ID   PTF1A_MOUSE             Reviewed;         324 AA.
AC   Q9QX98; Q9QYF5; Q9QYF6;
DT   02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 162.
DE   RecName: Full=Pancreas transcription factor 1 subunit alpha;
DE   AltName: Full=Pancreas-specific transcription factor 1a;
DE   AltName: Full=bHLH transcription factor p48;
DE   AltName: Full=p48 DNA-binding subunit of transcription factor PTF1;
DE            Short=PTF1-p48;
GN   Name=Ptf1a; Synonyms=Ptf1p48;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], DEVELOPMENTAL STAGE, AND
RP   INTERACTION WITH TCF3 AND RBPSUH.
RC   STRAIN=ICR; TISSUE=Embryo;
RX   PubMed=11318877; DOI=10.1046/j.1365-2443.2001.00422.x;
RA   Obata J., Yano M., Mimura H., Goto T., Nakayama R., Mibu Y., Oka C.,
RA   Kawaichi M.;
RT   "p48 subunit of mouse PTF1 binds to RBP-Jkappa/CBF-1, the intracellular
RT   mediator of Notch signalling, and is expressed in the neural tube of early
RT   stage embryos.";
RL   Genes Cells 6:345-360(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND INTERACTION WITH TCF12.
RC   STRAIN=129;
RX   PubMed=11562365; DOI=10.1074/jbc.m106264200;
RA   Rose S.D., Swift G.H., Peyton M.J., Hammer R.E., MacDonald R.J.;
RT   "The role of PTF1-P48 in pancreatic acinar gene expression.";
RL   J. Biol. Chem. 276:44018-44026(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129/SvJ;
RA   Wellauer P.K.;
RL   Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Pancreas;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [5]
RP   FUNCTION IN PANCREAS DEVELOPMENT, TISSUE SPECIFICITY, AND DISRUPTION
RP   PHENOTYPE.
RC   STRAIN=129/SvJ;
RX   PubMed=9851981; DOI=10.1101/gad.12.23.3752;
RA   Krapp A., Knoefler M., Ledermann B., Buerki K., Berney C., Zoerkler N.,
RA   Hagenbuechle O., Wellauer P.K.;
RT   "The bHLH protein PTF1-p48 protein is essential for the formation of the
RT   exocrine and the correct spatial organization of the endocrine pancreas.";
RL   Genes Dev. 12:3752-3763(1998).
RN   [6]
RP   FUNCTION IN PANCREAS DEVELOPMENT, AND DEVELOPMENTAL STAGE.
RX   PubMed=12185368; DOI=10.1038/ng959;
RA   Kawaguchi Y., Cooper B., Gannon M., Ray M., MacDonald R.J., Wright C.V.;
RT   "The role of the transcriptional regulator Ptf1a in converting intestinal
RT   to pancreatic progenitors.";
RL   Nat. Genet. 32:128-134(2002).
RN   [7]
RP   FUNCTION IN PANCREAS AND CEREBELLAR DEVELOPMENT, DISRUPTION PHENOTYPE, AND
RP   DEVELOPMENTAL STAGE.
RX   PubMed=15543146; DOI=10.1038/ng1475;
RA   Sellick G.S., Barker K.T., Stolte-Dijkstra I., Fleischmann C.,
RA   Coleman R.J., Garrett C., Gloyn A.L., Edghill E.L., Hattersley A.T.,
RA   Wellauer P.K., Goodwin G., Houlston R.S.;
RT   "Mutations in PTF1A cause pancreatic and cerebellar agenesis.";
RL   Nat. Genet. 36:1301-1305(2004).
