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PDX1_RAT
ID   PDX1_RAT                Reviewed;         283 AA.
AC   P52947;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   03-AUG-2022, entry version 153.
DE   RecName: Full=Pancreas/duodenum homeobox protein 1;
DE   AltName: Full=Insulin promoter factor 1;
DE            Short=IPF-1;
DE   AltName: Full=Islet/duodenum homeobox 1;
DE            Short=IDX-1;
DE   AltName: Full=Somatostatin-transactivating factor 1;
DE            Short=STF-1;
GN   Name=Pdx1; Synonyms=Ipf1;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=7907546; DOI=10.1002/j.1460-2075.1994.tb06363.x;
RA   Miller C.P., McGehee R.E. Jr., Habener J.F.;
RT   "IDX-1: a new homeodomain transcription factor expressed in rat pancreatic
RT   islets and duodenum that transactivates the somatostatin gene.";
RL   EMBO J. 13:1145-1156(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=7505393; DOI=10.1210/mend.7.10.7505393;
RA   Leonard J., Peers B., Johnson T., Ferreri K., Lee S., Montminy M.R.;
RT   "Characterization of somatostatin transactivating factor-1, a novel
RT   homeobox factor that stimulates somatostatin expression in pancreatic islet
RT   cells.";
RL   Mol. Endocrinol. 7:1275-1283(1993).
RN   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
CC   -!- FUNCTION: Activates insulin and somatostatin gene transcription. Key
CC       regulator of islet peptide hormone expression but also responsible for
CC       the development of the pancreas, most probably by determining
CC       maturation and differentiation of common pancreatic precursor cells in
CC       the developing gut. As part of a PDX1:PBX1b:MEIS2b complex in
CC       pancreatic acinar cells is involved in the transcriptional activation
CC       of the ELA1 enhancer; the complex binds to the enhancer B element and
CC       cooperates with the transcription factor 1 complex (PTF1) bound to the
CC       enhancer A element. Binds the DNA sequence 5'-CC[CT]TAATGGG-3'.
CC   -!- SUBUNIT: Interacts with the basic helix-loop-helix domains of TCF3(E47)
CC       and NEUROD1 and with HMG-I(Y). Interacts with SPOP and the
CC       methyltransferase SETD7. Part of a PDX1:PBX1b:MEIS2b complex (By
CC       similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       P52947; Q9WTV5: Psmd9; NbExp=3; IntAct=EBI-7626093, EBI-7626072;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC       Cytoplasm, cytosol {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Duodenum and pancreas (Langerhans islet beta cells
CC       and small subsets of endocrine non-beta-cells, at low levels in acinar
CC       cells).
CC   -!- DOMAIN: The Antp-type hexapeptide mediates heterodimerization with PBX
CC       on a regulatory element of the somatostatin promoter.
CC   -!- DOMAIN: The homeodomain, which contains the nuclear localization
CC       signal, not only mediates DNA-binding, but also acts as a protein-
CC       protein interaction domain for TCF3(E47), NEUROD1 and HMG-I(Y).
CC       {ECO:0000250}.
CC   -!- PTM: Phosphorylated by the SAPK2 pathway at high intracellular glucose
CC       concentration. Phosphorylated by HIPK2 on Ser-268 upon glucose
CC       accumulation. This phosphorylation mediates subnuclear localization
CC       shifting. Phosphorylation by PASK may lead to translocation into the
CC       cytosol (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the Antp homeobox family. IPF1/XlHbox-8
CC       subfamily. {ECO:0000305}.
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DR   EMBL; U04833; AAA18355.1; -; mRNA.
DR   EMBL; S67435; AAB29317.1; -; mRNA.
DR   PIR; S42634; S42634.
DR   RefSeq; NP_074043.3; NM_022852.3.
DR   AlphaFoldDB; P52947; -.
DR   SMR; P52947; -.
DR   IntAct; P52947; 1.
DR   MINT; P52947; -.
DR   STRING; 10116.ENSRNOP00000066935; -.
DR   iPTMnet; P52947; -.
DR   PhosphoSitePlus; P52947; -.
DR   PaxDb; P52947; -.
DR   PRIDE; P52947; -.
DR   Ensembl; ENSRNOT00000071942; ENSRNOP00000066935; ENSRNOG00000046458.
DR   GeneID; 29535; -.
DR   KEGG; rno:29535; -.
DR   CTD; 3651; -.
DR   RGD; 62387; Pdx1.
DR   eggNOG; KOG0489; Eukaryota.
DR   GeneTree; ENSGT00940000162542; -.
DR   HOGENOM; CLU_087401_0_0_1; -.
DR   InParanoid; P52947; -.
DR   OMA; HTWKGQW; -.
DR   OrthoDB; 1102286at2759; -.
DR   PhylomeDB; P52947; -.
DR   PRO; PR:P52947; -.
DR   Proteomes; UP000002494; Chromosome 12.
DR   Bgee; ENSRNOG00000046458; Expressed in duodenum and 2 other tissues.
DR   Genevisible; P52947; RN.
DR   GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0016607; C:nuclear speck; ISO:RGD.
DR   GO; GO:0005634; C:nucleus; IDA:RGD.
DR   GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:RGD.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IEA:InterPro.
DR   GO; GO:1990841; F:promoter-specific chromatin binding; IDA:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR   GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR   GO; GO:0030154; P:cell differentiation; IMP:RGD.
DR   GO; GO:0007417; P:central nervous system development; IEP:RGD.
