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PAX2 (Paired box gene 2)

Identity

Other namesPaired box homeotic gene 2
HGNC (Hugo) PAX2
LocusID (NCBI) 5076
Location 10q24.31
Location_base_pair Starts at 102505468 and ends at 102589698 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics

DNA/RNA

Description 12 exons, including alternative spliced exons 6 and 10
Transcription 7 alternative splicing isoforms
Pseudogene No

Protein

Description 416 amino acids; 44.7 kDa
Expression PAX2 is expressed in the developing eye, ear, central nervous system (CNS), spinal cord, pancreas and urogenital tract. PAX2 contains a DNA binding paired domain, a truncated homeodomain, an octapeptide region and a carboxyl-terminal transactivation domain.
Localisation Nuclear.
Function PAX2 is a transcription factor that acts to regulate the expression of genes involved in mediating cell proliferation and growth, resistance to apoptosis, and cell migration. PAX2 null mutant mice die perinatally with absent cochlea, kidneys, ureters, oviducts, vas deferens and epididymis, also demonstrating mid- and hindbrain deficiency and defective optic nerve.
Homology PAX2 shares homology through the conserved paired box domain with the other members of the nine strong PAX gene family.

Mutations

Germinal A number of PAX2 mutations have been reported as associated with Renal Coloboma Syndrome (see below), oligomeganephronia and isolated renal hypoplasia. These are collated on the Human PAX2 Allelic Variant Database (see below).
Somatic see below.

Implicated in

Entity Renal Coloboma Syndrome (RCS)
Note Caused by heterozygous PAX2 mutations. Increased apoptosis arising as a result of impaired PAX2 function believed to be responsible for disrupted nephron formation and arrested cochlear outgrowth.
Prognosis Renal Coloboma Syndrome is associated with end-stage renal failure and blindness.
  
Entity Various cancers, including carcinomas of the kidney, carcinomas of the prostate, carcinomas of the breast and carcinomas of the ovary. Also Wilms¹ tumour and Kaposi¹s sarcoma.
Disease PAX2 is overexpressed in a variety of cancers (see below). A detailed understanding of the mechanistic contribution mediated by PAX2 has yet to be established. However, inhibition of PAX2 expression in a number of cancer cell lines induces cell death, indicating a role for PAX2 in tumour cell survival.
Prognosis PAX2 is not expressed in normal prostate tissue or benign prostatic hyperplasia, but is expressed in primary prostatic carcinomas suggesting that PAX2 expression may be a useful marker of prostate cancer. PAX2 expression correlates with proliferation index in the majority of kidney tumour subtypes, and expression levels are significantly higher in patients presenting metastatic disease. PAX2 may therefore provide a useful prognostic marker for determining the severity of kidney cancers.
  