RN   [8]
RP   FUNCTION IN RETINA DEVELOPMENT, DEVELOPMENTAL STAGE, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=17075007; DOI=10.1242/dev.02598;
RA   Fujitani Y., Fujitani S., Luo H., Qiu F., Burlison J., Long Q.,
RA   Kawaguchi Y., Edlund H., MacDonald R.J., Furukawa T., Fujikado T.,
RA   Magnuson M.A., Xiang M., Wright C.V.;
RT   "Ptf1a determines horizontal and amacrine cell fates during mouse retinal
RT   development.";
RL   Development 133:4439-4450(2006).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Pancreas;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Transcription factor implicated in the cell fate
CC       determination in various organs. Binds to the E-box consensus sequence
CC       5'-CANNTG-3'. Plays a role in early and late pancreas development and
CC       differentiation. Important for determining whether cells allocated to
CC       the pancreatic buds continue towards pancreatic organogenesis or revert
CC       back to duodenal fates. May be involved in the maintenance of exocrine
CC       pancreas-specific gene expression including ELA1 and amylase. Required
CC       for the formation of pancreatic acinar and ductal cells. Plays an
CC       important role in cerebellar development. Directly regulated by FOXN4
CC       and RORC during retinal development, FOXN4-PTF1A pathway plays a
CC       central role in directing the differentiation of retinal progenitors
CC       towards horizontal and amacrine fates. {ECO:0000269|PubMed:11562365,
CC       ECO:0000269|PubMed:12185368, ECO:0000269|PubMed:15543146,
CC       ECO:0000269|PubMed:17075007, ECO:0000269|PubMed:9851981}.
CC   -!- SUBUNIT: Component of the pancreas transcription factor 1 complex
CC       (PTF1) which is composed of TCF3/p75, TCF12/p64 and PTF1A/p48. TCF3 is
CC       responsible for the nuclear import of the p48/p64 complex. Interacts
CC       with TCF3 and RBPSUH/RBP-Jkappa. {ECO:0000269|PubMed:11318877,
CC       ECO:0000269|PubMed:11562365}.
CC   -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=In the cytoplasm loses
CC       its ability to form the PTF1 complex.
CC   -!- TISSUE SPECIFICITY: Expressed in precursors of pancreatic islets, acini
CC       and ducts. {ECO:0000269|PubMed:9851981}.
CC   -!- DEVELOPMENTAL STAGE: Expressed at an early stage of pancreas
CC       development, shortly after the onset of endodermal budding that forms
CC       the pancreatic anlage. In 9.5 dpc embryo, expression is in the
CC       myelencephalon and the neural tube at the cervical level. In the 10.5
CC       dpc embryo expression expands as a thin stripe to the posterior end of
CC       the neural tube. The central nervous system anterior to the
CC       myelencephalon is devoid of expression at this stage. In 12-12.5 dpc
CC       embryo, expression expands anteriorly to the cerebellum region. During
CC       retinogenesis, restricted to postmitotic neuronal precursor population
CC       in the ventricular zone of the developing retina. Not expressed before
CC       12.5 dpc when is detected in the central region of the retina. By 14.5,
CC       expands from the center to the entire retina. Between 16.5 dpc and P1,
CC       continues to be expressed strongly in a subset of cells within the
CC       outer neuroblastic layer. Expression begins to be down-regulated by P2
CC       and is undetectable in retinas from P6. {ECO:0000269|PubMed:11318877,
CC       ECO:0000269|PubMed:12185368, ECO:0000269|PubMed:15543146,
CC       ECO:0000269|PubMed:17075007}.
CC   -!- DISRUPTION PHENOTYPE: Early postnatal lethal phenotype characterized by
CC       a lack of the exocrine pancreas, however, islet-like endocrine cell
CC       clusters are formed. A redirection of pancreatic precursors to
CC       intestinal fates is seen. At 16.5 dpc embryos show reduced size of
CC       cerebellar primordium and cerebellar aplasia.
CC       {ECO:0000269|PubMed:15543146, ECO:0000269|PubMed:17075007,
CC       ECO:0000269|PubMed:9851981}.
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DR   EMBL; AB035674; BAA88247.1; -; Genomic_DNA.
DR   EMBL; AB035675; BAA88249.1; -; mRNA.
DR   EMBL; AF298116; AAG31604.1; -; Genomic_DNA.
DR   EMBL; AJ252156; CAB65273.1; -; Genomic_DNA.
DR   EMBL; AK007922; BAE43208.1; -; mRNA.
DR   CCDS; CCDS15715.1; -.
DR   RefSeq; NP_061279.2; NM_018809.2.
DR   AlphaFoldDB; Q9QX98; -.
DR   SMR; Q9QX98; -.
DR   BioGRID; 202451; 2.
DR   CORUM; Q9QX98; -.
DR   IntAct; Q9QX98; 1.
DR   MINT; Q9QX98; -.
DR   STRING; 10090.ENSMUSP00000028068; -.
DR   iPTMnet; Q9QX98; -.
