Affinage

PAX2

Paired box protein Pax-2 · UniProt Q02962

Length
417 aa
Mass
44.7 kDa
Annotated
2026-04-29
100 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PAX2 is a paired-domain transcription factor that plays essential roles in kidney, eye, ear, and midbrain-hindbrain boundary development by controlling nephric lineage specification, mesenchymal-to-epithelial transition, optic fissure closure, and cochlear morphogenesis (PMID:8951055, PMID:12435636, PMID:8383297). PAX2 binds DNA through its paired domain and activates transcription of target genes including WNT4, WNT5A, NAIP, Brn1, ADAM10, and IL-5 via its C-terminal activation domain (residues 279–373), which recruits the BRCT-domain adaptor PTIP to engage histone methyltransferase complexes; JNK-mediated phosphorylation of this domain promotes transactivation (PMID:8702876, PMID:10908331, PMID:16368682, PMID:14532124). PAX2 is converted from an activator to a repressor by Groucho/TLE family corepressors, which recruit the phosphatase PPM1B to dephosphorylate the activation domain, displacing PTIP and inhibiting H3K4 methylation at target loci (PMID:14532124, PMID:25631048). Loss-of-function mutations in PAX2 cause renal-coloboma syndrome and focal segmental glomerulosclerosis through haploinsufficiency or dominant-negative impairment of DNA binding and transactivation (PMID:20221250, PMID:24676634).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1993 High

    Deregulated Pax2 expression in transgenic mice established that PAX2 must be tightly regulated for normal kidney epithelial differentiation, revealing it as a dosage-sensitive developmental regulator rather than simply required for kidney induction.

    Evidence Transgenic mice with constitutive Pax2 expression showing nephrotic syndrome-like histology

    PMID:8383297

    Open questions at the time
    • Target genes mediating the gain-of-function phenotype were unknown
    • Whether the effect was cell-autonomous in specific nephron segments was not determined
  2. 1995 High

    The discovery that WT1 directly represses Pax2 transcription via binding in the 5' leader established the first upstream regulator of PAX2 and linked PAX2 silencing to podocyte differentiation.

    Evidence DNase I footprinting of WT1 on Pax2 promoter and CAT reporter assays in co-transfection experiments

    PMID:7720589

    Open questions at the time
    • Whether WT1 repression is sufficient for Pax2 downregulation in vivo was not tested by WT1 conditional deletion at this point
  3. 1996 High

    Pax2 knockout mice revealed its indispensable role in optic fissure closure, cochlear development, and optic chiasm formation, defining the scope of PAX2 developmental requirements beyond kidney.

    Evidence Pax2-null mice analyzed by paint-fill, histology, and gene expression

    PMID:8951055

    Open questions at the time
    • Downstream target genes in eye and ear were not identified
    • Cell-autonomous versus non-autonomous effects were not resolved
  4. 1996 High

    Mapping of the PAX2 transactivation domain (aa 279–373) and identification of the octapeptide as an intrinsic repression domain established the modular architecture governing PAX2's dual activator/repressor function.

    Evidence GAL4 fusion deletion mapping with reporter assays in tissue culture

    PMID:8702876

    Open questions at the time
    • Cofactors mediating octapeptide-dependent repression were not yet identified
    • Post-translational modifications of the activation domain were unknown
  5. 2000 High

    Identification of PTIP as a direct binding partner of the PAX2 activation domain linked PAX2 to active chromatin and histone-modifying machinery, providing the first mechanistic explanation for how PAX2 activates transcription.

    Evidence Yeast two-hybrid, in vitro pulldown, and co-localization in nuclear matrix fractions

    PMID:10908331

    Open questions at the time
    • The specific histone modifications deposited via PTIP at PAX2 target genes were not determined
    • Whether PTIP is required for all PAX2-dependent activation was untested
  6. 2002 High

    Pax2/Pax8 double-knockout and Pax2 misexpression experiments demonstrated that Pax2 (with Pax8) is the earliest specification factor for the entire nephric lineage, resolving its position at the top of the kidney developmental hierarchy.

    Evidence Double-mutant mice lacking all nephric structures; retroviral Pax2 misexpression inducing ectopic nephric tissue in chick

    PMID:12435636

    Open questions at the time
    • Direct transcriptional targets mediating nephric specification (beyond Lim1 and c-Ret) were not identified
    • Relative contributions of Pax2 versus Pax8 were not fully resolved
  7. 2003 High

    The finding that Groucho/Grg4 suppresses PAX2 transactivation by specifically blocking JNK-mediated phosphorylation of the activation domain — independently of histone deacetylation — revealed the molecular switch converting PAX2 from activator to repressor.

