P52946 (PDX1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pancreas/duodenum homeobox protein 1

Alternative name(s):
Insulin promoter factor 1
Short name=IPF-1
Islet/duodenum homeobox 1
Short name=IDX-1
Somatostatin-transactivating factor 1
Short name=STF-1

Gene names

Name:	Pdx1
Synonyms:	Ipf1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	284 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Activates insulin and somatostatin gene transcription. Key regulator of islet peptide hormone expression but also responsible for the development of the pancreas, most probably by determining maturation and differentiation of common pancreatic precursor cells in the developing gut. As part of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element. Binds the DNA sequence 5'-CC[CT]TAATGGG-3'. Ref.4 Ref.5
Subunit structure	Interacts with the basic helix-loop-helix domains of TCF3(E47) and NEUROD1 and with HMG-I(Y). Interacts with the methyltransferase SETD7 By similarity. Interacts with SPOP. Part of a PDX1:PBX1b:MEIS2b complex. Ref.4 Ref.5 Ref.6
Subcellular location	Nucleus. Cytoplasm › cytosol Ref.7.
Tissue specificity	Duodenum and pancreas (Langerhans islet beta cells and small subsets of endocrine non-beta-cells, at low levels in acinar cells).
Developmental stage	At 8.5 dpc, detected in the gut epithelium from which the pancreatic buds are formed. Transient expression in pancreatic ducts, endocrine and acinar cells. Down-regulated around 10.5 dpc when expression becomes restricted to differentiated beta-cells.
Domain	The Antp-type hexapeptide mediates heterodimerization with PBX on a regulatory element of the somatostatin promoter By similarity. The homeodomain, which contains the nuclear localization signal, not only mediates DNA-binding, but also acts as a protein-protein interaction domain for TCF3(E47), NEUROD1 and HMG-I(Y) By similarity.
Post-translational modification	Phosphorylated by the SAPK2 pathway at high intracellular glucose concentration. Phosphorylated by HIPK2 on Ser-269 upon glucose accumulation. This phoyphorylation mediates subnuclear localization shifting. Phosphorylation by PASK may lead to translocation into the cytosol. Ref.7 Ref.8
Sequence similarities	Belongs to the Antp homeobox family. IPF1/XlHbox-8 subfamily. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Disease	Diabetes mellitus
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator Developmental protein
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from mutant phenotype PubMed 16418487. Source: MGI central nervous system development Inferred from electronic annotation. Source: Compara detection of glucose Inferred from electronic annotation. Source: Compara digestive tract development Inferred from mutant phenotype PubMed 19619492. Source: MGI endocrine pancreas development Inferred from mutant phenotype PubMed 18155690. Source: MGI exocrine pancreas development Inferred from mutant phenotype PubMed 16126192. Source: MGI glucose homeostasis Inferred from mutant phenotype PubMed 18155690. Source: MGI glucose metabolic process Inferred from direct assay PubMed 12904469. Source: MGI insulin secretion Inferred from electronic annotation. Source: Compara liver development Inferred from mutant phenotype PubMed 19619492. Source: MGI morphogenesis of embryonic epithelium Inferred from mutant phenotype PubMed 8625829. Source: MGI negative regulation of cell proliferation Inferred from mutant phenotype PubMed 18155690. Source: MGI negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 17056599. Source: MGI nitric oxide mediated signal transduction Inferred from electronic annotation. Source: Compara organ regeneration Inferred from electronic annotation. Source: Compara organ senescence Inferred from electronic annotation. Source: Compara positive regulation of DNA binding Inferred from electronic annotation. Source: Compara positive regulation of cell death Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from mutant phenotype PubMed 18155690. Source: MGI positive regulation of insulin secretion Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 14701942PubMed 15486225. Source: MGI response to chlorate Inferred from electronic annotation. Source: Compara response to cytokine stimulus Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to fatty acid Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to leucine Inferred from electronic annotation. Source: Compara response to nicotine Inferred from electronic annotation. Source: Compara response to vitamin Inferred from electronic annotation. Source: Compara response to wounding Inferred from electronic annotation. Source: Compara smoothened signaling pathway Inferred from electronic annotation. Source: Compara stem cell differentiation Inferred from electronic annotation. Source: Compara transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara transdifferentiation Inferred from electronic annotation. Source: Compara type B pancreatic cell differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	chromatin binding Inferred from direct assay PubMed 19651901. Source: MGI core promoter sequence-specific DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding Inferred from direct assay PubMed 14701942. Source: MGI sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 15486225. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 284	284	Pancreas/duodenum homeobox protein 1		PRO_0000049149
