TBX18_MOUSE
ID TBX18_MOUSE Reviewed; 613 AA.
AC Q9EPZ6;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=T-box transcription factor TBX18;
DE Short=T-box protein 18;
GN Name=Tbx18;
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], AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J;
RX PubMed=11118889; DOI=10.1016/s0925-4773(00)00494-9;
RA Kraus F., Haenig B., Kispert A.;
RT "Cloning and expression analysis of the mouse T-box gene Tbx18.";
RL Mech. Dev. 100:83-86(2001).
RN [2]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=15155583; DOI=10.1101/gad.300104;
RA Bussen M., Petry M., Schuster-Gossler K., Leitges M., Gossler A.,
RA Kispert A.;
RT "The T-box transcription factor Tbx18 maintains the separation of anterior
RT and posterior somite compartments.";
RL Genes Dev. 18:1209-1221(2004).
RN [3]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=16511601; DOI=10.1172/jci26027;
RA Airik R., Bussen M., Singh M.K., Petry M., Kispert A.;
RT "Tbx18 regulates the development of the ureteral mesenchyme.";
RL J. Clin. Invest. 116:663-674(2006).
RN [4]
RP SUBCELLULAR LOCATION, SUBUNIT, FUNCTION, NUCLEAR LOCALIZATION SIGNAL, AND
RP INTERACTION WITH TBX15; TLE3; GATA4 AND NKX2-5.
RX PubMed=17584735; DOI=10.1074/jbc.m703724200;
RA Farin H.F., Bussen M., Schmidt M.K., Singh M.K., Schuster-Gossler K.,
RA Kispert A.;
RT "Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends
RT on Groucho corepressors.";
RL J. Biol. Chem. 282:25748-25759(2007).
RN [5]
RP INTERACTION WITH PAX3.
RX PubMed=18644785; DOI=10.1074/jbc.m802723200;
RA Farin H.F., Mansouri A., Petry M., Kispert A.;
RT "T-box protein Tbx18 interacts with the paired box protein Pax3 in the
RT development of the paraxial mesoderm.";
RL J. Biol. Chem. 283:25372-25380(2008).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=19096026; DOI=10.1161/circresaha.108.187062;
RA Wiese C., Grieskamp T., Airik R., Mommersteeg M.T., Gardiwal A.,
RA de Gier-de Vries C., Schuster-Gossler K., Moorman A.F., Kispert A.,
RA Christoffels V.M.;
RT "Formation of the sinus node head and differentiation of sinus node
RT myocardium are independently regulated by Tbx18 and Tbx3.";
RL Circ. Res. 104:388-397(2009).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=24016759; DOI=10.1016/j.ydbio.2013.08.019;
RA Wu S.P., Dong X.R., Regan J.N., Su C., Majesky M.W.;
RT "Tbx18 regulates development of the epicardium and coronary vessels.";
RL Dev. Biol. 383:307-320(2013).
RN [8]
RP DEVELOPMENTAL STAGE.
RX PubMed=26235987; DOI=10.1016/j.ajhg.2015.07.001;
RA Vivante A., Kleppa M.J., Schulz J., Kohl S., Sharma A., Chen J., Shril S.,
RA Hwang D.Y., Weiss A.C., Kaminski M.M., Shukrun R., Kemper M.J.,
RA Lehnhardt A., Beetz R., Sanna-Cherchi S., Verbitsky M., Gharavi A.G.,
RA Stuart H.M., Feather S.A., Goodship J.A., Goodship T.H., Woolf A.S.,
RA Westra S.J., Doody D.P., Bauer S.B., Lee R.S., Adam R.M., Lu W.,
RA Reutter H.M., Kehinde E.O., Mancini E.J., Lifton R.P., Tasic V.,
RA Lienkamp S.S., Jueppner H., Kispert A., Hildebrandt F.;
RT "Mutations in TBX18 cause dominant urinary tract malformations via
RT transcriptional dysregulation of ureter development.";
RL Am. J. Hum. Genet. 97:291-301(2015).