    Evidence Co-IP, in vitro kinase assay, reporter assays with HDAC inhibitors and mutagenesis

    PMID:14532124

    Open questions at the time
    • The JNK phosphorylation sites on PAX2 were not mapped
    • Whether Grg4 recruitment occurs at all PAX2 target loci was unknown
  8. 2005 High

    Direct PAX2 binding to and activation of the WNT4 promoter connected PAX2 to the mesenchymal-to-epithelial transition signal, identifying the first direct downstream effector linking PAX2 to nephron induction.

    Evidence EMSA, reporter assays, and reduced Wnt4 mRNA in Pax2 heterozygous kidneys

    PMID:16368682

    Open questions at the time
    • Whether PAX2 is sufficient for WNT4 activation in the absence of cofactors was not established
    • Other PAX2 targets required for MET were not mapped
  9. 2008 High

    PAX2 was shown to mediate ER-dependent ERBB2 repression in breast cancer, with PAX2 and AIB-1/SRC-3 competing at the ERBB2 locus, establishing PAX2 as a determinant of tamoxifen response and expanding its role beyond development.

    Evidence ChIP, co-IP, reporter assays, and siRNA knockdown in human breast cancer cell lines

    PMID:19005469

    Open questions at the time
    • Structural basis of PAX2–AIB-1 competition at the ERBB2 element was not resolved
    • Whether PAX2 represses ERBB2 in normal breast epithelium was unknown
  10. 2010 Medium

    Characterization of a PAX2 disease missense mutation (T74A) as a hypomorphic allele with reduced transactivation and protein stability — without loss of DNA binding — revealed that PAX2-associated renal disease can arise from quantitative functional impairment rather than complete loss of DNA recognition.

    Evidence Reporter assays, in vitro binding, protein stability analysis, and mouse knock-in model

    PMID:20221250

    Open questions at the time
    • The mechanism by which T74A reduces protein stability was not determined
    • Whether all renal-coloboma mutations act as hypomorphs was not systematically tested
  11. 2015 High

    Identification of PPM1B as the phosphatase within the Groucho repressor complex that dephosphorylates the PAX2 activation domain and displaces PTIP completed the activator-to-repressor switch mechanism, showing that H3K4 methylation status at PAX2 targets is dynamically controlled by the balance between JNK phosphorylation and PPM1B dephosphorylation.

    Evidence Co-IP, ChIP, reporter assays, siRNA knockdown of PPM1B, histone methylation analysis

    PMID:25631048

    Open questions at the time
    • Whether PPM1B activity is itself regulated in a tissue-specific manner was not explored
    • The full set of loci where the PTIP/PPM1B switch operates genome-wide was not mapped
  12. 2020 Medium

    Inducible Pax2/Pax8 deletion in adult kidney demonstrated a maintained role for these factors in regulating urine concentration through urea transporter and aquaporin expression, extending PAX2 function from developmental patterning to adult homeostasis.

    Evidence Conditional double KO in adult mice with gene expression profiling and ChIP for histone methyltransferase recruitment

    PMID:32381599

    Open questions at the time
    • Individual contributions of Pax2 versus Pax8 to adult collecting duct gene regulation were not separated
    • Whether PAX2 directly binds Slc14a2 regulatory elements (as opposed to Pax8) was not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A genome-wide map of direct PAX2 binding sites and the structural basis for its context-dependent switch between activation and repression remain to be determined.
  • No genome-wide ChIP-seq for PAX2 across developmental stages has been reported in the timeline
  • No crystal structure of PAX2 paired domain bound to a physiological target site is described
  • How tissue-specific cofactor availability determines activator versus repressor output at individual loci is unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 3 R-HSA-4839726 Chromatin organization 2
Partners
AIB1ASH2LGRG4PHD3PPM1BPTIPTLXWT1

