ID   TBX5_MOUSE              Reviewed;         518 AA.
AC   P70326; Q9R003;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2000, sequence version 2.
DT   27-MAR-2024, entry version 188.
DE   RecName: Full=T-box transcription factor TBX5;
DE            Short=T-box protein 5;
GN   Name=Tbx5;
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].
RC   TISSUE=Limb;
RX   PubMed=10373308; DOI=10.1006/dbio.1999.9298;
RA   Bruneau B.G., Logan M., Davis N., Levi T., Tabin C.J., Seidman J.G.,
RA   Seidman C.E.;
RT   "Chamber-specific cardiac expression of Tbx5 and heart defects in Holt-Oram
RT   syndrome.";
RL   Dev. Biol. 211:100-108(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 63-246.
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   [3]
RP   DEVELOPMENTAL STAGE.
RX   PubMed=8853987;
RX   DOI=10.1002/(sici)1097-0177(199608)206:4<379::aid-aja4>3.0.co;2-f;
RA   Chapman D.L., Garvey N., Hancock S., Alexiou M., Agulnik S.I.,
RA   Gibson-Brown J.J., Cebra-Thomas J., Bollag R.J., Silver L.M.,
RA   Papaioannou V.E.;
RT   "Expression of the T-box family genes, Tbx1-Tbx5, during early mouse
RT   development.";
RL   Dev. Dyn. 206:379-390(1996).
CC   -!- FUNCTION: DNA-binding protein that regulates the transcription of
CC       several genes and is involved in heart development and limb pattern
CC       formation. Binds to the core DNA motif of NPPA promoter.
CC       {ECO:0000250|UniProtKB:Q99593}.
CC   -!- SUBUNIT: Monomer. Homodimer (via the T-box); binds DNA as homodimer.
CC       Interacts (via the T-box) with NKX2-5 (via the homeobox); this complex
CC       binds DNA. Interacts with GATA4. Interacts with KAT2A and KAT2B.
CC       {ECO:0000250|UniProtKB:Q99593}.
CC   -!- INTERACTION:
CC       P70326; Q6PDQ2: Chd4; NbExp=3; IntAct=EBI-8411807, EBI-3043852;
CC       P70326; Q9JJZ6: Klf13; NbExp=3; IntAct=EBI-8411807, EBI-8407880;
CC       P70326; Q14839: CHD4; Xeno; NbExp=3; IntAct=EBI-8411807, EBI-372916;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q99593,
CC       ECO:0000255|PROSITE-ProRule:PRU00201}. Cytoplasm
CC       {ECO:0000250|UniProtKB:Q99593}. Note=Shuttles between the cytoplasm and
CC       the nucleus. Acetylation at Lys-339 promotes nuclear retention.
CC       {ECO:0000250|UniProtKB:Q99593}.
CC   -!- DEVELOPMENTAL STAGE: First expressed at day 7.5, exclusively in the
CC       allantois. At day 8.5, expressed only in the sinous venosus of the
CC       developing heart. At day 9.5, expression observed in the forelimb bud,
CC       optic vesicle and sinous venosus. By day 12.5, expression is limited to
CC       the retina, the body wall and the mesenchyme of the lung, of the
CC       mandible and of that surrounding the trachea.
CC       {ECO:0000269|PubMed:8853987}.
CC   -!- DOMAIN: The T-Box domain binds to double-stranded DNA.
CC       {ECO:0000250|UniProtKB:Q99593}.
CC   -!- PTM: Acetylation at Lys-339 by KAT2A and KAT2B promotes nuclear
CC       retention. {ECO:0000250|UniProtKB:Q99593}.
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DR   EMBL; AF140427; AAF00112.1; -; mRNA.
DR   EMBL; U57330; AAC53109.1; -; mRNA.
DR   CCDS; CCDS19615.1; -.
DR   PIR; S72231; S72231.
DR   RefSeq; NP_035667.1; NM_011537.3.
DR   RefSeq; XP_006530343.1; XM_006530280.1.
DR   RefSeq; XP_006530344.1; XM_006530281.2.
DR   RefSeq; XP_006530345.1; XM_006530282.3.
DR   RefSeq; XP_006530346.1; XM_006530283.2.
DR   RefSeq; XP_011246493.1; XM_011248191.2.
DR   RefSeq; XP_017176276.1; XM_017320787.1.
DR   PDB; 5FLV; X-ray; 3.00 A; A/E/I/M=51-251.
DR   PDBsum; 5FLV; -.
DR   AlphaFoldDB; P70326; -.
