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PAX2
Identifiers
Aliases	PAX2, PAPRS, FSGS7, paired box 2, PAX-2
External IDs	OMIM: 167409; MGI: 97486; HomoloGene: 2968; GeneCards: PAX2; OMA:PAX2 - orthologs
Gene location (Human) Chr. Chromosome 10 (human) Band 10q24.31 Start 100,735,396 bp End 100,829,944 bp
Gene location (Mouse) Chr. Chromosome 19 (mouse) Band 19 C3|19 38.09 cM Start 44,756,045 bp End 44,837,871 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in renal medulla right uterine tube human kidney tail of epididymis corpus epididymis seminal vesicula endometrium testicle paraflocculus of cerebellum kidney tubule Top expressed in mesonephros mesonephric tubules mesonephric duct optic stalk ureteric bud otic placode neural ectoderm epithelium of epididymis Gray matter of spinal cord optic recess More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding superoxide-generating NAD(P)H oxidase activity transcription factor binding cis-regulatory region sequence-specific DNA binding protein binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity Cellular component Golgi apparatus centriolar satellite microtubule organizing center protein-DNA complex nucleolus lysosome nucleus protein-containing complex Biological process cellular response to hydrogen peroxide cellular response to glucose stimulus cochlea development pronephros development cellular response to retinoic acid regulation of metanephric nephron tubule epithelial cell differentiation animal organ development ureter development cell differentiation negative regulation of cysteine-type endopeptidase activity involved in apoptotic process positive regulation of branching involved in ureteric bud morphogenesis regulation of transcription, DNA-templated positive regulation of metanephric DCT cell differentiation regulation of metanephros size axonogenesis protein kinase B signaling negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis negative regulation of apoptotic process involved in metanephric collecting duct development positive regulation of epithelial cell proliferation optic nerve morphogenesis pronephric field specification positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis metanephric mesenchymal cell differentiation ageing metanephric epithelium development mesenchymal to epithelial transition involved in metanephros morphogenesis negative regulation of apoptotic process glial cell differentiation transcription by RNA polymerase II retinal pigment epithelium development nephric duct formation transcription, DNA-templated stem cell differentiation metanephric distal convoluted tubule development reactive oxygen species metabolic process negative regulation of mesenchymal cell apoptotic process involved in metanephros development mesonephros development optic nerve structural organization positive regulation of transcription, DNA-templated cellular response to epidermal growth factor stimulus metanephric nephron tubule formation positive regulation of metanephric glomerulus development multicellular organism development branching involved in ureteric bud morphogenesis neural tube closure response to nutrient levels negative regulation of apoptotic process involved in metanephric nephron tubule development ureter maturation inner ear morphogenesis cochlea morphogenesis positive regulation of optic nerve formation positive regulation of cell population proliferation optic cup morphogenesis involved in camera-type eye development urogenital system development cell fate determination negative regulation of programmed cell death vestibulocochlear nerve formation camera-type eye development metanephric collecting duct development negative regulation of reactive oxygen species metabolic process mesodermal cell fate specification negative regulation of transcription, DNA-templated metanephric mesenchyme development optic chiasma development optic nerve development positive regulation of transcription by RNA polymerase II visual perception negative regulation of cytolysis brain morphogenesis mesenchymal to epithelial transition Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5076 18504 Ensembl ENSG00000075891 ENSMUSG00000004231 UniProt Q02962 Q5SZP1 P32114 RefSeq (mRNA) NM_003990 NM_000278 NM_001304569 NM_003987 NM_003988 NM_003989 NM_001374303 NM_011037 RefSeq (protein) NP_000269 NP_001291498 NP_003978 NP_003979 NP_003980 NP_003981 NP_001361232 NP_035167 NP_001355672 NP_001355673 NP_001355674 NP_001355675 NP_001355676 NP_001355677 NP_001355678 NP_001355679 NP_001355680 Location (UCSC) Chr 10: 100.74 – 100.83 Mb Chr 19: 44.76 – 44.84 Mb PubMed search
Wikidata
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Paired box gene 2, also known as Pax-2, is a protein which in humans is encoded by the PAX2 gene.

Function

The Pax Genes, or Paired-Box Containing Genes, play important roles in the development and proliferation of multiple cell lines, development of organs, and development and organization of the central nervous system. The transcription factor gene PAX2 is important in the regionalized embryological development of the central nervous system. In mammals, the brain is developed in three regions: the forebrain, midbrain, and the hindbrain. Concentration gradients of fibroblast growth factor 8 (FGF8) and Wingless-Type MMTV Integration Site Family, Member 1 (Wnt1) control expression of Pax-2 during development of the Mesencephalon, or midbrain. Similar patterning during embryological development can be observed in “basal chordates or ascidians,” in which organization of the central nervous system in ascidian larvae are also controlled by fibroblast growth factor genes. PAX2 encodes for the transcription factor which appears to be essential in the organization of the midbrain and hindbrain regions, and at the earliest can be detected on either side of the sulcus limitans, which separates motor and sensory nerve nuclei.

