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

 TBX6_HUMAN              Reviewed;         436 AA.
O95947; Q8TAS4; Q9HA44;
15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
03-OCT-2006, sequence version 2.
25-OCT-2017, entry version 158.
RecName: Full=T-box transcription factor TBX6;
Short=T-box protein 6;
Name=TBX6;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=9933572; DOI=10.1006/geno.1998.5646;
Papapetrou C., Putt W., Fox M., Edwards Y.H.;
"The human TBX6 gene: cloning and assignment to chromosome 16p11.2.";
Genomics 55:238-241(1999).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Mammary gland;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15616553; DOI=10.1038/nature03187;
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
Rubin E.M., Pennacchio L.A.;
"The sequence and analysis of duplication-rich human chromosome 16.";
Nature 432:988-994(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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).
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 135-272.
TISSUE=Myeloid;
PubMed=9888994; DOI=10.1006/geno.1998.5632;
Yi C.-H., Terrett J.A., Li Q.-Y., Ellington K., Packham E.A.,
Amstrong-Buisseret L., McClure P., Slingsby T., Brook J.D.;
"Identification, mapping and phylogenomic analysis of four new human
members of the T-box gene family: EOMES, TBX6, TBX18, and TBX19.";
Genomics 55:10-20(1999).
[7]
INVOLVEMENT IN SCDO5.
PubMed=23335591; DOI=10.1093/hmg/ddt012;
Sparrow D.B., McInerney-Leo A., Gucev Z.S., Gardiner B., Marshall M.,
Leo P.J., Chapman D.L., Tasic V., Shishko A., Brown M.A., Duncan E.L.,
Dunwoodie S.L.;
"Autosomal dominant spondylocostal dysostosis is caused by mutation in
TBX6.";
Hum. Mol. Genet. 22:1625-1631(2013).
[8]
VARIANT SCDO5 LEU-145.
PubMed=25564734; DOI=10.1056/NEJMoa1406829;
Wu N., Ming X., Xiao J., Wu Z., Chen X., Shinawi M., Shen Y., Yu G.,
Liu J., Xie H., Gucev Z.S., Liu S., Yang N., Al-Kateb H., Chen J.,
Zhang J., Hauser N., Zhang T., Tasic V., Liu P., Su X., Pan X.,
Liu C., Wang L., Shen J., Shen J., Chen Y., Zhang T., Zhang J.,
Choy K.W., Wang J., Wang Q., Li S., Zhou W., Guo J., Wang Y.,
Zhang C., Zhao H., An Y., Zhao Y., Wang J., Liu Z., Zuo Y., Tian Y.,
Weng X., Sutton V.R., Wang H., Ming Y., Kulkarni S., Zhong T.P.,
Giampietro P.F., Dunwoodie S.L., Cheung S.W., Zhang X., Jin L.,
Lupski J.R., Qiu G., Zhang F.;
"TBX6 null variants and a common hypomorphic allele in congenital
scoliosis.";
N. Engl. J. Med. 372:341-350(2015).
[9]
VARIANTS CONGENITAL SCOLIOSIS ILE-111 AND CYS-150, AND
CHARACTERIZATION OF VARIANTS CONGENITAL SCOLIOSIS ILE-111 AND CYS-150.
PubMed=28054739; DOI=10.1002/humu.23168;
Japan Early Onset Scoliosis Research Group;
Takeda K., Kou I., Kawakami N., Iida A., Nakajima M., Ogura Y.,
Imagawa E., Miyake N., Matsumoto N., Yasuhiko Y., Sudo H., Kotani T.,
Nakamura M., Matsumoto M., Watanabe K., Ikegawa S.;
"Compound heterozygosity for null mutations and a common hypomorphic
risk haplotype in TBX6 causes congenital scoliosis.";
Hum. Mutat. 38:317-323(2017).
-!- 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 (By
similarity). {ECO:0000250}.
-!- SUBUNIT: Forms a dimeric complex with DNA (in vitro).
