AC T01675
XX
ID T01675
XX
DT 15.02.1996 (created); ewi.
DT 19.02.2015 (updated); pro.
CO Copyright (C), QIAGEN.
XX
FA CSX
XX
SY cardiac-specific homeobox protein; Csx; Nkx-2.5.
XX
OS mouse, Mus musculus
OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; rodentia; myomorpha; muridae; murinae
XX
GE G002237 Nkx2-5.
XX
HO tinman T03612 (Drosophila).
XX
CL C0006; homeo; 3.1.2.17.2.
XX
SF at least two different consensus binding sequences [1];
SF the potent trans-activation domain is masked by the alanine- and proline-rich C-terminus [1];
XX
CP (cell lines). Fibroblast: NIH3T3; Bone marrow stroma: BAd; Thymic stroma: SCL-19; Lymph node stroma: TSL-1 [2]; developing heart of early stage mouse embryos, cardiogenic region, inner trabeculated myocardium of the right ventricle of the primitive heart, pharyngeal endoderm at E8, outer wall of outflow tract, right ventricle at E10,5, anterior primitive heart tube, spleen, myocardium surrounding the pulmonary and aortic valves in neonatal and adult hearts [15] [15] [2].
CN (cell lines): Fibroblasts: Balb/c 3T3, STO; Myoblasts: 3H10T1/2, C2C12; Myocytes: C3H10T1/2, C2C12; Bone marrow stroma: A6. BMS; Thymic stroma: B6T-ea, SCL-5,SCL-13; Lymph node stroma: TSL-3 [2]; endothelial layer of the primitive heart tube, primitive atrium, endocardial cushions of the outflow tract, left ventricle, liver, stomach, inner valves, atria [15] [15] [2].
EX atrium of heart (right and left),,,Theiler Stage 21; detectable; RNA-in situ hybridization (radioactive); RNA (undefined); [2].
EX bone marrow,,,adult; none; RNAse protection assay; total RNA; [2].
EX brain,,,Theiler Stage 28; none; RNAse protection assay; total RNA; [2].
EX brain,,,adult; none; RNAse protection assay; total RNA; [2].
EX brain,,,fetal; none; RNAse protection assay; total RNA; [2].
EX dorsal aorta,,,Theiler Stage 14; none; RNA-in situ hybridization (radioactive); RNA (undefined); [2].
EX endocardial cushion tissue,,,Theiler Stage 21; none; RNA-in situ hybridization (radioactive); RNA (undefined); [2].
EX endoderm of foregut,,,Theiler Stage 12; detectable; RNA-in situ hybridization (radioactive); RNA (undefined); [2].
EX heart,,,Theiler Stage 19; detectable; RNA-in situ hybridization (radioactive); RNA (undefined); [2].
EX heart,,,adult; high; RNAse protection assay; total RNA; [2].
EX heart,,,fetal; very high; RNAse protection assay; total RNA; [2].
EX heart,myogenic cell,,Theiler Stage 13; detectable; RNA-in situ hybridization (radioactive); RNA (undefined); [2].
EX kidney (right and left),,,adult; none; RNAse protection assay; total RNA; [2].
EX large intestine,,,adult; none; RNAse protection assay; total RNA; [2].
EX liver,,,adult; none; RNAse protection assay; total RNA; [2].
EX liver,,,fetal; none; RNAse protection assay; total RNA; [2].
EX lung,,,adult; none; RNAse protection assay; total RNA; [2].
EX lymph node,,,adult; none; RNAse protection assay; total RNA; [2].
EX muscles,,,adult; none; RNAse protection assay; total RNA; [2].
EX ovary,,,adult; none; RNAse protection assay; total RNA; [2].
EX pericardium,,,Theiler Stage 21; none; RNA-in situ hybridization (radioactive); RNA (undefined); [2].
EX primitive heart tube,,,Theiler Stage 13; detectable; RNA-in situ hybridization (radioactive); RNA (undefined); [2].
EX roof of pharynx,,,Theiler Stage 15; none; RNA-in situ hybridization (radioactive); RNA (undefined); [2].
EX small intestine,,,adult; none; RNAse protection assay; total RNA; [2].
EX splanchnopleure,,,Theiler Stage 12; detectable; RNA-in situ hybridization (radioactive); RNA (undefined); [2].
EX spleen,,,adult; low; RNAse protection assay; total RNA; [2].
EX stomach,,,adult; none; RNAse protection assay; total RNA; [2].
EX testis (right and left),,,adult; none; RNAse protection assay; total RNA; [2].
EX thymus,,,adult; none; RNAse protection assay; total RNA; [2].