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

Pathologically, Pax2 has been demonstrated to activate hepatocyte growth factor (HGF) gene promoter, and both have been indicated as playing a role in human prostate cancers.

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. 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.

Pax2 misexpression is frequently observed in proliferative disorders of the kidney. For example, Pax2 is highly expressed in polycystic kidney disease (PKD), Wilms' tumor (WT), and renal cell carcinoma (RCC). Pax2 expression in these diseases appears fuel cell cycling, inhibit cell death, and confer resistance to chemotherapy. Due to its role in these diseases, Pax2 is an attractive therapeutic target and a number of methods for inhibiting its activity have been investigated. In fact, a small-molecule was recently identified with the ability to disrupt Pax2 mediated transcription by blocking Pax2 from binding to DNA.

Interactions

PAX2 has been shown to interact with PAXIP1.

See also

• Pax genes

References

1. ^ GRCh38: Ensembl release 89: ENSG00000075891 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000004231 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Pilz AJ, Povey S, Gruss P, Abbott CM (1993). "Mapping of the human homologs of the murine paired-box-containing genes". Mammalian Genome. 4 (2): 78–82. doi:10.1007/BF00290430. PMID 8431641. S2CID 30845070.
6. Stapleton P, Weith A, Urbánek P, Kozmik Z, Busslinger M (Apr 1993). "Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9". Nature Genetics. 3 (4): 292–8. doi:10.1038/ng0493-292. PMID 7981748. S2CID 21338655.
7. ^ Mansouri A, Gruss P (2013). "Pax Gene". In Hughes K, Maloy K (eds.). Brenner's Encyclopedia of Genetics (2nd ed.). San Diego: Elsevier Science. pp. 246–248. doi:10.1016/B978-0-12-374984-0.01128-1. ISBN 978-0-08-096156-9.
8. ^ Imai KS, Satoh N, Satou Y (2002). "Region specific gene expressions in the central nervous system of the ascidian embryo". Mechanisms of Development. 119 (Suppl 1): S275–7. doi:10.1016/S0925-4773(03)00128-X. PMID 14516697. S2CID 16714343.
9. GeneCard for WNT1
10. Nolte J (2009). The human brain: an introduction to its functional anatomy (6th ed.). Philadelphia, PA: Mosby/Elsevier. p. 685. ISBN 978-0-323-04131-7.
11. Ueda T, Ito S, Shiraishi T, Taniguchi H, Kayukawa N, Nakanishi H, Nakamura T, Naya Y, Hongo F, Kamoi K, Okihara K, Kawauchi A, Miki T (2015). "PAX2 promoted prostate cancer cell invasion through transcriptional regulation of HGF in an in vitro model". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1852 (11): 2467–73. doi:10.1016/j.bbadis.2015.08.008. PMID 26296757.
12. "Entrez Gene: PAX2 paired box gene 2".
13. ^ Sharma R, Sanchez-Ferras O, Bouchard M (2015). "Pax genes in renal development, disease and regeneration". Seminars in Cell and Developmental Biology. 44: 97–106. doi:10.1016/j.semcdb.2015.09.016. PMID 26410163.
14. Grimley E, Liao C, Ranghini E, Nikolovska-Coleska Z, Dressler G (2017). "Inhibition of Pax2 Transcription Activation with a Small Molecule that Targets the DNA Binding Domain". ACS Chemical Biology. 12 (3): 724–734. doi:10.1021/acschembio.6b00782. PMC 5761330. PMID 28094913.
15. Grimley E, Dressler GR (2018). "Are Pax proteins potential therapeutic targets in kidney disease and cancer?". Kidney International. 94 (2): 259–267. doi:10.1016/j.kint.2018.01.025. PMC 6054895. PMID 29685496.
16. Lechner MS, Levitan I, Dressler GR (Jul 2000). "PTIP, a novel BRCT domain-containing protein interacts with Pax2 and is associated with active chromatin". Nucleic Acids Research. 28 (14): 2741–51. doi:10.1093/nar/28.14.2741. PMC 102659. PMID 10908331.

