SOX2_MOUSE
ID SOX2_MOUSE Reviewed; 319 AA.
AC P48432;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Transcription factor SOX-2;
GN Name=Sox2; Synonyms=Sox-2;
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], AND TISSUE SPECIFICITY.
RX PubMed=7590241; DOI=10.1101/gad.9.21.2635;
RA Yuan H., Corbi N., Basilico C., Dailey L.;
RT "Developmental-specific activity of the FGF-4 enhancer requires the
RT synergistic action of Sox2 and Oct-3.";
RL Genes Dev. 9:2635-2645(1995).
RN [2]
RP SEQUENCE REVISION.
RA Yuan H., Corbi N., Basilico C., Dailey L.;
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129;
RX PubMed=8625802; DOI=10.1242/dev.122.2.509;
RA Collignon J., Sockanathan S., Hacker A., Cohen-Tannoudji M., Norris D.,
RA Rastan S., Stevanovic M., Goodfellow P.N., Lovell-Badge R.;
RT "A comparison of the properties of Sox-3 with Sry and two related genes,
RT Sox-1 and Sox-2.";
RL Development 122:509-520(1996).
RN [4]
RP FUNCTION, INTERACTION WITH POU5F1, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=15863505; DOI=10.1074/jbc.m501423200;
RA Maruyama M., Ichisaka T., Nakagawa M., Yamanaka S.;
RT "Differential roles for Sox15 and Sox2 in transcriptional control in mouse
RT embryonic stem cells.";
RL J. Biol. Chem. 280:24371-24379(2005).
RN [5]
RP SUMOYLATION AT LYS-247, MUTAGENESIS OF LYS-247, SUBCELLULAR LOCATION, AND
RP FUNCTION.
RX PubMed=17097055; DOI=10.1016/j.bbrc.2006.10.130;
RA Tsuruzoe S., Ishihara K., Uchimura Y., Watanabe S., Sekita Y., Aoto T.,
RA Saitoh H., Yuasa Y., Niwa H., Kawasuji M., Baba H., Nakao M.;
RT "Inhibition of DNA binding of Sox2 by the SUMO conjugation.";
RL Biochem. Biophys. Res. Commun. 351:920-926(2006).
RN [6]
RP BIOTECHNOLOGY.
RX PubMed=16904174; DOI=10.1016/j.cell.2006.07.024;
RA Takahashi K., Yamanaka S.;
RT "Induction of pluripotent stem cells from mouse embryonic and adult
RT fibroblast cultures by defined factors.";
RL Cell 126:663-676(2006).
RN [7]
RP INTERACTION WITH SOX3 AND FGFR1.
RX PubMed=17728342; DOI=10.1242/dev.007906;
RA Rizzoti K., Lovell-Badge R.;
RT "SOX3 activity during pharyngeal segmentation is required for craniofacial
RT morphogenesis.";
RL Development 134:3437-3448(2007).
RN [8]
RP FUNCTION, AND INTERACTION WITH ZSCAN10.
RX PubMed=19740739; DOI=10.1074/jbc.m109.016162;
RA Yu H.B., Kunarso G., Hong F.H., Stanton L.W.;
RT "Zfp206, Oct4, and Sox2 are integrated components of a transcriptional
RT regulatory network in embryonic stem cells.";
RL J. Biol. Chem. 284:31327-31335(2009).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=19349578; DOI=10.1083/jcb.200810106;
RA Gontan C., Guettler T., Engelen E., Demmers J., Fornerod M., Grosveld F.G.,
RA Tibboel D., Goerlich D., Poot R.A., Rottier R.J.;
RT "Exportin 4 mediates a novel nuclear import pathway for Sox family
RT transcription factors.";
RL J. Cell Biol. 185:27-34(2009).
RN [10]
RP FUNCTION, AND INDUCTION.
RX PubMed=22198669; DOI=10.1038/nature10712;
RA Andreu-Agullo C., Maurin T., Thompson C.B., Lai E.C.;
RT "Ars2 maintains neural stem-cell identity through direct transcriptional
RT activation of Sox2.";
RL Nature 481:195-198(2012).
