ID SOX12_MOUSE Reviewed; 314 AA.
AC Q04890; A2AS82; P70417; Q6NXL2;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 24-JAN-2024, entry version 166.
DE RecName: Full=Transcription factor SOX-12;
GN Name=Sox12; Synonyms=Sox-12;
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 [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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 48-103, AND DEVELOPMENTAL STAGE.
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 51-103, AND TISSUE SPECIFICITY.
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 [5]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=18505825; DOI=10.1128/mcb.00338-08;
RA Hoser M., Potzner M.R., Koch J.M., Boesl M.R., Wegner M., Sock E.;
RT "Sox12 deletion in the mouse reveals nonreciprocal redundancy with the
RT related Sox4 and Sox11 transcription factors.";
RL Mol. Cell. Biol. 28:4675-4687(2008).
RN [6]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=18403418; DOI=10.1093/nar/gkn162;
RA Dy P., Penzo-Mendez A., Wang H., Pedraza C.E., Macklin W.B., Lefebvre V.;
RT "The three SoxC proteins--Sox4, Sox11 and Sox12--exhibit overlapping
RT expression patterns and molecular properties.";
RL Nucleic Acids Res. 36:3101-3117(2008).
RN [7]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=20596238; DOI=10.1038/ncomms1008;
RA Bhattaram P., Penzo-Mendez A., Sock E., Colmenares C., Kaneko K.J.,
RA Vassilev A., Depamphilis M.L., Wegner M., Lefebvre V.;
RT "Organogenesis relies on SoxC transcription factors for the survival of
RT neural and mesenchymal progenitors.";
RL Nat. Commun. 1:9-9(2010).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION BY TCR SIGNALING, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=30190287; DOI=10.1084/jem.20172082;
RA Tanaka S., Suto A., Iwamoto T., Kageyama T., Tamachi T., Takatori H.,
RA Suzuki K., Hirose K., Ohara O., Lefebvre V., Nakajima H.;
RT "Sox12 promotes T reg differentiation in the periphery during colitis.";
RL J. Exp. Med. 215:2509-2519(2018).
CC -!- FUNCTION: Transcription factor that binds to DNA at the consensus
CC sequence 5'-ACCAAAG-3' (PubMed:18505825, PubMed:18403418,
CC PubMed:30190287). Acts as a transcriptional activator (PubMed:18505825,
CC PubMed:18403418, PubMed:30190287). Binds cooperatively with POU3F2/BRN2
CC or POU3F1/OCT6 to gene promoters, which enhances transcriptional
CC activation (PubMed:18505825, PubMed:18403418). Involved in the
CC differentiation of naive CD4-positive T-cells into peripherally induced
CC regulatory T (pT reg) cells under inflammatory conditions
CC (PubMed:30190287). Binds to the promoter region of the FOXP3 gene and
CC promotes its transcription, and might thereby contribute to pT reg cell
CC differentiation in the spleen and lymph nodes during inflammation
CC (PubMed:30190287). Plays a redundant role with SOX4 and SOX11 in cell
CC survival of developing tissues such as the neural tube, branchial
CC arches and somites, thereby contributing to organogenesis
CC (PubMed:20596238). {ECO:0000269|PubMed:18403418,
CC ECO:0000269|PubMed:18505825, ECO:0000269|PubMed:20596238,
CC ECO:0000269|PubMed:30190287}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00267}.
CC -!- TISSUE SPECIFICITY: Expressed in splenic and thymic regulatory T-cells
CC (at protein level) (PubMed:30190287). Expressed in embryonic molar and
CC incisor teeth (PubMed:8921394). {ECO:0000269|PubMed:30190287,
CC ECO:0000269|PubMed:8921394}.
CC -!- DEVELOPMENTAL STAGE: Widely expressed in the developing embryo from 9.5
CC dpc to 12.5 dpc (PubMed:8441686, PubMed:18505825, PubMed:18403418,
CC PubMed:20596238). Expressed throughout the central and peripheral
CC nervous system, as well as the mesenchyme of many developing organs
CC between 12.5 dpc and 14.5 dpc (PubMed:18403418). Strongly expressed in
CC the lens of the eye, developing cerebral cortex, the dorsal cortical
CC plate, thalamus, hippocampus and cerebellar cortex in the brain at 14.5
CC dpc (PubMed:18505825). Expressed in skin, spinal cord, lung, liver,
CC intestine, kidney, heart, muscle, cartilage from 14.5 dpc to 18.5 dpc
CC (PubMed:18505825). Abundantly expressed in the brain, heart and lung,
CC with low expression in the liver, pancreas, and small intestine at
CC postnatal day 2 (PubMed:18403418). {ECO:0000269|PubMed:18403418,
CC ECO:0000269|PubMed:18505825, ECO:0000269|PubMed:20596238,
CC ECO:0000269|PubMed:8441686}.
CC -!- INDUCTION: Induced by T-cell receptor signaling in naive CD4-positive
CC T-cells and in splenic and thymic regulatory T-cells (PubMed:30190287).
