Homeobox protein Nkx-2.5

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NK2 homeobox 5
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols NKX2-5 ; CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E; NKX4-1; VSD3
External IDs OMIM600584 MGI97350 HomoloGene3230 GeneCards: NKX2-5 Gene
RNA expression pattern
PBB GE NKX2-5 206578 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1482 18091
Ensembl ENSG00000183072 ENSMUSG00000015579
UniProt P52952 P42582
RefSeq (mRNA) NM_001166175 NM_008700
RefSeq (protein) NP_001159647 NP_032726
Location (UCSC) Chr 5:
172.66 – 172.66 Mb
Chr 17:
26.84 – 26.84 Mb
PubMed search [1] [2]

Homeobox protein Nkx-2.5 is a protein that in humans is encoded by the NKX2-5 gene.[1][2][3]

Homeobox-containing genes play critical roles in regulating tissue-specific gene expression essential for tissue differentiation, as well as determining the temporal and spatial patterns of development (Shiojima et al., 1995). It has been demonstrated that a Drosophila homeobox-containing gene called 'tinman' is expressed in the developing dorsal vessel and in the equivalent of the vertebrate heart. Mutations in tinman result in loss of heart formation in the embryo, suggesting that tinman is essential for Drosophila heart formation. Furthermore, abundant expression of Csx, the presumptive mouse homolog of tinman, is observed only in the heart from the time of cardiac differentiation. CSX, the human homolog of murine Csx, has a homeodomain sequence identical to that of Csx and is expressed only in the heart, again suggesting that CSX plays an important role in human heart formation.[supplied by OMIM][3]

Interactions[edit]

NKX2-5 has been shown to interact with GATA4[4][5][6] and TBX5.[4][7] NKX 2.5 is a transcription factor that regulates heart development in humans. NKX2.5 works along with MEF2, HAND1, and HAND2 transcription factors to direct heart looping during early heart development. NKX2.5 in vertebrates is equivalent to the ‘tinman’ gene in Drosophila and directly activates the MEF2 gene to control cardiomyocyte differentiation. NKX2.5 operates in a positive feedback loop with GATA transcription factors to regulate cardiomyocyte formation. NKX2.5 influences HAND1 and HAND2 transcription factors that control the essential asymmetrical development of the heart’s ventricles. Gene mutations of NKX2.5 lead to heart looping defects, conduction defects, and atrial septal defects in the developing heart. Scientists developed a gene knockout model of NKX2.5 in mice and found that the number of myocytes that develop into conduction cells depends on the amount of NKX2.5 influence. Therefore, lack of NKX2.5 leads to reduced function of the atrioventricular (AV) node. Since the AV node electrically connects the atrial and ventricular chambers of the heart to control conductance, defects of the AV node would lead to congenital heart disease.

References[edit]

  1. ^ Shiojima I, Komuro I, Inazawa J, Nakahori Y, Matsushita I, Abe T, Nagai R, Yazaki Y (October 1995). "Assignment of cardiac homeobox gene CSX to human chromosome 5q34". Genomics 27 (1): 204–6. doi:10.1006/geno.1995.1027. PMID 7665173. 
  2. ^ Turbay D, Wechsler SB, Blanchard KM, Izumo S (January 1997). "Molecular cloning, chromosomal mapping, and characterization of the human cardiac-specific homeobox gene hCsx". Mol Med 2 (1): 86–96. PMC 2230031. PMID 8900537. 
  3. ^ a b "Entrez Gene: NKX2-5 NK2 transcription factor related, locus 5 (Drosophila)". 
  4. ^ a b Garg, Vidu; Kathiriya Irfan S, Barnes Robert, Schluterman Marie K, King Isabelle N, Butler Cheryl A, Rothrock Caryn R, Eapen Reenu S, Hirayama-Yamada Kayoko, Joo Kunitaka, Matsuoka Rumiko, Cohen Jonathan C, Srivastava Deepak (July 2003). "GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5". Nature (England) 424 (6947): 443–7. doi:10.1038/nature01827. PMID 12845333. 
  5. ^ Durocher, D; Charron F; Warren R; Schwartz R J; Nemer M (September 1997). "The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors". EMBO J. (ENGLAND) 16 (18): 5687–96. doi:10.1093/emboj/16.18.5687. ISSN 0261-4189. PMC 1170200. PMID 9312027. 
  6. ^ Zhu, W; Shiojima I; Hiroi Y; Zou Y; Akazawa H; Mizukami M; Toko H; Yazaki Y; Nagai R; Komuro I (November 2000). "Functional analyses of three Csx/Nkx-2.5 mutations that cause human congenital heart disease". J. Biol. Chem. (UNITED STATES) 275 (45): 35291–6. doi:10.1074/jbc.M000525200. ISSN 0021-9258. PMID 10948187. 
  7. ^ Hiroi, Y; Kudoh S; Monzen K; Ikeda Y; Yazaki Y; Nagai R; Komuro I (July 2001). "Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation". Nat. Genet. (United States) 28 (3): 276–80. doi:10.1038/90123. ISSN 1061-4036. PMID 11431700. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.