Paired box gene 2, also known as PAX2 is a protein which in humans is encoded by the PAX2 gene.[1][2]
Contents
Function
PAX2 encodes paired box gene 2, one of many human homologues of the Drosophila melanogaster gene prd. The central feature of this transcription factor gene family is the conserved DNA-binding paired box domain. PAX2 is believed to be a target of transcriptional suppression by the tumor suppressor gene WT1. Pax 2 is a transcription factor controlled by the signaling molecules Wnt1 and Fgf8. Pax2 along with other transcription factors Pax5, Pax8, En1, and En 2 are expressed across the Otx2-Gbx2 boundary in the mid-hindbrain region. These transcription factors work with the signaling molecules Wnt1 and Fgf8 to maintain the MHB organizer. The MHB controls midbrain and cerebellum development. Pax2 is the earliest known gene to be expressed across the Otx2-Gbx2 boundary. It is first expressed in the late primitive streak stage and is expressed in a narrow ring centered at the MHB during somitogenesis. Transgene expression of the mid-hindbrain and developing kidney is directed by Pax2. There are three distinct MHB-specific enhancers in the upstream region of Pax2. Expression at the MHB from the four-somite stage onwards is directed by the two late enhancers in the proximal and distal regions of Pax2. The early enhancer located in the intermediate region activates the mid-hindbrain region of late gastrula embryos. The activation of Pax2, Pax5, and Pax8 is a conserved feature of all vertebrates.
Clinical significance
Mutations within PAX2 have been shown to result in optic nerve colobomas and renal hypoplasia. Alternative splicing of this gene results in multiple transcript variants.[3] Pax2 and Pax8 are also necessary for the formation of the pronephros and subsequent kidney structures. Pax2 and Pax8 regulate the expression of Gata3. Without these genes mutations in the urogenital system arise.
Interactions
PAX2 has been shown to interact with PAXIP1.[4]
See also
- ^ Pilz AJ, Povey S, Gruss P, Abbott CM (1993). "Mapping of the human homologs of the murine paired-box-containing genes". Mamm. Genome 4 (2): 78–82. doi:10.1007/BF00290430. PMID 8431641.
- ^ Stapleton P, Weith A, Urbánek P, Kozmik Z, Busslinger M (April 1993). "Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9". Nat. Genet. 3 (4): 292–8. doi:10.1038/ng0493-292. PMID 7981748.
- ^ "Entrez Gene: PAX2 paired box gene 2".
- ^ Lechner, M S; Levitan I; Dressler G R (July 2000). "PTIP, a novel BRCT domain-containing protein interacts with Pax2 and is associated with active chromatin". Nucleic Acids Res. (ENGLAND) 28 (14): 2741–51. doi:10.1093/nar/28.14.2741. PMC 102659. PMID 10908331.
- ^ Pfeffer, Peter L.; Bernhard Payter; Gerlinde Reim; Marina Pasca di Magliano; Meinrad Busslinger (2001). "The activation and maintenance of Pax2 expression at the mid-hindbrain boundary is controlled by separate enhancers". Development (133): 307–318.
- ^ Grote, David; Souabni, Abdallah, Busslinger, Meinrad, Bouchard, Maxime. "Pax2/8-regulated Gata3 expression is necessary for morphogenesis and guidance of the nephric duct in the developing kidney". Devopment (133): 53–61.
Data on Xenopus pax2 from Xenbase; [3]
Further reading
- Noll M (1993). "Evolution and role of Pax genes.". Curr. Opin. Genet. Dev. 3 (4): 595–605. doi:10.1016/0959-437X(93)90095-7. PMID 8241771.
- Dahl E, Koseki H, Balling R (1997). "Pax genes and organogenesis.". Bioessays 19 (9): 755–65. doi:10.1002/bies.950190905. PMID 9297966.
- Eccles MR, He S, Legge M et al. (2003). "PAX genes in development and disease: the role of PAX2 in urogenital tract development.". Int. J. Dev. Biol. 46 (4): 535–44. PMID 12141441.