Regions
	DNA binding	147 – 206	60	Homeobox
	Region	13 – 73	61	Transactivation domain By similarity
	Motif	119 – 124	6	Antp-type hexapeptide
	Motif	198 – 204	7	Nuclear localization signal
	Compositional bias	42 – 48	7	Poly-Pro
	Compositional bias	217 – 221	5	Poly-Gly
Amino acid modifications
	Modified residue	152	1	Phosphothreonine; by PASK Ref.7
	Modified residue	269	1	Phosphoserine; by HIPK2 Ref.8
Experimental info
	Mutagenesis	152	1	T → D or E: Displays a more cytosolic distribution. Ref.7
	Mutagenesis	269	1	S → A: Reduced phosphorylation by HIPK2. Ref.8
	Mutagenesis	269	1	S → E: Abnormal subnuclear localization upon glucose accumulation. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	P52946 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: A57D04569D14E3C4	FASTA	284	30,999
	10 20 30 40 50 60 MNSEEQYYAA TQLYKDPCAF QRGPVPEFSA NPPACLYMGR QPPPPPPPQF TSSLGSLEQG 70 80 90 100 110 120 SPPDISPYEV PPLASDDPAG AHLHHHLPAQ LGLAHPPPGP FPNGTEPGGL EEPNRVQLPF 130 140 150 160 170 180 PWMKSTKAHA WKGQWAGGAY TAEPEENKRT RTAYTRAQLL ELEKEFLFNK YISRPRRVEL 190 200 210 220 230 240 AVMLNLTERH IKIWFQNRRM KWKKEEDKKR SSGTPSGGGG GEEPEQDCAV TSGEELLAVP 250 260 270 280 PLPPPGGAVP PGVPAAVREG LLPSGLSVSP QPSSIAPLRP QEPR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"IPF1, a homeodomain-containing transactivator of the insulin gene." Ohlsson H., Karlsson K., Edlund T. EMBO J. 12:4251-4259(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Cecum.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"An endocrine-exocrine switch in the activity of the pancreatic homeodomain protein PDX1 through formation of a trimeric complex with PBX1b and MRG1 (MEIS2)." Swift G.H., Liu Y., Rose S.D., Bischof L.J., Steelman S., Buchberg A.M., Wright C.V., MacDonald R.J. Mol. Cell. Biol. 18:5109-5120(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH MEIS2 AND PBX1.
[5]	"DNA binding and transcriptional activation by a PDX1.PBX1b.MEIS2b trimer and cooperation with a pancreas-specific basic helix-loop-helix complex." Liu Y., MacDonald R.J., Swift G.H. J. Biol. Chem. 276:17985-17993(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH MEIS2 AND PBX1.
[6]	"Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4) transcriptional activity." Liu A., Desai B.M., Stoffers D.A. Mol. Cell. Biol. 24:4372-4383(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SPOP. Strain: BALB/c. Tissue: Pancreas.
[7]	"Regulation by Per-Arnt-Sim (PAS) kinase of pancreatic duodenal homeobox-1 nuclear import in pancreatic beta-cells." An R., da Silva Xavier G., Hao H.X., Semplici F., Rutter J., Rutter G.A. Biochem. Soc. Trans. 34:791-793(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-152, MUTAGENESIS OF THR-152.
[8]	"Pancreatic and duodenal homeobox 1 (PDX1) phosphorylation at serine-269 is HIPK2-dependent and affects PDX1 subnuclear localization." An R., da Silva Xavier G., Semplici F., Vakhshouri S., Hao H.X., Rutter J., Pagano M.A., Meggio F., Pinna L.A., Rutter G.A. Biochem. Biophys. Res. Commun. 399:155-161(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-269 BY HIPK2, MUTAGENESIS OF SER-269.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X74342 mRNA. Translation: CAA52389.1. AK020261 mRNA. Translation: BAB32045.1. BC103572 mRNA. Translation: AAI03573.1. BC103581 mRNA. Translation: AAI03582.1. BC103582 mRNA. Translation: AAI03583.1. BC105642 mRNA. Translation: AAI05643.1.
IPI	IPI00132557.
PIR	S39581.
RefSeq	NP_032840.1. NM_008814.3.
UniGene	Mm.389714.
3D structure databases
ProteinModelPortal	P52946.
SMR	P52946. Positions 147-206.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-3982089.
PTM databases
PhosphoSite	P52946.
Proteomic databases
PRIDE	P52946.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000085591; ENSMUSP00000082729; ENSMUSG00000029644.
GeneID	18609.
KEGG	mmu:18609.
UCSC	uc009any.2. mouse.
Organism-specific databases
CTD	3651.
MGI	MGI:102851. Pdx1.
Phylogenomic databases
eggNOG	NOG271681.
GeneTree	ENSGT00700000104446.
HOGENOM	HOG000115484.
HOVERGEN	HBG004525.
InParanoid	Q3ZB03.
KO	K07594.
OMA	PYEVPPI.
OrthoDB	EOG4M0F2P.
Enzyme and pathway databases
Reactome	REACT_127416. Developmental Biology. REACT_13641. Regulation of Beta-Cell Development.
Gene expression databases
ArrayExpress	P52946.
Bgee	P52946.
CleanEx	MM_PDX1.
Genevestigator	P52946.
GermOnline	ENSMUSG00000029644. Mus musculus.
Family and domain databases
Gene3D	1.10.10.60. 1 hit.
InterPro	IPR017995. Homeobox_antennapedia. IPR017970. Homeobox_CS. IPR020479. Homeobox_metazoa. IPR001356. Homeodomain. IPR009057. Homeodomain-like. [Graphical view]
Pfam	PF00046. Homeobox. 1 hit. [Graphical view]
PRINTS	PR00025. ANTENNAPEDIA. PR00024. HOMEOBOX.
SMART	SM00389. HOX. 1 hit. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 1 hit.
PROSITE	PS00032. ANTENNAPEDIA. False negative. PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	294534.
SOURCE	Search...

Entry information

Entry name

PDX1_MOUSE

Accession

Primary (citable) accession number: P52946
Secondary accession number(s): Q3ZB03

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	April 3, 2013
This is version 123 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program