NKX2-5

NK2 homeobox 5
Identifiers
Symbols	NKX2-5; CHNG5; CSX; CSX1; FLJ52202; FLJ97166; FLJ97195; FLJ97197; FLJ99536; NKX2.5; NKX2E; NKX4-1
External IDs	OMIM: 600584 MGI: 97350 HomoloGene: 3230 GeneCards: NKX2-5 Gene
Gene Ontology Molecular function • DNA binding • chromatin binding • sequence-specific DNA binding transcription factor activity • sequence-specific DNA binding transcription factor activity • sequence-specific DNA binding transcription factor activity • protein binding • transcription factor binding • serum response element binding • protein homodimerization activity • sequence-specific DNA binding • transcription regulatory region DNA binding • protein heterodimerization activity Cellular component • nucleus • transcription factor complex • cytoplasm Biological process • negative regulation of transcription from RNA polymerase II promoter • negative regulation of transcription from RNA polymerase II promoter • vasculogenesis • heart looping • heart morphogenesis • outflow tract septum morphogenesis • cardiac conduction system development • atrioventricular node development • bundle of His development • cardiac Purkinje fiber cell differentiation • cardiac ventricle formation • right ventricular cardiac muscle tissue morphogenesis • ventricular trabecular myocardium morphogenesis • apoptosis involved in heart morphogenesis • septum secundum development • proepicardium development • pulmonary myocardium development • transcription, DNA-dependent • multicellular organismal development • adult heart development • positive regulation of cell proliferation • negative regulation of cardiac muscle cell apoptosis • positive regulation of transcription via serum response element binding • positive regulation of sodium ion transport • negative regulation of myotube differentiation • hemopoiesis • cell differentiation • thyroid gland development • response to estradiol stimulus • embryonic heart tube development • negative regulation of apoptosis • tongue development • positive regulation of neuron differentiation • positive regulation of heart contraction • positive regulation of survival gene product expression • negative regulation of transcription, DNA-dependent • positive regulation of transcription, DNA-dependent • positive regulation of transcription, DNA-dependent • positive regulation of transcription, DNA-dependent • positive regulation of transcription from RNA polymerase II promoter • positive regulation of transcription from RNA polymerase II promoter • positive regulation of transcription from RNA polymerase II promoter • positive regulation of transcription from RNA polymerase II promoter • spleen development • positive regulation of cardioblast differentiation • positive regulation of calcium ion transport via voltage-gated calcium channel activity • ventricular cardiac myofibril development • cardiac muscle cell differentiation • cardiac muscle tissue morphogenesis • atrial cardiac muscle cell development • ventricular cardiac muscle cell development • regulation of cardiac muscle contraction • pharyngeal system development • positive regulation of transcription initiation from RNA polymerase II promoter • heart trabecula formation • ventricular septum morphogenesis • atrial septum morphogenesis • atrioventricular node cell development • atrioventricular node cell fate commitment • embryonic heart tube left/right pattern formation • negative regulation of canonical Wnt receptor signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1482	18091
Ensembl	ENSG00000183072	ENSMUSG00000015579
UniProt	P52952	Q3UQU2
RefSeq (mRNA)	NM_001166175.1	NM_008700.2
RefSeq (protein)	NP_001159647.1	NP_032726.1
Location (UCSC)	Chr 5: 172.66 – 172.66 Mb	Chr 17: 26.98 – 26.98 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

NKX2-5 has been shown to interact with GATA4^[4][5][6] and TBX5.^[4][7]

References

1. ^ Shiojima I, Komuro I, Inazawa J, Nakahori Y, Matsushita I, Abe T, Nagai R, Yazaki Y (Oct 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 (Jan 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2230031. 
3. ^ ^{a b} "Entrez Gene: NKX2-5 NK2 transcription factor related, locus 5 (Drosophila)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1482. 
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 (Jul. 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 (Sep. 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170200. 
6. ^ Zhu, W; Shiojima I, Hiroi Y, Zou Y, Akazawa H, Mizukami M, Toko H, Yazaki Y, Nagai R, Komuro I (Nov. 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 (Jul. 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

