Affinage

PAX2

Paired box protein Pax-2 · UniProt Q02962

Length
417 aa
Mass
44.7 kDa
Annotated
2026-06-10
100 papers in source corpus 32 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PAX2 is a paired-domain, sequence-specific DNA-binding transcription factor that governs urogenital and neural development by activating or repressing lineage-specific target genes (PMID:1977574, PMID:1977575, PMID:1311084). It is required for the earliest mesenchyme-to-epithelium conversion of the metanephric mesenchyme, and embryos lacking PAX2 (or both PAX2 and its partner PAX8) fail to form kidneys, ureters, and genital tracts, while PAX2/PAX8 double loss abolishes nephric lineage specification altogether and PAX2 misexpression alone induces ectopic nephric structures (PMID:8187639, PMID:8575306, PMID:12435636). PAX2 also patterns the optic chiasm, optic fissure, cochlea, and—cooperating with PAX5—the midbrain-hindbrain boundary organizer (PMID:8951055, PMID:9159136). Its transcriptional outputs include direct activation of WNT4, WNT5A, the midbrain-hindbrain factor Brn1/Pou3f3, and a self-maintaining enhancer of its own locus, and it drives epithelial gene programs (raising WT1 and E-cadherin while suppressing vimentin) (PMID:16368682, PMID:19048125, PMID:15872005, PMID:11807024, PMID:9459485). PAX2 transactivation is positively regulated by JNK-mediated phosphorylation of its C-terminal serine/threonine-rich activation module—an interaction scaffolded by JIP1 and DLK—and is antagonized by Groucho/TLE protein Grg4, which suppresses this phosphorylation in a DNA-binding-dependent, HDAC-independent manner (PMID:8617244, PMID:11700324, PMID:14532124). PAX2 specifies intermediate mesoderm and renal progenitors epigenetically by recruiting PTIP-dependent histone methyltransferase complexes to activate target genes, and PAX2/PAX8 sustain adult collecting-duct urine-concentrating genes such as Slc14a2 through the same epigenetic machinery (PMID:25617721, PMID:32381599). Because PAX2 suppresses renal epithelial apoptosis and its persistence blocks terminal differentiation, deregulated PAX2 produces dysplastic, cystic renal phenotypes, and PAX2 is co-opted in cancers where it regulates ERBB2, ADAM10, and IL-5 (PMID:8383297, PMID:10694420, PMID:19005469, PMID:21880579, PMID:25613757). FSGS-associated PAX2 missense mutations disrupt DNA binding and transactivation or enhance repressor interactions, linking PAX2 dysfunction to human renal disease (PMID:24676634).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1990 Medium

    Establishing that PAX2 encodes a nuclear paired-domain protein expressed in developing kidney and nervous system defined it as a candidate developmental transcription factor and revealed isoform diversity.

    Evidence cDNA cloning, sequencing, in situ hybridization and immunocytochemistry

    PMID:1977574 PMID:1977575

    Open questions at the time
    • DNA-binding activity not yet demonstrated
    • functional roles of distinct isoforms unresolved
  2. 1992 High

    Demonstrating that PAX2 binds a paired-domain recognition sequence confirmed it acts as a sequence-specific DNA-binding transcription factor in the developing kidney.

    Evidence EMSA with paired-domain recognition sequence plus immunolocalization on kidney sections

    PMID:1311084

    Open questions at the time
    • no endogenous target genes identified
    • activator vs repressor function not yet defined
  3. 1993 High

    Loss- and gain-of-function showed PAX2 is required for mesenchyme-to-epithelium conversion and that its persistence blocks terminal differentiation, defining a window of required expression.

    Evidence antisense knockdown in mouse kidney organ culture; transgenic overexpression in mice

    PMID:8187639 PMID:8383297

    Open questions at the time
    • direct transcriptional targets driving conversion not identified
    • mechanism of required down-regulation unknown
  4. 1995 High

    Targeted knockout established that PAX2 is essential across urogenital development, with null mice lacking kidneys, ureters, and genital tracts.

    Evidence homozygous Pax2-null mice with histological and marker analysis

    PMID:8575306

    Open questions at the time
    • cell-autonomous vs non-autonomous requirements not dissected
    • molecular targets in each duct lineage unknown
  5. 1996 High

    Mapping the C-terminal transactivation module and extending null phenotypes to eye and ear revealed both the regulatory architecture of PAX2 and the breadth of its developmental roles.

