TBX18_HUMAN
ID TBX18_HUMAN Reviewed; 607 AA.
AC O95935; A2RU13; Q7Z6U4; Q9UJI6;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 3.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=T-box transcription factor TBX18;
DE Short=T-box protein 18;
GN Name=TBX18;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-48.
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 149-330.
RX PubMed=9888994; DOI=10.1006/geno.1998.5632;
RA Yi C.-H., Terrett J.A., Li Q.-Y., Ellington K., Packham E.A.,
RA Amstrong-Buisseret L., McClure P., Slingsby T., Brook J.D.;
RT "Identification, mapping and phylogenomic analysis of four new human
RT members of the T-box gene family: EOMES, TBX6, TBX18, and TBX19.";
RL Genomics 55:10-20(1999).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SIX1 AND TLE3, INVOLVEMENT
RP IN CAKUT2, VARIANTS CAKUT2 GLU-163 AND TYR-524, CHARACTERIZATION OF
RP VARIANTS CAKUT2 GLU-163 AND TYR-524, AND VARIANTS THR-164 AND SER-526.
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 and
CC coronary vessels, the ureter and the vertebral column. Required for
CC embryonic development of the sino atrial node (SAN) head area.
CC {ECO:0000250|UniProtKB:Q9EPZ6, ECO:0000269|PubMed:26235987}.
CC -!- SUBUNIT: Homodimer. Can form a heterodimer with TBX15. Interacts with
CC GATA4 AND NKX2-5. Interacts with PAX3 (By similarity). Interacts (via
CC engrailed homology 1 repressor motif) with TLE3; this interaction
CC represses TBX18 transcriptional activity (By similarity)
CC (PubMed:26235987). Interacts with SIX1 (PubMed:26235987).
CC {ECO:0000250|UniProtKB:Q9EPZ6, ECO:0000269|PubMed:26235987}.
CC -!- INTERACTION:
CC O95935; Q7LC44: ARC; NbExp=3; IntAct=EBI-12085364, EBI-750550;
CC O95935; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-12085364, EBI-10261141;
CC O95935; Q58EX7: PLEKHG4; NbExp=3; IntAct=EBI-12085364, EBI-949255;
CC O95935; Q13077: TRAF1; NbExp=3; IntAct=EBI-12085364, EBI-359224;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00201,
CC ECO:0000269|PubMed:26235987}.
CC -!- DISEASE: Congenital anomalies of kidney and urinary tract 2 (CAKUT2)
CC [MIM:143400]: A disorder encompassing a broad spectrum of renal and
CC urinary tract malformations that include renal agenesis, kidney
CC hypodysplasia, multicystic kidney dysplasia, duplex collecting system,
CC posterior urethral valves and ureter abnormalities. Congenital
CC anomalies of kidney and urinary tract are the commonest cause of
CC chronic kidney disease in children. {ECO:0000269|PubMed:26235987}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
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; AL035694; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC132715; AAI32716.1; -; mRNA.
DR EMBL; BC157841; AAI57842.1; -; mRNA.
DR EMBL; AJ010278; CAB37937.1; -; mRNA.
DR CCDS; CCDS34495.1; -.
DR RefSeq; NP_001073977.1; NM_001080508.2.
DR AlphaFoldDB; O95935; -.
DR SMR; O95935; -.
DR BioGRID; 114550; 10.
DR CORUM; O95935; -.
DR IntAct; O95935; 4.
DR STRING; 9606.ENSP00000358677; -.
DR iPTMnet; O95935; -.
DR PhosphoSitePlus; O95935; -.
DR BioMuta; TBX18; -.
DR jPOST; O95935; -.
DR MassIVE; O95935; -.
DR MaxQB; O95935; -.
DR PaxDb; O95935; -.
DR PeptideAtlas; O95935; -.
DR PRIDE; O95935; -.
DR ProteomicsDB; 51134; -.
DR Antibodypedia; 18548; 275 antibodies from 35 providers.
DR DNASU; 9096; -.
DR Ensembl; ENST00000369663.10; ENSP00000358677.4; ENSG00000112837.17.
DR GeneID; 9096; -.
DR KEGG; hsa:9096; -.
DR MANE-Select; ENST00000369663.10; ENSP00000358677.4; NM_001080508.3; NP_001073977.1.
DR UCSC; uc003pkl.4; human.
DR CTD; 9096; -.
DR DisGeNET; 9096; -.
DR GeneCards; TBX18; -.
DR HGNC; HGNC:11595; TBX18.
DR HPA; ENSG00000112837; Low tissue specificity.
DR MalaCards; TBX18; -.
DR MIM; 143400; phenotype.
DR MIM; 604613; gene.
DR neXtProt; NX_O95935; -.
DR OpenTargets; ENSG00000112837; -.
DR PharmGKB; PA36358; -.
DR VEuPathDB; HostDB:ENSG00000112837; -.
DR eggNOG; KOG3586; Eukaryota.
DR GeneTree; ENSGT00940000155566; -.
DR HOGENOM; CLU_030727_0_0_1; -.