-!- INTERACTION:
Q6P1W5:C1orf94; NbExp=3; IntAct=EBI-2824328, EBI-946029;
O43186:CRX; NbExp=4; IntAct=EBI-2824328, EBI-748171;
Q96A09:FAM46B; NbExp=4; IntAct=EBI-2824328, EBI-752030;
Q96LI6:HSFY2; NbExp=7; IntAct=EBI-2824328, EBI-3957665;
P86480:PRR20D; NbExp=4; IntAct=EBI-2824328, EBI-12754095;
Q93062:RBPMS; NbExp=3; IntAct=EBI-2824328, EBI-740322;
Q93062-3:RBPMS; NbExp=4; IntAct=EBI-2824328, EBI-740343;
Q9NUJ3:TCP11L1; NbExp=4; IntAct=EBI-2824328, EBI-2555179;
O94842:TOX4; NbExp=5; IntAct=EBI-2824328, EBI-948613;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00201}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=O95947-1; Sequence=Displayed;
Name=2;
IsoId=O95947-2; Sequence=VSP_054003, VSP_054004;
Note=No experimental confirmation available.;
-!- TISSUE SPECIFICITY: Expressed in fetal tail bud, posterior spinal
tissue, intervertebral disk and testis. Also expressed in adult
testis, kidney, lung, muscle and thymus.
-!- DEVELOPMENTAL STAGE: Expressed during gastrulation and during a
second phase in some adult tissues.
-!- DISEASE: Spondylocostal dysostosis 5 (SCDO5) [MIM:122600]: A rare
condition of variable severity characterized by vertebral and
costal anomalies. The main feature include dwarfism, vertebral
fusion, hemivertebrae, posterior rib fusion, reduced rib number,
and other rib malformations. SCDO5 inheritance can be autosomal
dominant or recessive. {ECO:0000269|PubMed:23335591,
ECO:0000269|PubMed:25564734}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
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EMBL; AJ007989; CAA07812.1; -; mRNA.
EMBL; AK022330; BAB14014.1; -; mRNA.
EMBL; AC012645; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC093512; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471238; EAW79927.1; -; Genomic_DNA.
EMBL; BC026031; AAH26031.1; -; mRNA.
EMBL; AJ010279; CAB37938.1; -; Genomic_DNA.
CCDS; CCDS10670.1; -. [O95947-1]
RefSeq; NP_004599.2; NM_004608.3. [O95947-1]
RefSeq; XP_005255580.1; XM_005255523.2. [O95947-1]
RefSeq; XP_011544228.1; XM_011545926.2. [O95947-1]
RefSeq; XP_016879103.1; XM_017023614.1. [O95947-1]
UniGene; Hs.198301; -.
ProteinModelPortal; O95947; -.
SMR; O95947; -.
BioGrid; 112774; 7.
IntAct; O95947; 33.
MINT; MINT-6772404; -.
STRING; 9606.ENSP00000279386; -.
PhosphoSitePlus; O95947; -.
BioMuta; TBX6; -.
PaxDb; O95947; -.
PeptideAtlas; O95947; -.
PRIDE; O95947; -.
DNASU; 6911; -.
Ensembl; ENST00000279386; ENSP00000279386; ENSG00000149922. [O95947-1]
Ensembl; ENST00000395224; ENSP00000378650; ENSG00000149922. [O95947-1]
Ensembl; ENST00000553607; ENSP00000461223; ENSG00000149922. [O95947-2]
Ensembl; ENST00000567664; ENSP00000460425; ENSG00000149922. [O95947-2]
GeneID; 6911; -.
KEGG; hsa:6911; -.
UCSC; uc002dwk.1; human. [O95947-1]
CTD; 6911; -.
DisGeNET; 6911; -.
EuPathDB; HostDB:ENSG00000149922.10; -.
GeneCards; TBX6; -.
HGNC; HGNC:11605; TBX6.
MalaCards; TBX6; -.
MIM; 122600; phenotype.
MIM; 602427; gene.
neXtProt; NX_O95947; -.
OpenTargets; ENSG00000149922; -.
Orphanet; 1797; Autosomal dominant spondylocostal dysostosis.
Orphanet; 247775; Classic Mayer-Rokitansky-Kuster-Hauser syndrome.
Orphanet; 2578; MURCS association.
PharmGKB; PA36368; -.
eggNOG; KOG3585; Eukaryota.
eggNOG; ENOG410XSTS; LUCA.
GeneTree; ENSGT00760000118897; -.
HOGENOM; HOG000286000; -.
HOVERGEN; HBG101171; -.
InParanoid; O95947; -.
KO; K10180; -.
OMA; LHPAAFH; -.
