TBX5_HUMAN
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 03-AUG-2022, entry version 206.
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};
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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; 10.
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; Q99593; -.
DR PeptideAtlas; Q99593; -.
DR PRIDE; Q99593; -.
DR ProteomicsDB; 78347; -. [Q99593-1]
DR ProteomicsDB; 78348; -. [Q99593-2]
DR ProteomicsDB; 886; -.
DR ABCD; Q99593; 6 sequenced antibodies.
DR Antibodypedia; 18791; 278 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 CTD; 6910; -.
DR DisGeNET; 6910; -.
DR GeneCards; TBX5; -.
DR GeneReviews; TBX5; -.
DR HGNC; HGNC:11604; TBX5.
DR HPA; ENSG00000089225; Group enriched (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; GVANHGS; -.
DR OrthoDB; 344556at2759; -.
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 SignaLink; Q99593; -.
DR SIGNOR; Q99593; -.
DR BioGRID-ORCS; 6910; 9 hits in 1094 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 tissues.
DR Genevisible; Q99593; HS.
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: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:0045893; P:positive regulation of transcription, DNA-templated; 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; 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 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 (probable disease-associated variant found in
FT a patient with atrial fibrillation; reduces transcriptional
FT activity; affects transcriptional regulation of NKX2-5)"
FT /evidence="ECO:0000269|PubMed:27035640"
FT /id="VAR_076673"
FT VARIANT 143
FT /note="A -> T (probable disease-associated variant found in
FT a patient with sporadic dilated cardiomyopathy; associated
FT with disease susceptibility; associated with significantly
FT decreased transcriptional activity; dbSNP:rs374906778)"
FT /evidence="ECO:0000269|PubMed:25963046"
FT /id="VAR_074599"
FT VARIANT 154
FT /note="S -> A (probable disease-associated variant found in
FT patients with familial dilated cardiomyopathy; associated
FT with disease susceptibility; associated with significantly
FT decreased transcriptional activity)"
FT /evidence="ECO:0000269|PubMed:25725155"
FT /id="VAR_074600"
FT VARIANT 170
FT /note="H -> D (probable disease-associated variant found in
FT a patient with atrial fibrillation; reduces transcriptional
FT activity; affects transcriptional regulation of NKX2-5 or
FT 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
