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

GO curators for mouse genes have assigned the following annotations to the gene product of Pitx2. (This text reflects annotations as of Thursday, July 24, 2014.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. The encoded protein acts as a transcription factor and regulates procollagen lysyl hydroxylase gene expression. This protein plays a role in the terminal differentiation of somatotroph and lactotroph cell phenotypes, is involved in the development of the eye, tooth and abdominal organs, and acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. Mutations in this gene are associated with Axenfeld-Rieger syndrome, iridogoniodysgenesis syndrome, and sporadic cases of Peters anomaly. A similar protein in other vertebrates is involved in the determination of left-right asymmetry during development. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Pitx2
  • participates in the following biological processes:
    • myoblast fusion ^[16]
    • positive regulation of DNA binding ^{[22, 27]}
    • positive regulation of myoblast proliferation ^[16]
    • positive regulation of transcription from RNA polymerase II promoter ^{[7, 22]}
    • regulation of transcription, DNA-templated ^[10]
    • transcription from RNA polymerase II promoter ^[22]
    • Wnt signaling pathway ^[10]
  • performs the following molecular functions:
    • chromatin binding ^{[7, 28]}
    • chromatin DNA binding ^[27]
    • DNA binding ^[22]
    • sequence-specific DNA binding ^[3]
    • sequence-specific DNA binding RNA polymerase II transcription factor activity ^{[22, 27]}
    • sequence-specific DNA binding transcription factor activity ^{[7, 10]}
  • is located in the following cellular components:
    • cytoplasm ^[21]
    • nucleus ^{[8, 21, 22]}
    • transcription factor complex ^[10]
• The gene product of Pitx2 has been shown to bind to the gene products of Kat5, Pdlim1, Srf, Tbx1. ^{[3, 10, 22]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Pitx2
  • participates in the following biological processes:
    • anatomical structure morphogenesis ^[15]
    • atrial cardiac muscle tissue morphogenesis ^[14]
    • atrioventricular valve development ^[24]
    • cardiac muscle cell differentiation ^{[13, 17]}
    • cardiac muscle tissue development ^[1]
    • cardiac neural crest cell migration involved in outflow tract morphogenesis ^[10]
    • cell proliferation involved in outflow tract morphogenesis ^{[1, 10]}
    • deltoid tuberosity development ^[9]
    • determination of left/right symmetry ^{[6, 11, 12, 13, 14, 25, 26]}
    • digestive system development ^[14]
    • embryonic camera-type eye development ^{[6, 11]}
    • embryonic digestive tract morphogenesis ^[19]
    • endodermal digestive tract morphogenesis ^[19]
    • extraocular skeletal muscle development ^{[5, 27]}
    • heart development ^{[6, 10, 11, 13, 14, 15]}
    • hypothalamus cell migration ^[23]
    • in utero embryonic development ^[14]
    • left lung morphogenesis ^[14]
    • left/right axis specification ^[2]
    • lung development ^{[4, 6, 11, 12]}
    • neuron migration ^[23]
    • odontogenesis ^{[6, 12]}
    • organ morphogenesis ^[11]
    • patterning of blood vessels ^[13]
    • pituitary gland development ^{[6, 12]}
    • positive regulation of transcription, DNA-templated ^[28]
    • pulmonary myocardium development ^[18]
    • pulmonary vein morphogenesis ^[14]
    • regulation of cell migration ^[13]
    • regulation of cell proliferation ^[10]
    • skeletal muscle tissue development ^[11]
    • spleen development ^[2]
    • subthalamic nucleus development ^[23]
    • superior vena cava morphogenesis ^[14]
    • vascular smooth muscle cell differentiation ^[22]
    • vasculogenesis ^[4]
    • ventricular cardiac muscle cell development ^[24]
    • ventricular septum morphogenesis ^[24]
• Researchers have inferred, based on genetic interactions, that the gene product of Pitx2
  • participates in the following biological processes:
    • embryonic hindlimb morphogenesis based on interactions with Pitx1 ^[4]
    • heart development based on interactions with Tbx1 ^[20]
    • regulation of transcription from RNA polymerase II promoter based on interactions with Tbx1 ^[3]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Pitx2:
  • participates in the following biological processes:
    • camera-type eye development
    • deltoid tuberosity development
    • iris morphogenesis
    • negative regulation of transcription from RNA polymerase II promoter
    • odontogenesis
    • positive regulation of transcription from RNA polymerase II promoter
    • regulation of transcription from RNA polymerase II promoter
    • regulation of transcription, DNA-templated
  • performs the following molecular functions:
    • phosphoprotein binding
    • protein homodimerization activity
    • RNA polymerase II activating transcription factor binding
    • RNA polymerase II core promoter proximal region sequence-specific DNA binding
    • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription
    • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
    • RNA polymerase II transcription coactivator activity
    • RNA polymerase II transcription factor binding
    • RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription
    • sequence-specific DNA binding transcription factor activity
    • transcription factor binding
    • transcription regulatory region sequence-specific DNA binding
  • is located in the following cellular components:
    • nucleus
    • transcription factor complex

