SOX4_MOUSE
ID SOX4_MOUSE Reviewed; 440 AA.
AC Q06831; Q5SW95;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Transcription factor SOX-4 {ECO:0000305};
GN Name=Sox4 {ECO:0000303|PubMed:23562159, ECO:0000312|MGI:MGI:98366};
GN Synonyms=Sox-4 {ECO:0000303|PubMed:8404853};
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], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=8404853;
RA van de Wetering M., Oosterwegel M., van Norren K., Clevers H.C.;
RT "Sox-4, an Sry-like HMG box protein, is a transcriptional activator in
RT lymphocytes.";
RL EMBO J. 12:3847-3854(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8493110; DOI=10.1093/nar/21.8.2009;
RA Schilham M.W., van Eijk M., van de Wetering M., Clevers H.C.;
RT "The murine Sox-4 protein is encoded on a single exon.";
RL Nucleic Acids Res. 21:2009-2009(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 69-122, AND DEVELOPMENTAL STAGE.
RC STRAIN=Swiss Webster; TISSUE=Embryonic tooth;
RX PubMed=8921394; DOI=10.1006/geno.1996.0548;
RA Stock D.W., Buchanan A.V., Zhao Z., Weiss K.M.;
RT "Numerous members of the Sox family of HMG box-containing genes are
RT expressed in developing mouse teeth.";
RL Genomics 37:234-237(1996).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=17218525; DOI=10.1126/science.1135344;
RA Melichar H.J., Narayan K., Der S.D., Hiraoka Y., Gardiol N., Jeannet G.,
RA Held W., Chambers C.A., Kang J.;
RT "Regulation of gammadelta versus alphabeta T lymphocyte differentiation by
RT the transcription factor SOX13.";
RL Science 315:230-233(2007).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23562159; DOI=10.1016/j.immuni.2013.01.010;
RG Immunological Genome Project Consortium;
RA Malhotra N., Narayan K., Cho O.H., Sylvia K.E., Yin C., Melichar H.,
RA Rashighi M., Lefebvre V., Harris J.E., Berg L.J., Kang J.;
RT "A network of high-mobility group box transcription factors programs innate
RT interleukin-17 production.";
RL Immunity 38:681-693(2013).
RN [10]
RP FUNCTION.
RX PubMed=26291311; DOI=10.1038/cddis.2015.190;
RA Jang S.M., Kim J.W., Kim C.H., An J.H., Johnson A., Song P.I., Rhee S.,
RA Choi K.H.;
RT "KAT5-mediated SOX4 acetylation orchestrates chromatin remodeling during
RT myoblast differentiation.";
RL Cell Death Dis. 6:e1857-e1857(2015).
CC -!- FUNCTION: Transcriptional activator that binds with high affinity to
CC the T-cell enhancer motif 5'-AACAAAG-3' motif (PubMed:8404853).
CC Required for IL17A-producing Vgamma2-positive gamma-delta T-cell
CC maturation and development, via binding to regulator loci of RORC to
CC modulate expression (PubMed:23562159). Involved in skeletal myoblast
CC differentiation by promoting gene expression of CALD1
CC (PubMed:26291311). {ECO:0000269|PubMed:23562159,
CC ECO:0000269|PubMed:26291311, ECO:0000269|PubMed:8404853}.
CC -!- SUBUNIT: Interacts with UBE2I. Interacts with HDAC1; interaction
CC inhibits the transcriptional activator activity.
CC {ECO:0000250|UniProtKB:Q06945}.
CC -!- INTERACTION:
CC Q06831; P15884: TCF4; Xeno; NbExp=2; IntAct=EBI-6262177, EBI-533224;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q06945}.
CC -!- TISSUE SPECIFICITY: Expressed in both gamma-delta T-cells and Cd4+ Cd8+
CC double-positive (DP) alpha-beta T-cells (PubMed:17218525). Expressed in
CC the ovaries and the thymus (PubMed:8404853, PubMed:17218525).
CC {ECO:0000269|PubMed:17218525, ECO:0000269|PubMed:8404853}.
CC -!- DEVELOPMENTAL STAGE: Expressed in molar and incisor tooth germs at 14.5
CC dpc. {ECO:0000269|PubMed:8921394}.
