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FLASH GENE

Symbol

PAX2

contributors: mct/npt/pgu - updated : 15-06-2015

HGNC name	paired box 2
HGNC id	8616

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	84.23 kb     11 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

Map

see WNT8B

RNA

TRANSCRIPTS	type	messenger

text	with an alternatively spliced form PAX2D, extended C terminus (PMID: 9439670)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003988 11 splicing 4137 NP_003979 - 396 - 1994 7819127 also called PAX2-Ic a conserved 83-nucleotide segment in the 3prime coding sequence transcripts with the 83-nucleotide insertion encoding a putative protein with an alternative COOH-terminus NM_003987 11 splicing 4123 NP_003978 44.7 416 - 1994 7819127 also called PAX2-Ia NM_000278 10 splicing 4054 NP_000269 - 393 fetal kidney 1994 7819127 also called PAX2-Ib NM_003990 11 splicing 4104 NP_003981 - 431 - 1994 7819127 also called PAX2-Ie NM_003989 10 splicing 4035 NP_003980 - 408 - 1994 7819127 also called PAX2-Id variant 6 - splicing - isoform 6 - - in B-cell neoplasia and in solid tumors on mRNA and protein level 2009 19467152 intron 9

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Hearing/Equilibrium ear         Homo sapiens Fetal Nervous brain midbrain       Homo sapiens Fetal   brain hindbrain       Homo sapiens Fetal   spinal cord         Homo sapiens Fetal Urinary kidney       highly Homo sapiens Fetal Visual eye         Homo sapiens Fetal

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Urinary mesenchymal cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal, pregnancy

Text	kidney, throughout the branching ureteric bud Wolffian and Mullerian ducts, primitive cell of kidney, ureter, eye, ear and central nervous system

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	paired domain with 2 similar globular protein sub-domains, known as N (AAs 16-74) and C (AAs 88-148) subdomains, linked by the extended 12-AA polypeptide chain (AAs 75-87) similar to that of PAX6 paired domain
	two structurally distinct N terminal (NTS)
	a homonucleotide tracts of seven guanines
	C terminal subdomains
	a truncated helix-turn helix DNA binding domain and an intermediary octapeptide motif

HOMOLOGY

interspecies

homolog to murine Pax2

Homologene

FAMILY

paired box gene family

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,lysosome
	intracellular,nucleus

basic FUNCTION	playing an essential role for the branching of ureteric bud during the development of renal epithelium
	playing a role in the regulation of the progesterone response of the mature mammary gland
	may play a role in early ureteric obstruction and subsequent renal maldevelopment
	expressed in condensing metanephrogenic mesenchyme and arborizing ureteric bud, and plays an important role in kidney development
	promotes assembly of an H3K4 methyltransferase complex through the ubiquitously expressed nuclear factor PAXIP1
	developmental nuclear transcription factor, which is primarily expressed during embryogenesis in kidneys, eyes, ears and in the central nervous system
	may function as transcriptional regulator, participating in a hierarchical network of gene regulation during embryogenesis
	transcription factor that is up-regulated during nephrogenesis and becomes silenced in mature epithelium of the glomeruli, the proximal, and distal tubules
	necessary for mesenchymal to epithelial transformation that occurs within the metanephros
	suppresses DEFB1 expression in cancer and further implicate PAX2 as a novel therapeutic target for prostate cancer treatment
	role in optic fissure development and in retinal vasculature patterning
	plays an important role in kidney development, differentiation, and renal cell proliferation (
	pivotal in kidney development and it is implicated in the pathogenesis of renal interstitial fibrosis (RIF) and glomerulosclerosis (GS)
	promotes proliferation of colon cancer cells through JUN

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

sensory transduction/hearing , sensory transduction/vision

	biological function of menin-WT1 regulated PAX2 signaling in endocrine neoplasia and renal disease
	potential signaling pathway between PAX2 and CD2AP in the renal interstitial fibrosis disease

a component

INTERACTION

DNA	binding (truncated homeodomain)

RNA

small molecule

protein	interacting with PKD1
	novel role of HNF1B as a modifier of the PAX2 haplo-insufficient phenotype and these two transcription factors operate in common pathways governing both kidney morphogenesis and ureter differentiation
	cross-talk between TP53 and PAX2 provides a transcriptional platform that promotes nephrogenesis, thus contributing to nephron endowment
	is a positive regulator of expression of CCND1 (PAX2 induces CCND1 through AP1)
	PPM1B can dephosphorylate the PAX2 activation domain and displace the adaptor protein PAXIP1, thus inhibiting H3K4 methylation and gene activation

cell & other

REGULATION

repressed by

WT1 in podocyte during early stage of nephrogenesis

Other

TLX during retinal development

ASSOCIATED DISORDERS

corresponding disease(s)

ONCR , RADP2

related resource

PAX2 Mutation Database

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral         in breast cancer constitutional mosaic       germinal mosaicism constitutional     --low   dysregulated and leading to diseases in cases of haploinsufficiency(see ONCRV) or persistent expression (see DDS) tumoral         activated by oestrogen and tamoxifen in endometrial carcinomas tumoral       loss of function reactivation of PAX2 frequently observed in clear cell renal cell carcinoma (ccRCC), a tumor type characterized by loss of von Hippel-Lindau (VHL) tumor suppressor function tumoral       gain of function in low-grade ovarian serous carcinoma tumoral     --over   in human colon cancers (

Susceptibility

Variant & Polymorphism

Candidate gene	strong candidate gene for cases in which human patients have optic disc coloboma not associated with renal dysplasia
Marker	biomarker for a more aggressive medulloblastoma phenotype
Therapy target
	System Type Disorder Pubmed cancer reproductive prostate therapeutic target for prostate cancer treatment tumor kidney   appropriate target for the development of novel therapies for PKD1 cancer urinary   potential therapeutic gene target in renal cancer and adjunctive PAX2 knockdown may enhance the efficacy of other chemotherapeutic agents cancer brain   may represent a novel therapeutic target in medulloblastoma

ANIMAL & CELL MODELS

	homozygous Pax2 knockout mice fail to develop kidneys, ureters and genital tracts
	heterozygous mice for Hnf1b and Pax2 null alleles display phenotypes similar to severe congenital anomalies of the kidney and the urinary tract (CAKUT), including strong hypoplasia of the kidneys, caudal ectopic aborted ureter buds, duplex kidneys, megaureters and hydronephrosis