External links

Nomenclature
HGNC (Hugo)PAX2   8616
Cards
AtlasPAX2ID41642ch10q24
Entrez_Gene (NCBI)PAX2  5076  paired box 2
GeneCards (Weizmann)PAX2
Ensembl (Hinxton)ENSG00000075891 [Gene_View]  chr10:102505468-102589698 [Contig_View]  PAX2 [Vega]
ICGC DataPortalENSG00000075891
cBioPortalPAX2
AceView (NCBI)PAX2
Genatlas (Paris)PAX2
WikiGenes5076
SOURCE (Princeton)NM_000278 NM_003987 NM_003988 NM_003989 NM_003990
Genomic and cartography
GoldenPath (UCSC)PAX2  -  10q24.31   chr10:102505468-102589698 +  10q24.31   [Description]    (hg19-Feb_2009)
EnsemblPAX2 - 10q24.31 [CytoView]
Mapping of homologs : NCBIPAX2 [Mapview]
OMIM120330   167409   191830   
Gene and transcription
Genbank (Entrez)AY153483 AY153484 BC141452 BC148710 BM671839
RefSeq transcript (Entrez)NM_000278 NM_003987 NM_003988 NM_003989 NM_003990
RefSeq genomic (Entrez)AC_000142 NC_000010 NC_018921 NG_008680 NT_030059 NW_001838006 NW_004929376
Consensus coding sequences : CCDS (NCBI)PAX2
Cluster EST : UnigeneHs.155644 [ NCBI ]
CGAP (NCI)Hs.155644
Alternative Splicing : Fast-db (Paris)GSHG0003622
Alternative Splicing GalleryENSG00000075891
Gene ExpressionPAX2 [ NCBI-GEO ]     PAX2 [ SEEK ]   PAX2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ02962 (Uniprot)
NextProtQ02962  [Medical]
With graphics : InterProQ02962
Splice isoforms : SwissVarQ02962 (Swissvar)
Domaine pattern : Prosite (Expaxy)PAIRED_1 (PS00034)    PAIRED_2 (PS51057)   
Domains : Interpro (EBI)Homeodomain-like [organisation]   Paired_dom [organisation]   Pax2_C [organisation]   WHTH_DNA-bd_dom [organisation]  
Related proteins : CluSTrQ02962
Domain families : Pfam (Sanger)PAX (PF00292)    Pax2_C (PF12403)   
Domain families : Pfam (NCBI)pfam00292    pfam12403   
Domain families : Smart (EMBL)PAX (SM00351)  
DMDM Disease mutations5076
Blocks (Seattle)Q02962
Human Protein AtlasENSG00000075891 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ02962
HPRD01330
IPIIPI00395548   IPI00220545   IPI00179609   IPI01026454   IPI01026240   IPI01026336   IPI00375136   IPI00872704   IPI00375134   
Protein Interaction databases
DIP (DOE-UCLA)Q02962
IntAct (EBI)Q02962
FunCoupENSG00000075891
BioGRIDPAX2
InParanoidQ02962
Interologous Interaction database Q02962
IntegromeDBPAX2
STRING (EMBL)PAX2
Ontologies - Pathways
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  core promoter proximal region sequence-specific DNA binding  urogenital system development  branching involved in ureteric bud morphogenesis  branching involved in ureteric bud morphogenesis  cell fate determination  mesonephros development  neural tube closure  optic cup morphogenesis involved in camera-type eye development  mesenchymal to epithelial transition involved in metanephros morphogenesis  retinal pigment epithelium development  DNA binding  protein binding  nucleus  lysosome  microtubule organizing center  transcription, DNA-templated  transcription from RNA polymerase II promoter  axonogenesis  mesodermal cell fate specification  aging  visual perception  glial cell differentiation  superoxide-generating NADPH oxidase activity  optic nerve development  optic nerve morphogenesis  optic nerve structural organization  vestibulocochlear nerve formation  pancreas development  response to nutrient levels  protein-DNA complex  centriolar satellite  regulation of metanephros size  ureter maturation  pronephric field specification  inner ear morphogenesis  camera-type eye development  negative regulation of apoptotic process  negative regulation of apoptotic process  negative regulation of programmed cell death  negative regulation of cysteine-type endopeptidase activity involved in apoptotic process  protein complex  protein kinase B signaling  transcription regulatory region DNA binding  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  negative regulation of cytolysis  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  pronephros development  brain morphogenesis  stem cell differentiation  positive regulation of epithelial cell proliferation  oxidation-reduction process  oxidation-reduction process  mesenchymal to epithelial transition  paramesonephric duct development  optic chiasma development  cellular response to hydrogen peroxide  C2H2 zinc finger domain binding  cellular response to mechanical stimulus  cellular response to retinoic acid  cellular response to glucose stimulus  cellular response to epidermal growth factor stimulus  metanephric mesenchyme development  positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis  metanephric mesenchymal cell differentiation  mesonephric tubule formation  mesonephric duct development  nephric duct formation  ureter development  ureter morphogenesis  metanephric collecting duct development  metanephric epithelium development  metanephric distal convoluted tubule development  metanephric nephron tubule formation  positive regulation of metanephric glomerulus development  negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis  regulation of metanephric nephron tubule epithelial cell differentiation  reactive oxygen species metabolic process  cochlea development  cochlea