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Homeobox protein Nkx-2.5

Definition:

Transcription factor required for the development of the heart and the spleen. During heart development, acts as a transcriptional activator of NPPA/ANF in cooperation with GATA4 (By similarity). May cooperate with TBX2 to negatively modulate expression of NPPA/ANF in the atrioventricular canal (By similarity). Binds to the core DNA motif of NPPA promoter. Together with PBX1, required for spleen development through a mechanism that involves CDKN2B repression. Positively regulates transcription of genes such as COL3A1 and MMP2, resulting in increased pulmonary endothelial fibrosis in response to hypoxia.

References:

[1]. Matthew Koss, et al. Congenital asplenia in mice and humans with mutations in a Pbx/Nkx2-5/p15 module. Dev Cell. 2012 May 15;22(5):913-26. [Content Brief]

[2]. Lagnajeet Pradhan, et al. Crystal structure of the human NKX2.5 homeodomain in complex with DNA target. Biochemistry. 2012 Aug 14;51(32):6312-9. [Content Brief]

[3]. Lagnajeet Pradhan, et al. Intermolecular Interactions of Cardiac Transcription Factors NKX2.5 and TBX5. Biochemistry. 2016 Mar 29;55(12):1702-10. [Content Brief]

[4]. Andriy O Samokhin, et al. NEDD9 targets COL3A1 to promote endothelial fibrosis and pulmonary arterial hypertension. Sci Transl Med. 2018 Jun 13;10(445):eaap7294. [Content Brief]

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