EX thyroid gland,,,Theiler Stage 19; detectable; RNA-in situ hybridization (radioactive); RNA (undefined); [2].
EX tongue,,,adult; low; RNAse protection assay; total RNA; [2].
EX uterus,,,adult; none; RNAse protection assay; total RNA; [2].
EX venous sinus of primitive heart,,,Theiler Stage 14; high; RNA-in situ hybridization (radioactive); RNA (undefined); [2].
EX venous sinus of primitive heart,,,Theiler Stage 15; detectable; RNA-in situ hybridization (radioactive); RNA (undefined); [2].
EX ventricle of heart (right and left),,,Theiler Stage 21; detectable; RNA-in situ hybridization (radioactive); RNA (undefined); [2].
XX
FF modest activator [1];
FF probably important for myocard development [2];
FF expression first detected in myocardiogenic progenitor cells during early headfold stages, then maintained in cardiomyocytes of embryonic, fetal and adult heart [2];
FF also expressed in pharyngeal endoderm precursors, later in pharyngeal floor;
FF finally, expression is restricted to the thyroid primordium [2];
FF activates with SRF cardiac alpha-actin transcription [7];
FF induces left-sided expression of Hand1 T01569 but not Hand2 T04370 [6];
FF directly or indirectly autoregulated by negative feedback [8];
FF transcriptional activator, CSX and HMX1 T04443 act as transcriptional antagonists [10];
FF coimmunoprecipitation experiments demonstrate that Nkx2.5 and Gata4 T02532 associate intracellularly, helix III of the homeodomain of Nkx2.5 is required to interact with Gata4 and the carboxyl-terminal zinc finger of Gata4 is necessary to associate with Nkx2.5 [12];
FF CSX can activate ANF promoter and coexpression of Nkx2.5 and Gata4 shows synergistically activation [12] [5];
FF synergistic activation with GATA-4 and GATA-5 on cardiac-specific promoters like rat ANF and rat BMP [11] [5];
FF together with SRF T00764 provided strong transcriptional activation of the avian cardiac alpha actin promoter [13];
FF SRF and Nkx2.5 overcome YY1 T00915 repression on the alpha cardiac actin promoter [13];
FF Nkx2.5 and Gata4 T02532 synergistically transactivate the human but not the rat DIO2 promoter [14];
FF during embryonic development Nkx2.5 T01675 plays a central role in activating the expression of calreticulin. In embryonic hearts Nkx2.5 expression is high, and COUP-TF1 cannot bind to the CRT site 2 in the calreticulin promoter. Down-regulation of Nkx2.5 expression, which occurs as cardiac development progresses and in newborns, permits association between COUP-TF1 and the calreticulin promoter, resulting in repression of the calreticulin gene - Nkx2.5 and COUP-TF1 may play antagonistic roles [16];
XX
IN T02532 GATA-4; mouse, Mus musculus.
IN T04347 Tbx5; mouse, Mus musculus.
XX
MX M00240 V$NKX25_01.
MX M00241 V$NKX25_02.
MX M01414 V$NKX25_03.
MX M07116 V$NKX25_07.
MX M01043 V$NKX25_Q5.
MX M02108 V$NKX25_Q6.
XX
BS R16076.
BS R35898.
BS R35899.
BS R15784.
BS R15786.
BS R56157.
BS R56177.
BS R56180.
BS R56185.
BS R15793.
BS R15794.
BS R72235.
BS R72237.
BS R15776.
BS R15783.
BS R66351.
BS R63244.
BS R04598.
BS R04599.
BS R15790.
BS R15792.
BS R15775.
BS R15781.
BS R15787.
BS R15789.
XX
DR TRANSPATH: MO000025860.
DR UniProtKB: P42582;
XX
RN [1]; RE0003808.
RX PUBMED: 7797561.
RA Chen C. Y., Schwartz R. J.
RT Identification of novel DNA binding targets and regulatory domains of a murine tinman homeodomain factor, nkx-2.5
RL J. Biol. Chem. 270:15628-15633 (1995).
RN [2]; RE0003810.
RX PUBMED: 7904557.
RA Lints T. J., Parsons L. M., Hartley L., Lyons I., Harvey R. P.
RT Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants
RL Development 119:419-431 (1993).
RN [3]; RE0003811.
RX PUBMED: 7910553.
RA Lints T. J., Parsons L. M., Hartley L., Lyons I., Harvey R. P.
RT Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants (erratum)
RL Development 119:969-969 (1993).
RN [4]; RE0003812.
RX PUBMED: 7690144.
RA Komuro I., Izumo S.
