ID   PTF1A_HUMAN             Reviewed;         328 AA.
AC   Q7RTS3; Q9HC25;
DT   02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-2003, sequence version 1.
DT   27-MAR-2024, entry version 161.
DE   RecName: Full=Pancreas transcription factor 1 subunit alpha;
DE   AltName: Full=Class A basic helix-loop-helix protein 29;
DE            Short=bHLHa29;
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=BHLHA29, PTF1P48;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 168-215, FUNCTION, SUBCELLULAR LOCATION, AND
RP   TISSUE SPECIFICITY.
RX   PubMed=10768861;
RA   Adell T., Gomez-Cuadrado A., Skoudy A., Pettengill O.S., Longnecker D.S.,
RA   Real F.X.;
RT   "Role of the basic helix-loop-helix transcription factor p48 in the
RT   differentiation phenotype of exocrine pancreas cancer cells.";
RL   Cell Growth Differ. 11:137-147(2000).
RN   [3]
RP   IDENTIFICATION.
RX   PubMed=12617822; DOI=10.1016/s0925-4773(02)00390-8;
RA   McLellan A.S., Langlands K., Kealey T.;
RT   "Exhaustive identification of human class II basic helix-loop-helix
RT   proteins by virtual library screening.";
RL   Gene Expr. Patterns 2:329-335(2002).
RN   [4]
RP   INVOLVEMENT IN PACA, AND FUNCTION IN PANCREAS AND CEREBELLAR DEVELOPMENT.
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   [5]
RP   INVOLVEMENT IN PAGEN2.
RX   PubMed=24212882; DOI=10.1038/ng.2826;
RG   International Pancreatic Agenesis Consortium;
RA   Weedon M.N., Cebola I., Patch A.M., Flanagan S.E., De Franco E.,
RA   Caswell R., Rodriguez-Segui S.A., Shaw-Smith C., Cho C.H., Lango Allen H.,
RA   Houghton J.A., Roth C.L., Chen R., Hussain K., Marsh P., Vallier L.,
RA   Murray A., Ellard S., Ferrer J., Hattersley A.T.;
RT   "Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic
RT   agenesis.";
RL   Nat. Genet. 46:61-64(2014).
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:10768861,
CC       ECO:0000269|PubMed:15543146}.
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 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC       Cytoplasm {ECO:0000250}. Note=In chronic pancreatitis associated with
CC       pancreas cancer preferentially accumulates in the cytoplasm of
CC       acinar/ductular complexes. In the cytoplasm loses its ability to form
CC       the PTF1 complex (By similarity). {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Pancreas-specific (at protein level). Loss of
CC       expression is seen in ductal type pancreas cancers.
CC       {ECO:0000269|PubMed:10768861}.
CC   -!- DISEASE: Pancreatic and cerebellar agenesis (PACA) [MIM:609069]: A
CC       disease characterized by neonatal diabetes mellitus, cerebellar
CC       agenesis or hypoplasia, severe intrauterine growth retardation, the
CC       presence of very little subcutaneous fat, and dysmorphic facial
CC       features. {ECO:0000269|PubMed:15543146}. Note=The disease is caused by
CC       variants affecting the gene represented in this entry.
CC   -!- DISEASE: Pancreatic agenesis 2 (PAGEN2) [MIM:615935]: A disease
CC       characterized by isolated hypoplasia or agenesis of the pancreas,
CC       pancreatic beta-cell failure resulting in neonatal insulin-dependent
CC       diabetes mellitus, and exocrine pancreatic insufficiency.
CC       {ECO:0000269|PubMed:24212882}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry. In some families with
CC       pancreatic agenesis, disease causing mutations affect the sequence and
CC       activity of an enhancer region of 400-bp located 25 kb downstream of
CC       PTF1A (PubMed:24212882). {ECO:0000269|PubMed:24212882}.
CC   -!- MISCELLANEOUS: An excellent marker of acinar cell differentiation in
CC       the pancreas.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AL139281; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AF181999; AAG09441.1; -; mRNA.
DR   EMBL; BK000272; DAA01052.1; -; Genomic_DNA.
DR   CCDS; CCDS7143.1; -.
DR   RefSeq; NP_835455.1; NM_178161.2.
DR   AlphaFoldDB; Q7RTS3; -.
DR   SMR; Q7RTS3; -.
DR   BioGRID; 129154; 14.
DR   CORUM; Q7RTS3; -.
DR   STRING; 9606.ENSP00000365687; -.
DR   iPTMnet; Q7RTS3; -.
DR   PhosphoSitePlus; Q7RTS3; -.
DR   BioMuta; PTF1A; -.
DR   DMDM; 74749931; -.
DR   jPOST; Q7RTS3; -.
DR   MassIVE; Q7RTS3; -.
DR   MaxQB; Q7RTS3; -.