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Loss-of-function (knockout) of Pax2 in mice results in agenesis of the optic chiasma (ipsilateral optic tracts), coloboma due to failure of optic fissure closure, and agenesis of the cochlea and spiral ganglion, establishing Pax2 as a major regulator of patterning and morphogenesis in the eye and inner ear. Pax2 null mutant mice; paint-fill, gene expression analysis, histology Development High 8951055
2002 Pax2 and Pax8 together are required to specify the nephric lineage: double-mutant mouse embryos lacking both genes fail to form the pronephros or any subsequent nephric structures, fail to undergo mesenchymal-epithelial transition, and fail to initiate Lim1 and c-Ret expression. Retroviral misexpression of Pax2 alone was sufficient to induce ectopic nephric structures in chick intermediate mesoderm. Pax2/Pax8 double-mutant mice; retroviral misexpression in chick embryos; gene expression analysis Genes & Development High 12435636
1993 Deregulated (gain-of-function) Pax-2 expression in transgenic mice causes histologically abnormal, dysfunctional renal epithelium with properties similar to congenital nephrotic syndrome, demonstrating that repression of Pax-2 is required for normal kidney development and that persistent Pax-2 expression restricts differentiation potential of renal epithelial cells. Transgenic mice with deregulated Pax-2 expression; histological and functional analysis Nature High 8383297
2008 PAX2 acts as a crucial mediator of estrogen receptor (ER)-dependent transcriptional repression of ERBB2/HER-2 in response to tamoxifen in breast cancer cells; PAX2 and the ER co-activator AIB-1/SRC-3 compete for binding and regulation of ERBB2 transcription at a cis-regulatory element within the ERBB2 gene. ChIP, co-IP, reporter assays, siRNA knockdown in human breast cancer cell lines Nature High 19005469
1995 WT1 protein directly represses Pax-2 transcription by binding to three high-affinity sites in the 5' untranslated Pax-2 leader sequence, as demonstrated by DNase I footprinting and co-transfection/reporter assays; this coincides with down-regulation of Pax-2 in developing podocyte precursors. DNase I footprinting, co-transfection with CAT reporter constructs, immunostaining Development High 7720589
1996 Pax-2 transactivation requires amino acids 279–373 in the C-terminus; the conserved octapeptide sequence acts as a repression domain that down-modulates Pax-2 transactivation in heterologous contexts. Deletion/mutation mapping with GAL4 fusion reporter assays in tissue culture cells Journal of Biological Chemistry High 8702876
2000 PTIP, a novel BRCT domain-containing protein, directly binds to the Pax2 activation domain (but not when the octapeptide repression domain is present), as shown by yeast two-hybrid, in vitro binding, and co-localization in tissue culture nuclei/active chromatin/nuclear matrix fraction, linking Pax2 to active chromatin machinery. Yeast two-hybrid, in vitro pulldown, co-localization in tissue culture cells, nuclear fractionation Nucleic Acids Research High 10908331
2003 The Groucho/TLE family protein Grg4 interacts with Pax2 to suppress transactivation by specifically inhibiting JNK-mediated phosphorylation of the Pax2 activation domain; this suppression depends on Pax2 binding to its target DNA and is independent of histone deacetylation. Co-IP, in vitro kinase assay, reporter assay, mutagenesis, HDAC inhibitor treatment EMBO Journal High 14532124
2015 The phosphatase PPM1B is a component of the Groucho4 repressor complex recruited by Pax2 to chromatin; PPM1B dephosphorylates the Pax2 activation domain and displaces the adaptor protein PTIP, thereby inhibiting H3K4 methylation and switching Pax2 from a transcriptional activator to a repressor. Loss of PPM1B prevents Groucho-mediated gene repression. Co-IP, ChIP, reporter assays, siRNA knockdown, histone methylation analysis Journal of Biological Chemistry High 25631048
2005 PAX2 directly activates WNT4 transcription during kidney development by binding to three specific recognition motifs in the WNT4 promoter, as shown by EMSA, co-transfection reporter assays, and reduced Wnt4 mRNA in heterozygous Pax2 mutant mouse kidneys. EMSA, co-transfection reporter assay, RT-PCR in Pax2 heterozygous fetal kidneys Journal of Biological Chemistry High 16368682
2006 PAX2 directly binds the neuronal apoptosis inhibitory protein (NAIP) gene promoter and activates NAIP transcription (~7-fold in vitro; 4-fold increase in stably transfected HEK293 cells); Naip mRNA is reduced 50% in heterozygous Pax2 mutant mice, and NAIP suppresses caspase-3/7-mediated apoptosis in collecting duct cells. EMSA, reporter assay, stable transfection, RT-PCR in Pax2 mutant mice, caspase activity assay American Journal of Physiology: Renal Physiology High 16735463
2006 Inducible podocyte-specific expression of PAX2 in adult mice represses WT1 and consequently reduces nephrin expression, causing end-stage renal failure; recruitment of the Groucho-related protein TLE4 may convert Pax2 into a transcriptional repressor of Wt1. Inducible transgenic mouse model (Cre-lox), immunostaining, gene expression analysis Current Biology High 16631587
