BHA15_MOUSE
ID BHA15_MOUSE Reviewed; 197 AA.
AC Q9QYC3; Q9QYE4;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Class A basic helix-loop-helix protein 15;
DE Short=bHLHa15;
DE AltName: Full=Class B basic helix-loop-helix protein 8;
DE Short=bHLHb8;
DE AltName: Full=Muscle, intestine and stomach expression 1;
DE Short=MIST-1;
GN Name=Bhlha15; Synonyms=Bhlhb8, Mist1;
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].
RX PubMed=10575209; DOI=10.1159/000015342;
RA Pin C.L., Lemercier C., Konieczny S.F.;
RT "Cloning of the murine Mist1 gene and assignment to mouse chromosome band
RT 5G2-5G3.";
RL Cytogenet. Cell Genet. 86:219-222(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spleen;
RA Lemercier C., Konieczny S.F.;
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Urinary bladder;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=9073453; DOI=10.1006/dbio.1996.8454;
RA Lemercier C., To R.Q., Swanson B.J., Lyons G.E., Konieczny S.F.;
RT "Mist1: a novel basic helix-loop-helix transcription factor exhibits a
RT developmentally regulated expression pattern.";
RL Dev. Biol. 182:101-113(1997).
RN [6]
RP FUNCTION.
RX PubMed=9482738; DOI=10.1093/emboj/17.5.1412;
RA Lemercier C., To R.Q., Carrasco R.A., Konieczny S.F.;
RT "The basic helix-loop-helix transcription factor Mist1 functions as a
RT transcriptional repressor of myoD.";
RL EMBO J. 17:1412-1422(1998).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=11696558; DOI=10.1083/jcb.200105060;
RA Pin C.L., Rukstalis J.M., Johnson C., Konieczny S.F.;
RT "The bHLH transcription factor Mist1 is required to maintain exocrine
RT pancreas cell organization and acinar cell identity.";
RL J. Cell Biol. 155:519-530(2001).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15003629; DOI=10.1016/j.mod.2004.01.003;
RA Johnson C.L., Kowalik A.S., Rajakumar N., Pin C.L.;
RT "Mist1 is necessary for the establishment of granule organization in serous
RT exocrine cells of the gastrointestinal tract.";
RL Mech. Dev. 121:261-272(2004).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15665001; DOI=10.1074/jbc.m411973200;
RA Luo X., Shin D.M., Wang X., Konieczny S.F., Muallem S.;
RT "Aberrant localization of intracellular organelles, Ca2+ signaling, and
RT exocytosis in Mist1 null mice.";
RL J. Biol. Chem. 280:12668-12675(2005).
RN [10]
RP FUNCTION, AND INDUCTION.
RX PubMed=17612490; DOI=10.1016/j.molcel.2007.06.011;
RA Acosta-Alvear D., Zhou Y., Blais A., Tsikitis M., Lents N.H., Arias C.,
RA Lennon C.J., Kluger Y., Dynlacht B.D.;
RT "XBP1 controls diverse cell type- and condition-specific transcriptional
RT regulatory networks.";
RL Mol. Cell 27:53-66(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-12 AND THR-25, AND
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: Plays a role in controlling the transcriptional activity of
CC MyoD, ensuring that expanding myoblast populations remain
CC undifferentiated (PubMed:17612490). Repression may occur through
CC muscle-specific E-box occupancy by homodimers. May also negatively
CC regulate bHLH-mediated transcription through an N-terminal repressor
CC domain. Serves as a key regulator of acinar cell function, stability,
CC and identity. Also required for normal organelle localization in
CC exocrine cells and for mitochondrial calcium ion transport. May
CC function as a unique regulator of gene expression in several different
CC embryonic and postnatal cell lineages. Binds to the E-box consensus
CC sequence 5'-CANNTG-3'. {ECO:0000269|PubMed:15003629,
CC ECO:0000269|PubMed:15665001, ECO:0000269|PubMed:17612490,
CC ECO:0000269|PubMed:9482738}.
CC -!- SUBUNIT: Forms homodimers or heterodimers with TCF3 gene products E12
CC and E47. These dimers bind to the E-box site, however, heterodimer with
CC MYOD1 does not bind target DNA.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in pancreatic tissue only in acinar
CC cells. There is a complete absence of expression in intra- or
CC interlobular pancreatic ducts and in all islet cells.
CC {ECO:0000269|PubMed:11696558}.
CC -!- DEVELOPMENTAL STAGE: First observed at 10.5 dpc in the primitive gut
CC and in the developing lung bud. Expression in the gut persists through
CC 16.5 dpc and remains restricted primarily to the epithelial lining of
CC the esophagus, stomach and intestine. Expression in the lung is
CC detected in the bronchial epithelium at 14.5 dpc and at 15.5 dpc.
CC Expressed specifically in acinar cells during pancreatic development.