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:Q06945}.
CC -!- PTM: Acetylation at Lys-95 by KAT5 promotes the transcription activator
CC activity and is required during myoblast differentiation (By
CC similarity). Acetylation by KAT5 abolishes the interaction between SOX4
CC and HDAC1 and switches SOX4 into a transcriptional activator (By
CC similarity). {ECO:0000250|UniProtKB:Q06945}.
CC -!- DISRUPTION PHENOTYPE: In T-cell-specific knockout mice, loss of mature
CC Il17a-producing Vgamma2-positive gamma-delta T-cells and reduction of
CC Rorc expression in immature Vgamma2-positive thymocytes
CC (PubMed:23562159). In a mouse model for psoriasis, dermal inflammation
CC induced by skin application of TLR7 synthetic ligand imiquimod is
CC substantially reduced due to the absence of Vgamma2-positive gamma-
CC delta T-cells (PubMed:23562159). {ECO:0000269|PubMed:23562159}.
CC -!- MISCELLANEOUS: May be involved in the T-cell immune response in the
CC psoriasis-like disease which is induced in mice by the application of
CC the TLR7 ligand Imiquimod to skin. {ECO:0000269|PubMed:23562159}.
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DR EMBL; X70298; CAA49779.1; -; mRNA.
DR EMBL; AL606511; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466561; EDL32406.1; -; Genomic_DNA.
DR EMBL; BC052736; AAH52736.1; -; mRNA.
DR EMBL; U70440; AAC52858.1; -; mRNA.
DR CCDS; CCDS26411.1; -.
DR PIR; S37303; S37303.
DR RefSeq; NP_033264.2; NM_009238.2.
DR PDB; 3U2B; X-ray; 2.40 A; C=57-135.
DR PDBsum; 3U2B; -.
DR AlphaFoldDB; Q06831; -.
DR SMR; Q06831; -.
DR IntAct; Q06831; 5.
DR STRING; 10090.ENSMUSP00000100013; -.
DR iPTMnet; Q06831; -.
DR PhosphoSitePlus; Q06831; -.
DR jPOST; Q06831; -.
DR MaxQB; Q06831; -.
DR PaxDb; Q06831; -.
DR PeptideAtlas; Q06831; -.
DR PRIDE; Q06831; -.
DR ProteomicsDB; 261116; -.
DR Antibodypedia; 25243; 297 antibodies from 35 providers.
DR DNASU; 20677; -.
DR Ensembl; ENSMUST00000067230; ENSMUSP00000100013; ENSMUSG00000076431.
DR GeneID; 20677; -.
DR KEGG; mmu:20677; -.
DR UCSC; uc007pyk.1; mouse.
DR CTD; 6659; -.
DR MGI; MGI:98366; Sox4.
DR VEuPathDB; HostDB:ENSMUSG00000076431; -.
DR eggNOG; KOG0527; Eukaryota.
DR GeneTree; ENSGT00940000161470; -.
DR HOGENOM; CLU_043342_0_0_1; -.
DR InParanoid; Q06831; -.
DR OMA; PAEHHHN; -.
DR OrthoDB; 1186233at2759; -.
DR Reactome; R-MMU-3769402; Deactivation of the beta-catenin transactivating complex.
DR BioGRID-ORCS; 20677; 11 hits in 75 CRISPR screens.
DR PRO; PR:Q06831; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q06831; protein.
DR Bgee; ENSMUSG00000076431; Expressed in medial ganglionic eminence and 309 other tissues.
DR Genevisible; Q06831; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
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:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:GO_Central.
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:0035198; F:miRNA binding; IDA:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region 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:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0035910; P:ascending aorta morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003289; P:atrial septum primum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003215; P:cardiac right ventricle morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003211; P:cardiac ventricle formation; IMP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IMP:UniProtKB.
DR GO; GO:0031018; P:endocrine pancreas development; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IDA:MGI.
DR GO; GO:0021782; P:glial cell development; IMP:UniProtKB.
DR GO; GO:0014009; P:glial cell proliferation; IMP:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0007507; P:heart development; IMP:BHF-UCL.
DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; IMP:MGI.
DR GO; GO:0060993; P:kidney morphogenesis; IMP:BHF-UCL.