CC -!- FUNCTION: Acts as transcriptional repressor involved in developmental
CC processes of a variety of tissues and organs, including the heart, the
CC coronary vessels, the ureter, and the vertebral column. Required for
CC embryonic development of the sino atrial node (SAN) head area.
CC {ECO:0000269|PubMed:15155583, ECO:0000269|PubMed:16511601,
CC ECO:0000269|PubMed:17584735, ECO:0000269|PubMed:19096026,
CC ECO:0000269|PubMed:24016759}.
CC -!- SUBUNIT: Homodimer. Can form a heterodimer with TBX15. Interacts with
CC GATA4 AND NKX2-5. Interacts (via engrailed homology 1 repressor motif)
CC with TLE3; this interaction represses TBX18 transcriptional activity.
CC Interacts with PAX3. Interacts with SIX1 (By similarity).
CC {ECO:0000250|UniProtKB:O95935, ECO:0000269|PubMed:17584735,
CC ECO:0000269|PubMed:18644785}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00201,
CC ECO:0000269|PubMed:17584735}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the renal pelvis and ureter smooth
CC muscle layer at 17.5 dpc (at protein level) (PubMed:26235987). During
CC development expression is most prominent in the proepicardial organ and
CC in the epicardium. Expressed also in the cranial paraxial mesoderm, the
CC presomitic mesoderm, the anterior somite half, the genital ridge and
CC the developing limb buds (PubMed:11118889).
CC {ECO:0000269|PubMed:11118889, ECO:0000269|PubMed:26235987}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice fail to maintain anterior-
CC posterior polarity, resulting in abnormal dorsal-ventral polarity of
CC the somites. Mutant mice display neonatal lethality and abnormal
CC morphology of vertebrae, ribs, spinal nerves and coronary vessels.
CC Besides, mutant mice develop anomalies of the urinary tract, including
CC hydroureter and hydronephrosis. {ECO:0000269|PubMed:15155583,
CC ECO:0000269|PubMed:16511601, ECO:0000269|PubMed:19096026,
CC ECO:0000269|PubMed:24016759}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=At the heart of things
CC - Issue 165 of November 2014;
CC URL="https://web.expasy.org/spotlight/back_issues/165/";
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DR EMBL; AF306666; AAG48598.1; -; mRNA.
DR CCDS; CCDS40718.1; -.
DR RefSeq; NP_076303.3; NM_023814.4.
DR AlphaFoldDB; Q9EPZ6; -.
DR SMR; Q9EPZ6; -.
DR BioGRID; 218079; 2.
DR IntAct; Q9EPZ6; 1.
DR STRING; 10090.ENSMUSP00000034991; -.
DR iPTMnet; Q9EPZ6; -.
DR PhosphoSitePlus; Q9EPZ6; -.
DR PaxDb; Q9EPZ6; -.
DR PRIDE; Q9EPZ6; -.
DR DNASU; 76365; -.
DR GeneID; 76365; -.
DR KEGG; mmu:76365; -.
DR CTD; 9096; -.
DR MGI; MGI:1923615; Tbx18.
DR eggNOG; KOG3586; Eukaryota.
DR InParanoid; Q9EPZ6; -.
DR OrthoDB; 828211at2759; -.
DR PhylomeDB; Q9EPZ6; -.
DR BioGRID-ORCS; 76365; 5 hits in 76 CRISPR screens.
DR PRO; PR:Q9EPZ6; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9EPZ6; protein.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0090571; C:RNA polymerase II transcription repressor complex; IDA:BHF-UCL.
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; IDA:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
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:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL.
DR GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; IMP:MGI.
DR GO; GO:0009948; P:anterior/posterior axis specification; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IMP:MGI.
DR GO; GO:0001708; P:cell fate specification; IBA:GO_Central.
