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T-box transcription factor TBX6 (T-box protein 6)

 TBX6_MOUSE              Reviewed;         436 AA.
P70327; B2RU37; Q5SDA2;
01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
16-MAY-2012, sequence version 2.
25-OCT-2017, entry version 135.
RecName: Full=T-box transcription factor TBX6;
Short=T-box protein 6;
Name=Tbx6;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Embryo;
PubMed=8878690;
Agulnik S.I., Garvey N., Hancock S., Ruvinsky I., Chapman D.L.,
Agulnik I., Bollag R.J., Papaioannou V.E., Silver L.M.;
"Evolution of mouse T-box genes by tandem duplication and cluster
dispersion.";
Genetics 144:249-254(1996).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Embryo;
PubMed=8954725; DOI=10.1006/dbio.1996.0326;
Chapman D.L., Agulnik I., Hancock S., Silver L.M., Papaioannou V.E.;
"Tbx6, a mouse T-Box gene implicated in paraxial mesoderm formation at
gastrulation.";
Dev. Biol. 180:534-542(1996).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
STRAIN=C3H/He;
PubMed=15545628; DOI=10.1101/gad.1248604;
Hofmann M., Schuster-Gossler K., Watabe-Rudolph M., Aulehla A.,
Herrmann B.G., Gossler A.;
"WNT signaling, in synergy with T/TBX6, controls Notch signaling by
regulating Dll1 expression in the presomitic mesoderm of mouse
embryos.";
Genes Dev. 18:2712-2717(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=9490412; DOI=10.1038/35624;
Chapman D.L., Papaioannou V.E.;
"Three neural tubes in mouse embryos with mutations in the T-box gene
Tbx6.";
Nature 391:695-697(1998).
[6]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=18575602; DOI=10.1371/journal.pone.0002511;
Hadjantonakis A.K., Pisano E., Papaioannou V.E.;
"Tbx6 regulates left/right patterning in mouse embryos through effects
on nodal cilia and perinodal signaling.";
PLoS ONE 3:E2511-E2511(2008).
[7]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=21331042; DOI=10.1038/nature09729;
Takemoto T., Uchikawa M., Yoshida M., Bell D.M., Lovell-Badge R.,
Papaioannou V.E., Kondoh H.;
"Tbx6-dependent Sox2 regulation determines neural or mesodermal fate
in axial stem cells.";
Nature 470:394-398(2011).
-!- FUNCTION: T-box transcription factor that plays an essential role
in the determination of the fate of axial stem cells: neural vs
mesodermal. Acts in part by down-regulating, a specific enhancer
(N1) of SOX2, to inhibit neural development. Seems to play also an
essential role in left/right axis determination and acts through
effects on Notch signaling around the node as well as through an
effect on the morphology and motility of the nodal cilia.
{ECO:0000269|PubMed:15545628, ECO:0000269|PubMed:18575602,
ECO:0000269|PubMed:21331042, ECO:0000269|PubMed:9490412}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00201}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=P70327-1; Sequence=Displayed;
Name=2;
IsoId=P70327-2; Sequence=VSP_043221;
Note=No experimental confirmation available.;
-!- DEVELOPMENTAL STAGE: TBX6 is first detected in the gastrulation
stage in the primitive streak and newly recruited paraxial
mesoderm. Later in development it is restricted to presomitic,
paraxial mesoderm and to the tail bud, which replaces the streak
as the source of mesoderm.
-!- DISRUPTION PHENOTYPE: Defects in the differentiation of paraxial
mesoderm. Irregular somites formed in the neck region of mutant
embryos, whereas more posterior paraxial tissue did not form
somites but instead differentiated along a neural pathway, forming
neural-tube-like structures that flanked the axial neural tube.
These paraxial tubes showed dorsal/ventral patterning that is
characteristic of the neural tube and had differentiated motor
neurons. Embryos lacking TBX6 show also randomization of the
direction of heart looping and independent alterations in the
direction of embryo turning. {ECO:0000269|PubMed:18575602,
ECO:0000269|PubMed:21331042, ECO:0000269|PubMed:9490412}.
-!- SEQUENCE CAUTION:
Sequence=AAC53110.1; Type=Frameshift; Positions=67, 72, 329, 377; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; U57331; AAC53110.1; ALT_FRAME; mRNA.
EMBL; AY654733; AAT72924.1; -; mRNA.
EMBL; BC140951; AAI40952.1; -; mRNA.
CCDS; CCDS21843.1; -. [P70327-1]
PIR; S72233; S72233.
