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Gene Ontology Classifications
Symbol
Name
ID
Nkx2-5
NK2 homeobox 5
MGI:97350

Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Nkx2-5. (This text reflects annotations as of Thursday, July 24, 2014.) MGI curation of this mouse gene is considered complete, including annotations derived from the biomedical literature as of December 14, 2009. If you know of any additional information regarding this mouse gene please let us know. Please supply mouse gene symbol and a PubMed ID.
Summary from NCBI RefSeq


[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a homeobox-containing transcription factor. This transcription factor functions in heart formation and development. Mutations in this gene cause atrial septal defect with atrioventricular conduction defect, and also tetralogy of Fallot, which are both heart malformation diseases. Mutations in this gene can also cause congenital hypothyroidism non-goitrous type 5, a non-autoimmune condition. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
Summary text based on GO annotations supported by experimental evidence in mouse
Summary text based on GO annotations supported by experimental evidence in other organisms
Summary text based on GO annotations supported by structural data
Summary text for additional MGI annotations
References
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  2. Boogerd KJ et al. (2008) Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43. Cardiovasc Res, 78:485-93. (PubMed:18285513)
  3. Briggs LE et al. (2008) Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects. Circ Res, 103:580-90. (PubMed:18689573)
  4. Bruneau BG et al. (2001) A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. Cell, 106:709-21. (PubMed:11572777)
  5. Chen CY et al. (1996) Recruitment of the tinman homolog Nkx-2.5 by serum response factor activates cardiac alpha-actin gene transcription. Mol Cell Biol, 16:6372-84. (PubMed:8887666)
  6. Chen CY et al. (1996) Activation of the cardiac alpha-actin promoter depends upon serum response factor, Tinman homologue, Nkx-2.5, and intact serum response elements. Dev Genet, 19:119-30. (PubMed:8900044)
  7. Chen F et al. (2002) Hop Is an Unusual Homeobox Gene that Modulates Cardiac Development. Cell, 110:713. (PubMed:12297045)
  8. Costa MW et al. (2011) Complex SUMO-1 regulation of cardiac transcription factor Nkx2-5. PLoS One, 6:e24812. (PubMed:21931855)
  9. Dentice M et al. (2006) Missense mutation in the transcription factor NKX2-5: a novel molecular event in the pathogenesis of thyroid dysgenesis. J Clin Endocrinol Metab, 91:1428-33. (PubMed:16418214)
  10. Elliott DA et al. (2006) A tyrosine-rich domain within homeodomain transcription factor Nkx2-5 is an essential element in the early cardiac transcriptional regulatory machinery. Development, 133:1311-22. (PubMed:16510504)
  11. Farin HF et al. (2007) Transcriptional Repression by the T-box Proteins Tbx18 and Tbx15 Depends on Groucho Corepressors. J Biol Chem, 282:25748-59. (PubMed:17584735)
  12. Garg V et al. (2003) GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature, 424:443-7. (PubMed:12845333)
  13. Habets PE et al. (2002) Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation. Genes Dev, 16:1234-46. (PubMed:12023302)
  14. Inagawa M et al. (2013) Histone H3 lysine 9 methyltransferases, G9a and GLP are essential for cardiac morphogenesis. Mech Dev, 130:519-31. (PubMed:23892084)
  15. Jay PY et al. (2004) Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system. J Clin Invest, 113:1130-7. (PubMed:15085192)
  16. Kasahara H et al. (2001) Characterization of homo- and heterodimerization of cardiac Csx/Nkx2.5 homeoprotein. J Biol Chem, 276:4570-80. (PubMed:11042197)
  17. Kim TG et al. (2004) Jumonji represses atrial natriuretic factor gene expression by inhibiting transcriptional activities of cardiac transcription factors. Mol Cell Biol, 24:10151-60. (PubMed:15542826)
  18. Kim YH et al. (1998) Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors. J Biol Chem, 273:25875-9. (PubMed:9748262)
  19. Koshiba-Takeuchi K et al. (2006) Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart. Nat Genet, 38:175-183. (PubMed:16380715)
  20. Koss M et al. (2012) Congenital Asplenia in Mice and Humans with Mutations in a Pbx/Nkx2-5/p15 Module. Dev Cell, 22:913-26. (PubMed:22560297)
  21. Lee S et al. (2012) UTX, a Histone H3-Lysine 27 Demethylase, Acts as a Critical Switch to Activate the Cardiac Developmental Program. Dev Cell, 22:25-37. (PubMed:22192413)
  22. Lee Y et al. (1998) 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. Mol Cell Biol, 18:3120-9. (PubMed:9584153)
  23. Liu Y et al. (2007) Sox17 is essential for the specification of cardiac mesoderm in embryonic stem cells. Proc Natl Acad Sci U S A, 104:3859-64. (PubMed:17360443)
  24. Lyons I et al. (1995) Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5. Genes Dev, 9:1654-66. (PubMed:7628699)
  25. Meysen S et al. (2007) Nkx2.5 cell-autonomous gene function is required for the postnatal formation of the peripheral ventricular conduction system. Dev Biol, 303:740-53. (PubMed:17250822)
  26. Mommersteeg MT et al. (2007) Molecular pathway for the localized formation of the sinoatrial node. Circ Res, 100:354-62. (PubMed:17234970)