RT Csx: A murine homeobox-containing gene specifically expressed in the developing heart
RL Proc. Natl. Acad. Sci. USA 90:8145-8149 (1993).
RN [5]; RE0005960.
RX PUBMED: 9312027.
RA Durocher D., Charron F., Warren R., Schwartz R. J., Nemer M.
RT The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors
RL EMBO J. 16:5687-5696 (1997).
RN [6]; RE0006047.
RX PUBMED: 9192865.
RA Biben C., Harvey R. P.
RT Homeodomain factor Nkx2-5 controls left/right asymmetric expression of bHLH gene eHand during murine heart development
RL Genes Dev. 11:1357-1369 (1997).
RN [7]; RE0015484.
RX PUBMED: 8887666.
RA Chen C.Y., Schwartz R.J.
RT Recruitment of the tinman homolog Nkx-2.5 by serum response factor activates cardiac alpha-actin gene transcription
RL Mol. Cell. Biol. 16:6372-6384 (1996).
RN [8]; RE0015753.
RX PUBMED: 10068637.
RA Tanaka M., Wechsler S. B., Lee I. W., Yamasaki N., Lawitts J. A., Izumo S.
RT Complex modular cis-acting elements regulate expression of the cardiac specifying homeobox gene Csx/Nkx2.5
RL Development 126:1439-1450 (1999).
RN [9]; RE0015782.
RX PUBMED: 11042197.
RA Kasahara H., Usheva A., Ueyama T., Aoki H., Horikoshi N., Izumo S.
RT Characterization of homo- and heterodimerization of cardiac Csx/Nkx2.5 homeoprotein
RL J. Biol. Chem. 276:4570-4580 (2001).
RN [10]; RE0016078.
RX PUBMED: 10206974.
RA Amendt B. A., Sutherland L. B., Russo A. F.
RT Transcriptional antagonism between Hmx1 and Nkx2.5 for a shared DNA-binding site
RL J. Biol. Chem. 274:11635-11642 (1999).
RN [11]; RE0025027.
RX PUBMED: 9584181.
RA Sepulveda J. L., Belaguli N., Nigam V., Chen C. Y., Nemer M., Schwartz R. J.
RT GATA-4 and Nkx-2.5 coactivate Nkx-2 DNA binding targets: role for regulating early cardiac gene expression.
RL Mol. Cell. Biol. 18:3405-3415 (1998).
RN [12]; RE0025078.
RX PUBMED: 9584153.
RA Lee Y., Shioi T., Kasahara H., Jobe S. M., Wiese R. J., Markham B. E., Izumo S.
RT The cardiac tissue-restricted homeobox protein Csx/Nkx2.5 physically associates with the zinc finger protein GATA4 and cooperatively activates atrial natriuretic factor gene expression.
RL Mol. Cell. Biol. 18:3120-3129 (1998).
RN [13]; RE0025100.
RX PUBMED: 9171244.
RA Chen C. Y., Schwartz R. J.
RT Competition between negative acting YY1 versus positive acting serum response factor and tinman homologue Nkx-2.5 regulates cardiac alpha-actin promoter activity.
RL Mol. Endocrinol. 11:812-822 (1997).
RN [14]; RE0025173.
RX PUBMED: 12775767.
RA Dentice M., Morisco C., Vitale M., Rossi G., Fenzi G., Salvatore D.
RT The different cardiac expression of the type 2 iodothyronine deiodinase gene between human and rat is related to the differential response of the Dio2 genes to Nkx-2.5 and GATA-4 transcription factors.
RL Mol. Endocrinol. 17:1508-1521 (2003).
RN [15]; RE0025175.
RX PUBMED: 9778505.
RA Searcy R. D., Vincent E. B., Liberatore C. M., Yutzey K. E.
RT A GATA-dependent nkx-2.5 regulatory element activates early cardiac gene expression in transgenic mice.
RL Development 125:4461-4470 (1998).
RN [16]; RE0025190.
RX PUBMED: 11106640.
RA Guo L., Lynch J., Nakamura K., Fliegel L., Kasahara H., Izumo S., Komuro I., Agellon L. B., Michalak M.
RT COUP-TF1 antagonizes Nkx2.5-mediated activation of the calreticulin gene during cardiac development.
RL J. Biol. Chem. 276:2797-2801 (2001).
RN [17]; RE0064927.
RX PUBMED: 9858576.
RA Kasahara H., Izumo S.
RT Identification of the in vivo casein kinase II phosphorylation site within the homeodomain of the cardiac tisue-specifying homeobox gene product Csx/Nkx2.5.
RL Mol. Cell. Biol. 19:526-536 (1999).
XX
//