    Evidence GAL4 fusion/mutagenesis reporter assays; Pax2-null neuroanatomical analysis

    PMID:8617244 PMID:8951055

    Open questions at the time
    • signals controlling the inhibitory module unknown at this stage
    • neural target genes not identified
  6. 1997 High

    Double-mutant genetics demonstrated PAX2-PAX5 cooperation at the midbrain-hindbrain organizer, establishing functional redundancy among PAX family members in dosage-sensitive patterning.

    Evidence Pax5 knockout × Pax2 (Krd) deletion compound-mutant mouse genetics

    PMID:9159136

    Open questions at the time
    • shared vs distinct target genes not resolved
    • biochemical basis of cooperation unknown
  7. 1998 Medium

    Inducible PAX2 expression in human kidney epithelial cells linked PAX2 to the epithelial gene program by raising WT1 and E-cadherin and suppressing vimentin.

    Evidence tetracycline-regulated PAX2 stable transfection with RT-PCR and Western blot in HEK293

    PMID:9459485

    Open questions at the time
    • direct vs indirect regulation of these genes not established
    • single cell-line context
  8. 2000 High

    Identification of Tlx as a direct upstream regulator and the demonstration that PAX2 suppresses renal epithelial apoptosis placed PAX2 within signaling hierarchies and clarified its growth-permissive role.

    Evidence promoter binding-site analysis with Tlx knockout; cpk × Pax2-heterozygous intercross with TUNEL and proliferation assays

    PMID:10694420 PMID:10706625

    Open questions at the time
    • anti-apoptotic target genes of PAX2 not identified
    • Tlx site occupancy not validated in vivo by ChIP
  9. 2001 High

    Discovery that JNK phosphorylates the PAX2 transactivation domain—scaffolded by JIP1/DLK—and that PAX2 controls progesterone-driven mammary branching connected signaling to PAX2 transcriptional output across tissues.

    Evidence in vitro JNK kinase assays, co-IP with JIP1, reporter assays; PAX2-null mammary fat-pad transplantation with WT1 readout

    PMID:11700324 PMID:11850818

    Open questions at the time
    • phosphoacceptor residues and their in vivo requirement not mapped
    • MAPK pathway specificity in vivo not tested
  10. 2002 High

    Defining PAX2/PAX8 redundancy for nephric lineage specification and the auto/cross-regulatory enhancer at the mid-hindbrain boundary revealed how PAX2 establishes and maintains its own expression domains.

    Evidence Pax2/Pax8 double-knockout and chick retroviral misexpression; transgenic reporter mutagenesis and BAC deletion of Pax2 enhancers

    PMID:11807024 PMID:12435636

    Open questions at the time
    • direct targets initiating nephric specification not enumerated
    • biochemical basis of PAX2/PAX8 functional equivalence unresolved
  11. 2003 High

    Showing that Grg4/TLE suppresses PAX2 transactivation by inhibiting JNK-mediated phosphorylation defined the molecular switch toggling PAX2 between active and repressed states.

    Evidence co-IP, in vitro phosphorylation, reporter assays with DNA-binding-dependency tests

    PMID:14532124

    Open questions at the time
    • in vivo developmental contexts of Grg4 antagonism not mapped
    • how Grg4 mechanistically blocks the kinase unknown
  12. 2004 Medium

    Linking Angiotensin II/AT2 signaling through JAK2/STAT to PAX2 induction extended the upstream regulatory network controlling PAX2 abundance in nephrogenic cells.

    Evidence pharmacological inhibitor dissection in embryonic kidney cells and explants

    PMID:15153556

    Open questions at the time
    • direct STAT binding to the Pax2 promoter not shown
    • single-lab pharmacological evidence
  13. 2005 High

    Direct identification of WNT4, Brn1/Pou3f3, and other targets (with En2, Sef, Gata3) converted PAX2 from a genetically required factor into a defined transcriptional activator of developmental programs.

    Evidence EMSA/ChIP and reporter assays for WNT4; microarray plus transgenic lacZ reporter validation for Brn1 and mid-hindbrain targets; microarray for Gata3

    PMID:15872005 PMID:16319112 PMID:16368682

    Open questions at the time
    • genome-wide direct binding map not yet available
    • Gata3 direct promoter binding not demonstrated
  14. 2008 High

    Identification of WNT5A as a direct target and the discovery that PAX2 mediates tamoxifen-induced ERBB2 repression revealed PAX2 functions in cancer-relevant transcriptional contexts.

    Evidence ChIP/EMSA/reporter assays for WNT5A; ChIP, siRNA, and AIB1/SRC-3 competition assays at ERBB2 in breast cancer cells

    PMID:19005469 PMID:19048125

    Open questions at the time
    • determinants of PAX2 activator-vs-repressor outcome at a given locus unresolved
    • in vivo relevance of ERBB2 repression beyond cell lines
  15. 2011 Medium

    Demonstrating PAX2 direct regulation of ADAM10 in renal cancer and melanoma connected PAX2 to sheddase-driven L1-CAM/PI3K-Akt signaling and tumor cell aggressiveness.

