TBX6_MOUSE
ID TBX6_MOUSE Reviewed; 436 AA.
AC P70327; B2RU37; Q5SDA2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2012, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=T-box transcription factor TBX6;
DE Short=T-box protein 6;
GN Name=Tbx6;
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] (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=8878690; DOI=10.1093/genetics/144.1.249;
RA Agulnik S.I., Garvey N., Hancock S., Ruvinsky I., Chapman D.L., Agulnik I.,
RA Bollag R.J., Papaioannou V.E., Silver L.M.;
RT "Evolution of mouse T-box genes by tandem duplication and cluster
RT dispersion.";
RL Genetics 144:249-254(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=8954725; DOI=10.1006/dbio.1996.0326;
RA Chapman D.L., Agulnik I., Hancock S., Silver L.M., Papaioannou V.E.;
RT "Tbx6, a mouse T-Box gene implicated in paraxial mesoderm formation at
RT gastrulation.";
RL Dev. Biol. 180:534-542(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC STRAIN=C3H/He;
RX PubMed=15545628; DOI=10.1101/gad.1248604;
RA Hofmann M., Schuster-Gossler K., Watabe-Rudolph M., Aulehla A.,
RA Herrmann B.G., Gossler A.;
RT "WNT signaling, in synergy with T/TBX6, controls Notch signaling by
RT regulating Dll1 expression in the presomitic mesoderm of mouse embryos.";
RL Genes Dev. 18:2712-2717(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC 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 [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9490412; DOI=10.1038/35624;
RA Chapman D.L., Papaioannou V.E.;
RT "Three neural tubes in mouse embryos with mutations in the T-box gene
RT Tbx6.";
RL Nature 391:695-697(1998).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18575602; DOI=10.1371/journal.pone.0002511;
RA Hadjantonakis A.K., Pisano E., Papaioannou V.E.;
RT "Tbx6 regulates left/right patterning in mouse embryos through effects on
RT nodal cilia and perinodal signaling.";
RL PLoS ONE 3:E2511-E2511(2008).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21331042; DOI=10.1038/nature09729;
RA Takemoto T., Uchikawa M., Yoshida M., Bell D.M., Lovell-Badge R.,
RA Papaioannou V.E., Kondoh H.;
RT "Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in
RT axial stem cells.";
RL Nature 470:394-398(2011).
CC -!- FUNCTION: T-box transcription factor that plays an essential role in
CC the determination of the fate of axial stem cells: neural vs
CC mesodermal. Acts in part by down-regulating, a specific enhancer (N1)
CC of SOX2, to inhibit neural development. Seems to play also an essential
CC role in left/right axis determination and acts through effects on Notch
CC signaling around the node as well as through an effect on the
CC morphology and motility of the nodal cilia.
CC {ECO:0000269|PubMed:15545628, ECO:0000269|PubMed:18575602,
CC ECO:0000269|PubMed:21331042, ECO:0000269|PubMed:9490412}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00201}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P70327-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P70327-2; Sequence=VSP_043221;
CC -!- DEVELOPMENTAL STAGE: TBX6 is first detected in the gastrulation stage
CC in the primitive streak and newly recruited paraxial mesoderm. Later in
CC development it is restricted to presomitic, paraxial mesoderm and to
CC the tail bud, which replaces the streak as the source of mesoderm.
CC -!- DISRUPTION PHENOTYPE: Defects in the differentiation of paraxial
CC mesoderm. Irregular somites formed in the neck region of mutant
CC embryos, whereas more posterior paraxial tissue did not form somites
CC but instead differentiated along a neural pathway, forming neural-tube-
CC like structures that flanked the axial neural tube. These paraxial
CC tubes showed dorsal/ventral patterning that is characteristic of the
CC neural tube and had differentiated motor neurons. Embryos lacking TBX6
CC show also randomization of the direction of heart looping and
CC independent alterations in the direction of embryo turning.
CC {ECO:0000269|PubMed:18575602, ECO:0000269|PubMed:21331042,
CC ECO:0000269|PubMed:9490412}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC53110.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U57331; AAC53110.1; ALT_FRAME; mRNA.
DR EMBL; AY654733; AAT72924.1; -; mRNA.
DR EMBL; BC140951; AAI40952.1; -; mRNA.
DR CCDS; CCDS21843.1; -. [P70327-1]
DR PIR; S72233; S72233.
DR RefSeq; NP_035668.2; NM_011538.2. [P70327-1]
DR AlphaFoldDB; P70327; -.
DR SMR; P70327; -.
DR BioGRID; 203991; 1.
DR IntAct; P70327; 2.
DR STRING; 10090.ENSMUSP00000091579; -.
DR iPTMnet; P70327; -.
DR PhosphoSitePlus; P70327; -.