RefSeq; NP_035668.2; NM_011538.2. [P70327-1]
UniGene; Mm.727; -.
ProteinModelPortal; P70327; -.
SMR; P70327; -.
BioGrid; 203991; 3.
IntAct; P70327; 2.
STRING; 10090.ENSMUSP00000091579; -.
iPTMnet; P70327; -.
PhosphoSitePlus; P70327; -.
PaxDb; P70327; -.
PRIDE; P70327; -.
Ensembl; ENSMUST00000094037; ENSMUSP00000091579; ENSMUSG00000030699. [P70327-1]
Ensembl; ENSMUST00000172352; ENSMUSP00000126418; ENSMUSG00000030699. [P70327-2]
GeneID; 21389; -.
KEGG; mmu:21389; -.
UCSC; uc009jsr.1; mouse. [P70327-1]
UCSC; uc012ftu.1; mouse. [P70327-2]
CTD; 6911; -.
MGI; MGI:102539; Tbx6.
eggNOG; KOG3585; Eukaryota.
eggNOG; ENOG410XSTS; LUCA.
GeneTree; ENSGT00760000118897; -.
HOGENOM; HOG000286000; -.
HOVERGEN; HBG017897; -.
InParanoid; P70327; -.
KO; K10180; -.
OMA; LHPAAFH; -.
OrthoDB; EOG091G0I8R; -.
TreeFam; TF106341; -.
PRO; PR:P70327; -.
Proteomes; UP000000589; Chromosome 7.
Bgee; ENSMUSG00000030699; -.
CleanEx; MM_TBX6; -.
Genevisible; P70327; MM.
GO; GO:0005634; C:nucleus; IDA:MGI.
GO; GO:0003677; F:DNA binding; IDA:MGI.
GO; GO:0001102; F:RNA polymerase II activating transcription factor binding; IPI:BHF-UCL.
GO; GO:0000980; F:RNA polymerase II distal enhancer sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0001085; F:RNA polymerase II transcription factor binding; IPI:BHF-UCL.
GO; GO:0001206; F:transcriptional repressor activity, RNA polymerase II distal enhancer sequence-specific binding; IC:NTNU_SB.
GO; GO:0001191; F:transcriptional repressor activity, RNA polymerase II transcription factor binding; IDA:BHF-UCL.
GO; GO:0001708; P:cell fate specification; IMP:MGI.
GO; GO:0001707; P:mesoderm formation; IMP:MGI.
GO; GO:0014043; P:negative regulation of neuron maturation; IGI:MGI.
GO; GO:0010977; P:negative regulation of neuron projection development; IGI:MGI.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:MGI.
GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IDA:MGI.
GO; GO:0032525; P:somite rostral/caudal axis specification; IDA:MGI.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
CDD; cd00182; TBOX; 1.
Gene3D; 2.60.40.820; -; 1.
InterPro; IPR008967; p53-like_TF_DNA-bd.
InterPro; IPR036960; T-box_sf.
InterPro; IPR002070; TF_Brachyury.
InterPro; IPR001699; TF_T-box.
InterPro; IPR018186; TF_T-box_CS.
PANTHER; PTHR11267; PTHR11267; 1.
Pfam; PF00907; T-box; 1.
PRINTS; PR00938; BRACHYURY.
PRINTS; PR00937; TBOX.
SMART; SM00425; TBOX; 1.
SUPFAM; SSF49417; SSF49417; 1.
PROSITE; PS01283; TBOX_1; 1.
PROSITE; PS01264; TBOX_2; 1.
PROSITE; PS50252; TBOX_3; 1.
2: Evidence at transcript level;
Alternative splicing; Complete proteome; Developmental protein;
DNA-binding; Nucleus; Reference proteome; Transcription;
Transcription regulation.
CHAIN 1 436 T-box transcription factor TBX6.
/FTId=PRO_0000184439.
DNA_BIND 100 273 T-box. {ECO:0000255|PROSITE-
ProRule:PRU00201}.
VAR_SEQ 281 304 ERDARVKRKLRGPEPVATEACGSG -> WASFIQGMLTNYC
VPGTVPGYQEHD (in isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_043221.
CONFLICT 156 157 QH -> PD (in Ref. 1; AAC53110).
{ECO:0000305}.
CONFLICT 331 331 Q -> R (in Ref. 1; AAC53110 and 4;
AAI40952). {ECO:0000305}.
CONFLICT 370 370 F -> L (in Ref. 1; AAC53110).
{ECO:0000305}.
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


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