DR   PhosphoSitePlus; Q9QX98; -.
DR   PaxDb; 10090-ENSMUSP00000028068; -.
DR   ProteomicsDB; 301850; -.
DR   Antibodypedia; 25762; 451 antibodies from 31 providers.
DR   DNASU; 19213; -.
DR   Ensembl; ENSMUST00000028068.3; ENSMUSP00000028068.3; ENSMUSG00000026735.3.
DR   GeneID; 19213; -.
DR   KEGG; mmu:19213; -.
DR   UCSC; uc012brh.1; mouse.
DR   AGR; MGI:1328312; -.
DR   CTD; 256297; -.
DR   MGI; MGI:1328312; Ptf1a.
DR   VEuPathDB; HostDB:ENSMUSG00000026735; -.
DR   eggNOG; KOG4029; Eukaryota.
DR   GeneTree; ENSGT00940000161000; -.
DR   HOGENOM; CLU_053709_0_0_1; -.
DR   InParanoid; Q9QX98; -.
DR   OMA; GYCCEAA; -.
DR   OrthoDB; 5403747at2759; -.
DR   PhylomeDB; Q9QX98; -.
DR   TreeFam; TF315153; -.
DR   BioGRID-ORCS; 19213; 1 hit in 78 CRISPR screens.
DR   ChiTaRS; Ptf1a; mouse.
DR   PRO; PR:Q9QX98; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; Q9QX98; Protein.
DR   Bgee; ENSMUSG00000026735; Expressed in dorsal pancreas and 43 other cell types or tissues.
DR   ExpressionAtlas; Q9QX98; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:HGNC.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; ISS:HGNC.
DR   GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR   GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR   GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0070888; F:E-box binding; IDA:MGI.
DR   GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0035881; P:amacrine cell differentiation; IMP:UniProtKB.
DR   GO; GO:0045165; P:cell fate commitment; IMP:MGI.
DR   GO; GO:0021549; P:cerebellum development; IMP:UniProtKB.
DR   GO; GO:0032502; P:developmental process; IBA:GO_Central.
DR   GO; GO:0031017; P:exocrine pancreas development; ISS:HGNC.
DR   GO; GO:0048699; P:generation of neurons; IDA:UniProtKB.
DR   GO; GO:0030902; P:hindbrain development; IDA:UniProtKB.
DR   GO; GO:0030182; P:neuron differentiation; IMP:MGI.
DR   GO; GO:0048663; P:neuron fate commitment; IDA:MGI.
DR   GO; GO:0031016; P:pancreas development; IMP:MGI.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0061074; P:regulation of neural retina development; IMP:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0010842; P:retina layer formation; IMP:UniProtKB.
DR   GO; GO:0060042; P:retina morphogenesis in camera-type eye; IMP:MGI.
DR   GO; GO:0048384; P:retinoic acid receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0009888; P:tissue development; ISS:UniProtKB.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; IDA:MGI.
DR   CDD; cd11417; bHLH_TS_PTF1A; 1.
DR   Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1.
DR   InterPro; IPR011598; bHLH_dom.
DR   InterPro; IPR036638; HLH_DNA-bd_sf.
DR   PANTHER; PTHR23349; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTOR, TWIST; 1.
DR   PANTHER; PTHR23349:SF59; PANCREAS TRANSCRIPTION FACTOR 1 SUBUNIT ALPHA; 1.
DR   Pfam; PF00010; HLH; 1.
DR   SMART; SM00353; HLH; 1.
DR   SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1.
DR   PROSITE; PS50888; BHLH; 1.
DR   Genevisible; Q9QX98; MM.
PE   1: Evidence at protein level;
KW   Cytoplasm; Developmental protein; Differentiation; DNA-binding;
KW   Neurogenesis; Nucleus; Reference proteome; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..324
FT                   /note="Pancreas transcription factor 1 subunit alpha"
FT                   /id="PRO_0000233144"
FT   DOMAIN          160..212
FT                   /note="bHLH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT   REGION          302..324
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        7
FT                   /note="E -> K (in Ref. 1; BAA88247)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        11
FT                   /note="G -> R (in Ref. 1; BAA88247)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        223
FT                   /note="R -> H (in Ref. 1; BAA88247)"
FT                   /evidence="ECO:0000305"
SQ   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
//