    Evidence ChIP, siRNA, overexpression with invasion/migration and drug-sensitivity assays in renal and melanoma cell lines

    PMID:21876729 PMID:21880579

    Open questions at the time
    • in vivo tumor relevance not established
    • single-lab cell-line evidence
  16. 2015 High

    Establishing the PAX2-PTIP axis showed that PAX2 specifies renal progenitors epigenetically by recruiting histone methyltransferase complexes, and identification of the IL-5 target extended its oncogenic reach.

    Evidence FACS-sorted transcriptomics with conditional PTIP deletion in kidney organ culture; ChIP and reporter assays for IL-5 in ESCC cells

    PMID:25613757 PMID:25617721

    Open questions at the time
    • identity of the recruited HMT complex components not fully defined
    • how early vs late targets are differentially maintained mechanistically unresolved
  17. 2020 High

    Inducible adult deletion revealed an ongoing PAX2/PAX8 requirement for urine concentration via epigenetic activation of Slc14a2 and aquaporins, showing PAX2 function extends beyond development.

    Evidence inducible conditional Pax2/Pax8 knockout in adult mice with expression analysis and ChIP for HMT recruitment to Slc14a2

    PMID:32381599

    Open questions at the time
    • relative contributions of PAX2 vs PAX8 in adult collecting duct not fully separated
    • salt-sensing mechanism upstream of induction unresolved
  18. 2022 High

    Genome-wide mapping in endometrial cancer placed PAX2 at estrogen/progesterone-responsive regulatory regions, defining a role in fine-tuning hormone-receptor transcriptional interplay.

    Evidence PAX2/ER/PR ChIP-seq, Hi-C, ATAC-seq and siRNA RNA-seq in Ishikawa cells

    PMID:35018885

    Open questions at the time
    • mechanism by which PAX2 modulates ER/PR output at PgCRs unresolved
    • in vivo endometrial relevance not tested
  19. 2014 Medium

    Functional characterization of FSGS-associated PAX2 missense variants established that disease mutations act by impairing DNA binding/transactivation or enhancing repressor interactions, linking PAX2 dysfunction to human renal disease.

    Evidence in vitro DNA-binding and transactivation assays guided by in silico structural modeling

    PMID:24676634

    Open questions at the time
    • genotype-phenotype correlations not established in vivo
    • single-lab functional assays

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PAX2 selects between activation and repression at a given locus, and the full composition of the histone methyltransferase machinery it recruits, remain unresolved.
  • determinants of activator-vs-repressor outcome unknown
  • subunit composition of recruited HMT complexes incompletely defined
  • structural basis of paired-domain target selection in vivo not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 2 R-HSA-4839726 Chromatin organization 2
Partners
JIP1PAX5PAX8PTIPTLE4WT1