2005 Pax2 directly regulates Brn1 (Pou3f3) transcription at the mid-hindbrain boundary via two functional Pax2-binding sites in the Brn1 promoter and upstream regulatory element, as shown by reporter assay; Brn1 in turn is implicated in Fgf8 gene regulation. cDNA microarray with FACS-sorted GFP+ cells from Pax2-/- embryos, lacZ reporter transgene analysis, mutagenesis of Pax2-binding sites, dominant-negative electroporation in chick Development High 15872005
2000 Pax2 and homeodomain proteins cooperatively regulate the Pax5 mhb enhancer through direct binding; mutation of the Pax2/5/8 binding site in the Pax5 enhancer reduces transgene expression at the midbrain-hindbrain boundary, and Pax2 mutant embryos show reduced Pax5 expression specifically in regions dependent on the Pax-binding site. Transgenic reporter assay, site-directed mutagenesis of enhancer binding sites, protein binding assays with mhb-specific extracts, analysis in Pax2 mutant embryos Development High 10662641
2002 The activation and maintenance of Pax2 expression at the midbrain-hindbrain boundary are controlled by separate enhancers: an early enhancer (~-3.7 kb, dependent on homeodomain/POU binding sites including Oct3/4) and two late enhancers (~-4.1 kb and ~-2.8 kb); the proximal late enhancer contains a functional Pax2/5/8-binding site mediating auto- and cross-regulatory maintenance. Transgenic reporter analysis, site-directed mutagenesis, BAC transgene deletion analysis, Oct3/4 binding assay Development High 11807024
2014 p53 directly occupies chromatin regions of the Pax2 promoter and gene in embryonic kidneys (ChIP-Seq), stimulates Pax2 promoter activity in transfection assays, and p53 knockout mice show reduced Pax2 in nephron progenitors; reducing p53 gene dosage worsens renal hypoplasia in Pax2+/- mice, establishing a p53–Pax2 epistatic relationship in nephrogenesis. ChIP-Seq, transient transfection reporter assay, p53 KO and conditional KO mice, siRNA knockdown in cultured metanephric mesenchyme cells PLoS One High 22984579
2000 Tlx (orphan nuclear receptor) directly regulates Pax2 transcription: Tlx binds a conserved site in the Pax2 promoter, Tlx-null mice show reduced Pax2 expression, and Pax2 is identified as a direct transcriptional target of Tlx in retinal development. Tlx targeted knockout mice, P19 neural precursor screen, promoter binding assay, sequence conservation analysis PNAS Medium 10706625
1996 Pax-2 proteins (2A and 2B isoforms) bind DNA through the paired domain with similar specificity; chromatin immunoprecipitation from embryonic neural tube identified novel in vivo Pax-2 binding sites sharing homology with Pax-5 and Pax-2 consensus sequences. Chromatin immunoprecipitation from embryonic neural tube, in vitro DNA binding assays with recombinant Pax-2 Journal of Biological Chemistry Medium 8626478
2011 PHD3 (prolyl hydroxylase domain protein 3) physically binds to Pax2 protein and mediates its proteasomal destruction; inhibition of PHD3 hydroxylase activity increases Pax2 protein but not mRNA levels, identifying PHD3 as a post-translational negative regulator of Pax2 stability. Co-IP, PHD3 inhibitor treatment, Western blot for Pax2 protein vs. mRNA levels Biochemical and Biophysical Research Communications Medium 21575608
2008 PAX2 directly binds to and transactivates the WNT5A promoter in HEK293 cells, as shown by transactivation assays and EMSA; reduced WNT5A expression in Wilms tumor correlates with blastemal predominance. Chromatin enrichment, ChIP, EMSA, transactivation assay in HEK293 cells Neoplasia Medium 19048125
2011 PAX2 binds to the ADAM10 promoter and regulates ADAM10 protein expression in renal cancer cells; PAX2 silencing leads to reduced ADAM10, reduced L1-CAM shedding, altered EMT markers, and activation of PI3K/Akt pathway via L1-CAM. ChIP (PAX2 binding to ADAM10 promoter), siRNA knockdown, Western blot, invasion/migration assays Carcinogenesis Medium 21880579
2004 Angiotensin II stimulates Pax-2 gene expression in rat proximal tubular cells via the AT2 receptor and the JAK2/STAT signaling pathway; cells lacking Pax-2 are prone to apoptosis rather than proliferation, and stable sense Pax-2 increases proliferation while antisense Pax-2 reduces it. Western blot, RT-PCR, pharmacological inhibitors (PD123319, AG490, genistein), stable transfection, TUNEL, BrdU assays Kidney International Medium 15569307
2010 Pax2 controls inner ear placode morphogenesis by regulating apical localization of N-cadherin and N-CAM: in the absence of Pax2, otic progenitors lose apically localized N-cadherin and N-CAM and fail to elongate, while misexpression of Pax2 leads to ectopic activation of both adhesion molecules. Pax2 regulates cell shape independently from otic cell identity. Loss-of-function (morpholino/knockout), gain-of-function (misexpression), immunostaining for N-cadherin and N-CAM in chick otic placode Developmental Biology Medium 20643116
2006 Pax2 overexpression in the optic nerve is sufficient to block neuronal differentiation and promote astroglial development; Pax2 expression in optic nerve progenitors is maintained by a Sonic hedgehog–FGF signaling cascade. Electroporation-based overexpression in chick optic nerve/neural tube, in vitro signaling pathway inhibition, loss-of-function explant cultures Developmental Biology Medium 17173889