PhylomeDB; O95947; -.
TreeFam; TF106341; -.
GenomeRNAi; 6911; -.
PRO; PR:O95947; -.
Proteomes; UP000005640; Chromosome 16.
Bgee; ENSG00000149922; -.
CleanEx; HS_TBX6; -.
ExpressionAtlas; O95947; baseline and differential.
Genevisible; O95947; HS.
GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
GO; GO:0003677; F:DNA binding; TAS:ProtInc.
GO; GO:0001102; F:RNA polymerase II activating transcription factor binding; ISS:BHF-UCL.
GO; GO:0000980; F:RNA polymerase II distal enhancer sequence-specific DNA binding; IEA:Ensembl.
GO; GO:0001085; F:RNA polymerase II transcription factor binding; ISS:BHF-UCL.
GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IEA:InterPro.
GO; GO:0001191; F:transcriptional repressor activity, RNA polymerase II transcription factor binding; ISS:BHF-UCL.
GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
GO; GO:0001708; P:cell fate specification; IEA:Ensembl.
GO; GO:0007498; P:mesoderm development; TAS:ProtInc.
GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
GO; GO:0014043; P:negative regulation of neuron maturation; IEA:Ensembl.
GO; GO:0010977; P:negative regulation of neuron projection development; IEA:Ensembl.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; ISS:BHF-UCL.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl.
GO; GO:0032525; P:somite rostral/caudal axis specification; IEA:Ensembl.
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.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Developmental protein;
DNA-binding; Dwarfism; Nucleus; Polymorphism; Reference proteome;
Transcription; Transcription regulation.
CHAIN 1 436 T-box transcription factor TBX6.
/FTId=PRO_0000184438.
DNA_BIND 100 273 T-box. {ECO:0000255|PROSITE-
ProRule:PRU00201}.
VAR_SEQ 281 294 ERDARVKRKLRGPE -> WELFIHLFMHSTNV (in
isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_054003.
VAR_SEQ 295 435 Missing (in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_054004.
VARIANT 111 111 M -> I (in congenital scoliosis; unknown
pathological significance; decreases
transcriptional activity).
{ECO:0000269|PubMed:28054739}.
/FTId=VAR_078494.
VARIANT 145 145 P -> L (in SCDO5; unknown pathological
significance; dbSNP:rs202193096).
{ECO:0000269|PubMed:25564734}.
/FTId=VAR_078495.
VARIANT 150 150 R -> C (in congenital scoliosis; unknown
pathological significance; not change
transcriptional activity).
{ECO:0000269|PubMed:28054739}.
/FTId=VAR_078496.
VARIANT 162 162 G -> S (in dbSNP:rs56098093).
/FTId=VAR_061837.
VARIANT 178 178 S -> F (in dbSNP:rs12925839).
/FTId=VAR_027836.
VARIANT 179 179 P -> S (in dbSNP:rs12925838).
/FTId=VAR_027837.
CONFLICT 207 207 H -> HV (in Ref. 6; CAB37938).
{ECO:0000305}.
CONFLICT 388 389 EL -> DV (in Ref. 1; CAA07812).
{ECO:0000305}.
SEQUENCE 436 AA; 47045 MW; 649CDFB141B966F4 CRC64;
MYHPRELYPS LGAGYRLGPA QPGADSSFPP ALAEGYRYPE LDTPKLDCFL SGMEAAPRTL
AAHPPLPLLP PAMGTEPAPS APEALHSLPG VSLSLENREL WKEFSSVGTE MIITKAGRRM
FPACRVSVTG LDPEARYLFL LDVIPVDGAR YRWQGRRWEP SGKAEPRLPD RVYIHPDSPA
TGAHWMRQPV SFHRVKLTNS TLDPHGHLIL HSMHKYQPRI HLVRAAQLCS QHWGGMASFR
FPETTFISVT AYQNPQITQL KIAANPFAKG FRENGRNCKR ERDARVKRKL RGPEPAATEA
YGSGDTPGGP CDSTLGGDIR ESDPEQAPAP GEATAAPAPL CGGPSAEAYL LHPAAFHGAP
SHLPTRSPSF PEAPDSGRSA PYSAAFLELP HGSGGSGYPA APPAVPFAPH FLQGGPFPLP
YTAPGGYLDV GSKPMY


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