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 PAX2 encodes a paired-domain protein expressed in nuclei of developing kidney and nervous system; the protein contains a conserved paired domain and an octapeptide sequence, and at least two protein isoforms are produced from differentially spliced mRNAs. cDNA cloning, sequencing, in situ hybridization, immunocytochemistry Development Medium 1977574 1977575
1992 PAX2 protein can bind a DNA sequence recognized by the Drosophila paired domain, confirming its function as a sequence-specific DNA-binding transcription factor; nuclear localization was demonstrated in condensing mesenchyme cells and their epithelial derivatives in the developing kidney. DNA-binding assay (EMSA using paired-domain recognition sequence), immunocytochemistry on developing kidney sections Proceedings of the National Academy of Sciences of the United States of America High 1311084
1993 PAX2 protein function is required for the earliest phase of mesenchyme-to-epithelium conversion in the developing kidney; reduction of PAX2 protein with antisense oligonucleotides in mouse kidney organ cultures prevents mesenchyme aggregation and sequential morphological changes of epithelial cell formation. Antisense oligonucleotide-mediated loss-of-function in mouse kidney organ culture, immunostaining with uvomurulin and laminin antibodies Development High 8187639
1993 Deregulated (persistent) expression of PAX2 in transgenic mice results in histologically abnormal and dysfunctional renal epithelium resembling congenital nephrotic syndrome, demonstrating that repression of PAX2 is required for normal terminal differentiation of renal epithelium. Transgenic mouse overexpression (four independently derived transgenic embryos and one line), histological and functional analysis Nature High 8383297
1995 PAX2 is required for multiple steps of urogenital development: homozygous Pax2-null mice lack kidneys, ureters, and genital tracts due to dysgenesis of both ductal and mesenchymal components; Wolffian/Müllerian ducts degenerate, metanephric mesenchyme fails to undergo epithelial transformation, and expression of tissue-specific markers is de-regulated. Targeted gene knockout in mice (homozygous null), histological and molecular marker analysis Development High 8575306
1996 The C-terminal serine/threonine/proline-rich region of PAX2 contains a potent transactivation domain (~55 amino acids) that is negatively regulated by adjacent extreme C-terminal sequences; both activating and inhibitory domains function as an independent regulatory module, conserved across PAX2, PAX5, PAX8, zebrafish Pax-b and sea urchin Pax-258. In vitro mutagenesis, transient transfection reporter assays, GAL4 DNA-binding domain fusion experiments in multiple cell types The EMBO journal High 8617244
1996 PAX2 is required for formation of the optic chiasm and closure of the optic fissure; PAX2-null mice show total ipsilateral optic tracts (agenesis of optic chiasma), coloboma due to optic fissure closure failure, and agenesis of the cochlea and spiral ganglion. Targeted Pax2 null mutation in mice, neuroanatomical tracing and histological analysis Development High 8951055
1997 PAX2 and PAX5 cooperate at the midbrain-hindbrain boundary organizer: compound heterozygous Pax5(+/-)Pax2(+/-) mice show severe loss of inferior colliculi and cerebellar vermis, and Pax5(-/-)Pax2(+/-) mice show complete deletion of posterior midbrain and cerebellum, demonstrating genetic cooperation between the two factors for normal organizer function. Double-mutant mouse genetics (Pax5 targeted knockout × Krd deletion of Pax2 locus), morphological analysis Proceedings of the National Academy of Sciences of the United States of America High 9159136
1998 PAX2 expression in human fetal kidney epithelial (HEK293) cells increases WT1 mRNA (~2-fold) and E-cadherin mRNA (~7-fold), and strongly suppresses vimentin mRNA (to ~8% of control), without affecting proliferation rate, suggesting PAX2 directly regulates mesenchyme-to-epithelium gene expression changes during nephrogenesis. Stable transfection with tetracycline-regulatable PAX2 expression vector, RT-PCR, Western blot Biochimica et biophysica acta Medium 9459485
2000 Tlx, an orphan nuclear receptor, directly regulates Pax2 transcription; a Tlx binding site is present in the Pax2 promoter and is conserved between mouse and human, placing Tlx upstream of PAX2 in retinal development. Candidate target gene screen, promoter analysis, conservation of Tlx-binding site identified by sequence analysis; Tlx knockout mice showing loss of Pax2 in the retina Proceedings of the National Academy of Sciences of the United States of America Medium 10706625
2000 Reduced Pax2 gene dosage (heterozygous) increases apoptosis in normal developing kidneys and inhibits cystic epithelium expansion in cpk polycystic kidney disease mice, without reducing proliferation, demonstrating that PAX2 normally suppresses apoptosis in renal epithelium. Genetic intercross (cpk × Pax2 heterozygous), histological quantification of cyst growth, apoptosis assays (TUNEL), proliferation assays Developmental biology High 10694420
