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Pancreas transcription factor 1 subunit alpha (Pancreas-specific transcription factor 1a) (bHLH transcription factor p48) (p48 DNA-binding subunit of transcription factor PTF1) (PTF1-p48)
PTF1A_MOUSE Reviewed; 324 AA.
Q9QX98; Q9QYF5; Q9QYF6;
02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
01-MAY-2000, sequence version 1.
13-FEB-2019, entry version 138.
RecName: Full=Pancreas transcription factor 1 subunit alpha;
AltName: Full=Pancreas-specific transcription factor 1a;
AltName: Full=bHLH transcription factor p48;
AltName: Full=p48 DNA-binding subunit of transcription factor PTF1;
Short=PTF1-p48;
Name=Ptf1a; Synonyms=Ptf1p48;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], DEVELOPMENTAL STAGE, AND
INTERACTION WITH TCF3 AND RBPSUH.
STRAIN=ICR; TISSUE=Embryo;
PubMed=11318877; DOI=10.1046/j.1365-2443.2001.00422.x;
Obata J., Yano M., Mimura H., Goto T., Nakayama R., Mibu Y., Oka C.,
Kawaichi M.;
"p48 subunit of mouse PTF1 binds to RBP-Jkappa/CBF-1, the
intracellular mediator of Notch signalling, and is expressed in the
neural tube of early stage embryos.";
Genes Cells 6:345-360(2001).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND INTERACTION WITH
TCF12.
STRAIN=129;
PubMed=11562365; DOI=10.1074/jbc.M106264200;
Rose S.D., Swift G.H., Peyton M.J., Hammer R.E., MacDonald R.J.;
"The role of PTF1-P48 in pancreatic acinar gene expression.";
J. Biol. Chem. 276:44018-44026(2001).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
STRAIN=129/SvJ;
Wellauer P.K.;
Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=C57BL/6J; TISSUE=Pancreas;
PubMed=16141072; DOI=10.1126/science.1112014;
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.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[5]
FUNCTION IN PANCREAS DEVELOPMENT, TISSUE SPECIFICITY, AND DISRUPTION
PHENOTYPE.
STRAIN=129/SvJ;
PubMed=9851981; DOI=10.1101/gad.12.23.3752;
Krapp A., Knoefler M., Ledermann B., Buerki K., Berney C.,
Zoerkler N., Hagenbuechle O., Wellauer P.K.;
"The bHLH protein PTF1-p48 protein is essential for the formation of
the exocrine and the correct spatial organization of the endocrine
pancreas.";
Genes Dev. 12:3752-3763(1998).
[6]
FUNCTION IN PANCREAS DEVELOPMENT, AND DEVELOPMENTAL STAGE.
PubMed=12185368; DOI=10.1038/ng959;
Kawaguchi Y., Cooper B., Gannon M., Ray M., MacDonald R.J.,
Wright C.V.;
"The role of the transcriptional regulator Ptf1a in converting
intestinal to pancreatic progenitors.";
Nat. Genet. 32:128-134(2002).
[7]
FUNCTION IN PANCREAS AND CEREBELLAR DEVELOPMENT, DISRUPTION PHENOTYPE,
AND DEVELOPMENTAL STAGE.
PubMed=15543146; DOI=10.1038/ng1475;
Sellick G.S., Barker K.T., Stolte-Dijkstra I., Fleischmann C.,
Coleman R.J., Garrett C., Gloyn A.L., Edghill E.L., Hattersley A.T.,
Wellauer P.K., Goodwin G., Houlston R.S.;
"Mutations in PTF1A cause pancreatic and cerebellar agenesis.";
Nat. Genet. 36:1301-1305(2004).
[8]
FUNCTION IN RETINA DEVELOPMENT, DEVELOPMENTAL STAGE, AND DISRUPTION
PHENOTYPE.
PubMed=17075007; DOI=10.1242/dev.02598;
Fujitani Y., Fujitani S., Luo H., Qiu F., Burlison J., Long Q.,
Kawaguchi Y., Edlund H., MacDonald R.J., Furukawa T., Fujikado T.,
Magnuson M.A., Xiang M., Wright C.V.;
"Ptf1a determines horizontal and amacrine cell fates during mouse
retinal development.";
Development 133:4439-4450(2006).
[9]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Pancreas;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
-!- FUNCTION: Transcription factor implicated in the cell fate
determination in various organs. Binds to the E-box consensus
sequence 5'-CANNTG-3'. Plays a role in early and late pancreas
development and differentiation. Important for determining whether
cells allocated to the pancreatic buds continue towards pancreatic
organogenesis or revert back to duodenal fates. May be involved in
the maintenance of exocrine pancreas-specific gene expression
including ELA1 and amylase. Required for the formation of
pancreatic acinar and ductal cells. Plays an important role in
cerebellar development. Directly regulated by FOXN4 and RORC
during retinal development, FOXN4-PTF1A pathway plays a central
role in directing the differentiation of retinal progenitors
towards horizontal and amacrine fates.
