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FLASH GENE

Symbol

PDX1

contributors: mct/pgu - updated : 29-05-2009

HGNC name	pancreatic and duodenal homeobox 1
HGNC id	6107

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MODY4 maturity onset diabetes of the young, type IV PHYC pancreatic hypoplasia congenital
Location	13q12.2      Physical location : 28.494.167 - 28.500.451
Synonym name	somatostatin transactivating factor 1
	insulin promoter factor 1, homeodomain transcription factor
	pancreatic-duodenal homeobox factor 1
	glucose- sensitive factor
	pancreatic-duodenal homeobox factor 1
	pyruvate dehydrogenase complex, component X
	islet/duodenum homeobox-1
Synonym symbol(s)	STF1, IDX1, IUF1, IPF1, GSF

DNA

TYPE	functioning gene
STRUCTURE	6.28 kb     2 Exon(s)

regulatory sequence	Promoter
	Binding site   enhancer   HRE
text structure	a region of the promoter between - 2715 and - 1960 which was essential to direct pancreatic islet-cell-specific expression
	GG2 element, despite its divergence from the core homeodomain consensus binding motif, is a site for IPF1 activation in the insulin gene
	a proximal E-box, located at 105 bp is highly conserved between species,and has been proposed to confer beta-cell specificity to the PDX1 promoter
	ATF3-responsive element in the PDX1 promoter

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000209 2 - 2573 NP_000200 30.6 283 - 1996 8635654

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 Digestive intestine small intestine duodenum   highly Homo sapiens Adult   intestine large intestine colon       stomach       highly Homo sapiens Endocrine pancreas       highly Homo sapiens Adult

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier/lining epidermis stratum basale   Epithelial secretory glandular endocrine   Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...)

cell lineage	down-regulated in the ductal and acinar cell lineages
cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal transactivation domain
	an homeodomain responsible for DNA binding
	a nuclear localization signal (NLS)
	a conserved C terminus that is mutated in human diabetes

HOMOLOGY

interspecies

homolog to murine Pax1

Homologene

FAMILY	ANTP homeobox family
	IPF1/XlHbox-8 subfamily

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	key regulator of pancreatic islet development and insulin gene transcription
	involved in islet beta cell function and formation
	playing a critical role for the initiation of all pancreatic lineages
	may inhibit the ductal differentiation program in the pancreatic endocrine compartment, particularly beta cells
	transcription factor, necessary for differentiation of exocrine and endocrine pancreas, and regulating insulin gene transcription
	regulates cell proliferation and invasion in human pancreatic cancer cells
	plays a crucial role in pancreas development and beta-cell differentiation, and maintaining mature beta-cell function
	functions as a putative tumor suppressor in gastric cancer
	transcription factor that critically regulates early pancreas formation and multiple aspects of mature beta cell function, including insulin secretion, mitochondrial metabolism, and cell survival
	homeodomain transcription factor, that serves as a master regulator in the pancreas because of its importance during organogenesis and in adult islet insulin-producing beta cell activity
	recruits EP300 and enhances the transcriptional activity of PDX1, which results in the stimulation of insulin secretion in response to high glucose levels

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

carbohydrate

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	WIFTCF3 and NEUROD1
	negatively regulates the pancreatic ductal cell-specific keratin 19 promoter
	interacting with SPOP (targets PDX1 for ubiquitination and proteasomal degradation
	substrate for protein CSNK2A1
	RB1 associates with and stabilizes pancreatic duodenal homeobox-1 (PDX1) that is essential for embryonic pancreas development and adult beta-cell function (
	ATF3 interacted with PDX1, and effectively inhibited EP300-mediated transcriptional coactivation of the PBE-containing promoter, whereas C-terminal domain-deleted ATF3 did not inhibit the transcoactivation of EP300

cell & other

REGULATION

inhibited by	C20orf67 (interaction that may regulate normal beta cell differentiation)
	ATF3, that negatively regulated PDX1 expression in pancreatic beta-cells

repressed by

MLXIPL

Other	regulated by HNF1A and HNF3B
	regulated by glucose, GLP-1, insulin, T(3), HB-EGF, and TNF-alpha in pancreatic beta cells
	regulation of its expression by FOXA1 and FOXA2 is a key early event controlling the expansion and differentiation of the pancreatic primordia
	regulated by MAFA, MAFB (regulate PDX1 transcription in pancreatic beta cells)
	regulated by KLF11

ASSOCIATED DISORDERS

corresponding disease(s)

MODY4 , PHYC

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in prostate cancer / benign prostate tissue constitutional       loss of function with MAFA in beta-cells of diabetic patient (leads to suppression of insulin biosynthesis and secretion) constitutional       loss of function leads to a failure of &946; cell compensation for insulin resistance at least in part by impairing critical functions of the ER constitutional     --low   gastric expression is down-regulated in H. pylori infection and incisural antralisation tumoral     --low   in intestinal metaplasia tumoral     --low   in gastric cancer constitutional     --low   plays an important role in development of type 2 diabetes

Susceptibility

for early and late-onset type 2 diabetes

Variant & Polymorphism other	polymorphisms increasing the risk of late-onset type 2 diabetes

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer digestive pancreas down-regulation of PDX1 expression inhibits pancreatic cancer cell growth implying its use as a potential therapeutic target for the treatment of pancreatic cancer diabete     PDX1 regulation of ER homeostasis is a potential therapeutic target for type 2 diabetes

ANIMAL & CELL MODELS