ID TBX5_HUMAN Reviewed; 518 AA. AC Q99593; A6ND77; O15301; Q96TB0; Q9Y4I2; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 2. DT 27-MAR-2024, entry version 215. DE RecName: Full=T-box transcription factor TBX5; DE Short=T-box protein 5; GN Name=TBX5; 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 [MRNA] (ISOFORM 1), FUNCTION, AND INVOLVEMENT IN HOS. RX PubMed=8988164; DOI=10.1038/ng0197-21; RA Li Q.Y., Newbury-Ecob R., Terrett J.A., Wilson D.I., Curtis A., Yi C.H., RA Bullen P.J., Strachan T., Robson S., Bonnet D., Young I.E., Raeburn J.A., RA Buckler A.J., Gebuhr T., Law D.J., Brook J.D.; RT "Holt-Oram syndrome is caused by mutations in TBX5, a member of the RT Brachyury (T) gene family."; RL Nat. Genet. 15:21-29(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING, AND VARIANT RP HOS GLN-237. RX PubMed=8988165; DOI=10.1038/ng0197-30; RA Basson C.T., Bachinsky D.R., Lin R.C., Levi T., Elkins J.A., Soults J., RA Grayzel D., Kroumpouzou E., Traill T.A., Leblanc-Straceski J., Renault B., RA Kucherlapati R., Seidman J.G., Seidman C.E.; RT "Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram RT syndrome."; RL Nat. Genet. 15:30-35(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS HOS ARG-80; GLN-237 RP AND TRP-237. RX PubMed=10077612; DOI=10.1073/pnas.96.6.2919; RA Basson C.T., Huang T., Lin R.C., Bachinksy D.R., Weremowicz S., Vaglio A., RA Bruzzone R., Quadrelli R., Lerone M., Romeo G., Silengo M., Pereira A., RA Krieger J., Mesquita S.F., Kamisago M., Morton C.C., Pierpont M.E.M., RA Muller C.W., Seidman J.G., Seidman C.E.; RT "Different TBX5 interactions in heart and limb defined by Holt-Oram RT syndrome mutations."; RL Proc. Natl. Acad. Sci. U.S.A. 96:2919-2924(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=11183182; DOI=10.1136/jmg.37.10.785; RA Cross S.J., Ching Y.-H., Li Q.Y., Armstrong-Buisseret L., Spranger S., RA Lyonnet S., Bonnet D., Penttinen M., Jonveaux P., Leheup B., Mortier G., RA Van Ravenswaaij C., Gardiner C.A.; RT "The mutation spectrum in Holt-Oram syndrome."; RL J. Med. Genet. 37:785-787(2000). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RA Demura M., Yoneda T., Takeda Y., Furukawa K., Mabuti H.; RT "Human transcription factor TBX5mRNA, alternatively spliced."; RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung, and Spleen; 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 [9] RP INVOLVEMENT IN HOS. RX PubMed=12818525; DOI=10.1016/s0003-3995(03)00006-6; RA Gruenauer-Kloevekorn C., Froster U.G.; RT "Holt-Oram syndrome: a new mutation in the TBX5 gene in two unrelated RT families."; RL Ann. Genet. 46:19-23(2003). RN [10] RP INTERACTION WITH GATA4. RX PubMed=24000169; DOI=10.1002/humu.22434; RA Yang Y.Q., Gharibeh L., Li R.G., Xin Y.F., Wang J., Liu Z.M., Qiu X.B., RA Xu Y.J., Xu L., Qu X.K., Liu X., Fang W.Y., Huang R.T., Xue S., Nemer G.; RT "GATA4 loss-of-function mutations underlie familial tetralogy of fallot."; RL Hum. Mutat. 34:1662-1671(2013). RN [11] RP FUNCTION, INVOLVEMENT IN DCM, VARIANT ALA-154, AND CHARACTERIZATION OF RP VARIANT ALA-154. RX PubMed=25725155; DOI=10.1016/j.bbrc.2015.02.094; RA Zhang X.L., Qiu X.B., Yuan F., Wang J., Zhao C.M., Li R.G., Xu L., Xu Y.J., RA Shi H.Y., Hou X.M., Qu X.K., Xu Y.W., Yang Y.Q.; RT "TBX5 loss-of-function mutation contributes to familial dilated RT cardiomyopathy."; RL Biochem. Biophys. Res. Commun. 