DR GO; GO:0090103; P:cochlea morphogenesis; IMP:MGI.
DR GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI.
DR GO; GO:0010463; P:mesenchymal cell proliferation; IMP:MGI.
DR GO; GO:0072198; P:mesenchymal cell proliferation involved in ureter development; IGI:MGI.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; IMP:MGI.
DR GO; GO:0051450; P:myoblast proliferation; IGI:MGI.
DR GO; GO:0060829; P:negative regulation of canonical Wnt signaling pathway involved in neural plate anterior/posterior pattern formation; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; IMP:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IMP:MGI.
DR GO; GO:2000729; P:positive regulation of mesenchymal cell proliferation involved in ureter development; IGI:MGI.
DR GO; GO:2000288; P:positive regulation of myoblast proliferation; IGI:MGI.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IMP:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0098907; P:regulation of SA node cell action potential; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI.
DR GO; GO:0060931; P:sinoatrial node cell development; ISO:MGI.
DR GO; GO:0060930; P:sinoatrial node cell fate commitment; ISO:MGI.
DR GO; GO:0003163; P:sinoatrial node development; IMP:MGI.
DR GO; GO:0051145; P:smooth muscle cell differentiation; IMP:MGI.
DR GO; GO:0001756; P:somitogenesis; IMP:MGI.
DR GO; GO:0048863; P:stem cell differentiation; IMP:MGI.
DR GO; GO:0072089; P:stem cell proliferation; IMP:MGI.
DR GO; GO:0072189; P:ureter development; IGI: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; IPR001699; TF_T-box.
DR InterPro; IPR018186; TF_T-box_CS.
DR PANTHER; PTHR11267; PTHR11267; 1.
DR Pfam; PF00907; T-box; 1.
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 1: Evidence at protein level;
KW Developmental protein; DNA-binding; Nucleus; Reference proteome; Repressor;
KW Transcription; Transcription regulation.
FT CHAIN 1..613
FT /note="T-box transcription factor TBX18"
FT /id="PRO_0000184447"
FT DNA_BIND 149..336
FT /note="T-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00201"
FT REGION 37..94
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 114..145
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 18..28
FT /note="Engrailed homology 1 repressor"
FT /evidence="ECO:0000305|PubMed:17584735"
FT MOTIF 36..40
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000305|PubMed:17584735"
SQ SEQUENCE 613 AA; 65464 MW; A9E64D395725AB38 CRC64;
MAEKRRGSPC SMLSLKAHAF SVEALIGAEK QQQLQKKRRK LATEEAAGAV EDAGCSRSGG
AGEHGCSEAD EEAAAPPPAA GAASGPARSC ADAERSCGSR GAAGSCEDGF LQGASPLASP
GGSPKGSPVP GLARPGTPLP APQAPRVDLQ GAELWKRFHE IGTEMIITKA GRRMFPAMRV
KISGLDPHQQ YYIAMDIVPV DNKRYRYVYH SSKWMVAGNA DSPVPPRVYI HPDSPASGET
WMRQVISFDK LKLTNNELDD QGHIILHSMH KYQPRVHVIR KDCGDDLSPI KPVPSGEGVK
AFSFPETVFT TVTAYQNQQI TRLKIDRNPF AKGFRDSGRN RMGLEALVES YAFWRPSLRT
LTFEDIPGIP KQGNTSSSAL LQGTGNAVPA THPHLLSGSS CSSPAFHLGP NTSQLCSLTP
ADYSACARSG LALNRYSTSL AETYSRLTNQ SSETFAPPRT PSYVSVSSNP SVNMSMGGTD
GDTFSCPQTS LSMQISGMSP QLQYIMPSPS GNAFAANQTH QSSYNTFRLH SPCALYGYNF
STSPKLAASP EKIVSSQGSF LGSSPSGTMT DRQMLPPVEG VHLLSSGGQQ SFFDSRTLGS
LTLPSSQVSA HMV