2009 BMP7 and SHH activate Pax2 expression in mouse retinal astrocyte precursors by relieving repression by TLX; BMP and SHH pathway members interact with TLX to derepress Pax2 expression. In vitro retinal astrocyte precursor cultures, BMP7/SHH treatment, pathway inhibition, co-immunoprecipitation of pathway components with TLX Developmental Biology Medium 19505455
2006 In C. elegans, Pax2/5/8-related proteins (egl-38 and pax-2) promote cell survival by acting as transcriptional regulators of ced-9, the C. elegans bcl-2 gene, as shown by genetic and molecular experiments. Genetic epistasis analysis, molecular/expression studies in C. elegans Development Medium 17021039
2015 PAX2 directly binds to two sites in the IL-5 promoter and stimulates IL-5 promoter activity and expression in esophageal cancer cells, as confirmed by ChIP; IL-5 is identified as a PAX2 effector mediating tumor metastasis. ChIP, luciferase reporter assay, mRNA microarray, shRNA knockdown Cellular Physiology and Biochemistry Medium 25613757
2017 A small molecule (EG1) identified by virtual screening of a Pax2 paired domain homology model inhibits Pax2-DNA binding with Kd 1.35–1.5 µM, blocks Pax2-mediated transactivation in cell-based assays, inhibits embryonic kidney development in a Pax2-dependent manner, and reduces proliferation of Pax2-positive cancer cell lines. Virtual screen on Pax2 paired domain homology model, in vitro DNA binding assay, cell-based transactivation assay, ex vivo kidney culture ACS Chemical Biology Medium 28094913
2020 Pax2 and Pax8 regulate urine concentration in the adult kidney by controlling expression of urea transporters (Slc14a2) and aquaporins in the inner and outer medulla; Pax8 expression is induced by high-salt in collecting duct cells and activates Slc14a2 by recruiting a histone methyltransferase complex to the promoter. Mice with induced double deletion develop severe polyuria. Inducible conditional KO of Pax2/Pax8 in adult mice, gene expression profiling, ChIP for histone methyltransferase recruitment Journal of the American Society of Nephrology Medium 32381599
2010 PAX2 missense mutations in the paired domain (e.g., p.T74A) reduce Pax2 transactivation activity and protein stability without affecting nuclear localization, steady-state mRNA, or DNA consensus binding in vitro, indicating that PAX2/Pax2 disease alleles can act as hypomorphic alleles. Reporter assay (transactivation), in vitro DNA binding assay, protein stability analysis, mouse knock-in model PLoS Genetics Medium 20221250
2014 FSGS-associated PAX2 mutations perturb PAX2 function by affecting proper DNA binding and transactivation activity, or by altering interaction of PAX2 with repressor proteins, resulting in enhanced repressor activity; mutations can cause disease through haploinsufficiency and dominant negative effects. In vitro functional studies (DNA binding, transactivation assays), in silico structural modeling Journal of the American Society of Nephrology Medium 24676634
1998 In HEK293 cells stably expressing PAX2, PAX2 increases WT1 and E-cadherin expression (~2-fold and ~7-fold respectively) and strongly suppresses vimentin expression (to ~8% of control), mimicking aspects of mesenchymal-to-epithelial transition during nephrogenesis. Stable tetracycline-regulatable transfection in HEK293 cells, RT-PCR, Western blot Biochimica et Biophysica Acta Medium 9459485
2002 Pax2 expression is upregulated in tubular cells during renal regeneration after ischemia; activin A signaling (via follistatin-sensitive pathway) modulates the growth of Pax2-positive proliferating tubular progenitor-like cells, and activin A reduces Pax2 expression in cultured metanephroi and in LLC-PK1 cells. Immunostaining in ischemic rat kidneys, follistatin/activin A administration in vivo, metanephros culture, dominant-negative receptor transfection in LLC-PK1 cells Journal of the American Society of Nephrology Medium 12444203
2012 Pax2 suppression in the posterior placodal area (PPA) reduces cell proliferation, and both over-expression and repression of Pax2 produce smaller otocysts and reduced epibranchial placodes, indicating Pax2 functions in maintaining cell cycle proliferation during PPA maintenance. Gain-of-function and loss-of-function (electroporation/morpholino) in chick embryos, cell cycle analysis (BrdU, pH3) Developmental Dynamics Medium 22972769
2005 Tamoxifen-mediated activation of PAX2 in endometrial carcinomas (but not normal endometrium) is associated with cancer-linked hypomethylation of the PAX2 promoter; PAX2 is crucially involved in cell proliferation and carcinogenesis in the endometrium. Promoter methylation analysis, reporter assays, siRNA knockdown in endometrial carcinoma cell lines Nature Medium 16355216
2020 ASH2L associates with ERα and is recruited to cis-regulatory elements of PAX2, altering histone H3K4me3 and H3K27me3 levels to enhance ERα-mediated transactivation of PAX2 in endometrial cancer cells. ChIP-seq, co-IP (ASH2L–ERα), siRNA knockdown, histone modification analysis Cancer Science Medium 32279431