RN [11]
RP DEVELOPMENTAL STAGE.
RX PubMed=32758484; DOI=10.1016/j.ydbio.2020.07.016;
RA Simonson L., Vold S., Mowers C., Massey R.J., Ong I.M., Longley B.J.,
RA Chang H.;
RT "Keratin 13 deficiency causes white sponge nevus in mice.";
RL Dev. Biol. 468:146-153(2020).
RN [12]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=32127020; DOI=10.1186/s13041-020-00570-z;
RA Miwa T., Ohta K., Ito N., Hattori S., Miyakawa T., Takeo T., Nakagata N.,
RA Song W.J., Minoda R.;
RT "Tsukushi is essential for the development of the inner ear.";
RL Mol. Brain 13:29-29(2020).
CC -!- FUNCTION: Transcription factor that forms a trimeric complex with
CC POU5F1 (OCT3/4) on DNA and controls the expression of a number of genes
CC involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206
CC (PubMed:15863505, PubMed:17097055, PubMed:19740739). Binds to the
CC proximal enhancer region of NANOG (PubMed:15863505). Critical for early
CC embryogenesis and for embryonic stem cell pluripotency (By similarity).
CC Downstream SRRT target that mediates the promotion of neural stem cell
CC self-renewal (PubMed:22198669). Keeps neural cells undifferentiated by
CC counteracting the activity of proneural proteins and suppresses
CC neuronal differentiation (By similarity). May function as a switch in
CC neuronal development (By similarity). {ECO:0000250|UniProtKB:P48430,
CC ECO:0000250|UniProtKB:P48431, ECO:0000269|PubMed:15863505,
CC ECO:0000269|PubMed:17097055, ECO:0000269|PubMed:19740739,
CC ECO:0000269|PubMed:22198669}.
CC -!- SUBUNIT: Interacts with ZSCAN10 (PubMed:19740739). Interacts with SOX3
CC and FGFR1 (PubMed:17728342). Interacts with GLIS1 (By similarity).
CC Interacts with POU5F1; binds synergistically with POU5F1 to DNA
CC (PubMed:15863505). {ECO:0000250|UniProtKB:P48431,
CC ECO:0000269|PubMed:15863505, ECO:0000269|PubMed:17728342,
CC ECO:0000269|PubMed:19740739}.
CC -!- INTERACTION:
CC P48432; Q80Z64: Nanog; NbExp=10; IntAct=EBI-2313612, EBI-2312517;
CC P48432; P20263: Pou5f1; NbExp=4; IntAct=EBI-2313612, EBI-1606219;
CC P48432; Q60520: Sin3a; NbExp=3; IntAct=EBI-2313612, EBI-349034;
CC P48432; Q00899: Yy1; NbExp=2; IntAct=EBI-2313612, EBI-6921536;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00267,
CC ECO:0000269|PubMed:17097055, ECO:0000269|PubMed:19349578,
CC ECO:0000269|PubMed:32127020}. Cytoplasm {ECO:0000269|PubMed:19349578}.
CC Note=Nuclear import is facilitated by XPO4, a protein that usually acts
CC as a nuclear export signal receptor. {ECO:0000269|PubMed:19349578}.
CC -!- TISSUE SPECIFICITY: Expressed in the cochlea (at protein level)
CC (PubMed:32127020). Expressed in the brain and retina (PubMed:7590241,
CC PubMed:15863505). A very low level of expression is seen in the stomach
CC and lung (PubMed:7590241, PubMed:15863505). Expressed in the kidney
CC (PubMed:15863505). {ECO:0000269|PubMed:15863505,
CC ECO:0000269|PubMed:32127020, ECO:0000269|PubMed:7590241}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the basal cells of the tongue
CC epithelium at birth until P20 (PubMed:32758484). Expressed in the
CC suprabasal cells of the buccal mucosa and esophagus at P20
CC (PubMed:32758484). {ECO:0000269|PubMed:32758484}.
CC -!- INDUCTION: By SRRT. {ECO:0000269|PubMed:22198669}.
