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PAX2 (Paired box gene 2)

Identity

Other namesPaired box homeotic gene 2
HGNC (Hugo) PAX2
Location 10q24
Location_base_pair Starts at 102495458 and ends at 102579688 bp from pter ( according to hg18-Mar_2006)  [Mapping]

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
Entrez_Gene (NCBI)PAX2  5076  paired box 2
Cards
AtlasPAX2ID41642ch10q24
GeneCards (Weizmann)PAX2
Ensembl (Hinxton)ENSG00000075891 [Gene_View]  PAX2 [Vega]
AceView (NCBI)PAX2
Genatlas (Paris)PAX2
euGene (Indiana)5076
SOURCE (Stanford)NM_000278 NM_003987 NM_003988 NM_003989 NM_003990
Gene Expression (Array Express) ENSG00000075891
Genomic and cartography
GoldenPath (UCSC)PAX2  -  10q24   chr10:102495458-102579688 +  10q24   [Description]    (hg18-Mar_2006)
EnsemblPAX2 - 10q24 [CytoView]
Mapping of homologs : NCBIPAX2 [Mapview]
OMIM120330   167409   
Gene and transcription
Gene : Genbank (Entrez)AY153483 AY153484 BC141452 BC148710 BM671839
Reference sequence (RefSeq transcript) :SRSNM_000278 NM_003987 NM_003988 NM_003989 NM_003990
Reference transcript : EntrezNM_000278 NM_003987 NM_003988 NM_003989 NM_003990
RefSeq genomic : SRSAC_000053 AC_000142 NC_000010 NG_008680 NT_030059 NW_001838006 NW_924884
RefSeq genomic : EntrezAC_000053 AC_000142 NC_000010 NG_008680 NT_030059 NW_001838006 NW_924884
Consensus coding sequences : CCDS NCBIPAX2
Cluster EST : UnigeneHs.155644 [ SRS ] Hs.155644 [ NCBI ]
Alternative Splicing : Fast-db (Paris)16431
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtQ02962 (SRS) Q02962 (Expasy) Q02962 (Uniprot)
With graphics : InterProQ02962
Splice isoforms : VarSplice FASTAQ02962(VarSplice FASTA)
Domaine pattern : Prosite (SRS)PAIRED_1 (PS00034)    PAIRED_2 (PS51057)   
Domain pattern : Prosite (Expaxy)PAIRED_1 (PS00034)    PAIRED_2 (PS51057)   
Domains : Interpro (SRS)Homeodomain-like    Paired_box_N    Wing_hlx_DNA_bd   
Domains : Interpro (EBI)Homeodomain-like    Paired_box_N    Wing_hlx_DNA_bd   
Related proteins : CluSTrQ02962
Domain families : Pfam SRSPAX (PF00292)   
Domain families : Pfam SangerPAX (PF00292)   
Domain families : Pfam NCBIpfam00292   
Domain families : Smart EMBLPAX (SM00351)  
Blocks (Seattle)Q02962
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
HPRD01330
Protein Interaction databases
DIP (DOE-UCLA)Q02962
IntAct (EBI)Q02962
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIPAX2
SNP : GeneSNP UtahPAX2
SNP : HGBasePAX2
Genetic variants : HAPMAPPAX2
Somatic Mutations in Cancer : COSMICPAX2 
Mutations and Diseases : HGMDPAX2
Hereditary diseases : OMIM120330    167409   
Hereditary diseases : GENETests120330    167409   
Diseases : Genetic AssociationPAX2
General knowledge
Homologs : HomoloGenePAX2
Homology/Alignments : Family Browser UCSCPAX2
Phylogenetic Trees/Animal Genes : TreeFamPAX2
Chemical/Protein Interactions : CTD5076
Keywords Ontology : AmiGOmesenchymal to epithelial transition involved in metanephros morphogenesis  DNA binding  nucleus  microtubule organizing center  transcription from RNA polymerase II promoter  multicellular organismal development  axonogenesis  visual perception  promoter binding  cell differentiation  centriolar satellite  regulation of transcription  
Keywords Ontology : EGO-EBImesenchymal to epithelial transition involved in metanephros morphogenesis  DNA binding  nucleus  microtubule organizing center  transcription from RNA polymerase II promoter  multicellular organismal development  axonogenesis  visual perception  promoter binding  cell differentiation  centriolar satellite  regulation of transcription  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Other databasePAX2 Allelic Variant Database http://pax2.hgu.mrc.ac.uk/
Probes
Probes : ImagenesPAX2 Related clones (RZPD - Berlin)
Literature
PubMed70 Pubmed reference(s) in Entrez
PubGenePAX2

Bibliography

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Role of Pax2 in apoptosis resistance and proinvasive phenotype of Kaposi's sarcoma cells.
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Rescue of defective branching nephrogenesis in renal-coloboma syndrome by the caspase inhibitor, Z-VAD-fmk.
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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
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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. July 2005 .
URL : http://AtlasGeneticsOncology.org/Genes/PAX2ID41642ch10q24.html

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indexed on : Sat Feb 27 10:50:09 CET 2010

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