DR GO; GO:0060174; P:limb bud formation; IMP:UniProtKB.
DR GO; GO:0003183; P:mitral valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0001841; P:neural tube formation; IMP:UniProtKB.
DR GO; GO:0060563; P:neuroepithelial cell differentiation; IMP:UniProtKB.
DR GO; GO:0003357; P:noradrenergic neuron differentiation; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0045588; P:positive regulation of gamma-delta T cell differentiation; IMP:UniProtKB.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IMP:UniProtKB.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; IDA:UniProtKB.
DR GO; GO:2000761; P:positive regulation of N-terminal peptidyl-lysine acetylation; ISS:UniProtKB.
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:0045727; P:positive regulation of translation; ISS:UniProtKB.
DR GO; GO:0002328; P:pro-B cell differentiation; IMP:BHF-UCL.
DR GO; GO:0050821; P:protein stabilization; IMP:BHF-UCL.
DR GO; GO:0043516; P:regulation of DNA damage response, signal transduction by p53 class mediator; ISO:MGI.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; IMP:UniProtKB.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IDA:MGI.
DR GO; GO:0021510; P:spinal cord development; IMP:UniProtKB.
DR GO; GO:0021522; P:spinal cord motor neuron differentiation; IMP:UniProtKB.
DR GO; GO:0048485; P:sympathetic nervous system development; IMP:UniProtKB.
DR GO; GO:0030217; P:T cell differentiation; IMP:BHF-UCL.
DR GO; GO:0060412; P:ventricular septum morphogenesis; IMP:BHF-UCL.
DR Gene3D; 1.10.30.10; -; 1.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR017386; SOX-12/11/4.
DR Pfam; PF00505; HMG_box; 1.
DR PIRSF; PIRSF038098; SOX-12/11/4a; 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; DNA-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..440
FT /note="Transcription factor SOX-4"
FT /id="PRO_0000048725"
FT DNA_BIND 59..127
FT /note="HMG box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 1..58
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 128..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 234..258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 272..382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 392..400
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:Q06945"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 236..250
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 305..319
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 337..362
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 95
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q06945"
FT CONFLICT 175
FT /note="S -> T (in Ref. 1; CAA49779)"
FT /evidence="ECO:0000305"
FT CONFLICT 179
FT /note="A -> T (in Ref. 1; CAA49779)"
FT /evidence="ECO:0000305"
FT CONFLICT 235..236
FT /note="SA -> QL (in Ref. 1; CAA49779)"
FT /evidence="ECO:0000305"
FT CONFLICT 263
FT /note="R -> H (in Ref. 1; CAA49779)"
FT /evidence="ECO:0000305"
FT CONFLICT 283
FT /note="S -> C (in Ref. 1; CAA49779)"
FT /evidence="ECO:0000305"
FT HELIX 65..78
FT /evidence="ECO:0007829|PDB:3U2B"
FT HELIX 86..99
FT /evidence="ECO:0007829|PDB:3U2B"
FT HELIX 102..122
FT /evidence="ECO:0007829|PDB:3U2B"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:3U2B"
SQ SEQUENCE 440 AA; 45044 MW; 979AADBA7F674B6D CRC64;
MVQQTNNAEN TEALLAGESS DSGAGLELGI ASSPTPGSTA STGGKADDPS WCKTPSGHIK
RPMNAFMVWS QIERRKIMEQ SPDMHNAEIS KRLGKRWKLL KDSDKIPFIQ EAERLRLKHM
ADYPDYKYRP RKKVKSGNAG AGSAATAKPG EKGDKVAGSS GHAGSSHAGG GAGGSSKPAP
KKSCGPKVAG SSVGKPHAKL VPAGGSKAAA SFSPEQAALL PLGEPTAVYK VRTPSAATPA
ASSSPSSALA TPAKHPADKK VKRVYLFGSL GASASPVGGL GASADPSDPL GLYEDGGPGC
SPDGRSLSGR SSAASSPAAS RSPADHRGYA SLRAASPAPS SAPSHASSSL SSSSSSSSGS
SSSDDEFEDD LLDLNPSSNF ESMSLGSFSS SSALDRDLDF NFEPGSGSHF EFPDYCTPEV
SEMISGDWLE SSISNLVFTY