morphogenesis  positive regulation of branching involved in ureteric bud morphogenesis  negative regulation of mesenchymal cell apoptotic process involved in metanephros development  negative regulation of apoptotic process involved in metanephric collecting duct development  negative regulation of apoptotic process involved in metanephric nephron tubule development  negative regulation of reactive oxygen species metabolic process  positive regulation of metanephric DCT cell differentiation  positive regulation of optic nerve formation  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  core promoter proximal region sequence-specific DNA binding  urogenital system development  branching involved in ureteric bud morphogenesis  branching involved in ureteric bud morphogenesis  cell fate determination  mesonephros development  neural tube closure  optic cup morphogenesis involved in camera-type eye development  mesenchymal to epithelial transition involved in metanephros morphogenesis  retinal pigment epithelium development  DNA binding  protein binding  nucleus  lysosome  microtubule organizing center  transcription, DNA-templated  transcription from RNA polymerase II promoter  axonogenesis  mesodermal cell fate specification  aging  visual perception  glial cell differentiation  superoxide-generating NADPH oxidase activity  optic nerve development  optic nerve morphogenesis  optic nerve structural organization  vestibulocochlear nerve formation  pancreas development  response to nutrient levels  protein-DNA complex  centriolar satellite  regulation of metanephros size  ureter maturation  pronephric field specification  inner ear morphogenesis  camera-type eye development  negative regulation of apoptotic process  negative regulation of apoptotic process  negative regulation of programmed cell death  negative regulation of cysteine-type endopeptidase activity involved in apoptotic process  protein complex  protein kinase B signaling  transcription regulatory region DNA binding  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  negative regulation of cytolysis  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  pronephros development  brain morphogenesis  stem cell differentiation  positive regulation of epithelial cell proliferation  oxidation-reduction process  oxidation-reduction process  mesenchymal to epithelial transition  paramesonephric duct development  optic chiasma development  cellular response to hydrogen peroxide  C2H2 zinc finger domain binding  cellular response to mechanical stimulus  cellular response to retinoic acid  cellular response to glucose stimulus  cellular response to epidermal growth factor stimulus  metanephric mesenchyme development  positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis  metanephric mesenchymal cell differentiation  mesonephric tubule formation  mesonephric duct development  nephric duct formation  ureter development  ureter morphogenesis  metanephric collecting duct development  metanephric epithelium development  metanephric distal convoluted tubule development  metanephric nephron tubule formation  positive regulation of metanephric glomerulus development  negative regulation of mesenchymal cell apoptotic process involved in metanephric nephron morphogenesis  regulation of metanephric nephron tubule epithelial cell differentiation  reactive oxygen species metabolic process  cochlea development  cochlea morphogenesis  positive regulation of branching involved in ureteric bud morphogenesis  negative regulation of mesenchymal cell apoptotic process involved in metanephros development  negative regulation of apoptotic process involved in metanephric collecting duct development  negative regulation of apoptotic process involved in metanephric nephron tubule development  negative regulation of reactive oxygen species metabolic process  positive regulation of metanephric DCT cell differentiation  positive regulation of optic nerve formation  
Protein Interaction DatabasePAX2
Wikipedia pathwaysPAX2
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)PAX2
snp3D : Map Gene to Disease5076
SNP (GeneSNP Utah)PAX2
SNP : HGBasePAX2
Genetic variants : HAPMAPPAX2
Exome VariantPAX2
1000_GenomesPAX2 
ICGC programENSG00000075891 
Somatic Mutations in Cancer : COSMICPAX2 
CONAN: Copy Number AnalysisPAX2 
Mutations and Diseases : HGMDPAX2
Mutations and Diseases : intOGenPAX2
Genomic VariantsPAX2  PAX2 [DGVbeta]
dbVarPAX2
ClinVarPAX2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM120330    167409    191830   
MedgenPAX2
GENETestsPAX2
Disease Genetic AssociationPAX2
Huge Navigator PAX2 [HugePedia]  PAX2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGenePAX2
Homology/Alignments : Family Browser (UCSC)PAX2
Phylogenetic Trees/Animal Genes : TreeFamPAX2
Chemical/Protein Interactions : CTD5076
Chemical/Pharm GKB GenePA32956
Clinical trialPAX2
Cancer Resource (Charite)ENSG00000075891
Other databases
Other databasePAX2 Allelic Variant Database http://pax2.hgu.mrc.ac.uk/
Probes
Litterature
PubMed123 Pubmed reference(s) in Entrez
CoreMinePAX2
iHOPPAX2
OncoSearchPAX2