459:166-171(2015). RN [12] RP FUNCTION, INVOLVEMENT IN DCM, VARIANT THR-143, AND CHARACTERIZATION OF RP VARIANT THR-143. RX PubMed=25963046; DOI=10.3892/ijmm.2015.2206; RA Zhou W., Zhao L., Jiang J.Q., Jiang W.F., Yang Y.Q., Qiu X.B.; RT "A novel TBX5 loss-of-function mutation associated with sporadic dilated RT cardiomyopathy."; RL Int. J. Mol. Med. 36:282-288(2015). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, ACETYLATION AT LYS-339, AND MUTAGENESIS OF RP LYS-234; LYS-325; LYS-327; LYS-339 AND LYS-340. RX PubMed=29174768; DOI=10.1016/j.yjmcc.2017.11.013; RA Ghosh T.K., Aparicio-Sanchez J.J., Buxton S., Ketley A., Mohamed T., RA Rutland C.S., Loughna S., Brook J.D.; RT "Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb RT development."; RL J. Mol. Cell. Cardiol. 114:185-198(2017). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 51-251 IN COMPLEX WITH DNA, RP CHARACTERIZATION OF VARIANTS HOS ARG-80 AND TRP-237, AND SUBUNIT. RX PubMed=20450920; DOI=10.1016/j.jmb.2010.04.052; RA Stirnimann C.U., Ptchelkine D., Grimm C., Muller C.W.; RT "Structural basis of TBX5-DNA recognition: the T-box domain in its DNA- RT bound and -unbound form."; RL J. Mol. Biol. 400:71-81(2010). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS) OF 1-239 OF HOMODIMER AND DNA, X-RAY RP CRYSTALLOGRAPHY (2.82 ANGSTROMS) OF 53-238 IN COMPLEX WITH NKX2-5 AND DNA, RP INTERACTION WITH NKX2-5, AND DNA-BINDING. RX PubMed=26926761; DOI=10.1021/acs.biochem.6b00171; RA Pradhan L., Gopal S., Li S., Ashur S., Suryanarayanan S., Kasahara H., RA Nam H.J.; RT "Intermolecular interactions of cardiac transcription factors NKX2.5 and RT TBX5."; RL Biochemistry 55:1702-1710(2016). RN [16] RP VARIANTS HOS LYS-49 AND THR-54. RX PubMed=10842287; RX DOI=10.1002/(sici)1096-8628(20000605)92:4<237::aid-ajmg2>3.0.co;2-g; RA Yang J., Hu D., Xia J., Yang Y., Ying B., Hu J., Zhou X.; RT "Three novel TBX5 mutations in Chinese patients with Holt-Oram syndrome."; RL Am. J. Med. Genet. 92:237-240(2000). RN [17] RP CHARACTERIZATION OF VARIANT HOS GLN-237. RX PubMed=15735645; DOI=10.1038/ng1526; RA Ching Y.-H., Ghosh T.K., Cross S.J., Packham E.A., Honeyman L., Loughna S., RA Robinson T.E., Dearlove A.M., Ribas G., Bonser A.J., Thomas N.R., RA Scotter A.J., Caves L.S.D., Tyrrell G.P., Newbury-Ecob R.A., Munnich A., RA Bonnet D., Brook J.D.; RT "Mutation in myosin heavy chain 6 causes atrial septal defect."; RL Nat. Genet. 37:423-428(2005). RN [18] RP VARIANT ASP-170, CHARACTERIZATION OF VARIANT ASP-170, INVOLVEMENT IN AF, RP AND FUNCTION. RX PubMed=26917986; DOI=10.7150/ijms.13264; RA Wang Z.C., Ji W.H., Ruan C.W., Liu X.Y., Qiu X.B., Yuan F., Li R.G., RA Xu Y.J., Liu X., Huang R.T., Xue S., Yang Y.Q.; RT "Prevalence and Spectrum of TBX5 Mutation in Patients with Lone Atrial RT Fibrillation."; RL Int. J. Med. Sci. 13:60-67(2016). RN [19] RP VARIANT SER-132, INVOLVEMENT IN AF, CHARACTERIZATION OF VARIANT SER-132, RP AND FUNCTION. RX PubMed=27035640; DOI=10.3892/mmr.2016.5043; RA Guo D.F., Li R.G., Yuan F., Shi H.Y., Hou X.M., Qu X.K., Xu Y.J., Zhang M., RA Liu X., Jiang J.Q., Yang Y.Q., Qiu X.B.; RT "TBX5 loss-of-function mutation contributes to atrial fibrillation and RT atypical Holt-Oram syndrome."; RL Mol. Med. Report. 