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Pitx2 indicates that it:
  • participates in the following biological processes:
    • multicellular organismal development

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References

1. Ai D et al. (2006) Pitx2 regulates cardiac left-right asymmetry by patterning second cardiac lineage-derived myocardium. Dev Biol, 296:437-49. (PubMed:16836994)
2. Bamforth SD et al. (2004) Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway. Nat Genet, 36:1189-96. (PubMed:15475956)
3. Cao H et al. (2010) Tbx1 regulates progenitor cell proliferation in the dental epithelium by modulating Pitx2 activation of p21. Dev Biol, 347:289-300. (PubMed:20816801)
4. De Langhe SP et al. (2008) Formation and Differentiation of Multiple Mesenchymal Lineages during Lung Development Is Regulated by beta-catenin Signaling. PLoS ONE, 3:e1516. (PubMed:18231602)
5. Diehl AG et al. (2006) Extraocular muscle morphogenesis and gene expression are regulated by Pitx2 gene dose. Invest Ophthalmol Vis Sci, 47:1785-93. (PubMed:16638982)
6. Gage PJ et al. (1999) Dosage requirement of Pitx2 for development of multiple organs. Development, 126:4643-51. (PubMed:10498698)
7. Hjalt T et al. (2001) PITX2 Regulates Procollagen Lysyl Hydroxylase (PLOD) Gene Expression. Implications for the pathology of rieger syndrome. J Cell Biol, 152:545-52. (PubMed:11157981)
8. Hjalt TA et al. (2000) The Pitx2 protein in mouse development. Dev Dyn, 218:195-200. (PubMed:10822271)
9. Holmberg J et al. (2008) PITX2 gain-of-function induced defects in mouse forelimb development. BMC Dev Biol, 8:25. (PubMed:18312615)
10. Kioussi C et al. (2002) Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 Pathway Mediating Cell-Type-Specific Proliferation during Development. Cell, 111:673-85. (PubMed:12464179)
11. Kitamura K et al. (1999) Mouse Pitx2 deficiency leads to anomalies of the ventral body wall, heart, extra- and periocular mesoderm and right pulmonary isomerism. Development, 126:5749-58. (PubMed:10572050)
12. Lin CR et al. (1999) Pitx2 regulates lung asymmetry, cardiac positioning and pituitary and tooth morphogenesis. Nature, 401:279-82. (PubMed:10499586)
13. Liu C et al. (2002) Pitx2c patterns anterior myocardium and aortic arch vessels and is required for local cell movement into atrioventricular cushions. Development, 129:5081-91. (PubMed:12397115)
14. Liu C et al. (2001) Regulation of left-right asymmetry by thresholds of Pitx2c activity. Development, 128:2039-48. (PubMed:11493526)
15. Lu MF et al. (1999) Function of Rieger syndrome gene in left-right asymmetry and craniofacial development. Nature, 401:276-8. (PubMed:10499585)
16. Martinez-Fernandez S et al. (2006) Pitx2c overexpression promotes cell proliferation and arrests differentiation in myoblasts. Dev Dyn, 235:2930-9. (PubMed:16958127)
17. Mommersteeg MT et al. (2007) Molecular pathway for the localized formation of the sinoatrial node. Circ Res, 100:354-62. (PubMed:17234970)
18. 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)
19. Nichol PF et al. (2011) Pitx2 is a Critical Early Regulatory Gene in Normal Cecal Development. J Surg Res, 170:107-11. (PubMed:21550054)
20. Nowotschin S et al. (2006) Tbx1 affects asymmetric cardiac morphogenesis by regulating Pitx2 in the secondary heart field. Development, 133:1565-73. (PubMed:16556915)
21. Sambasivan R et al. (2009) Distinct regulatory cascades govern extraocular and pharyngeal arch muscle progenitor cell fates. Dev Cell, 16:810-21. (PubMed:19531352)
22. Shang Y et al. (2008) Pitx2 is functionally important in the early stages of vascular smooth muscle cell differentiation. J Cell Biol, 181:461-73. (PubMed:18458156)
23. Skidmore JM et al. (2008) Cre fate mapping reveals lineage specific defects in neuronal migration with loss of Pitx2 function in the developing mouse hypothalamus and subthalamic nucleus. Mol Cell Neurosci, 37:696-707. (PubMed:18206388)
24. Tessari A et al. (2008) Myocardial Pitx2 differentially regulates the left atrial identity and ventricular asymmetric remodeling programs. Circ Res, 102:813-22. (PubMed:18292603)
25. Welsh IC et al. (2013) Integration of left-right Pitx2 transcription and Wnt signaling drives asymmetric gut morphogenesis via Daam2. Dev Cell, 26:629-44. (PubMed:24091014)
26. Yoshioka H et al. (1998) Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry. Cell, 94:299-305. (PubMed:9708732)
27. Zacharias AL et al. (2011) Pitx2 is an upstream activator of extraocular myogenesis and survival. Dev Biol, 349:395-405. (PubMed:21035439)
28. Zhou W et al. (2007) Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2. Nat Genet, 39:1225-34. (PubMed:17767158)

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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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