000250|UniProtKB:P48436"
FT COMPBIAS 18..53
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 157..187
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 208..233
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 247..274
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 304..384
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 61
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:16256735"
FT CROSSLNK 365
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:16256735"
FT MUTAGEN 61
FT /note="K->R: Abolishes interaction with sumoylation
FT factors. Alters neural crest formation and inner ear
FT development; when associated with R-365."
FT /evidence="ECO:0000269|PubMed:16256735"
FT MUTAGEN 365
FT /note="K->R: Eliminates the major sumoylated product.
FT Alters neural crest formation and inner ear development;
FT when associated with R-61."
FT /evidence="ECO:0000269|PubMed:16256735"
FT CONFLICT 184
FT /note="N -> Y (in Ref. 2; AAI70060)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="H -> R (in Ref. 1; AAK61366)"
FT /evidence="ECO:0000305"
FT CONFLICT 289
FT /note="T -> I (in Ref. 1; AAK61366)"
FT /evidence="ECO:0000305"
FT CONFLICT 334
FT /note="W -> C (in Ref. 1; AAK61366)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 477 AA; 53431 MW; E544E09D9CF8FEDD CRC64;
MNLLDPFMKM TEEQDKCMSG APSPTMSDDS AGSPCPSGSG SDTENTRPQE NTFPKGDQEL
KKETEDEKFP VCIREAVSQV LKGYDWTLVP MPVRVNGSSK NKPHVKRPMN AFMVWAQAAR
RKLADQYPHL HNAELSKTLG KLWRLLNEGE KRPFVEEAER LRVQHKKDHP DYKYQPRRRK
SVKNGQTEQE DGAEQTHISP NAIFKALQAD SPHSSSSMSE VHSPGEHSGQ SQGPPTPPTT
PKTDIQPGKP DLKREGRPLQ ENGRQPPHID FRDVDIGELS SEVISTIETF DVNEFDQYLP
PNGHPGVGST QASYTGSYGI SSTPSATTGA GPAWMSKQQQ QQPQQHSLST LNSEQSQSQQ
RTHIKTEQLS PSHYSDQQQQ HSPQQLNYSS FNLQHYSSSY PTITRAQYDY TEHQGSSTYY
SHASGQNSGL YSTFSYMNPS QRPLYTPIAD TTGVPSIPQT HSPQHWEQPV YTQLTRP