• Harvey RP, Lai D, Elliott D, et al. (2003). "Homeodomain factor Nkx2-5 in heart development and disease.". Cold Spring Harb. Symp. Quant. Biol. 67: 107–14. doi:10.1101/sqb.2002.67.107. PMID 12858530. 
• Chen CY, Schwartz RJ (1996). "Recruitment of the tinman homolog Nkx-2.5 by serum response factor activates cardiac alpha-actin gene transcription.". Mol. Cell. Biol. 16 (11): 6372–84. PMC 231639. PMID 8887666. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231639. 
• Durocher D, Charron F, Warren R, et al. (1997). "The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors.". EMBO J. 16 (18): 5687–96. doi:10.1093/emboj/16.18.5687. PMC 1170200. PMID 9312027. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170200. 
• Schott JJ, Benson DW, Basson CT, et al. (1998). "Congenital heart disease caused by mutations in the transcription factor NKX2-5.". Science 281 (5373): 108–11. doi:10.1126/science.281.5373.108. PMID 9651244. 
• Kim YH, Choi CY, Lee SJ, et al. (1998). "Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors.". J. Biol. Chem. 273 (40): 25875–9. doi:10.1074/jbc.273.40.25875. PMID 9748262. 
• Kasahara H, Izumo S (1999). "Identification of the in vivo casein kinase II phosphorylation site within the homeodomain of the cardiac tisue-specifying homeobox gene product Csx/Nkx2.5.". Mol. Cell. Biol. 19 (1): 526–36. PMC 83910. PMID 9858576. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=83910. 
• Benson DW, Silberbach GM, Kavanaugh-McHugh A, et al. (2000). "Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways.". J. Clin. Invest. 104 (11): 1567–73. doi:10.1172/JCI8154. PMC 409866. PMID 10587520. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=409866. 
• Kasahara H, Lee B, Schott JJ, et al. (2000). "Loss of function and inhibitory effects of human CSX/NKX2.5 homeoprotein mutations associated with congenital heart disease.". J. Clin. Invest. 106 (2): 299–308. doi:10.1172/JCI9860. PMC 314312. PMID 10903346. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=314312. 
• Zhu W, Shiojima I, Hiroi Y, et al. (2001). "Functional analyses of three Csx/Nkx-2.5 mutations that cause human congenital heart disease.". J. Biol. Chem. 275 (45): 35291–6. doi:10.1074/jbc.M000525200. PMID 10948187. 
• Hiroi Y, Kudoh S, Monzen K, et al. (2001). "Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation.". Nat. Genet. 28 (3): 276–80. doi:10.1038/90123. PMID 11431700. 
• Goldmuntz E, Geiger E, Benson DW (2001). "NKX2.5 mutations in patients with tetralogy of fallot.". Circulation 104 (21): 2565–8. doi:10.1161/hc4601.098427. PMID 11714651. 
• Toko H, Zhu W, Takimoto E, et al. (2002). "Csx/Nkx2-5 is required for homeostasis and survival of cardiac myocytes in the adult heart.". J. Biol. Chem. 277 (27): 24735–43. doi:10.1074/jbc.M107669200. PMID 11889119. 
• Habets PE, Moorman AF, Clout DE, et al. (2002). "Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation.". Genes Dev. 16 (10): 1234–46. doi:10.1101/gad.222902. PMC 186286. PMID 12023302. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=186286. 
• Ikeda Y, Hiroi Y, Hosoda T, et al. (2002). "Novel point mutation in the cardiac transcription factor CSX/NKX2.5 associated with congenital heart disease.". Circ. J. 66 (6): 561–3. doi:10.1253/circj.66.561. PMID 12074273. 
• Shirai M, Osugi T, Koga H, et al. (2002). "The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis.". J. Clin. Invest. 110 (2): 177–84. doi:10.1172/JCI14839. PMC 151044. PMID 12122109. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=151044. 
• Watanabe Y, Benson DW, Yano S, et al. (2002). "Two novel frameshift mutations in NKX2.5 result in novel features including visceral inversus and sinus venosus type ASD.". J. Med. Genet. 39 (11): 807–11. doi:10.1136/jmg.39.11.807. PMC 1735007. PMID 12414819. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1735007. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Fan C, Liu M, Wang Q (2003). "Functional analysis of TBX5 missense mutations associated with Holt-Oram syndrome.". J. Biol. Chem. 278 (10): 8780–5. doi:10.1074/jbc.M208120200. PMC 1579789. PMID 12499378. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1579789. 

External links

• MeSH NKX2-5+protein,+human

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