CC Up-regulated in splenic T reg cells by dextran sulfate sodium (DSS)-
CC induced colitis (PubMed:30190287). {ECO:0000269|PubMed:30190287}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are viable, fertile and
CC morphologically normal (PubMed:18505825, PubMed:20596238). Increased
CC expression of Sox11 in brain and cartilage at 14.5 dpc, with increased
CC expression in liver and kidney at 16.5 dpc (PubMed:18505825). Increased
CC expression of Sox4 in spinal cord and cartilage at 14.5 dpc, with
CC increased expression in liver at 16.5 dpc (PubMed:18505825). Sox12
CC knockout naive CD4-positive T cells fail to differentiate into pT reg
CC cells in mice with dextran sulfate sodium (DSS)-induced colitis
CC (PubMed:30190287). Sox4, Sox11, and Sox12 triple knockout mice are
CC embryonically lethal and show severe thinning and undulation of the
CC neural tube (PubMed:20596238). {ECO:0000269|PubMed:18505825,
CC ECO:0000269|PubMed:20596238, ECO:0000269|PubMed:30190287}.
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DR EMBL; AL928568; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC067019; AAH67019.1; -; mRNA.
DR EMBL; Z18961; CAA79486.1; -; mRNA.
DR EMBL; U70442; AAC52860.1; -; mRNA.
DR CCDS; CCDS38274.1; -.
DR PIR; S30240; S30240.
DR RefSeq; NP_035568.1; NM_011438.2.
DR AlphaFoldDB; Q04890; -.
DR SMR; Q04890; -.
DR STRING; 10090.ENSMUSP00000138293; -.
DR PhosphoSitePlus; Q04890; -.
DR MaxQB; Q04890; -.
DR PaxDb; 10090-ENSMUSP00000138293; -.
DR ProteomicsDB; 258712; -.
DR Antibodypedia; 6130; 257 antibodies from 32 providers.
DR DNASU; 20667; -.
DR Ensembl; ENSMUST00000063332.9; ENSMUSP00000064250.8; ENSMUSG00000051817.9.
DR Ensembl; ENSMUST00000182625.2; ENSMUSP00000138293.2; ENSMUSG00000051817.9.
DR GeneID; 20667; -.
DR KEGG; mmu:20667; -.
DR UCSC; uc008nfi.1; mouse.
DR AGR; MGI:98360; -.
DR CTD; 6666; -.
DR MGI; MGI:98360; Sox12.
DR VEuPathDB; HostDB:ENSMUSG00000051817; -.
DR eggNOG; KOG0527; Eukaryota.
DR GeneTree; ENSGT00940000163140; -.
DR HOGENOM; CLU_043342_0_0_1; -.
DR InParanoid; Q04890; -.
DR OMA; GEPAWCK; -.
DR OrthoDB; 2902801at2759; -.
DR PhylomeDB; Q04890; -.
DR BioGRID-ORCS; 20667; 8 hits in 80 CRISPR screens.
DR ChiTaRS; Sox12; mouse.
DR PRO; PR:Q04890; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q04890; Protein.
DR Bgee; ENSMUSG00000051817; Expressed in cortical plate and 201 other cell types or tissues.
DR Genevisible; Q04890; MM.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0032993; C:protein-DNA complex; 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:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
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:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0021510; P:spinal cord development; IDA:UniProtKB.
DR CDD; cd22038; HMG-box_SoxC_SOX12; 1.
DR Gene3D; 1.10.30.10; High mobility group box domain; 1.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR017386; SOX-12/11/4.
DR PANTHER; PTHR10270; SOX TRANSCRIPTION FACTOR; 1.
DR PANTHER; PTHR10270:SF221; TRANSCRIPTION FACTOR SOX-12; 1.
DR Pfam; PF00505; HMG_box; 1.
DR PIRSF; PIRSF038098; SOX-12/11/4a; 1.
DR SMART; SM00398; HMG; 1.
DR SUPFAM; SSF47095; HMG-box; 1.
DR PROSITE; PS50118; HMG_BOX_2; 1.
PE 1: Evidence at protein level;
KW Activator; DNA-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..314
FT /note="Transcription factor SOX-12"
FT /id="PRO_0000048755"
FT DNA_BIND 40..108
FT /note="HMG box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 101..287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 282..314
FT /note="Required for transcriptional activation activity and
FT synergistic coactivation of transcriptional activity with
FT POU3F2"
FT /evidence="ECO:0000269|PubMed:18403418"
FT COMPBIAS 161..175
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 221..245
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 90
FT /note="V -> E (in Ref. 4; CAA79486)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 314 AA; 34083 MW; CAB9DEF059F2C5A0 CRC64;
MVQQRGARAK RDGGPPPPGP GPAAEGAREP GWCKTPSGHI KRPMNAFMVW SQHERRKIMD
QWPDMHNAEI SKRLGRRWQL LQDSEKIPFV REAERLRLKH MADYPDYKYR PRKKSKGAPA
KARPRPPGGG GGGSRLKPGP QLPGRGGRRA SGGPLGGGAA APEDDDEDEE EELLEVRLLE
TPGRELWRMV PAGRAARGPA ERAQGPSGEG AAASAASPTL SEDEEPEEEE EEAATAEEGE
EETVVSGEEP LGFLSRMPPG PAGLDCSALD RDPDLLPPSG TSHFEFPDYC TPEVTEMIAG
DWRSSSIADL VFTY
//