CC Detected in skeletal muscle tissues beginning at 12.5 dpc, persisting
CC throughout all embryonic stages examined although, in older embryos
CC expression becomes severely reduced. {ECO:0000269|PubMed:9073453}.
CC -!- INDUCTION: Up-regulated by XBP1. Induced by chemical activators of the
CC unfolded protein response (UPR) such as tunicamycin and thapsigargin,
CC and also by glucose starvation (PubMed:17612490).
CC -!- DOMAIN: Lacks a classic transcription activation domain and instead
CC possesses an N-terminal region capable of inhibiting heterologous
CC activators.
CC -!- DISRUPTION PHENOTYPE: Mice display incorrect granule organization in
CC pancreatic acinar cells and other serous exocrine cells such as parotid
CC acini and gastric chief cells. They also display mislocalization of
CC mitochondria and Golgi apparatus and reduced Ca(2+) uptake by
CC mitochondria. {ECO:0000269|PubMed:15003629,
CC ECO:0000269|PubMed:15665001}.
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DR EMBL; AF091858; AAD51766.1; -; Genomic_DNA.
DR EMBL; AF049660; AAF17706.1; -; mRNA.
DR EMBL; AK020643; BAB32160.1; -; mRNA.
DR EMBL; BC011486; AAH11486.1; -; mRNA.
DR CCDS; CCDS19847.1; -.
DR RefSeq; NP_034930.1; NM_010800.4.
DR AlphaFoldDB; Q9QYC3; -.
DR SMR; Q9QYC3; -.
DR BioGRID; 201426; 1.
DR STRING; 10090.ENSMUSP00000055493; -.
DR iPTMnet; Q9QYC3; -.
DR PhosphoSitePlus; Q9QYC3; -.
DR PaxDb; Q9QYC3; -.
DR PRIDE; Q9QYC3; -.
DR ProteomicsDB; 265211; -.
DR Antibodypedia; 30223; 125 antibodies from 25 providers.
DR DNASU; 17341; -.
DR Ensembl; ENSMUST00000060747; ENSMUSP00000055493; ENSMUSG00000052271.
DR GeneID; 17341; -.
DR KEGG; mmu:17341; -.
DR UCSC; uc009alh.1; mouse.
DR CTD; 168620; -.
DR MGI; MGI:891976; Bhlha15.
DR VEuPathDB; HostDB:ENSMUSG00000052271; -.
DR eggNOG; KOG3898; Eukaryota.
DR GeneTree; ENSGT00940000161824; -.
DR HOGENOM; CLU_097977_2_0_1; -.
DR InParanoid; Q9QYC3; -.
DR OMA; HRYSTQI; -.
DR OrthoDB; 1528350at2759; -.
DR PhylomeDB; Q9QYC3; -.
DR TreeFam; TF315153; -.
DR BioGRID-ORCS; 17341; 2 hits in 77 CRISPR screens.
DR ChiTaRS; Bhlha15; mouse.
DR PRO; PR:Q9QYC3; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9QYC3; protein.
DR Bgee; ENSMUSG00000052271; Expressed in submandibular gland and 70 other tissues.
DR Genevisible; Q9QYC3; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI: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; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0019722; P:calcium-mediated signaling; IMP:MGI.
DR GO; GO:0007267; P:cell-cell signaling; IMP:MGI.
DR GO; GO:0042149; P:cellular response to glucose starvation; IDA:UniProtKB.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IDA:UniProtKB.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:0002071; P:glandular epithelial cell maturation; IMP:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
DR GO; GO:0007030; P:Golgi organization; IMP:MGI.
DR GO; GO:0048312; P:intracellular distribution of mitochondria; IMP:MGI.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; IMP:MGI.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; IDA:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:MGI.
DR GO; GO:0072560; P:type B pancreatic cell maturation; IMP:MGI.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW DNA-binding; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation.
FT CHAIN 1..197
FT /note="Class A basic helix-loop-helix protein 15"
FT /id="PRO_0000127151"
FT DOMAIN 72..124
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 178..197
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..40
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 52..82
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 180..197
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 12
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 25
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 107
FT /note="Missing (in Ref. 2; AAF17706)"
FT /evidence="ECO:0000305"
FT CONFLICT 166
FT /note="Q -> QV (in Ref. 2; AAF17706)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 197 AA; 22150 MW; BB34F1EE76FEE787 CRC64;
MKTKNRPPRR RTPMQDTEAT PGEQTPDRPQ SGSGGSELTK GLRSRTARAS GGRGEVSRRR
QGSGGRRENS VQRRLESNER ERQRMHKLNN AFQALREVIP HVRADKKLSK IETLTLAKNY
IKSLTATILT MSSSRLPGLE APGPAPGPKL YQHYHHQQQQ QQQQQQVAGA MLGVTEDQPQ
GHLQRYSTQI HSFREGS