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:P41225}.
CC -!- PTM: Sumoylation inhibits binding on DNA and negatively regulates the
CC FGF4 transactivation. {ECO:0000269|PubMed:17097055}.
CC -!- DISRUPTION PHENOTYPE: Embryonically lethal.
CC {ECO:0000269|PubMed:15863505}.
CC -!- BIOTECHNOLOGY: POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four
CC Yamanaka factors. When combined, these factors are sufficient to
CC reprogram differentiated cells to an embryonic-like state designated
CC iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology
CC and growth properties of ES cells and express ES cell marker genes.
CC {ECO:0000269|PubMed:16904174}.
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DR EMBL; U31967; AAC31791.1; -; mRNA.
DR EMBL; X94127; CAA63847.1; -; Genomic_DNA.
DR CCDS; CCDS38413.1; -.
DR PIR; S10949; S10949.
DR RefSeq; NP_035573.3; NM_011443.4.
DR PDB; 1GT0; X-ray; 2.60 A; D=41-120.
DR PDB; 6HT5; X-ray; 3.45 A; D=41-120.
DR PDBsum; 1GT0; -.
DR PDBsum; 6HT5; -.
DR AlphaFoldDB; P48432; -.
DR BMRB; P48432; -.
DR SMR; P48432; -.
DR BioGRID; 203406; 141.
DR DIP; DIP-54522N; -.
DR IntAct; P48432; 11.
DR MINT; P48432; -.
DR STRING; 10090.ENSMUSP00000096755; -.
DR iPTMnet; P48432; -.
DR PhosphoSitePlus; P48432; -.
DR MaxQB; P48432; -.
DR PaxDb; P48432; -.
DR PeptideAtlas; P48432; -.
DR PRIDE; P48432; -.
DR ProteomicsDB; 261480; -.
DR DNASU; 20674; -.
DR GeneID; 20674; -.
DR KEGG; mmu:20674; -.
DR CTD; 6657; -.
DR MGI; MGI:98364; Sox2.
DR eggNOG; KOG0527; Eukaryota.
DR InParanoid; P48432; -.
DR OrthoDB; 1161594at2759; -.
DR PhylomeDB; P48432; -.
DR Reactome; R-MMU-3769402; Deactivation of the beta-catenin transactivating complex.
DR BioGRID-ORCS; 20674; 2 hits in 73 CRISPR screens.
DR EvolutionaryTrace; P48432; -.
DR PRO; PR:P48432; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P48432; protein.
DR GO; GO:0000785; C:chromatin; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0035198; F:miRNA binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0021984; P:adenohypophysis development; IMP:MGI.
DR GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; IMP:MGI.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0045165; P:cell fate commitment; IDA:MGI.
DR GO; GO:0001708; P:cell fate specification; IMP:MGI.
DR GO; GO:0071276; P:cellular response to cadmium ion; IDA:MGI.
DR GO; GO:0021987; P:cerebral cortex development; IMP:MGI.
DR GO; GO:0050973; P:detection of mechanical stimulus involved in equilibrioception; IMP:MGI.
DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; IMP:MGI.
DR GO; GO:0048852; P:diencephalon morphogenesis; IMP:MGI.
DR GO; GO:0048568; P:embryonic organ development; IMP:MGI.
DR GO; GO:0001714; P:endodermal cell fate specification; ISO:MGI.
DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IDA:MGI.
DR GO; GO:0030900; P:forebrain development; IBA:GO_Central.
DR GO; GO:0021879; P:forebrain neuron differentiation; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0048839; P:inner ear development; IBA:GO_Central.
DR GO; GO:0042472; P:inner ear morphogenesis; IMP:MGI.
DR GO; GO:0060235; P:lens induction in camera-type eye; IGI:MGI.
DR GO; GO:0048286; P:lung alveolus development; IDA:MGI.
DR GO; GO:0030539; P:male genitalia development; IMP:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; ISO:MGI.
DR GO; GO:0045596; P:negative regulation of cell differentiation; IMP:MGI.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISO:MGI.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IDA:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IGI:MGI.