- Eccles MR, Wallis LJ, Fidler AE et al. (1992). "Expression of the PAX2 gene in human fetal kidney and Wilms' tumor.". Cell Growth Differ. 3 (5): 279–89. PMID 1378753.
- Sanyanusin P, Schimmenti LA, McNoe LA et al. (1995). "Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux.". Nat. Genet. 9 (4): 358–64. doi:10.1038/ng0495-358. PMID 7795640.
- Ward TA, Nebel A, Reeve AE, Eccles MR (1995). "Alternative messenger RNA forms and open reading frames within an additional conserved region of the human PAX-2 gene.". Cell Growth Differ. 5 (9): 1015–21. PMID 7819127.
- Stapleton P, Weith A, Urbánek P et al. (1995). "Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9.". Nat. Genet. 3 (4): 292–8. doi:10.1038/ng0493-292. PMID 7981748.
- Pilz AJ, Povey S, Gruss P, Abbott CM (1993). "Mapping of the human homologs of the murine paired-box-containing genes.". Mamm. Genome 4 (2): 78–82. doi:10.1007/BF00290430. PMID 8431641.
- Sanyanusin P, McNoe LA, Sullivan MJ et al. (1996). "Mutation of PAX2 in two siblings with renal-coloboma syndrome.". Hum. Mol. Genet. 4 (11): 2183–4. doi:10.1093/hmg/4.11.2183. PMID 8589702.
- Sanyanusin P, Norrish JH, Ward TA et al. (1996). "Genomic structure of the human PAX2 gene.". Genomics 35 (1): 258–61. doi:10.1006/geno.1996.0350. PMID 8661132.
- Dehbi M, Ghahremani M, Lechner M et al. (1996). "The paired-box transcription factor, PAX2, positively modulates expression of the Wilms' tumor suppressor gene (WT1).". Oncogene 13 (3): 447–53. PMID 8760285.
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Schimmenti LA, Cunliffe HE, McNoe LA et al. (1997). "Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations.". Am. J. Hum. Genet. 60 (4): 869–78. PMC 1712484. PMID 9106533.
- Narahara K, Baker E, Ito S et al. (1997). "Localisation of a 10q breakpoint within the PAX2 gene in a patient with a de novo t(10;13) translocation and optic nerve coloboma-renal disease.". J. Med. Genet. 34 (3): 213–6. doi:10.1136/jmg.34.3.213. PMC 1050895. PMID 9132492.
- Tavassoli K, Rüger W, Horst J (1998). "Alternative splicing in PAX2 generates a new reading frame and an extended conserved coding region at the carboxy terminus.". Hum. Genet. 101 (3): 371–5. doi:10.1007/s004390050644. PMID 9439670.
- Stayner CK, Cunliffe HE, Ward TA, Eccles MR (1998). "Cloning and characterization of the human PAX2 promoter.". J. Biol. Chem. 273 (39): 25472–9. doi:10.1074/jbc.273.39.25472. PMID 9738017.
- Devriendt K, Matthijs G, Van Damme B et al. (1998). "Missense mutation and hexanucleotide duplication in the PAX2 gene in two unrelated families with renal-coloboma syndrome (MIM 120330).". Hum. Genet. 103 (2): 149–53. doi:10.1007/s004390050798. PMID 9760197.
- Schimmenti LA, Shim HH, Wirtschafter JD et al. (2000). "Homonucleotide expansion and contraction mutations of PAX2 and inclusion of Chiari 1 malformation as part of renal-coloboma syndrome.". Hum. Mutat. 14 (5): 369–76. doi:10.1002/(SICI)1098-1004(199911)14:5<369::AID-HUMU2>3.0.CO;2-E. PMID 10533062.
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External links
- GeneReviews/NCBI/NIH/UW entry on Renal Coloboma Syndrome
- PAX2 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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