{ECO:0000269|PubMed:11562365, ECO:0000269|PubMed:12185368,
ECO:0000269|PubMed:15543146, ECO:0000269|PubMed:17075007,
ECO:0000269|PubMed:9851981}.
-!- SUBUNIT: Component of the pancreas transcription factor 1 complex
(PTF1) which is composed of TCF3/p75, TCF12/p64 and PTF1A/p48.
TCF3 is responsible for the nuclear import of the p48/p64 complex.
Interacts with TCF3 and RBPSUH/RBP-Jkappa.
{ECO:0000269|PubMed:11318877, ECO:0000269|PubMed:11562365}.
-!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=In the cytoplasm
loses its ability to form the PTF1 complex.
-!- TISSUE SPECIFICITY: Expressed in precursors of pancreatic islets,
acini and ducts. {ECO:0000269|PubMed:9851981}.
-!- DEVELOPMENTAL STAGE: Expressed at an early stage of pancreas
development, shortly after the onset of endodermal budding that
forms the pancreatic anlage. In 9.5 dpc embryo, expression is in
the myelencephalon and the neural tube at the cervical level. In
the 10.5 dpc embryo expression expands as a thin stripe to the
posterior end of the neural tube. The central nervous system
anterior to the myelencephalon is devoid of expression at this
stage. In 12-12.5 dpc embryo, expression expands anteriorly to the
cerebellum region. During retinogenesis, restricted to postmitotic
neuronal precursor population in the ventricular zone of the
developing retina. Not expressed before 12.5 dpc when is detected
in the central region of the retina. By 14.5, expands from the
center to the entire retina. Between 16.5 dpc and P1, continues to
be expressed strongly in a subset of cells within the outer
neuroblastic layer. Expression begins to be down-regulated by P2
and is undetectable in retinas from P6.
{ECO:0000269|PubMed:11318877, ECO:0000269|PubMed:12185368,
ECO:0000269|PubMed:15543146, ECO:0000269|PubMed:17075007}.
-!- DISRUPTION PHENOTYPE: Early postnatal lethal phenotype
characterized by a lack of the exocrine pancreas, however, islet-
like endocrine cell clusters are formed. A redirection of
pancreatic precursors to intestinal fates is seen. At 16.5 dpc
embryos show reduced size of cerebellar primordium and cerebellar
aplasia. {ECO:0000269|PubMed:15543146,
ECO:0000269|PubMed:17075007, ECO:0000269|PubMed:9851981}.
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EMBL; AB035674; BAA88247.1; -; Genomic_DNA.
EMBL; AB035675; BAA88249.1; -; mRNA.
EMBL; AF298116; AAG31604.1; -; Genomic_DNA.
EMBL; AJ252156; CAB65273.1; -; Genomic_DNA.
EMBL; AK007922; BAE43208.1; -; mRNA.
CCDS; CCDS15715.1; -.
RefSeq; NP_061279.2; NM_018809.2.
UniGene; Mm.69647; -.
ProteinModelPortal; Q9QX98; -.
SMR; Q9QX98; -.
BioGrid; 202451; 1.
CORUM; Q9QX98; -.
STRING; 10090.ENSMUSP00000028068; -.
PhosphoSitePlus; Q9QX98; -.
PaxDb; Q9QX98; -.
PRIDE; Q9QX98; -.
Ensembl; ENSMUST00000028068; ENSMUSP00000028068; ENSMUSG00000026735.
GeneID; 19213; -.
KEGG; mmu:19213; -.
UCSC; uc012brh.1; mouse.
CTD; 256297; -.
MGI; MGI:1328312; Ptf1a.
eggNOG; KOG4029; Eukaryota.
eggNOG; ENOG411227D; LUCA.
GeneTree; ENSGT00940000161000; -.
HOGENOM; HOG000231913; -.
HOVERGEN; HBG082224; -.
InParanoid; Q9QX98; -.
KO; K09073; -.
OMA; YCCEAGA; -.
OrthoDB; 1269550at2759; -.
PhylomeDB; Q9QX98; -.
TreeFam; TF315153; -.
ChiTaRS; Ptf1a; mouse.
PRO; PR:Q9QX98; -.
Proteomes; UP000000589; Chromosome 2.
Bgee; ENSMUSG00000026735; Expressed in 50 organ(s), highest expression level in dorsal pancreas.
ExpressionAtlas; Q9QX98; baseline and differential.
Genevisible; Q9QX98; MM.
GO; GO:0005737; C:cytoplasm; ISS:HGNC.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
GO; GO:0005634; C:nucleus; ISS:HGNC.
GO; GO:0005667; C:transcription factor complex; IDA:MGI.
GO; GO:0003682; F:chromatin binding; IDA:MGI.
GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI.
GO; GO:0070888; F:E-box binding; IDA:MGI.
GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
GO; GO:0000980; F:RNA polymerase II distal enhancer sequence-specific DNA binding; ISO:MGI.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
GO; GO:0035881; P:amacrine cell differentiation; IMP:UniProtKB.
GO; GO:0030154; P:cell differentiation; IMP:MGI.
GO; GO:0045165; P:cell fate commitment; IMP:MGI.
GO; GO:0021549; P:cerebellum development; IMP:UniProtKB.
GO; GO:0031018; P:endocrine pancreas development; TAS:Reactome.
GO; GO:0031017; P:exocrine pancreas development; ISS:HGNC.
GO; GO:0048699; P:generation of neurons; IDA:UniProtKB.
GO; GO:0030902; P:hindbrain development; IDA:UniProtKB.
GO; GO:0048663; P:neuron fate commitment; IDA:MGI.
GO; GO:0031016; P:pancreas development; IMP:MGI.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0061074; P:regulation of neural retina development; IMP:UniProtKB.
GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0010842; P:retina layer formation; IMP:UniProtKB.
GO; GO:0060042; P:retina morphogenesis in camera-type eye; IMP:MGI.
GO; GO:0048384; P:retinoic acid receptor signaling pathway; IDA:UniProtKB.
GO; GO:0009888; P:tissue development; ISS:UniProtKB.
CDD; cd00083; HLH; 1.
Gene3D; 4.10.280.10; -; 1.
InterPro; IPR011598; bHLH_dom.
InterPro; IPR036638; HLH_DNA-bd_sf.
Pfam; PF00010; HLH; 1.
SMART; SM00353; HLH; 1.
SUPFAM; SSF47459; SSF47459; 1.
PROSITE; PS50888; BHLH; 1.
1: Evidence at protein level;
Complete proteome; Cytoplasm; Developmental protein; Differentiation;
DNA-binding; Neurogenesis; Nucleus; Reference proteome; Transcription;
Transcription regulation.
CHAIN 1 324 Pancreas transcription factor 1 subunit
alpha.
/FTId=PRO_0000233144.
DOMAIN 160 212 bHLH. {ECO:0000255|PROSITE-
ProRule:PRU00981}.
CONFLICT 7 7 E -> K (in Ref. 1; BAA88247).
{ECO:0000305}.
CONFLICT 11 11 G -> R (in Ref. 1; BAA88247).
{ECO:0000305}.
CONFLICT 223 223 R -> H (in Ref. 1; BAA88247).
{ECO:0000305}.
SEQUENCE 324 AA; 35185 MW; E74109A84B5CFD79 CRC64;
MDAVLLEHFP GGLDTFPSPY FDEEDFFTDQ SSRDPLEDSD ELLGDEQAEV EFLSHQLHEY
CYRDGACLLL QPAPSAAPHA LAPPPLGDPG EPEDNVSYCC DAGAPLAAFP YSPGSPPSCL
AYPCAAVLSP GARLGGLNGA AAAAAARRRR RVRSEAELQQ LRQAANVRER RRMQSINDAF
EGLRSHIPTL PYEKRLSKVD TLRLAIGYIN FLSELVQADL PLRGSGAGGC GGPGGSRHLG
EDSPGNQAQK VIICHRGTRS PSPSDPDYGL PPLAGHSLSW TDEKQLKEQN IIRTAKVWTP
EDPRKLNSKS FDNIENEPPF EFVS
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Pathways :
WP1789: Binding of RNA by Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs)
WP1899: Regulation of Insulin-like Growth Factor (IGF) Activity by Insulin-like Growth Factor Binding Proteins (IGFBPs)
WP1046: Signaling of Hepatocyte Growth Factor Receptor
WP1066: Eukaryotic Transcription Initiation
WP1162: Signaling of Hepatocyte Growth Factor Receptor
WP1182: Eukaryotic Transcription Initiation
WP1206: Signaling of Hepatocyte Growth Factor Receptor
WP1235: Signaling of Hepatocyte Growth Factor Receptor
WP1238: Eukaryotic Transcription Initiation
WP1541: Energy Metabolism
WP177: Eukaryotic Transcription Initiation
WP1822: Generic Transcription Pathway
WP1905: RNA Polymerase I, RNA Polymerase III, and Mitochondrial Transcription
WP1906: RNA Polymerase II Transcription
WP193: Signaling of Hepatocyte Growth Factor Receptor
WP1930: Transcription
WP1983: Splicing factor NOVA regulated synpatic proteins
WP2148: Brain derived neurotrophic factor
WP272: Blood Clotting Cascade
WP313: Signaling of Hepatocyte Growth Factor Receptor
WP344: Eukaryotic Transcription Initiation
WP405: Eukaryotic Transcription Initiation
WP425: Eukaryotic Transcription Initiation
WP444: Signaling of Hepatocyte Growth Factor Receptor
WP491: Eukaryotic Transcription Initiation
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