Further reading

• Noll M (Aug 1993). "Evolution and role of Pax genes". Current Opinion in Genetics & Development. 3 (4): 595–605. doi:10.1016/0959-437X(93)90095-7. PMID 8241771.
• Dahl E, Koseki H, Balling R (Sep 1997). "Pax genes and organogenesis". BioEssays. 19 (9): 755–65. doi:10.1002/bies.950190905. PMID 9297966. S2CID 23755557.
• Eccles MR, He S, Legge M, Kumar R, Fox J, Zhou C, French M, Tsai RW (2003). "PAX genes in development and disease: the role of PAX2 in urogenital tract development". The International Journal of Developmental Biology. 46 (4): 535–44. PMID 12141441.
• Eccles MR, Wallis LJ, Fidler AE, Spurr NK, Goodfellow PJ, Reeve AE (May 1992). "Expression of the PAX2 gene in human fetal kidney and Wilms' tumor". Cell Growth & Differentiation. 3 (5): 279–89. PMID 1378753.
• Sanyanusin P, Schimmenti LA, McNoe LA, Ward TA, Pierpont ME, Sullivan MJ, Dobyns WB, Eccles MR (Apr 1995). "Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux". Nature Genetics. 9 (4): 358–64. doi:10.1038/ng0495-358. PMID 7795640. S2CID 29180124.
• Ward TA, Nebel A, Reeve AE, Eccles MR (Sep 1994). "Alternative messenger RNA forms and open reading frames within an additional conserved region of the human PAX-2 gene". Cell Growth & Differentiation. 5 (9): 1015–21. PMID 7819127.
• Stapleton P, Weith A, Urbánek P, Kozmik Z, Busslinger M (Apr 1993). "Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9". Nature Genetics. 3 (4): 292–8. doi:10.1038/ng0493-292. PMID 7981748. S2CID 21338655.
• Pilz AJ, Povey S, Gruss P, Abbott CM (1993). "Mapping of the human homologs of the murine paired-box-containing genes". Mammalian Genome. 4 (2): 78–82. doi:10.1007/BF00290430. PMID 8431641. S2CID 30845070.
• Sanyanusin P, McNoe LA, Sullivan MJ, Weaver RG, Eccles MR (Nov 1995). "Mutation of PAX2 in two siblings with renal-coloboma syndrome". Human Molecular Genetics. 4 (11): 2183–4. doi:10.1093/hmg/4.11.2183. PMID 8589702.
• Sanyanusin P, Norrish JH, Ward TA, Nebel A, McNoe LA, Eccles MR (Jul 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, Dressler G, Pelletier J (Aug 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 (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Schimmenti LA, Cunliffe HE, McNoe LA, Ward TA, French MC, Shim HH, Zhang YH, Proesmans W, Leys A, Byerly KA, Braddock SR, Masuno M, Imaizumi K, Devriendt K, Eccles MR (Apr 1997). "Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations". American Journal of Human Genetics. 60 (4): 869–78. PMC 1712484. PMID 9106533.
• Narahara K, Baker E, Ito S, Yokoyama Y, Yu S, Hewitt D, Sutherland GR, Eccles MR, Richards RI (Mar 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". Journal of Medical Genetics. 34 (3): 213–6. doi:10.1136/jmg.34.3.213. PMC 1050895. PMID 9132492.
• Tavassoli K, Rüger W, Horst J (Dec 1997). "Alternative splicing in PAX2 generates a new reading frame and an extended conserved coding region at the carboxy terminus". Human Genetics. 101 (3): 371–5. doi:10.1007/s004390050644. PMID 9439670. S2CID 43590139.
• Stayner CK, Cunliffe HE, Ward TA, Eccles MR (Sep 1998). "Cloning and characterization of the human PAX2 promoter". The Journal of Biological Chemistry. 273 (39): 25472–9. doi:10.1074/jbc.273.39.25472. PMID 9738017.
• Devriendt K, Matthijs G, Van Damme B, Van Caesbroeck D, Eccles M, Vanrenterghem Y, Fryns JP, Leys A (Aug 1998). "Missense mutation and hexanucleotide duplication in the PAX2 gene in two unrelated families with renal-coloboma syndrome (MIM 120330)". Human Genetics. 103 (2): 149–53. doi:10.1007/s004390050798. PMID 9760197. S2CID 8930257.
• Schimmenti LA, Shim HH, Wirtschafter JD, Panzarino VA, Kashtan CE, Kirkpatrick SJ, Wargowski DS, France TD, Michel E, Dobyns WB (2000). "Homonucleotide expansion and contraction mutations of PAX2 and inclusion of Chiari 1 malformation as part of renal-coloboma syndrome". Human Mutation. 14 (5): 369–76. doi:10.1002/(SICI)1098-1004(199911)14:5<369::AID-HUMU2>3.0.CO;2-E. PMID 10533062. S2CID 25564812.

External links

• GeneReviews/NCBI/NIH/UW entry on Renal Coloboma Syndrome
• PAX2+protein,+human at the U.S. 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.

• Genes on human chromosome 10
• Transcription factors