DR   PaxDb; 9606-ENSP00000365687; -.
DR   PeptideAtlas; Q7RTS3; -.
DR   ProteomicsDB; 68892; -.
DR   Antibodypedia; 25762; 451 antibodies from 31 providers.
DR   DNASU; 256297; -.
DR   Ensembl; ENST00000376504.4; ENSP00000365687.3; ENSG00000168267.7.
DR   GeneID; 256297; -.
DR   KEGG; hsa:256297; -.
DR   MANE-Select; ENST00000376504.4; ENSP00000365687.3; NM_178161.3; NP_835455.1.
DR   UCSC; uc001irp.4; human.
DR   AGR; HGNC:23734; -.
DR   CTD; 256297; -.
DR   DisGeNET; 256297; -.
DR   GeneCards; PTF1A; -.
DR   HGNC; HGNC:23734; PTF1A.
DR   HPA; ENSG00000168267; Tissue enriched (pancreas).
DR   MalaCards; PTF1A; -.
DR   MIM; 607194; gene.
DR   MIM; 609069; phenotype.
DR   MIM; 615935; phenotype.
DR   neXtProt; NX_Q7RTS3; -.
DR   OpenTargets; ENSG00000168267; -.
DR   Orphanet; 2805; Partial pancreatic agenesis.
DR   Orphanet; 65288; Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome.
DR   PharmGKB; PA134864129; -.
DR   VEuPathDB; HostDB:ENSG00000168267; -.
DR   eggNOG; KOG4029; Eukaryota.
DR   GeneTree; ENSGT00940000161000; -.
DR   HOGENOM; CLU_053709_0_0_1; -.
DR   InParanoid; Q7RTS3; -.
DR   OMA; GYCCEAA; -.
DR   OrthoDB; 5403747at2759; -.
DR   PhylomeDB; Q7RTS3; -.
DR   TreeFam; TF315153; -.
DR   PathwayCommons; Q7RTS3; -.
DR   Reactome; R-HSA-210747; Regulation of gene expression in early pancreatic precursor cells.
DR   SignaLink; Q7RTS3; -.
DR   SIGNOR; Q7RTS3; -.
DR   BioGRID-ORCS; 256297; 16 hits in 1167 CRISPR screens.
DR   GeneWiki; PTF1A; -.
DR   GenomeRNAi; 256297; -.
DR   Pharos; Q7RTS3; Tbio.
DR   PRO; PR:Q7RTS3; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q7RTS3; Protein.
DR   Bgee; ENSG00000168267; Expressed in body of pancreas and 71 other cell types or tissues.
DR   ExpressionAtlas; Q7RTS3; baseline and differential.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005667; C:transcription regulator complex; ISS:UniProtKB.
DR   GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR   GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR   GO; GO:0070888; F:E-box binding; IEA:Ensembl.
DR   GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR   GO; GO:0035881; P:amacrine cell differentiation; ISS:UniProtKB.
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:UniProtKB.
DR   GO; GO:0048663; P:neuron fate commitment; IEA:Ensembl.
DR   GO; GO:0031016; P:pancreas development; IMP:UniProtKB.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0061074; P:regulation of neural retina development; ISS:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0010842; P:retina layer formation; ISS:UniProtKB.
DR   GO; GO:0048384; P:retinoic acid receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0009888; P:tissue development; IDA:UniProtKB.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
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.
PE   1: Evidence at protein level;
KW   Cytoplasm; Developmental protein; Diabetes mellitus; Differentiation;
KW   DNA-binding; Neurogenesis; Nucleus; Reference proteome; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..328
FT                   /note="Pancreas transcription factor 1 subunit alpha"
FT                   /id="PRO_0000233143"
FT   DOMAIN          163..215
FT                   /note="bHLH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT   REGION          259..278
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          305..328
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        307..321
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         263
FT                   /note="S -> P (in dbSNP:rs7918487)"
FT                   /id="VAR_049548"
SQ   SEQUENCE   328 AA;  34970 MW;  5AC84B482C55CEC3 CRC64;
     MDAVLLEHFP GGLDAFPSSY FDEDDFFTDQ SSRDPLEDGD ELLADEQAEV EFLSHQLHEY
     CYRDGACLLL QPAPPAAPLA LAPPSSGGLG EPDDGGGGGY CCETGAPPGG FPYSPGSPPS
     CLAYPCAGAA VLSPGARLRG LSGAAAAAAR RRRRVRSEAE LQQLRQAANV RERRRMQSIN
     DAFEGLRSHI PTLPYEKRLS KVDTLRLAIG YINFLSELVQ ADLPLRGGGA GGCGGPGGGG
     RLGGDSPGSQ AQKVIICHRG TRSPSPSDPD YGLPPLAGHS LSWTDEKQLK EQNIIRTAKV
     WTPEDPRKLN SKSSFNNIEN EPPFEFVS
//