DR InParanoid; O95935; -.
DR OMA; MSMSGND; -.
DR OrthoDB; 828211at2759; -.
DR PhylomeDB; O95935; -.
DR TreeFam; TF106341; -.
DR PathwayCommons; O95935; -.
DR SignaLink; O95935; -.
DR SIGNOR; O95935; -.
DR BioGRID-ORCS; 9096; 5 hits in 1109 CRISPR screens.
DR ChiTaRS; TBX18; human.
DR GenomeRNAi; 9096; -.
DR Pharos; O95935; Tbio.
DR PRO; PR:O95935; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O95935; protein.
DR Bgee; ENSG00000112837; Expressed in right coronary artery and 101 other tissues.
DR ExpressionAtlas; O95935; baseline and differential.
DR Genevisible; O95935; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090571; C:RNA polymerase II transcription repressor complex; ISS:ARUK-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:BHF-UCL.
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; IDA:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:BHF-UCL.
DR GO; GO:0001708; P:cell fate specification; IBA:GO_Central.
DR GO; GO:0090103; P:cochlea morphogenesis; ISS:ARUK-UCL.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; IBA:GO_Central.
DR GO; GO:0060829; P:negative regulation of canonical Wnt signaling pathway involved in neural plate anterior/posterior pattern formation; ISS:BHF-UCL.
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; IMP:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060931; P:sinoatrial node cell development; IMP:BHF-UCL.
DR GO; GO:0060930; P:sinoatrial node cell fate commitment; IMP:BHF-UCL.
DR GO; GO:0003163; P:sinoatrial node development; ISS:BHF-UCL.
DR GO; GO:0051145; P:smooth muscle cell differentiation; ISS:ARUK-UCL.
DR GO; GO:0001756; P:somitogenesis; ISS:ARUK-UCL.
DR GO; GO:0072189; P:ureter development; IMP:UniProtKB.
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; Disease variant; DNA-binding; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..607
FT /note="T-box transcription factor TBX18"
FT /id="PRO_0000184446"
FT DNA_BIND 143..330
FT /note="T-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00201"
FT REGION 30..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 18..28
FT /note="Engrailed homology 1 repressor"
FT /evidence="ECO:0000305"
FT MOTIF 36..40
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000305"
FT COMPBIAS 32..46
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 48
FT /note="G -> R (in dbSNP:rs172562)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_052263"
FT VARIANT 163
FT /note="K -> E (in CAKUT2; results in decreased
FT transcriptional repression through a dominant negative
FT effect; does not affect nuclear localization; does not bind
FT DNA; no effect on interaction with SIX1; no effect on
FT interaction with TLE3; dbSNP:rs797045022)"
FT /evidence="ECO:0000269|PubMed:26235987"
FT /id="VAR_074629"
FT VARIANT 164
FT /note="A -> T"
FT /evidence="ECO:0000269|PubMed:26235987"
FT /id="VAR_074630"
FT VARIANT 524
FT /note="H -> Y (in CAKUT2; results in decreased
FT transcriptional repression through a dominant negative
FT effect; does not affect nuclear localization; no effect on
FT DNA binding; no effect on interaction with SIX1; no effect
FT on interaction with TLE3; dbSNP:rs760905589)"
FT /evidence="ECO:0000269|PubMed:26235987"
FT /id="VAR_074631"
FT VARIANT 526
FT /note="P -> S"
FT /evidence="ECO:0000269|PubMed:26235987"
FT /id="VAR_074632"
SQ SEQUENCE 607 AA; 64753 MW; AFDCE41154CA55DA CRC64;
MAEKRRGSPC SMLSLKAHAF SVEALIGAEK QQQLQKKRRK LGAEEAAGAV DDGGCSRGGG
AGEKGSSEGD EGAALPPPAG ATSGPARSGA DLERGAAGGC EDGFQQGASP LASPGGSPKG
SPARSLARPG TPLPSPQAPR VDLQGAELWK RFHEIGTEMI ITKAGRRMFP AMRVKISGLD
PHQQYYIAMD IVPVDNKRYR YVYHSSKWMV AGNADSPVPP RVYIHPDSPA SGETWMRQVI
SFDKLKLTNN ELDDQGHIIL HSMHKYQPRV HVIRKDCGDD LSPIKPVPSG EGVKAFSFPE
TVFTTVTAYQ NQQITRLKID RNPFAKGFRD SGRNRMGLEA LVESYAFWRP SLRTLTFEDI
PGIPKQGNAS SSTLLQGTGN GVPATHPHLL SGSSCSSPAF HLGPNTSQLC SLAPADYSAC
ARSGLTLNRY STSLAETYNR LTNQAGETFA PPRTPSYVGV SSSTSVNMSM GGTDGDTFSC
PQTSLSMQIS GMSPQLQYIM PSPSSNAFAT NQTHQGSYNT FRLHSPCALY GYNFSTSPKL
AASPEKIVSS QGSFLGSSPS GTMTDRQMLP PVEGVHLLSS GGQQSFFDSR TLGSLTLSSS
QVSAHMV