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Pax2 contributes to inner ear patterning and optic nerve trajectory. Development (Cambridge, England) 492 8951055
2002 Nephric lineage specification by Pax2 and Pax8. Genes & development 410 12435636
1990 Spatially and temporally restricted expression of Pax2 during murine neurogenesis. Development (Cambridge, England) 371 1977575
1993 Deregulation of Pax-2 expression in transgenic mice generates severe kidney abnormalities. Nature 260 8383297
2008 Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen. Nature 247 19005469
2004 Generation of Pax2-Cre mice by modification of a Pax2 bacterial artificial chromosome. Genesis (New York, N.Y. : 2000) 246 15083520
1995 Repression of Pax-2 by WT1 during normal kidney development. Development (Cambridge, England) 233 7720589
2005 Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis. Nature 218 16355216
2007 Pax2 and pax8 regulate branching morphogenesis and nephron differentiation in the developing kidney. Journal of the American Society of Nephrology : JASN 181 17314325
1997 Cooperation of Pax2 and Pax5 in midbrain and cerebellum development. Proceedings of the National Academy of Sciences of the United States of America 143 9159136
2004 The role of Pax2 in mouse inner ear development. Developmental biology 142 15242798
2010 Pax2 and Pax8 cooperate in mouse inner ear morphogenesis and innervation. BMC developmental biology 127 20727173
2002 Expression of the transcription factors GATA3 and Pax2 during development of the mammalian inner ear. The Journal of comparative neurology 124 11793341
1997 Xenopus Pax-2 displays multiple splice forms during embryogenesis and pronephric kidney development. Mechanisms of development 121 9486533
1999 Renal-coloboma syndrome: a multi-system developmental disorder caused by PAX2 mutations. Clinical genetics 120 10466411
2010 Secretory cell outgrowth, PAX2 and serous carcinogenesis in the Fallopian tube. The Journal of pathology 119 20597068
2000 The orphan nuclear receptor Tlx regulates Pax2 and is essential for vision. Proceedings of the National Academy of Sciences of the United States of America 107 10706625
2010 High-grade fimbrial-ovarian carcinomas are unified by altered p53, PTEN and PAX2 expression. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 100 20562848
1999 Pax2 in development and renal disease. The International journal of developmental biology 95 10535325
2014 Mutations in PAX2 associate with adult-onset FSGS. Journal of the American Society of Nephrology : JASN 94 24676634
2011 HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort. Pediatric nephrology (Berlin, Germany) 93 21380624
2000 Reduced Pax2 gene dosage increases apoptosis and slows the progression of renal cystic disease. Developmental biology 92 10694420
2003 Zebrafish hhex, nk2.1a, and pax2.1 regulate thyroid growth and differentiation downstream of Nodal-dependent transcription factors. Developmental biology 89 14568547
2002 The activation and maintenance of Pax2 expression at the mid-hindbrain boundary is controlled by separate enhancers. Development (Cambridge, England) 85 11807024
2008 Ptf1a, Lbx1 and Pax2 coordinate glycinergic and peptidergic transmitter phenotypes in dorsal spinal inhibitory neurons. Developmental biology 82 18634777
2019 Exosomal MiR-744 Inhibits Proliferation and Sorafenib Chemoresistance in Hepatocellular Carcinoma by Targeting PAX2. Medical science monitor : international medical journal of experimental and clinical research 78 31553714
2009 PAX2 expression in low malignant potential ovarian tumors and low-grade ovarian serous carcinomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 78 19525924
2002 Involvement of Pax-2 in the action of activin A on tubular cell regeneration. Journal of the American Society of Nephrology : JASN 73 12444203
2003 Groucho suppresses Pax2 transactivation by inhibition of JNK-mediated phosphorylation. The EMBO journal 72 14532124
2000 PTIP, a novel BRCT domain-containing protein interacts with Pax2 and is associated with active chromatin. Nucleic acids research 70 10908331
2000 PAX2 mutations in renal-coloboma syndrome: mutational hotspot and germline mosaicism. European journal of human genetics : EJHG 66 11093271
2009 Expression of CD133, PAX2, ESA, and GPR30 in invasive ductal breast carcinomas. Chinese medical journal 63 19951611
2000 Pax2, Otx2, Gbx2 and Fgf8 expression in early otic vesicle development. Mechanisms of development 63 10906468
2002 Expression of the PAX2 oncogene in human breast cancer and its role in progesterone-dependent mammary growth. Oncogene 62 11850818