DR   SMR; P70326; -.
DR   BioGRID; 203990; 5.
DR   DIP; DIP-48887N; -.
DR   IntAct; P70326; 64.
DR   STRING; 10090.ENSMUSP00000018407; -.
DR   iPTMnet; P70326; -.
DR   PhosphoSitePlus; P70326; -.
DR   PaxDb; 10090-ENSMUSP00000018407; -.
DR   ProteomicsDB; 254673; -.
DR   Antibodypedia; 18791; 300 antibodies from 34 providers.
DR   DNASU; 21388; -.
DR   Ensembl; ENSMUST00000018407.10; ENSMUSP00000018407.7; ENSMUSG00000018263.12.
DR   GeneID; 21388; -.
DR   KEGG; mmu:21388; -.
DR   UCSC; uc008zgz.2; mouse.
DR   AGR; MGI:102541; -.
DR   CTD; 6910; -.
DR   MGI; MGI:102541; Tbx5.
DR   VEuPathDB; HostDB:ENSMUSG00000018263; -.
DR   eggNOG; KOG3585; Eukaryota.
DR   GeneTree; ENSGT00940000156506; -.
DR   HOGENOM; CLU_037025_1_0_1; -.
DR   InParanoid; P70326; -.
DR   OMA; YPLAQEH; -.
DR   PhylomeDB; P70326; -.
DR   TreeFam; TF106341; -.
DR   Reactome; R-MMU-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression.
DR   BioGRID-ORCS; 21388; 2 hits in 81 CRISPR screens.
DR   PRO; PR:P70326; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; P70326; Protein.
DR   Bgee; ENSMUSG00000018263; Expressed in cardiogenic plate and 94 other cell types or tissues.
DR   ExpressionAtlas; P70326; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR   GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR   GO; GO:0032993; C:protein-DNA complex; ISS:UniProtKB.
DR   GO; GO:0005667; C:transcription regulator complex; IPI:MGI.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR   GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR   GO; GO:0048513; P:animal organ development; ISS:UniProtKB.
DR   GO; GO:0003283; P:atrial septum development; IMP:MGI.
DR   GO; GO:0060413; P:atrial septum morphogenesis; IGI:MGI.
DR   GO; GO:0003167; P:atrioventricular bundle cell differentiation; IMP:BHF-UCL.
DR   GO; GO:0060928; P:atrioventricular node cell development; IMP:BHF-UCL.
DR   GO; GO:0060929; P:atrioventricular node cell fate commitment; IMP:BHF-UCL.
DR   GO; GO:0003181; P:atrioventricular valve morphogenesis; IGI:MGI.
DR   GO; GO:0086054; P:bundle of His cell to Purkinje myocyte communication by electrical coupling; IMP:BHF-UCL.
DR   GO; GO:0003166; P:bundle of His development; IMP:BHF-UCL.
DR   GO; GO:0003218; P:cardiac left ventricle formation; IMP:BHF-UCL.
DR   GO; GO:0055007; P:cardiac muscle cell differentiation; IMP:BHF-UCL.
DR   GO; GO:0060038; P:cardiac muscle cell proliferation; IGI:MGI.
DR   GO; GO:0001708; P:cell fate specification; IBA:GO_Central.
DR   GO; GO:0007267; P:cell-cell signaling; ISS:UniProtKB.
DR   GO; GO:0086019; P:cell-cell signaling involved in cardiac conduction; IGI:BHF-UCL.
DR   GO; GO:0035115; P:embryonic forelimb morphogenesis; IMP:MGI.
DR   GO; GO:0030326; P:embryonic limb morphogenesis; IMP:MGI.
DR   GO; GO:0003197; P:endocardial cushion development; IGI:MGI.
DR   GO; GO:0035136; P:forelimb morphogenesis; IMP:MGI.
DR   GO; GO:0007507; P:heart development; IMP:MGI.
DR   GO; GO:0030324; P:lung development; IMP:MGI.
DR   GO; GO:0002009; P:morphogenesis of an epithelium; IMP:MGI.
DR   GO; GO:0060044; P:negative regulation of cardiac muscle cell proliferation; ISS:UniProtKB.
DR   GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR   GO; GO:0007389; P:pattern specification process; IMP:MGI.
DR   GO; GO:0060039; P:pericardium development; ISS:UniProtKB.
DR   GO; GO:1903781; P:positive regulation of cardiac conduction; IMP:BHF-UCL.
DR   GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IGI:MGI.