DR   GO; GO:0051594; P:detection of glucose; IDA:BHF-UCL.
DR   GO; GO:0048565; P:digestive tract development; ISO:RGD.
DR   GO; GO:0031018; P:endocrine pancreas development; ISO:RGD.
DR   GO; GO:0031017; P:exocrine pancreas development; ISO:RGD.
DR   GO; GO:0042593; P:glucose homeostasis; IMP:RGD.
DR   GO; GO:0006006; P:glucose metabolic process; ISO:RGD.
DR   GO; GO:0030073; P:insulin secretion; ISO:RGD.
DR   GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IEA:Ensembl.
DR   GO; GO:0001889; P:liver development; ISO:RGD.
DR   GO; GO:0016331; P:morphogenesis of embryonic epithelium; ISO:RGD.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR   GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; ISO:RGD.
DR   GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:RGD.
DR   GO; GO:2000675; P:negative regulation of type B pancreatic cell apoptotic process; ISO:RGD.
DR   GO; GO:0007263; P:nitric oxide mediated signal transduction; ISO:RGD.
DR   GO; GO:0031016; P:pancreas development; IEP:RGD.
DR   GO; GO:0010942; P:positive regulation of cell death; IMP:RGD.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR   GO; GO:0043388; P:positive regulation of DNA binding; IMP:RGD.
DR   GO; GO:0032024; P:positive regulation of insulin secretion; IMP:RGD.
DR   GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:RGD.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:RGD.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:RGD.
DR   GO; GO:1904692; P:positive regulation of type B pancreatic cell proliferation; IEA:Ensembl.
DR   GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR   GO; GO:0010468; P:regulation of gene expression; IMP:CACAO.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:RGD.
DR   GO; GO:0043279; P:response to alkaloid; IEP:RGD.
DR   GO; GO:0010157; P:response to chlorate; IEP:RGD.
DR   GO; GO:0034097; P:response to cytokine; IEP:RGD.
DR   GO; GO:0070542; P:response to fatty acid; IEP:RGD.
DR   GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR   GO; GO:0009749; P:response to glucose; IMP:RGD.
DR   GO; GO:0010040; P:response to iron(II) ion; IEP:RGD.
DR   GO; GO:0043201; P:response to leucine; IEP:RGD.
DR   GO; GO:0033993; P:response to lipid; IEP:RGD.
DR   GO; GO:0035094; P:response to nicotine; IEP:RGD.
DR   GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR   GO; GO:0033273; P:response to vitamin; IEP:RGD.
DR   GO; GO:0009611; P:response to wounding; IEP:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR   GO; GO:0007224; P:smoothened signaling pathway; IMP:RGD.
DR   GO; GO:0048863; P:stem cell differentiation; IMP:RGD.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; IMP:RGD.
DR   GO; GO:0006351; P:transcription, DNA-templated; IMP:RGD.
DR   GO; GO:0060290; P:transdifferentiation; IEP:RGD.
DR   GO; GO:0097050; P:type B pancreatic cell apoptotic process; IEA:Ensembl.
DR   GO; GO:0003309; P:type B pancreatic cell differentiation; IMP:BHF-UCL.
DR   GO; GO:0044342; P:type B pancreatic cell proliferation; IEA:Ensembl.
DR   CDD; cd00086; homeodomain; 1.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017995; Homeobox_antennapedia.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR020479; Homeobox_metazoa.
DR   Pfam; PF00046; Homeodomain; 1.
DR   PRINTS; PR00025; ANTENNAPEDIA.
DR   PRINTS; PR00024; HOMEOBOX.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; SSF46689; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
PE   1: Evidence at protein level;
KW   Activator; Cytoplasm; DNA-binding; Homeobox; Nucleus; Phosphoprotein;
KW   Reference proteome; Transcription; Transcription regulation.
FT   CHAIN           1..283
FT                   /note="Pancreas/duodenum homeobox protein 1"
FT                   /id="PRO_0000049150"
FT   DNA_BIND        146..205
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          13..73
FT                   /note="Transactivation domain"
FT   REGION          36..81
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          201..283
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           118..123
FT                   /note="Antp-type hexapeptide"
FT   MOTIF           197..203
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        37..51
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         151
FT                   /note="Phosphothreonine; by PASK"
FT                   /evidence="ECO:0000250|UniProtKB:P52946"
FT   MOD_RES         268
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   CONFLICT        47
FT                   /note="P -> T (in Ref. 1; AAA18355)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        240
FT                   /note="P -> K (in Ref. 1; AAA18355)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        247
FT                   /note="A -> V (in Ref. 1; AAA18355)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   283 AA;  30831 MW;  C8C25FF2C75ED4E6 CRC64;
     MNSEEQYYAA TQLYKDPCAF QRGPVPEFSA NPPACLYMGR QPPPPPPPQF AGSLGTLEQG
     SPPDISPYEV PPLADDPAGA HLHHHLPAQL GLAHPPPGPF PNGTETGGLE EPSRVHLPFP
     WMKSTKAHAW KSQWAGGAYA AEPEENKRTR TAYTRAQLLE LEKEFLFNKY ISRPRRVELA
     VMLNLTERHI KIWFQNRRMK WKKEEDKKRS SGTTSGGGGG EEPEQDCAVT SGEELLALPP
     PPPPGGAVPS GVPAAAREGR LPSGLSASPQ PSSIAPLRPQ EPR
 
 
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