DR PaxDb; P70327; -.
DR PRIDE; P70327; -.
DR Antibodypedia; 13514; 391 antibodies from 31 providers.
DR DNASU; 21389; -.
DR Ensembl; ENSMUST00000094037; ENSMUSP00000091579; ENSMUSG00000030699. [P70327-1]
DR Ensembl; ENSMUST00000172352; ENSMUSP00000126418; ENSMUSG00000030699. [P70327-2]
DR GeneID; 21389; -.
DR KEGG; mmu:21389; -.
DR UCSC; uc009jsr.1; mouse. [P70327-1]
DR UCSC; uc012ftu.1; mouse. [P70327-2]
DR CTD; 6911; -.
DR MGI; MGI:102539; Tbx6.
DR VEuPathDB; HostDB:ENSMUSG00000030699; -.
DR eggNOG; KOG3585; Eukaryota.
DR GeneTree; ENSGT00940000160732; -.
DR HOGENOM; CLU_052181_0_0_1; -.
DR InParanoid; P70327; -.
DR OMA; EPVIMEN; -.
DR OrthoDB; 828211at2759; -.
DR TreeFam; TF106341; -.
DR BioGRID-ORCS; 21389; 2 hits in 72 CRISPR screens.
DR PRO; PR:P70327; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P70327; protein.
DR Bgee; ENSMUSG00000030699; Expressed in embryonic post-anal tail and 80 other tissues.
DR Genevisible; P70327; MM.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IC:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0003205; P:cardiac chamber development; IBA:GO_Central.
DR GO; GO:0001708; P:cell fate specification; IBA:GO_Central.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0001947; P:heart looping; IBA:GO_Central.
DR GO; GO:0001707; P:mesoderm formation; IMP:MGI.
DR GO; GO:0007501; P:mesodermal cell fate specification; IMP:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0014043; P:negative regulation of neuron maturation; IGI:MGI.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IGI:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IDA:MGI.
DR GO; GO:0032525; P:somite rostral/caudal axis specification; IDA:MGI.
DR CDD; cd00182; TBOX; 1.
DR Gene3D; 2.60.40.820; -; 1.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR046360; T-box_DNA-bd.
DR InterPro; IPR036960; T-box_sf.
DR InterPro; IPR002070; TF_Brachyury.
DR InterPro; IPR001699; TF_T-box.
DR InterPro; IPR018186; TF_T-box_CS.
DR PANTHER; PTHR11267; PTHR11267; 1.
DR Pfam; PF00907; T-box; 1.
DR PRINTS; PR00938; BRACHYURY.
DR PRINTS; PR00937; TBOX.
DR SMART; SM00425; TBOX; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR PROSITE; PS01283; TBOX_1; 1.
DR PROSITE; PS01264; TBOX_2; 1.
DR PROSITE; PS50252; TBOX_3; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Developmental protein; DNA-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..436
FT /note="T-box transcription factor TBX6"
FT /id="PRO_0000184439"
FT DNA_BIND 100..273
FT /note="T-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00201"
FT REGION 274..344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 360..383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 274..294
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 281..304
FT /note="ERDARVKRKLRGPEPVATEACGSG -> WASFIQGMLTNYCVPGTVPGYQEH
FT D (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043221"
FT CONFLICT 156..157
FT /note="QH -> PD (in Ref. 1; AAC53110)"
FT /evidence="ECO:0000305"
FT CONFLICT 331
FT /note="Q -> R (in Ref. 1; AAC53110 and 4; AAI40952)"
FT /evidence="ECO:0000305"
FT CONFLICT 370
FT /note="F -> L (in Ref. 1; AAC53110)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 436 AA; 47006 MW; DBAAD94C88E9CC4B CRC64;
MYHPRELYPS LGTGYRLGHP QPGADSTFPP ALTEGYRYPD LDTSKLDCFL SGIEAAPHTL
AAAAPLPLLP SALGPETAPP PPEALHSLPG VSLSLENQEL WKEFSAVGTE MIITKAGRRM
FPACRVSVTG LDPEARYLFL LDVVPVDGAR YRWQGQHWEP SGKAEPRLPD RVYIHPDSPA
TGAHWMRQPV SFHRVKLTNS TLDPHGHLIL HSMHKYQPRI HLVRATQLCS QHWGGVASFR
FPETTFISVT AYQNPRITQL KIAANPFAKG FRENGRNCKR ERDARVKRKL RGPEPVATEA
CGSGDTPGGP CDSTLGGDIR DSDPEQAPTP QEAASASAPP CGGPSAEAYL LHPAAFHGAP
SHLPARTPSF AEAPDPGRPA PYSAAFLDLQ PGPGGSAYQA APSVPSFAPH FIQGGPFPLP
YPGPGGYLDM GSKPMY