DR   GO; GO:0051891; P:positive regulation of cardioblast differentiation; ISS:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:MGI.
DR   GO; GO:1903598; P:positive regulation of gap junction assembly; IMP:BHF-UCL.
DR   GO; GO:0072513; P:positive regulation of secondary heart field cardioblast proliferation; IMP:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR   GO; GO:0060371; P:regulation of atrial cardiac muscle cell membrane depolarization; IGI:BHF-UCL.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; IMP:MGI.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0003163; P:sinoatrial node development; IMP:BHF-UCL.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; IGI:MGI.
DR   GO; GO:0060290; P:transdifferentiation; ISO:MGI.
DR   GO; GO:0003229; P:ventricular cardiac muscle tissue development; IGI:MGI.
DR   GO; GO:0003281; P:ventricular septum development; IMP:BHF-UCL.
DR   CDD; cd20189; T-box_TBX4_5-like; 1.
DR   Gene3D; 2.60.40.820; Transcription factor, T-box; 1.
DR   InterPro; IPR008967; p53-like_TF_DNA-bd_sf.
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; T-BOX PROTEIN-RELATED; 1.
DR   PANTHER; PTHR11267:SF28; T-BOX TRANSCRIPTION FACTOR TBX5; 1.
DR   Pfam; PF00907; T-box; 1.
DR   PRINTS; PR00937; TBOX.
DR   SMART; SM00425; TBOX; 1.
DR   SUPFAM; SSF49417; p53-like transcription factors; 1.
DR   PROSITE; PS01283; TBOX_1; 1.
DR   PROSITE; PS01264; TBOX_2; 1.
DR   PROSITE; PS50252; TBOX_3; 1.
DR   Genevisible; P70326; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Cytoplasm; Developmental protein; DNA-binding;
KW   Nucleus; Reference proteome; Transcription; Transcription regulation.
FT   CHAIN           1..518
FT                   /note="T-box transcription factor TBX5"
FT                   /id="PRO_0000184436"
FT   DNA_BIND        58..238
FT                   /note="T-box"
FT                   /evidence="ECO:0000250|UniProtKB:Q99593,
FT                   ECO:0000255|PROSITE-ProRule:PRU00201"
FT   REGION          1..46
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          254..307
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          330..352
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        263..299
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        330..346
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         339
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q99593"
FT   CONFLICT        68..71
FT                   /note="HEVG -> RSGV (in Ref. 2; AAC53109)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        81
FT                   /note="R -> G (in Ref. 2; AAC53109)"
FT                   /evidence="ECO:0000305"
FT   STRAND          55..58
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   HELIX           61..68
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   STRAND          73..75
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   STRAND          77..79
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   STRAND          88..93
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   STRAND          96..116
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   STRAND          121..126
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   STRAND          142..144
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   HELIX           145..150
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   STRAND          159..161
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   STRAND          177..187
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   STRAND          203..205
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   HELIX           207..209
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   STRAND          211..216
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   HELIX           220..227
FT                   /evidence="ECO:0007829|PDB:5FLV"
FT   HELIX           231..236
FT                   /evidence="ECO:0007829|PDB:5FLV"
SQ   SEQUENCE   518 AA;  57832 MW;  4990A802EB56624B CRC64;
     MADTDEGFGL ARTPLEPDSK DRSCDSKPES ALGAPSKSPS SPQAAFTQQG MEGIKVFLHE
     RELWLKFHEV GTEMIITKAG RRMFPSYKVK VTGLNPKTKY ILLMDIVPAD DHRYKFADNK
     WSVTGKAEPA MPGRLYVHPD SPATGAHWMR QLVSFQKLKL TNNHLDPFGH IILNSMHKYQ
     PRLHIVKADE NNGFGSKNTA FCTHVFPETA FIAVTSYQNH KITQLKIENN PFAKGFRGSD
     DLELHRMSRM QSKEYPVVPR STVRHKVTSN HSPFSSETRA LSTSSNLGSQ YQCENGVSGP
     SQDLLPPPNP YPLAQEHSQI YHCTKRKDEE CSSTEHPYKK PYMETSPSEE DTFYRSGYPQ
     QQGLSTSYRT ESAQRQACMY ASSAPPSEPV PSLEDISCNT WPSMPSYSSC TVTTVQPMDR
     LPYQHFSAHF TSGPLVPRLA GMANHGSPQL GEGMFQHQTS VAHQPVVRQC GPQTGLQSPG
     GLQPPEFLYT HGVPRTLSPH QYHSVHGVGM VPEWSENS
//