Bibliography

Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system.
Dressler GR, Deutsch U, Chowdhury K, Nornes HO, Gruss P
Development (Cambridge, England). 1990 ; 109 (4) : 787-795.
PMID 1977574
 
The paired box encodes a second DNA-binding domain in the paired homeo domain protein.
Treisman J, Harris E, Desplan C
Genes & development. 1991 ; 5 (4) : 594-604.
PMID 1672661
 
Expression of the PAX2 gene in human fetal kidney and Wilms' tumor.
Eccles MR, Wallis LJ, Fidler AE, Spurr NK, Goodfellow PJ, Reeve AE
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research. 1992 ; 3 (5) : 279-289.
PMID 1378753
 
Deregulation of Pax-2 expression in transgenic mice generates severe kidney abnormalities.
Dressler GR, Wilkinson JE, Rothenpieler UW, Patterson LT, Williams-Simons L, Westphal H
Nature. 1993 ; 362 (6415) : 65-67.
PMID 8383297
 
Alternative messenger RNA forms and open reading frames within an additional conserved region of the human PAX-2 gene.
Ward TA, Nebel A, Reeve AE, Eccles MR
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research. 1994 ; 5 (9) : 1015-1021.
PMID 7819127
 
Expression of Pax-2 in human renal cell carcinoma and growth inhibition by antisense oligonucleotides.
Gnarra JR, Dressler GR
Cancer research. 1995 ; 55 (18) : 4092-4098.
PMID 7664285
 
Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux.
Sanyanusin P, Schimmenti LA, McNoe LA, Ward TA, Pierpont ME, Sullivan MJ, Dobyns WB, Eccles MR
Nature genetics. 1995 ; 9 (4) : 358-364.
PMID 7795640
 
The mouse Pax2(1Neu) mutation is identical to a human PAX2 mutation in a family with renal-coloboma syndrome and results in developmental defects of the brain, ear, eye, and kidney.
Favor J, Sandulache R, Neuhˆ§user-Klaus A, Pretsch W, Chatterjee B, Senft E, Wurst W, Blanquet V, Grimes P, Spˆrle R, Schughart K
Proceedings of the National Academy of Sciences of the United States of America. 1996 ; 93 (24) : 13870-13875.
PMID 8943028
 
Pax2 contributes to inner ear patterning and optic nerve trajectory.
Torres M, Gˆ„mez-Pardo E, Gruss P
Development (Cambridge, England). 1996 ; 122 (11) : 3381-3391.
PMID 8951055
 
Pax genes and organogenesis.
Dahl E, Koseki H, Balling R
BioEssays : news and reviews in molecular, cellular and developmental biology. 1997 ; 19 (9) : 755-765.
PMID 9297966
 
Renal-coloboma syndrome: a multi-system developmental disorder caused by PAX2 mutations.
Eccles MR, Schimmenti LA
Clinical genetics. 1999 ; 56 (1) : 1-9.
PMID 10466411
 
Reduced Pax2 gene dosage increases apoptosis and slows the progression of renal cystic disease.
Ostrom L, Tang MJ, Gruss P, Dressler GR
Developmental biology. 2000 ; 219 (2) : 250-258.
PMID 10694420
 
Primary renal hypoplasia in humans and mice with PAX2 mutations: evidence of increased apoptosis in fetal kidneys of Pax2(1Neu) +/- mutant mice.
Porteous S, Torban E, Cho NP, Cunliffe H, Chua L, McNoe L, Ward T, Souza C, Gus P, Giugliani R, Sato T, Yun K, Favor J, Sicotte M, Goodyer P, Eccles M
Human molecular genetics. 2000 ; 9 (1) : 1-11.
PMID 10587573
 
Pax-2 expression in adult renal tumors.
Daniel L, Lechevallier E, Giorgi R, Sichez H, Zattara-Cannoni H, Figarella-Branger D, Coulange C
Human pathology. 2001 ; 32 (3) : 282-287.
PMID 11274636
 
Aberrant expression of Pax-2 mRNA in renal cell carcinoma tissue and parenchyma of the affected kidney.
Igarashi T, Ueda T, Suzuki H, Tobe T, Komiya A, Ichikawa T, Ito H
International journal of urology : official journal of the Japanese Urological Association. 2001 ; 8 (2) : 60-64.
PMID 11240827
 