13:4349-4356(2016). CC -!- FUNCTION: DNA-binding protein that regulates the transcription of CC several genes and is involved in heart development and limb pattern CC formation (PubMed:25725155, PubMed:25963046, PubMed:29174768, CC PubMed:26917986, PubMed:27035640, PubMed:8988164). Binds to the core CC DNA motif of NPPA promoter (PubMed:26926761). CC {ECO:0000269|PubMed:25725155, ECO:0000269|PubMed:25963046, CC ECO:0000269|PubMed:26917986, ECO:0000269|PubMed:26926761, CC ECO:0000269|PubMed:27035640, ECO:0000269|PubMed:29174768, CC ECO:0000269|PubMed:8988164}. CC -!- SUBUNIT: Monomer (PubMed:20450920). Homodimer (via the T-box); binds CC DNA as homodimer (PubMed:26926761). Interacts (via the T-box) with CC NKX2-5 (via the homeobox); this complex binds DNA (PubMed:26926761). CC Interacts with GATA4 (PubMed:24000169). Interacts with KAT2A and KAT2B CC (PubMed:29174768). {ECO:0000269|PubMed:20450920, CC ECO:0000269|PubMed:24000169, ECO:0000269|PubMed:26926761, CC ECO:0000269|PubMed:29174768}. CC -!- INTERACTION: CC Q99593; Q9UQB8-6: BAIAP2; NbExp=3; IntAct=EBI-297043, EBI-9092016; CC Q99593; P46937: YAP1; NbExp=4; IntAct=EBI-297043, EBI-1044059; CC Q99593; O75800: ZMYND10; NbExp=3; IntAct=EBI-297043, EBI-747061; CC Q99593; Q08369: Gata4; Xeno; NbExp=2; IntAct=EBI-297043, EBI-297008; CC Q99593-1; P52952: NKX2-5; NbExp=6; IntAct=EBI-304423, EBI-936601; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00201, CC ECO:0000269|PubMed:29174768}. Cytoplasm {ECO:0000269|PubMed:29174768}. CC Note=Shuttles between the cytoplasm and the nucleus. Acetylation at CC Lys-339 promotes nuclear retention. {ECO:0000269|PubMed:29174768}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=Long; CC IsoId=Q99593-1; Sequence=Displayed; CC Name=2; Synonyms=Short; CC IsoId=Q99593-2; Sequence=VSP_006387, VSP_006388; CC Name=3; CC IsoId=Q99593-3; Sequence=VSP_046845; CC -!- DOMAIN: The T-Box domain binds to double-stranded DNA CC (PubMed:26926761). {ECO:0000269|PubMed:26926761}. CC -!- PTM: Acetylation at Lys-339 by KAT2A and KAT2B promotes nuclear CC retention. {ECO:0000269|PubMed:29174768}. CC -!- DISEASE: Holt-Oram syndrome (HOS) [MIM:142900]: Developmental disorder CC affecting the heart and upper limbs. It is characterized by thumb CC anomaly and atrial septal defects. {ECO:0000269|PubMed:10077612, CC ECO:0000269|PubMed:10842287, ECO:0000269|PubMed:12818525, CC ECO:0000269|PubMed:15735645, ECO:0000269|PubMed:20450920, CC ECO:0000269|PubMed:8988164, ECO:0000269|PubMed:8988165}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Note=Defects in TBX5 are associated with susceptibility to CC heart disorders including dilated cardiomyopathy (DCM) and atrial CC fibrillation (AF). DCM is characterized by ventricular and impaired CC systolic function, resulting in heart failure and arrhythmia. Patient CC are at risk of premature death. AF is a common sustained cardiac rhythm CC disturbance. AF is characterized by disorganized atrial electrical CC activity and ineffective atrial contraction promoting blood stasis in CC the atria and reduces ventricular filling. It can result in CC palpitations, syncope, thromboembolic stroke, and congestive heart CC failure. {ECO:0000269|PubMed:25725155, ECO:0000269|PubMed:25963046, CC ECO:0000269|PubMed:26917986, ECO:0000269|PubMed:27035640}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB55448.