2001 PAX2 transactivation domain is specifically phosphorylated by c-Jun N-terminal kinase (JNK), but not ERK1/2 or p38 MAP kinases; JNK phosphorylation of PAX2 is coincident with enhanced PAX2-dependent transcription activation. PAX2 forms a complex with the JNK scaffolding protein JIP1, and this interaction is enhanced by the upstream kinase DLK. In vitro kinase assays with immunoprecipitated JNK and recombinant GST-Pax2 fusion proteins, transfection reporter assays, co-immunoprecipitation with JIP1 The Journal of biological chemistry High 11700324
2001 PAX2 expression in mouse mammary gland is required for progesterone-stimulated secondary ductal branching and lobular development; PAX2 loss-of-function (transplant of PAX2-null parenchyma) prevents progesterone response. A PAX2–WT1 regulatory axis was identified, with PAX2 required for WT1 mRNA expression in the mammary gland. Mammary fat pad transplantation of PAX2-null tissue into wild-type hosts, RT-PCR for WT1, double-antibody immunohistochemistry for PAX2/WT1 co-localization Oncogene Medium 11850818
2002 PAX2 and PAX8 together are essential for specification of the nephric lineage; mouse embryos lacking both Pax2 and Pax8 fail to form any nephric structures (pronephros or later kidneys), do not initiate Lim1 or c-Ret expression, and lose intermediate mesoderm by apoptosis. Retroviral misexpression of Pax2 alone is sufficient to induce ectopic nephric structures in chick intermediate mesoderm and genital ridge. Double-knockout mouse genetics, retroviral Pax2 misexpression in chick embryos, molecular marker analysis (Lim1, c-Ret), apoptosis assays Genes & development High 12435636
2003 Groucho/TLE family protein Grg4 interacts with PAX2 and suppresses PAX2 transactivation by specifically inhibiting JNK-mediated phosphorylation of the PAX2 activation domain; this inhibition depends on PAX2 binding to its target DNA and is independent of histone deacetylation. Co-immunoprecipitation, in vitro phosphorylation assays, reporter transactivation assays, DNA-binding dependency experiments The EMBO journal High 14532124
2004 Angiotensin II upregulates Pax2 protein and mRNA via the AT2 receptor (not AT1) in embryonic kidney mesenchymal-epithelial cells (MK4), and this signaling is mediated at least in part through the JAK2/STAT pathway; the stimulatory effect is blocked by the AT2 inhibitor PD123319, the JAK2 inhibitor AG490, and the tyrosine kinase inhibitor genistein, but not by AT1, p38, MEK, or JNK inhibitors. Pharmacological inhibitor dissection in embryonic kidney cell lines and kidney explant culture, Western blot, RT-PCR, immunofluorescence Journal of the American Society of Nephrology Medium 15153556
2005 PAX2 directly activates WNT4 gene expression during kidney development: PAX2 protein binds three novel PAX2 recognition motifs in the 5'-flanking sequence of human WNT4 (confirmed by EMSA), activates WNT4 promoter activity ~5-fold in co-transfection assays, induces ~7-fold increase in endogenous WNT4 mRNA in proximal tubule cells, and Wnt4 mRNA is reduced ~60% in Pax2 heterozygous fetal kidney mesenchymal condensates. EMSA, co-transfection reporter assays, RT-PCR in cell line and Pax2 heterozygous fetal kidney The Journal of biological chemistry High 16368682
2005 PAX2 regulates gene expression at the mid-hindbrain boundary including direct transcriptional activation of Brn1 (Pou3f3) via functional PAX2-binding sites in the Brn1 promoter and upstream regulatory element; PAX2-dependent targets also include En2, Sef, Tapp1, and Ncrms. Dominant-negative Brn1 in chick implicates Brn1 in Fgf8 regulation downstream of Pax2. cDNA microarray of FACS-sorted GFP+ cells from wild-type vs Pax2-null embryos; identification of PAX2-binding sites by transgenic lacZ reporter analysis; ectopic dominant-negative Brn1 electroporation in chick Development High 15872005
2005 Pax2 and Pax8 regulate Gata3 expression in the nephric duct: a cDNA microarray screen identified Gata3 as a gene specifically expressed in the pro/mesonephros and regulated by Pax proteins; Gata3 expression in the pronephric anlage coincides with Pax2/Pax8, suggesting direct upstream regulation. cDNA microarray screen of pro/mesonephros; Gata3 knockout phenotypic analysis (Ires-GFP knockin); molecular analysis of Ret expression in Gata3(-/-) nephric duct Development Medium 16319112
2002 Pax2 activates the mid-hindbrain boundary enhancer of Brn1 and maintains its own expression via auto- and cross-regulatory control: functional PAX2/5/8-binding sites in a proximal enhancer maintain Pax2 expression at the mid-hindbrain boundary; an early 120 bp enhancer requires homeodomain binding sites (including a POU homeodomain site bound by Oct3/4) for initial activation. Transgenic reporter analysis in mice, site-directed mutagenesis of enhancer binding sites, BAC transgene deletion analysis, electrophoretic mobility assays Development High 11807024
2008 PAX2 mediates ER-dependent repression of ERBB2 transcription in response to tamoxifen in breast cancer cells: tamoxifen-ER complexes repress ERBB2 via a cis-regulatory element in the ERBB2 gene, and PAX2 is a critical mediator of this repression. PAX2 and the ER co-activator AIB1/SRC-3 compete for binding and regulation of ERBB2 transcription, with the outcome determining tamoxifen response. Reporter assays, ChIP, siRNA knockdown of PAX2, competition binding experiments between PAX2 and AIB1/SRC-3 at the ERBB2 locus in human breast cancer cell lines Nature High 19005469