2000 Pax2 and homeodomain proteins cooperatively regulate a 435 bp enhancer of the mouse Pax5 gene at the midbrain-hindbrain boundary. Development (Cambridge, England) 61 10662641
1996 Mapping of Pax-2 transcription activation domains. The Journal of biological chemistry 61 8702876
1995 Involvement of wnt1 and pax2 in the formation of the midbrain-hindbrain boundary in the zebrafish gastrula. Developmental genetics 60 7586754
1999 Roles of Pax-2 in initiation of the chick tectal development. Brain research. Developmental brain research 59 10446345
2005 Identification of Pax2-regulated genes by expression profiling of the mid-hindbrain organizer region. Development (Cambridge, England) 57 15872005
2010 Pax2 coordinates epithelial morphogenesis and cell fate in the inner ear. Developmental biology 55 20643116
2005 PAX2 activates WNT4 expression during mammalian kidney development. The Journal of biological chemistry 55 16368682
1996 Identification of novel Pax-2 binding sites by chromatin precipitation. The Journal of biological chemistry 53 8626478
2005 Multicystic dysplastic kidney and variable phenotype in a family with a novel deletion mutation of PAX2. Journal of the American Society of Nephrology : JASN 47 16049068
2011 The transcription factor PAX2 regulates ADAM10 expression in renal cell carcinoma. Carcinogenesis 46 21880579
1998 The role of PAX2 in normal and abnormal development of the urinary tract. Pediatric nephrology (Berlin, Germany) 44 9874314
2019 Inhibition of soluble epoxide hydrolase attenuates a high-fat diet-mediated renal injury by activating PAX2 and AMPK. Proceedings of the National Academy of Sciences of the United States of America 43 30804206
2019 PAX2 in endometrial carcinogenesis and in differential diagnosis of endometrial hyperplasia: A systematic review and meta-analysis of diagnostic accuracy. Acta obstetricia et gynecologica Scandinavica 42 30511741
2003 Role of Pax2 in apoptosis resistance and proinvasive phenotype of Kaposi's sarcoma cells. The Journal of biological chemistry 42 14627715
1999 Expression of Pax2 and patterning of the chick inner ear. Journal of neurocytology 42 10900085
2011 PAX2-null secretory cell outgrowths in the oviduct and their relationship to pelvic serous cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 41 22080059
2011 PAX2 in human kidney malformations and disease. Pediatric nephrology (Berlin, Germany) 41 22138676
2006 Expression of Pax2 in human renal tumor-derived endothelial cells sustains apoptosis resistance and angiogenesis. The American journal of pathology 41 16436683
2006 Pax2 regulates neuronal-glial cell fate choice in the embryonic optic nerve. Developmental biology 41 17173889
2004 Angiotensin II stimulates Pax-2 in rat kidney proximal tubular cells: impact on proliferation and apoptosis. Kidney international 41 15569307
1996 Pax-2, kidney development, and oncogenesis. Medical and pediatric oncology 41 8827071
2006 Pax2/5/8 proteins promote cell survival in C. elegans. Development (Cambridge, England) 40 17021039
2015 Association of PAX2 and Other Gene Mutations with the Clinical Manifestations of Renal Coloboma Syndrome. PloS one 39 26571382
2019 miR-744-5p Inhibits Non-Small Cell Lung Cancer Proliferation and Invasion by Directly Targeting PAX2. Technology in cancer research & treatment 38 31522607
2012 Hnf1b and Pax2 cooperate to control different pathways in kidney and ureter morphogenesis. Human molecular genetics 38 22511595
2006 An inducible mouse model for PAX2-dependent glomerular disease: insights into a complex pathogenesis. Current biology : CB 38 16631587
2019 Diverse phenotypes in children with PAX2-related disorder. Molecular genetics & genomic medicine 37 31060108
1993 Aberrant expression of Pax-2 in Danforth's short tail (Sd) mice. Developmental biology 37 8482415
2022 Reliable Identification of Endometrial Precancers Through Combined Pax2, β-Catenin, and Pten Immunohistochemistry. The American journal of surgical pathology 35 34545858
2012 A p53-Pax2 pathway in kidney development: implications for nephrogenesis. PloS one 35 22984579
1998 Effects of PAX2 expression in a human fetal kidney (HEK293) cell line. Biochimica et biophysica acta 34 9459485
2017 Inhibition of Pax2 Transcription Activation with a Small Molecule that Targets the DNA Binding Domain. ACS chemical biology 33 28094913
2012 Evolution of a tissue-specific silencer underlies divergence in the expression of pax2 and pax8 paralogues. Nature communications 33 22617288
2008 WNT5A is regulated by PAX2 and may be involved in blastemal predominant Wilms tumorigenesis. Neoplasia (New York, N.Y.) 32 19048125