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y09445; CAA70592.1; -; mRNA. DR EMBL; U80987; AAC51644.1; -; mRNA. DR EMBL; U89353; AAC04619.1; -; mRNA. DR EMBL; AF221714; AAF34659.1; -; mRNA. DR EMBL; AB051068; BAB55448.1; ALT_FRAME; mRNA. DR EMBL; AC009260; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC069240; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471054; EAW98066.1; -; Genomic_DNA. DR EMBL; BC027942; AAH27942.1; -; mRNA. DR CCDS; CCDS9173.1; -. [Q99593-1] DR CCDS; CCDS9174.1; -. [Q99593-3] DR RefSeq; NP_000183.2; NM_000192.3. [Q99593-1] DR RefSeq; NP_542448.1; NM_080717.2. [Q99593-3] DR RefSeq; NP_852259.1; NM_181486.2. [Q99593-1] DR PDB; 2X6U; X-ray; 1.90 A; A=51-251. DR PDB; 2X6V; X-ray; 2.20 A; A/B=51-251. DR PDB; 4S0H; X-ray; 2.82 A; A/E=53-238. DR PDB; 5BQD; X-ray; 2.58 A; A/B=1-239. DR PDBsum; 2X6U; -. DR PDBsum; 2X6V; -. DR PDBsum; 4S0H; -. DR PDBsum; 5BQD; -. DR AlphaFoldDB; Q99593; -. DR SMR; Q99593; -. DR BioGRID; 112773; 148. DR CORUM; Q99593; -. DR IntAct; Q99593; 9. DR STRING; 9606.ENSP00000309913; -. DR ChEMBL; CHEMBL1687681; -. DR iPTMnet; Q99593; -. DR PhosphoSitePlus; Q99593; -. DR BioMuta; TBX5; -. DR DMDM; 12644474; -. DR jPOST; Q99593; -. DR MassIVE; Q99593; -. DR PaxDb; 9606-ENSP00000309913; -. DR PeptideAtlas; Q99593; -. DR ProteomicsDB; 78347; -. [Q99593-1] DR ProteomicsDB; 78348; -. [Q99593-2] DR ProteomicsDB; 886; -. DR ABCD; Q99593; 6 sequenced antibodies. DR Antibodypedia; 18791; 300 antibodies from 34 providers. DR DNASU; 6910; -. DR Ensembl; ENST00000310346.8; ENSP00000309913.4; ENSG00000089225.20. [Q99593-1] DR Ensembl; ENST00000349716.9; ENSP00000337723.5; ENSG00000089225.20. [Q99593-3] DR Ensembl; ENST00000405440.7; ENSP00000384152.3; ENSG00000089225.20. [Q99593-1] DR Ensembl; ENST00000526441.1; ENSP00000433292.1; ENSG00000089225.20. [Q99593-2] DR GeneID; 6910; -. DR KEGG; hsa:6910; -. DR MANE-Select; ENST00000405440.7; ENSP00000384152.3; NM_181486.4; NP_852259.1. DR UCSC; uc001tvo.5; human. [Q99593-1] DR AGR; HGNC:11604; -. DR CTD; 6910; -. DR DisGeNET; 6910; -. DR GeneCards; TBX5; -. DR GeneReviews; TBX5; -. DR HGNC; HGNC:11604; TBX5. DR HPA; ENSG00000089225; Tissue enhanced (heart muscle, lung, placenta). DR MalaCards; TBX5; -. DR MIM; 142900; phenotype. DR MIM; 601620; gene. DR neXtProt; NX_Q99593; -. DR OpenTargets; ENSG00000089225; -. DR Orphanet; 392; Holt-Oram syndrome. DR Orphanet; 101016; Romano-Ward syndrome. DR PharmGKB; PA36367; -. DR VEuPathDB; HostDB:ENSG00000089225; -. DR eggNOG; KOG3585; Eukaryota. DR GeneTree; ENSGT00940000156506; -. DR HOGENOM; CLU_037025_1_0_1; -. DR InParanoid; Q99593; -. DR OMA; YPLAQEH; -. DR OrthoDB; 5323209at2759; -. DR PhylomeDB; Q99593; -. DR TreeFam; TF106341; -. DR PathwayCommons; Q99593; -. DR Reactome; R-HSA-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression. DR Reactome; R-HSA-5578768; Physiological factors. DR Reactome; R-HSA-9733709; Cardiogenesis. DR SignaLink; Q99593; -. DR SIGNOR; Q99593; -. DR BioGRID-ORCS; 6910; 11 hits in 1170 CRISPR screens. DR ChiTaRS; TBX5; human. DR EvolutionaryTrace; Q99593; -. DR GeneWiki; TBX5_(gene); -. DR GenomeRNAi; 6910; -. DR Pharos; Q99593; Tbio. DR PRO; PR:Q99593; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q99593; Protein. DR Bgee; ENSG00000089225; Expressed in tendon of biceps brachii and 95 other cell types or tissues. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0032993; C:protein-DNA complex; IDA:UniProtKB. DR GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:BHF-UCL. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0060413; P:atrial septum morphogenesis; IEA:Ensembl. DR GO; GO:0003167; P:atrioventricular bundle cell differentiation; ISS:BHF-UCL. DR GO; GO:0060928; P:atrioventricular node cell development; ISS:BHF-UCL. DR GO; GO:0060929; P:atrioventricular node cell fate commitment; ISS:BHF-UCL. DR GO; GO:0003181; P:atrioventricular valve morphogenesis; IEA:Ensembl. DR GO; GO:0086054; P:bundle of His cell to Purkinje myocyte communication by electrical coupling; ISS:BHF-UCL. DR GO; GO:0003166; P:bundle of His development; ISS:BHF-UCL. DR GO; GO:0003218; P:cardiac left ventricle formation; ISS:BHF-UCL. DR GO; GO:0060038; P:cardiac muscle cell proliferation; IEA:Ensembl. DR GO; GO:0001708; P:cell fate specification; IBA:GO_Central. DR GO; GO:0060980; P:cell migration involved in coronary vasculogenesis; TAS:DFLAT. DR GO; GO:0007267; P:cell-cell signaling; IDA:UniProtKB. DR GO; GO:0086019; P:cell-cell signaling involved in cardiac conduction; ISS:BHF-UCL. DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IMP:UniProtKB. DR GO; GO:0030326; P:embryonic limb morphogenesis; IMP:UniProtKB. DR GO; GO:0003197; P:endocardial cushion development; IEA:Ensembl. DR GO; GO:0035136; P:forelimb morphogenesis; IMP:MGI. DR GO; GO:0007507; P:heart development; IDA:UniProtKB. DR GO; GO:0030324; P:lung development; IEA:Ensembl. DR GO; GO:0002009; P:morphogenesis of an epithelium; IEA:Ensembl. DR GO; GO:0060044; P:negative regulation of cardiac muscle cell proliferation; IDA:UniProtKB. DR GO; GO:0030336; P:negative regulation of cell migration; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; TAS:DFLAT. DR GO; GO:0007389; P:pattern specification process; IBA:GO_Central. DR GO; GO:0060039; P:pericardium development; IDA:UniProtKB. DR GO; GO:1903781; P:positive regulation of cardiac conduction; ISS:BHF-UCL. DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IEA:Ensembl. DR GO; GO:0051891; P:positive regulation of cardioblast differentiation; IDA:UniProtKB. DR GO; GO:1901846; P:positive regulation of cell communication by electrical coupling involved in cardiac conduction; TAS:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:1903598; P:positive regulation of gap junction assembly; ISS:BHF-UCL. DR GO; GO:0072513; P:positive regulation of secondary heart field cardioblast proliferation; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0060371; P:regulation of atrial cardiac muscle cell membrane depolarization; ISS:BHF-UCL. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0003163; P:sinoatrial node development; ISS:BHF-UCL. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0003281; P:ventricular septum development; ISS: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; Q99593; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Atrial fibrillation; KW Cardiomyopathy; Cytoplasm; Developmental protein; Disease variant; KW DNA-binding; Nucleus; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1..518 FT /note="T-box transcription factor TBX5" FT /id="PRO_0000184435" FT DNA_BIND 58..238 FT /note="T-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00201, FT ECO:0000269|PubMed:26926761" FT REGION 1..46 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 250..356 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 320..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:0000269|PubMed:29174768" FT VAR_SEQ 1..50 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_046845" FT VAR_SEQ 328..349 FT /note="EEECSTTDHPYKKPYMETSPSE -> GECDHPWSICFLSYLFLSLGWG (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:8988165" FT /id="VSP_006387" FT VAR_SEQ 350..518 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8988165" FT /id="VSP_006388" FT VARIANT 49 FT /note="Q -> K (in HOS; dbSNP:rs104894383)" FT /evidence="ECO:0000269|PubMed:10842287" FT /id="VAR_015381" FT VARIANT 54 FT /note="I -> T (in HOS; dbSNP:rs104894384)" FT /evidence="ECO:0000269|PubMed:10842287" FT /id="VAR_015382" FT VARIANT 80 FT /note="G -> R (in HOS; significant cardiac malformations FT but only minor skeletal abnormalities; reduced protein FT stability and strongly reduced affinity for DNA; FT dbSNP:rs104894381)" FT /evidence="ECO:0000269|PubMed:10077612, FT ECO:0000269|PubMed:20450920" FT /id="VAR_009701" FT VARIANT 132 FT /note="P -> S (found in a patient with atrial fibrillation; FT likely pathogenic; reduces transcriptional activity; FT affects transcriptional regulation of NKX2-5)" FT /evidence="ECO:0000269|PubMed:27035640" FT /id="VAR_076673" FT VARIANT 143 FT /note="A -> T (found in a patient with sporadic dilated FT cardiomyopathy; likely pathogenic; associated with disease FT susceptibility; associated with significantly decreased FT transcriptional activity; dbSNP:rs374906778)" FT /evidence="ECO:0000269|PubMed:25963046" FT /id="VAR_074599" FT VARIANT 154 FT /note="S -> A (found in patients with familial dilated FT cardiomyopathy; likely pathogenic; associated with disease FT susceptibility; associated with significantly decreased FT transcriptional activity)" FT /evidence="ECO:0000269|PubMed:25725155" FT /id="VAR_074600" FT VARIANT 170 FT /note="H -> D (found in a patient with atrial fibrillation; FT likely pathogenic; reduces transcriptional activity; FT affects transcriptional regulation of NKX2-5 or GATA4)" FT /evidence="ECO:0000269|PubMed:26917986" FT /id="VAR_076642" FT VARIANT 237 FT /note="R -> Q (in HOS; extensive upper limb malformations; FT affects transcriptional regulation of MYH6; FT dbSNP:rs104894378)" FT /evidence="ECO:0000269|PubMed:10077612, FT ECO:0000269|PubMed:15735645, ECO:0000269|PubMed:8988165" FT /id="VAR_007456" FT VARIANT 237 FT /note="R -> W (in HOS; extensive upper limb malformations; FT strongly reduced affinity for DNA; dbSNP:rs104894382)" FT /evidence="ECO:0000269|PubMed:10077612, FT ECO:0000269|PubMed:20450920" FT /id="VAR_009702" FT MUTAGEN 234 FT /note="K->R: Does not affect acetylation of the protein." FT /evidence="ECO:0000269|PubMed:29174768" FT MUTAGEN 325 FT /note="K->R: Does not affect transcription factor FT activity." FT /evidence="ECO:0000269|PubMed:29174768" FT MUTAGEN 327 FT /note="K->R: Does not affect transcription factor FT activity." FT /evidence="ECO:0000269|PubMed:29174768" FT MUTAGEN 339 FT /note="K->R: Abolishes acetylation of the protein, leading FT to impaired transcription factor activity. Impaired FT subcellular location." FT /evidence="ECO:0000269|PubMed:29174768" FT MUTAGEN 340 FT /note="K->R: Does not affect transcription factor FT activity." FT /evidence="ECO:0000269|PubMed:29174768" FT CONFLICT 7..49 FT /note="GFGLAHTPLEPDAKDLPCDSKPESALGAPSKSPSSPQAAFTQQ -> ALAGA FT HLWSLTQKTCLRFEPRARSGPPASPPGRPRSRLHPA (in Ref. 1; CAA70592)" FT /evidence="ECO:0000305" FT CONFLICT 71 FT /note="Missing (in Ref. 1; CAA70592)" FT /evidence="ECO:0000305" FT CONFLICT 94 FT /note="L -> I (in Ref. 1; CAA70592)" FT /evidence="ECO:0000305" FT CONFLICT 122 FT /note="S -> C (in Ref. 1; CAA70592)" FT /evidence="ECO:0000305" FT CONFLICT 132 FT /note="P -> A (in Ref. 1; CAA70592)" FT /evidence="ECO:0000305" FT CONFLICT 418..460 FT /note="MDRLPYQHFSAHFTSGPLVPRLAGMANHGSPQLGEGMFQHQTS -> WTGYP FT TSTSPLTSPRGPWSLGWLAWQPWLPTAGRGNVPSTRPP (in Ref. 1; FT CAA70592)" FT /evidence="ECO:0000305" FT CONFLICT 468..470 FT /note="RQC -> SSV (in Ref. 1; CAA70592)" FT /evidence="ECO:0000305" FT CONFLICT 494..518 FT /note="PRTLSPHQYHSVHGVGMVPEWSDNS -> QGLYPLISTTLCTELAWCRVERQ FT (in Ref. 1; CAA70592)" FT /evidence="ECO:0000305" FT STRAND 43..48 FT /evidence="ECO:0007829|PDB:5BQD" FT STRAND 55..58 FT /evidence="ECO:0007829|PDB:2X6U" FT HELIX 61..70 FT /evidence="ECO:0007829|PDB:2X6U" FT STRAND 73..75 FT /evidence="ECO:0007829|PDB:2X6U" FT STRAND 77..79 FT /evidence="ECO:0007829|PDB:2X6U" FT STRAND 88..93 FT /evidence="ECO:0007829|PDB:2X6U" FT STRAND 96..117 FT /evidence="ECO:0007829|PDB:2X6U" FT STRAND 120..126 FT /evidence="ECO:0007829|PDB:2X6U" FT STRAND 142..144 FT /evidence="ECO:0007829|PDB:2X6U" FT HELIX 145..150 FT /evidence="ECO:0007829|PDB:2X6U" FT STRAND 153..155 FT /evidence="ECO:0007829|PDB:4S0H" FT STRAND 159..161 FT /evidence="ECO:0007829|PDB:2X6U" FT STRAND 177..187 FT /evidence="ECO:0007829|PDB:2X6U" FT STRAND 194..197 FT /evidence="ECO:0007829|PDB:2X6U" FT STRAND 201..204 FT /evidence="ECO:0007829|PDB:2X6U" FT HELIX 207..209 FT /evidence="ECO:0007829|PDB:2X6U" FT STRAND 211..216 FT /evidence="ECO:0007829|PDB:2X6U" FT HELIX 220..229 FT /evidence="ECO:0007829|PDB:2X6U" FT HELIX 231..236 FT /evidence="ECO:0007829|PDB:2X6V" SQ SEQUENCE 518 AA; 57711 MW; 70118AD84FF5C00F CRC64; MADADEGFGL AHTPLEPDAK DLPCDSKPES ALGAPSKSPS SPQAAFTQQG MEGIKVFLHE RELWLKFHEV GTEMIITKAG RRMFPSYKVK VTGLNPKTKY ILLMDIVPAD DHRYKFADNK WSVTGKAEPA MPGRLYVHPD SPATGAHWMR QLVSFQKLKL TNNHLDPFGH IILNSMHKYQ PRLHIVKADE NNGFGSKNTA FCTHVFPETA FIAVTSYQNH KITQLKIENN PFAKGFRGSD DMELHRMSRM QSKEYPVVPR STVRQKVASN HSPFSSESRA LSTSSNLGSQ YQCENGVSGP SQDLLPPPNP YPLPQEHSQI YHCTKRKEEE CSTTDHPYKK PYMETSPSEE DSFYRSSYPQ QQGLGASYRT ESAQRQACMY ASSAPPSEPV PSLEDISCNT WPSMPSYSSC TVTTVQPMDR LPYQHFSAHF TSGPLVPRLA GMANHGSPQL GEGMFQHQTS VAHQPVVRQC GPQTGLQSPG TLQPPEFLYS HGVPRTLSPH QYHSVHGVGM VPEWSDNS //