  27. Mommersteeg MT et al. (2007) Pitx2c and Nkx2-5 are required for the formation and identity of the pulmonary myocardium. Circ Res, 101:902-9. (PubMed:17823370)
  28. Moskowitz IP et al. (2007) A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development. Cell, 129:1365-76. (PubMed:17604724)
  29. Nimura K et al. (2009) A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome. Nature, 460:287-91. (PubMed:19483677)
  30. Nowotschin S et al. (2006) Tbx1 affects asymmetric cardiac morphogenesis by regulating Pitx2 in the secondary heart field. Development, 133:1565-73. (PubMed:16556915)
  31. Pashmforoush M et al. (2004) Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block. Cell, 117:373-86. (PubMed:15109497)
  32. Plageman TF Jr et al. (2004) Differential expression and function of Tbx5 and Tbx20 in cardiac development. J Biol Chem, 279:19026-34. (PubMed:14978031)
  33. Prall OW et al. (2007) An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation. Cell, 128:947-59. (PubMed:17350578)
  34. Qian L et al. (2011) Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species. J Cell Biol, 193:1181-96. (PubMed:21690310)
  35. Riazi AM et al. (2009) NKX2-5 regulates the expression of beta-catenin and GATA4 in ventricular myocytes. PLoS One, 4:e5698. (PubMed:19479054)
  36. Riazi AM et al. (2005) CSX/Nkx2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells in vitro. J Biol Chem, 280:10716-20. (PubMed:15653675)
  37. Schlesinger J et al. (2011) The cardiac transcription network modulated by Gata4, Mef2a, Nkx2.5, Srf, histone modifications, and microRNAs. PLoS Genet, 7:e1001313. (PubMed:21379568)
  38. Shpargel KB et al. (2012) UTX and UTY demonstrate histone demethylase-independent function in mouse embryonic development. PLoS Genet, 8:e1002964. (PubMed:23028370)
  39. Skerjanc IS et al. (1998) Myocyte enhancer factor 2C and Nkx2-5 up-regulate each other's expression and initiate cardiomyogenesis in P19 cells. J Biol Chem, 273:34904-10. (PubMed:9857019)
  40. Song K et al. (2006) The transcriptional coactivator CAMTA2 stimulates cardiac growth by opposing class II histone deacetylases. Cell, 125:453-66. (PubMed:16678093)
  41. Stennard FA et al. (2005) Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation. Development, 132:2451-62. (PubMed:15843414)
  42. Stennard FA et al. (2003) Cardiac T-box factor Tbx20 directly interacts with Nkx2-5, GATA4, and GATA5 in regulation of gene expression in the developing heart. Dev Biol, 262:206-24. (PubMed:14550786)
  43. Takeda M et al. (2009) Slow progressive conduction and contraction defects in loss of Nkx2-5 mice after cardiomyocyte terminal differentiation. Lab Invest, 89:983-93. (PubMed:19546853)
  44. Tanaka M et al. (2001) Nkx2.5 and Nkx2.6, homologs of Drosophila tinman, are required for development of the pharynx. Mol Cell Biol, 21:4391-8. (PubMed:11390666)
  45. Tanaka M et al. (1999) The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. Development, 126:1269-80. (PubMed:10021345)
  46. Thattaliyath BD et al. (2002) The basic-helix-loop-helix transcription factor HAND2 directly regulates transcription of the atrial naturetic peptide gene. J Mol Cell Cardiol, 34:1335-44. (PubMed:12392994)
  47. Toko H et al. (2002) Csx/Nkx2-5 is required for homeostasis and survival of cardiac myocytes in the adult heart. J Biol Chem, 277:24735-43. (PubMed:11889119)
  48. Ueyama T et al. (2003) Myocardin expression is regulated by Nkx2.5, and its function is required for cardiomyogenesis. Mol Cell Biol, 23:9222-32. (PubMed:14645532)
  49. Ueyama T et al. (2003) Csm, a cardiac-specific isoform of the RNA helicase Mov10l1, is regulated by Nkx2.5 in embryonic heart. J Biol Chem, 278:28750-7. (PubMed:12754203)
  50. Vincentz JW et al. (2008) Cooperative interaction of Nkx2.5 and Mef2c transcription factors during heart development. Dev Dyn, 237:3809-19. (PubMed:19035347)
  51. von Both I et al. (2004) Foxh1 is essential for development of the anterior heart field. Dev Cell, 7:331-45. (PubMed:15363409)
  52. Wang Y et al. (2010) Pref-1 interacts with fibronectin to inhibit adipocyte differentiation. Mol Cell Biol, 30:3480-92. (PubMed:20457810)
  53. Yamagishi H et al. (2001) The Combinatorial Activities of Nkx2.5 and dHAND Are Essential for Cardiac Ventricle Formation. Dev Biol, 239:190-203. (PubMed:11784028)
  54. Zhang Y et al. (2010) Foxp1 coordinates cardiomyocyte proliferation through both cell-autonomous and nonautonomous mechanisms. Genes Dev, 24:1746-57. (PubMed:20713518)
  55. Zhou B et al. (2008) Nkx2-5- and Isl1-expressing cardiac progenitors contribute to proepicardium. Biochem Biophys Res Commun, 375:450-3. (PubMed:18722343)



Go Annotations in Tabular Form (Text View) (GO Graph)

 
 


Gene Ontology Evidence Code Abbreviations:

  EXP Inferred from experiment
  IC Inferred by curator
  IDA Inferred from direct assay
  IEA Inferred from electronic annotation
  IGI Inferred from genetic interaction
  IMP Inferred from mutant phenotype
  IPI Inferred from physical interaction
  ISS Inferred from sequence or structural similarity
  ISO Inferred from sequence orthology
  ISA Inferred from sequence alignment
  ISM Inferred from sequence model
  NAS Non-traceable author statement
  ND No biological data available
  RCA Reviewed computational analysis
  TAS Traceable author statement


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last database update
12/16/2014
MGI 5.20
The Jackson Laboratory