2008 PAX2 directly activates WNT5A gene expression; PAX2 binds to the WNT5A promoter (confirmed by chromatin immunoprecipitation and EMSA), and transactivation assays demonstrate direct PAX2-dependent regulation of WNT5A in HEK293 cells. Chromatin immunoprecipitation, EMSA, transactivation assays in HEK293 cells Neoplasia High 19048125
2008 Pax2 coordinates optic cup morphogenesis and cell fate independently: in the absence of Pax2, otic progenitors fail to elongate due to loss of apically localized N-cadherin and N-CAM; misexpression of Pax2 leads to ectopic activation of both adhesion molecules but is not sufficient to confer otic identity, indicating Pax2 controls cell shape independently from cell identity. Pax2 loss-of-function and gain-of-function in chick inner ear, immunofluorescence for N-cadherin, N-CAM, otic marker expression Developmental biology Medium 20643116
2009 BMP7 and SHH activate Pax2 expression in mouse retinal astrocyte precursors; SHH may regulate BMP7 expression, and BMP and SHH pathway members interact with TLX (a tailless transcription factor family repressor) to relieve TLX-mediated repression of Pax2 expression. In vitro and ex vivo retinal astrocyte precursor cultures with BMP7 and SHH treatment; pathway inhibitor experiments; demonstrated TLX interaction with BMP and SHH pathway members by co-immunoprecipitation Developmental biology Medium 19505455
2011 PAX2 directly binds the ADAM10 promoter and regulates ADAM10 protein expression in renal cancer cells; PAX2 knockdown reduces ADAM10 (a major sheddase for L1-CAM and c-Met), leading to increased L1-CAM expression and activation of PI3K/Akt signaling via soluble L1-CAM. ChIP, PAX2 siRNA knockdown, PAX2 overexpression, L1-CAM and ADAM10 protein measurements in renal cancer cell lines Carcinogenesis Medium 21880579
2011 PAX2 directly regulates ADAM10 expression in melanoma cells (confirmed by ChIP and PAX2 overexpression/siRNA); PAX2 knockdown inhibits anchorage-independent cell growth, migration, and invasion and restores cisplatin sensitivity in melanoma cells. ChIP, PAX2 siRNA knockdown, PAX2 overexpression, soft agar assays, migration/invasion assays, drug sensitivity assays PloS one Medium 21876729
2014 FSGS-associated PAX2 missense mutations perturb protein function by affecting DNA binding and transactivation activity, or by altering interaction with repressor proteins resulting in enhanced repressor activity; these effects were documented by in vitro functional studies guided by in silico structural modeling. In vitro functional studies (DNA-binding and transactivation assays), in silico structural modeling of PAX2 missense variants Journal of the American Society of Nephrology Medium 24676634
2015 PAX2 specifies the intermediate mesoderm and renal progenitor cells through epigenetic mechanisms dependent on the adaptor protein PTIP: PAX2 recruits PTIP-dependent histone methyltransferase complexes to activate early Pax2 target genes; loss of PTIP in kidney organ culture prevents full activation of later-expressed Pax2 target genes, while early Pax2 targets remain on once activated. PAX2 also represses paraxial mesodermal fate. EGFP knock-in allele cell sorting, gene expression profiling of Pax2 mutant vs wild-type intermediate mesoderm cells, conditional PTIP deletion in kidney organ culture, chromatin analysis Developmental biology High 25617721
2015 PAX2 directly binds the IL-5 promoter and activates IL-5 expression in esophageal cancer cells, promoting tumor metastasis; two PAX2 binding sites were identified in the IL-5 promoter, and PAX2 stimulated IL-5 promoter activity, with ChIP confirming direct binding. ChIP, promoter reporter assays, PAX2 overexpression and shRNA knockdown in ESCC cell lines, microarray analysis Cellular physiology and biochemistry Medium 25613757
2020 PAX2 and PAX8 are required in adult renal collecting duct epithelia for urine concentration: induced deletion of both Pax2 and Pax8 in adult mice causes severe polyuria attributable to loss of urea transporters (Slc14a2) and aquaporins in inner/outer medulla. Pax8 is induced by high-salt in collecting duct cells and activates Slc14a2 by recruiting a histone methyltransferase complex to its promoter. Inducible conditional knockout of Pax2 and/or Pax8 in adult mice, gene expression analysis, ChIP for histone methyltransferase complex recruitment to Slc14a2 promoter in inner medullary collecting duct cells Journal of the American Society of Nephrology High 32381599
2022 PAX2 binds in the vicinity of estrogen-promoted progesterone receptor (PR) binding sites in endometrial cancer cells and fine-tunes ERalpha and PR interplay in transcriptional regulation; PAX2 knockdown alters expression of hormone-regulated genes at these 'progestin control regions' (PgCRs) which have open chromatin even before hormone exposure. ChIP-seq for PAX2, ER, PR in hormone-treated Ishikawa endometrial cancer cells; Hi-C; ATAC-seq; PAX2 siRNA knockdown with RNA-seq eLife High 35018885

