ID   BHA15_HUMAN             Reviewed;         189 AA.
AC   Q7RTS1; A4D271; Q14DE4;
DT   19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-2003, sequence version 1.
DT   27-MAR-2024, entry version 152.
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   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=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12690205; DOI=10.1126/science.1083423;
RA   Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA   Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA   Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA   Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA   Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA   Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA   Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA   Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA   Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA   Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA   Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA   Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA   Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA   Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA   Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA   Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA   Adams M.D., Tsui L.-C.;
RT   "Human chromosome 7: DNA sequence and biology.";
RL   Science 300:767-772(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [4]
RP   IDENTIFICATION, AND TISSUE SPECIFICITY.
RX   PubMed=14516699; DOI=10.1016/s0925-4773(03)00130-8;
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   Mech. Dev. 119:S285-S291(2002).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
CC   -!- FUNCTION: Plays a role in controlling the transcriptional activity of
CC       MYOD1, ensuring that expanding myoblast populations remain
CC       undifferentiated. Repression may occur through muscle-specific E-box
CC       occupancy by homodimers. May also negatively regulate bHLH-mediated
CC       transcription through an N-terminal repressor domain. Serves as a key
CC       regulator of acinar cell function, stability, and identity. Also
CC       required for normal organelle localization in exocrine cells and for
CC       mitochondrial calcium ion transport. May function as a unique regulator
CC       of gene expression in several different embryonic and postnatal cell
CC       lineages. Binds to the E-box consensus sequence 5'-CANNTG-3' (By
CC       similarity). {ECO:0000250|UniProtKB:Q9QYC3}.
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 (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q7RTS1; P15173: MYOG; NbExp=3; IntAct=EBI-8844218, EBI-3906629;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed in brain, liver, spleen and skeletal
CC       muscle. {ECO:0000269|PubMed:14516699}.
CC   -!- DOMAIN: Lacks a classic transcription activation domain and instead
CC       possesses an N-terminal region capable of inhibiting heterologous
CC       activators. {ECO:0000250}.
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DR   EMBL; AC025605; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH236956; EAL23893.1; -; Genomic_DNA.
DR   EMBL; BC113394; AAI13395.1; -; mRNA.
DR   EMBL; BC113396; AAI13397.1; -; mRNA.
DR   EMBL; BK000276; DAA01056.1; -; mRNA.
DR   CCDS; CCDS5655.1; -.
DR   RefSeq; NP_803238.1; NM_177455.3.
DR   AlphaFoldDB; Q7RTS1; -.
DR   SMR; Q7RTS1; -.
DR   BioGRID; 127970; 76.
DR   IntAct; Q7RTS1; 44.
DR   MINT; Q7RTS1; -.
DR   STRING; 9606.ENSP00000476312; -.
DR   iPTMnet; Q7RTS1; -.
DR   PhosphoSitePlus; Q7RTS1; -.
DR   BioMuta; BHLHA15; -.
DR   DMDM; 50400944; -.
DR   jPOST; Q7RTS1; -.
DR   MassIVE; Q7RTS1; -.
DR   MaxQB; Q7RTS1; -.
DR   PaxDb; 9606-ENSP00000476312; -.
DR   PeptideAtlas; Q7RTS1; -.
DR   ProteomicsDB; 68891; -.
DR   Antibodypedia; 30223; 134 antibodies from 25 providers.
DR   DNASU; 168620; -.
DR   Ensembl; ENST00000314018.2; ENSP00000326391.2; ENSG00000180535.4.
DR   Ensembl; ENST00000609256.2; ENSP00000476312.1; ENSG00000180535.4.
DR   GeneID; 168620; -.
DR   KEGG; hsa:168620; -.
DR   MANE-Select; ENST00000609256.2; ENSP00000476312.1; NM_177455.4; NP_803238.1.
DR   UCSC; uc003upe.2; human.
DR   AGR; HGNC:22265; -.
DR   CTD; 168620; -.
DR   DisGeNET; 168620; -.
DR   GeneCards; BHLHA15; -.
DR   HGNC; HGNC:22265; BHLHA15.
DR   HPA; ENSG00000180535; Group enriched (pancreas, salivary gland).
DR   MIM; 608606; gene.
DR   neXtProt; NX_Q7RTS1; -.
DR   OpenTargets; ENSG00000180535; -.
DR   PharmGKB; PA164716601; -.
DR   VEuPathDB; HostDB:ENSG00000180535; -.
DR   eggNOG; KOG3898; Eukaryota.
DR   GeneTree; ENSGT00940000161824; -.
DR   HOGENOM; CLU_097977_2_0_1; -.
DR   InParanoid; Q7RTS1; -.
DR   OMA; HRYSTQI; -.
DR   OrthoDB; 5406208at2759; -.
DR   PhylomeDB; Q7RTS1; -.
DR   TreeFam; TF315153; -.
DR   PathwayCommons; Q7RTS1; -.
DR   SignaLink; Q7RTS1; -.
DR   BioGRID-ORCS; 168620; 71 hits in 1172 CRISPR screens.
DR   GeneWiki; BHLHB8; -.
DR   GenomeRNAi; 168620; -.
DR   Pharos; Q7RTS1; Tbio.
DR   PRO; PR:Q7RTS1; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; Q7RTS1; Protein.
DR   Bgee; ENSG00000180535; Expressed in parotid gland and 102 other cell types or tissues.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
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; IBA:GO_Central.
DR   GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR   GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR   GO; GO:0061564; P:axon development; IBA:GO_Central.
DR   GO; GO:0019722; P:calcium-mediated signaling; IEA:Ensembl.
DR   GO; GO:0007267; P:cell-cell signaling; IEA:Ensembl.
DR   GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR   GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR   GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR   GO; GO:0007030; P:Golgi organization; IEA:Ensembl.
DR   GO; GO:0048312; P:intracellular distribution of mitochondria; IEA:Ensembl.
DR   GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; IEA:Ensembl.
DR   GO; GO:0010832; P:negative regulation of myotube differentiation; ISS:UniProtKB.
DR   GO; GO:0048663; P:neuron fate commitment; IBA:GO_Central.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0007423; P:sensory organ development; IBA:GO_Central.
DR   GO; GO:0072560; P:type B pancreatic cell maturation; IEA:Ensembl.
DR   CDD; cd19711; bHLH_TS_MIST1; 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; PTHR19290; BASIC HELIX-LOOP-HELIX PROTEIN NEUROGENIN-RELATED; 1.
DR   PANTHER; PTHR19290:SF160; CLASS A BASIC HELIX-LOOP-HELIX PROTEIN 15; 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   DNA-binding; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW   Transcription; Transcription regulation.
FT   CHAIN           1..189
FT                   /note="Class A basic helix-loop-helix protein 15"
FT                   /id="PRO_0000127150"
FT   DOMAIN          75..127
FT                   /note="bHLH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT   REGION          1..85
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          167..189
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        51..65
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        172..189
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         25
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9QYC3"
SQ   SEQUENCE   189 AA;  20818 MW;  38D7230D85F16D22 CRC64;
     MKTKNRPPRR RAPVQDTEAT PGEGTPDGSL PNPGPEPAKG LRSRPARAAA RAPGEGRRRR
     PGPSGPGGRR DSSIQRRLES NERERQRMHK LNNAFQALRE VIPHVRADKK LSKIETLTLA
     KNYIKSLTAT ILTMSSSRLP GLEGPGPKLY QHYQQQQQVA GGALGATEAQ PQGHLQRYST
     QIHSFREGT
//