DR GO; GO:0007405; P:neuroblast proliferation; IMP:MGI.
DR GO; GO:0030182; P:neuron differentiation; IDA:MGI.
DR GO; GO:0048663; P:neuron fate commitment; IMP:MGI.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; IGI:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:MGI.
DR GO; GO:0030910; P:olfactory placode formation; IGI:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IDA:MGI.
DR GO; GO:0046148; P:pigment biosynthetic process; IMP:MGI.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:MGI.
DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; ISO:MGI.
DR GO; GO:0030858; P:positive regulation of epithelial cell differentiation; IDA:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IMP:MGI.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IMP:MGI.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0043281; P:regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
DR GO; GO:0050767; P:regulation of neurogenesis; IGI: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; IDA:MGI.
DR GO; GO:0070848; P:response to growth factor; ISO:MGI.
DR GO; GO:0010033; P:response to organic substance; IDA:MGI.
DR GO; GO:0032526; P:response to retinoic acid; IDA:MGI.
DR GO; GO:0060042; P:retina morphogenesis in camera-type eye; IMP:MGI.
DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IMP:MGI.
DR GO; GO:0048863; P:stem cell differentiation; IDA:MGI.
DR GO; GO:0019827; P:stem cell population maintenance; IMP:UniProtKB.
DR GO; GO:0043586; P:tongue development; IMP:MGI.
DR GO; GO:0001829; P:trophectodermal cell differentiation; IMP:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IGI:MGI.
DR Gene3D; 1.10.30.10; -; 1.
DR IDEAL; IID50261; -.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR032643; SOX-2.
DR InterPro; IPR022097; SOX_fam.
DR PANTHER; PTHR10270:SF231; PTHR10270:SF231; 1.
DR Pfam; PF00505; HMG_box; 1.
DR Pfam; PF12336; SOXp; 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; Activator; Cytoplasm; Developmental protein; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..319
FT /note="Transcription factor SOX-2"
FT /id="PRO_0000048716"
FT DNA_BIND 43..111
FT /note="HMG box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 247..267
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 299..319
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 274..282
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P41225"
FT COMPBIAS 247..266
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 253
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48431"
FT CROSSLNK 247
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT MUTAGEN 247
FT /note="K->R: Absence of sumoylation. Increased FGF4
FT activation. No effect on nuclear localization."
FT /evidence="ECO:0000269|PubMed:17097055"
FT CONFLICT 153..155
FT /note="GGL -> AGV (in Ref. 3; CAA63847)"
FT /evidence="ECO:0000305"
FT CONFLICT 203
FT /note="V -> D (in Ref. 3; CAA63847)"
FT /evidence="ECO:0000305"
FT CONFLICT 310..311
FT /note="KY -> IN (in Ref. 3; CAA63847)"
FT /evidence="ECO:0000305"
FT HELIX 49..62
FT /evidence="ECO:0007829|PDB:1GT0"
FT HELIX 70..81
FT /evidence="ECO:0007829|PDB:1GT0"
FT HELIX 86..106
FT /evidence="ECO:0007829|PDB:1GT0"
SQ SEQUENCE 319 AA; 34454 MW; C40DE49E524C49F1 CRC64;
MYNMMETELK PPGPQQASGG GGGGGNATAA ATGGNQKNSP DRVKRPMNAF MVWSRGQRRK
MAQENPKMHN SEISKRLGAE WKLLSETEKR PFIDEAKRLR ALHMKEHPDY KYRPRRKTKT
LMKKDKYTLP GGLLAPGGNS MASGVGVGAG LGGGLNQRMD SYAHMNGWSN GSYSMMQEQL
GYPQHPGLNA HGAAQMQPMH RYVVSALQYN SMTSSQTYMN GSPTYSMSYS QQGTPGMALG
SMGSVVKSEA SSSPPVVTSS SHSRAPCQAG DLRDMISMYL PGAEVPEPAA PSRLHMAQHY
QSGPVPGTAK YGTLPLSHM