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Pax-2 controls multiple steps of urogenital development. Development (Cambridge, England) 699 8575306
1990 Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system. Development (Cambridge, England) 502 1977574
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 412 12435636
1990 Spatially and temporally restricted expression of Pax2 during murine neurogenesis. Development (Cambridge, England) 371 1977575
1992 Pax-2 is a DNA-binding protein expressed in embryonic kidney and Wilms tumor. Proceedings of the National Academy of Sciences of the United States of America 368 1311084
1993 Deregulation of Pax-2 expression in transgenic mice generates severe kidney abnormalities. Nature 260 8383297
1993 Pax-2 is required for mesenchyme-to-epithelium conversion during kidney development. Development (Cambridge, England) 259 8187639
2005 Pax 2/8-regulated Gata 3 expression is necessary for morphogenesis and guidance of the nephric duct in the developing kidney. Development (Cambridge, England) 253 16319112
2008 Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen. Nature 248 19005469
2004 Generation of Pax2-Cre mice by modification of a Pax2 bacterial artificial chromosome. Genesis (New York, N.Y. : 2000) 247 15083520
2007 Pax2 and pax8 regulate branching morphogenesis and nephron differentiation in the developing kidney. Journal of the American Society of Nephrology : JASN 183 17314325
1999 Pax-2 expression defines a subset of GABAergic interneurons and their precursors in the developing murine cerebellum. Journal of neurobiology 181 10512984
1999 Re-expression of the developmental gene Pax-2 during experimental acute tubular necrosis in mice 1. Kidney international 161 10504494
1992 Comparative analysis of Pax-2 protein distributions during neurulation in mice and zebrafish. Mechanisms of development 154 1457381
1997 Cooperation of Pax2 and Pax5 in midbrain and cerebellum development. Proceedings of the National Academy of Sciences of the United States of America 144 9159136
1996 C-terminal activating and inhibitory domains determine the transactivation potential of BSAP (Pax-5), Pax-2 and Pax-8. The EMBO journal 133 8617244
2010 Pax2 and Pax8 cooperate in mouse inner ear morphogenesis and innervation. BMC developmental biology 128 20727173
1992 Expression of the PAX2 gene in human fetal kidney and Wilms' tumor. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 126 1378753
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
2010 Secretory cell outgrowth, PAX2 and serous carcinogenesis in the Fallopian tube. The Journal of pathology 120 20597068
1995 Expression of Pax-2 in human renal cell carcinoma and growth inhibition by antisense oligonucleotides. Cancer research 117 7664285
2005 Expression of aquaporins and PAX-2 compared to CD10 and cytokeratin 7 in renal neoplasms: a tissue microarray study. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 113 15502805
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 Joint loss of PAX2 and PTEN expression in endometrial precancers and cancer. Cancer research 105 20631067
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
2014 Mutations in PAX2 associate with adult-onset FSGS. Journal of the American Society of Nephrology : JASN 95 24676634
1999 Pax2 in development and renal disease. The International journal of developmental biology 95 10535325
2000 Reduced Pax2 gene dosage increases apoptosis and slows the progression of renal cystic disease. Developmental biology 92 10694420
2011 PAX2 and PAX8 expression in primary and metastatic müllerian epithelial tumors: a comprehensive comparison. The American journal of surgical pathology 91 21989345
2002 The activation and maintenance of Pax2 expression at the mid-hindbrain boundary is controlled by separate enhancers. Development (Cambridge, England) 85 11807024
1999 WT1 and PAX-2 podocyte expression in Denys-Drash syndrome and isolated diffuse mesangial sclerosis. The American journal of pathology 85 9916932
1999 Pax2/5 and Pax6 subdivide the early neural tube into three domains. Mechanisms of development 83 10354469
2008 Ptf1a, Lbx1 and Pax2 coordinate glycinergic and peptidergic transmitter phenotypes in dorsal spinal inhibitory neurons. Developmental biology 82 18634777
2012 PAX2 and PAX8 expression in primary and metastatic renal tumors: a comprehensive comparison. Archives of pathology & laboratory medicine 79 23194047
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
1998 Pax2 expression and retinal morphogenesis in the normal and Krd mouse. Developmental biology 74 9473325
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
2001 Pax-2 expression in adult renal tumors. Human pathology 73 11274636
2003 Groucho suppresses Pax2 transactivation by inhibition of JNK-mediated phosphorylation. The EMBO journal 72 14532124
2001 Phosphorylation of Pax2 by the c-Jun N-terminal kinase and enhanced Pax2-dependent transcription activation. The Journal of biological chemistry 72 11700324