2014 Pax8 and Pax2 are specifically required at different steps of Xenopus pronephros development. Developmental biology 31 25446030
2013 Cotransfection of Pax2 and Math1 promote in situ cochlear hair cell regeneration after neomycin insult. Scientific reports 30 24141260
2009 BMP7 and SHH regulate Pax2 in mouse retinal astrocytes by relieving TLX repression. Developmental biology 30 19505455
2014 The PAX2-null immunophenotype defines multiple lineages with common expression signatures in benign and neoplastic oviductal epithelium. The Journal of pathology 29 25130537
2018 From Otic Induction to Hair Cell Production: Pax2EGFP Cell Line Illuminates Key Stages of Development in Mouse Inner Ear Organoid Model. Stem cells and development 28 29272992
2015 Upregulation of PAX2 promotes the metastasis of esophageal cancer through interleukin-5. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 27 25613757
2015 The Groucho-associated phosphatase PPM1B displaces Pax transactivation domain interacting protein (PTIP) to switch the transcription factor Pax2 from a transcriptional activator to a repressor. The Journal of biological chemistry 27 25631048
2012 Conditional deletion of the human ortholog gene Dicer1 in Pax2-Cre expression domain impairs orofacial development. Indian journal of human genetics 27 23716939
1995 Transcription factors in renal development: the WT1 and Pax-2 story. Seminars in nephrology 27 7569406
2018 UnPAXing the Divergent Roles of PAX2 and PAX8 in High-Grade Serous Ovarian Cancer. Cancers 26 30096791
2010 Utility of PAX8 and PAX2 immunohistochemistry in the identification of renal cell carcinoma in diagnostic cytology. Diagnostic cytopathology 25 22807381
1998 Expression of PAX2 gene during human development. The International journal of developmental biology 25 9712525
2020 Clinical and genetic variability of PAX2-related disorder in the Japanese population. Journal of human genetics 23 32203253
2020 Pax2 and Pax8 Proteins Regulate Urea Transporters and Aquaporins to Control Urine Concentration in the Adult Kidney. Journal of the American Society of Nephrology : JASN 23 32381599
2012 Pax2 modulates proliferation during specification of the otic and epibranchial placodes. Developmental dynamics : an official publication of the American Association of Anatomists 23 22972769
2021 The Role of PAX2 in Neurodevelopment and Disease. Neuropsychiatric disease and treatment 21 34908837
2020 ASH2L is involved in promotion of endometrial cancer progression via upregulation of PAX2 transcription. Cancer science 21 32279431
2015 Divergent Roles of PAX2 in the Etiology and Progression of Ovarian Cancer. Cancer prevention research (Philadelphia, Pa.) 21 26373819
1997 Pax-2 in the chiasm. Cell and tissue research 21 9321680
2012 Signaling pathways of PAX2 and its role in renal interstitial fibrosis and glomerulosclerosis. Journal of receptor and signal transduction research 20 23137159
2006 Neuronal apoptosis inhibitory protein is expressed in developing kidney and is regulated by PAX2. American journal of physiology. Renal physiology 20 16735463
2015 Pax2 expression in simultaneously diagnosed WHO and EIN classification systems. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 19 25473752
2012 Value of PAX2 immunostaining in tumor diagnosis: a review and update. Advances in anatomic pathology 19 23060065
2010 En2, Pax2/5 and Tcf-4 transcription factors cooperate in patterning the Xenopus brain. Developmental biology 19 20171202
2010 Papillorenal syndrome-causing missense mutations in PAX2/Pax2 result in hypomorphic alleles in mouse and human. PLoS genetics 19 20221250
2006 The Pax2/5/8 gene egl-38 coordinates organogenesis of the C. elegans egg-laying system. Developmental biology 19 17020758
2022 Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells. eLife 18 35018885
2018 Diagnostic Utility of Pax8, Pax2, and NGFR Immunohistochemical Expression in Pediatric Renal Tumors. Applied immunohistochemistry & molecular morphology : AIMM 18 28426529
2011 Prolyl hydroxylase domain protein 3 targets Pax2 for destruction. Biochemical and biophysical research communications 18 21575608
2016 PAX2 function, regulation and targeting in fallopian tube-derived high-grade serous ovarian cancer. Oncogene 17 27991925
2007 PAX2 expression by HHV-8-infected endothelial cells induced a proangiogenic and proinvasive phenotype. Blood 17 18056486
2003 Mutations in lozenge and D-Pax2 invoke ectopic patterned cell death in the developing Drosophila eye using distinct mechanisms. Development genes and evolution 17 12690448