Expression of the developmental and oncogenic PAX2 gene in human prostate cancer.
Khoubehi B, Kessling AM, Adshead JM, Smith GL, Smith RD, Ogden CW
The Journal of urology. 2001 ; 165 (6 Pt 1) : 2115-2120.
PMID 11371938
 
PAX genes in development and disease: the role of PAX2 in urogenital tract development.
Eccles MR, He S, Legge M, Kumar R, Fox J, Zhou C, French M, Tsai RW
The International journal of developmental biology. 2002 ; 46 (4) : 535-544.
PMID 12141441
 
Expression of the PAX2 oncogene in human breast cancer and its role in progesterone-dependent mammary growth.
Silberstein GB, Dressler GR, Van Horn K
Oncogene. 2002 ; 21 (7) : 1009-1016.
PMID 11850818
 
Ureteric bud apoptosis and renal hypoplasia in transgenic PAX2-Bax fetal mice mimics the renal-coloboma syndrome.
Dziarmaga A, Clark P, Stayner C, Julien JP, Torban E, Goodyer P, Eccles M
Journal of the American Society of Nephrology : JASN. 2003 ; 14 (11) : 2767-2774.
PMID 14569086
 
Paired-Box genes are frequently expressed in cancer and often required for cancer cell survival.
Muratovska A, Zhou C, He S, Goodyer P, Eccles MR
Oncogene. 2003 ; 22 (39) : 7989-7997.
PMID 12970747
 
Gene expression patterns in ovarian carcinomas.
Schaner ME, Ross DT, Ciaravino G, Sorlie T, Troyanskaya O, Diehn M, Wang YC, Duran GE, Sikic TL, Caldeira S, Skomedal H, Tu IP, Hernandez-Boussard T, Johnson SW, O'Dwyer PJ, Fero MJ, Kristensen GB, Borresen-Dale AL, Hastie T, Tibshirani R, van de Rijn M, Teng NN, Longacre TA, Botstein D, Brown PO, Sikic BI
Molecular biology of the cell. 2003 ; 14 (11) : 4376-4386.
PMID 12960427
 
The role of Pax2 in mouse inner ear development.
Burton Q, Cole LK, Mulheisen M, Chang W, Wu DK
Developmental biology. 2004 ; 272 (1) : 161-175.
PMID 15242798
 
Role of Pax2 in apoptosis resistance and proinvasive phenotype of Kaposi's sarcoma cells.
Buttiglieri S, Deregibus MC, Bravo S, Cassoni P, Chiarle R, Bussolati B, Camussi G
The Journal of biological chemistry. 2004 ; 279 (6) : 4136-4143.
PMID 14627715
 
Rescue of defective branching nephrogenesis in renal-coloboma syndrome by the caspase inhibitor, Z-VAD-fmk.
Clark P, Dziarmaga A, Eccles M, Goodyer P
Journal of the American Society of Nephrology : JASN. 2004 ; 15 (2) : 299-305.
PMID 14747376
 
Pax2 mutant mice display increased number and size of islets of Langerhans but no change in insulin and glucagon content.
Zaiko M, Estreicher A, Ritz-Laser B, Herrera P, Favor J, Meda P, Philippe J
European journal of endocrinology / European Federation of Endocrine Societies. 2004 ; 150 (3) : 389-395.
PMID 15012626
 
Pax2 expression occurs in renal medullary epithelial cells in vivo and in cell culture, is osmoregulated, and promotes osmotic tolerance.
Cai Q, Dmitrieva NI, Ferraris JD, Brooks HL, van Balkom BW, Burg M
Proceedings of the National Academy of Sciences of the United States of America. 2005 ; 102 (2) : 503-508.
PMID 15623552
 
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Contributor(s)

Written07-2005Ewan Robson, Jess Whall, Michael Eccles
Developmental Genetics Group, Department of Pathology, University of Otago, PO Box 913,Dunedin 9015, New Zealand

Citation

This paper should be referenced as such :
Robson, E ; Whall, J ; Eccles, M
PAX2 (paired box gene 2)
Atlas Genet Cytogenet Oncol Haematol. 2005;9(4):293-294.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/PAX2ID41642ch10q24.html

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indexed on : Tue Aug 26 15:26:16 CEST 2014

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