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
2002 Expression of the PAX2 oncogene in human breast cancer and its role in progesterone-dependent mammary growth. Oncogene 62 11850818
2010 PAX-2 expression in non-neoplastic, primary neoplastic, and metastatic neoplastic tissue: A comprehensive immunohistochemical study. Applied immunohistochemistry & molecular morphology : AIMM 61 20216401
2010 The use of immunohistochemistry in the diagnosis of metastatic clear cell renal cell carcinoma: a review of PAX-8, PAX-2, hKIM-1, RCCma, and CD10. Advances in anatomic pathology 59 20966644
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
2005 PAX2 activates WNT4 expression during mammalian kidney development. The Journal of biological chemistry 56 16368682
2010 Pax2 coordinates epithelial morphogenesis and cell fate in the inner ear. Developmental biology 55 20643116
2001 PAX2 gene mutation in a family with isolated renal hypoplasia. Journal of the American Society of Nephrology : JASN 55 11461952
2009 Loss of VHL and hypoxia provokes PAX2 up-regulation in clear cell renal cell carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 49 19401348
2011 The transcription factor PAX2 regulates ADAM10 expression in renal cell carcinoma. Carcinogenesis 46 21880579
1998 Missense mutation and hexanucleotide duplication in the PAX2 gene in two unrelated families with renal-coloboma syndrome (MIM 120330). Human genetics 44 9760197
1998 The role of PAX2 in normal and abnormal development of the urinary tract. Pediatric nephrology (Berlin, Germany) 44 9874314
2001 Expression of the developmental and oncogenic PAX2 gene in human prostate cancer. The Journal of urology 43 11371938
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
2006 Pax2 regulates neuronal-glial cell fate choice in the embryonic optic nerve. Developmental biology 42 17173889
2000 Expression of the PAX2 gene in human embryos and exclusion in the CHARGE syndrome. American journal of medical genetics 42 10869107
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
2004 Correlation of Pax-2 expression with cell proliferation in the developing chicken inner ear. Journal of neurobiology 41 15188273
1996 Pax-2, kidney development, and oncogenesis. Medical and pediatric oncology 41 8827071
2015 Association of PAX2 and Other Gene Mutations with the Clinical Manifestations of Renal Coloboma Syndrome. PloS one 40 26571382
2006 Pax2/5/8 proteins promote cell survival in C. elegans. Development (Cambridge, England) 40 17021039
2004 Angiotensin II increases Pax-2 expression in fetal kidney cells via the AT2 receptor. Journal of the American Society of Nephrology : JASN 40 15153556
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
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
2006 Pax2 gene dosage influences cystogenesis in autosomal dominant polycystic kidney disease. Human molecular genetics 34 17082250
1998 Effects of PAX2 expression in a human fetal kidney (HEK293) cell line. Biochimica et biophysica acta 34 9459485
2011 Prospero and Pax2 combinatorially control neural cell fate decisions by modulating Ras- and Notch-dependent signaling. Neural development 32 21539742
2008 WNT5A is regulated by PAX2 and may be involved in blastemal predominant Wilms tumorigenesis. Neoplasia (New York, N.Y.) 32 19048125
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
2008 Ectopic Pax2 expression in chick ventral optic cup phenocopies loss of Pax2 expression. Developmental biology 30 18485342
2011 WT1 and Pax2 re-expression is required for epithelial-mesenchymal transition in 5/6 nephrectomized rats and cultured kidney tubular epithelial cells. Cells, tissues, organs 28 21778682
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
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
2013 PAX2 Expression in Ovarian Cancer. International journal of molecular sciences 26 23502471
2011 PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth of melanoma cells. PloS one 25 21876729
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
2015 Evidence for intermediate mesoderm and kidney progenitor cell specification by Pax2 and PTIP dependent mechanisms. Developmental biology 23 25617721
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
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
2020 PAX2 promotes epithelial ovarian cancer progression involving fatty acid metabolic reprogramming. International journal of oncology 20 31922217
2015 PAX2 and PAX8 reliably distinguishes ovarian serous tumors from mucinous tumors. Applied immunohistochemistry & molecular morphology : AIMM 20 24992169
2012 Signaling pathways of PAX2 and its role in renal interstitial fibrosis and glomerulosclerosis. Journal of receptor and signal transduction research 20 23137159
2022 Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells. eLife 19 35018885
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

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