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ATOH8_DANRE
ID   ATOH8_DANRE             Reviewed;         266 AA.
AC   D2CLZ9;
DT   22-JUL-2015, integrated into UniProtKB/Swiss-Prot.
DT   09-FEB-2010, sequence version 1.
DT   03-AUG-2022, entry version 73.
DE   RecName: Full=Transcription factor atoh8 {ECO:0000305};
DE   AltName: Full=Atonal bHLH transcription factor 8 {ECO:0000312|ZFIN:ZDB-GENE-061215-7};
DE   AltName: Full=Protein atonal homolog 8 {ECO:0000312|ZFIN:ZDB-GENE-061215-7};
GN   Name=atoh8 {ECO:0000312|ZFIN:ZDB-GENE-061215-7};
GN   ORFNames=zgc:158314 {ECO:0000312|ZFIN:ZDB-GENE-061215-7};
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND
RP   FUNCTION.
RX   PubMed=20532172; DOI=10.1371/journal.pone.0010945;
RA   Yao J., Zhou J., Liu Q., Lu D., Wang L., Qiao X., Jia W.;
RT   "Atoh8, a bHLH transcription factor, is required for the development of
RT   retina and skeletal muscle in zebrafish.";
RL   PLoS ONE 5:E10945-E10945(2010).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
RX   PubMed=23594743; DOI=10.1038/nature12111;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA   Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA   Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA   Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA   Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA   Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA   Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA   McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA   Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA   Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA   Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA   Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA   Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA   Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA   Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA   Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA   Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA   Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA   Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA   Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA   de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA   Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [3]
RP   FUNCTION, AND DEVELOPMENTAL STAGE.
RX   PubMed=23836893; DOI=10.1074/jbc.m113.463083;
RA   Rawnsley D.R., Xiao J., Lee J.S., Liu X., Mericko-Ishizuka P., Kumar V.,
RA   He J., Basu A., Lu M., Lynn F.C., Pack M., Gasa R., Kahn M.L.;
RT   "The transcription factor Atonal homolog 8 regulates Gata4 and Friend of
RT   Gata-2 during vertebrate development.";
RL   J. Biol. Chem. 288:24429-24440(2013).
CC   -!- FUNCTION: Transcription factor that binds a palindromic (canonical)
CC       core consensus DNA sequence 5'-CANNTG- 3' known as an E-box element,
CC       possibly as a heterodimer with other bHLH proteins (By similarity).
CC       During development, is required for heart looping and swim bladder
CC       formation by acting in concert with GATA4 AND ZFPM1 (PubMed:23836893).
CC       During the development of both the retina and skeletal muscles is
CC       required for neural retinal cell through modulating PAX6 and NEUROG3
CC       expression and myogenic differentiation (PubMed:20532172).
CC       {ECO:0000250|UniProtKB:Q96SQ7, ECO:0000269|PubMed:20532172,
CC       ECO:0000269|PubMed:23836893}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q99NA2}. Nucleus
CC       speckle {ECO:0000250|UniProtKB:Q96SQ7}. Cytoplasm
CC       {ECO:0000250|UniProtKB:Q99NA2}.
CC   -!- DEVELOPMENTAL STAGE: Weakly expressed in the heart tube at 30 hours
CC       post-fertilization (PubMed:23836893). Expressed at as early as epiboly
CC       stage, and is broadly distributed till early segmentation stage and in
CC       developing retina and skeletal muscle. In the eye, expression is
CC       detected in the optic primordium at the 6-somite stage and is steadily
CC       expressed during the invagination of the optic vesicle from its
CC       initiation to its expansion to the lens rudiment. In skeletal muscle, a
CC       faint signal is detected in muscle precursor cells at the early
CC       segmentation period, and in ventral somites from the 21-somite to 24
CC       hour post fertilization stage. Expression decreases sharply during 36
CC       to 48 hour post fertilization stage while it reached its highest level
CC       at about 72 hour post fertilization stage. During this period, the
CC       distribution extends to the dorsal somites. In addition also appeared
CC       in the brain and neural crest cell (PubMed:20532172).
CC       {ECO:0000269|PubMed:20532172, ECO:0000269|PubMed:23836893}.
CC   -!- DISRUPTION PHENOTYPE: Morpholino knockdown of atoh8 causes two
CC       phenotypes. The severe phenotype displays a shrunken head, reduced eye
CC       size and fused somites and most embryos die within 3 days. The mild
CC       phenotype displays an abnormal brain shape with smaller eyes, a curved
CC       body axis with indistinct somite boundaries and frequently reduced or
CC       no circulation. In addition, the yolk extension is hardly visible
CC       starting at the beginning of tail straightening from the 17-somite
CC       stage. {ECO:0000269|PubMed:20532172}.
CC   -!- CAUTION: Contains a degenerate basic motif not likely to bind DNA.
CC       {ECO:0000255|PROSITE-ProRule:PRU00981}.
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DR   EMBL; EU272033; ABY90093.1; -; mRNA.
DR   EMBL; BX957231; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_001073460.2; NM_001079991.2.
DR   AlphaFoldDB; D2CLZ9; -.
DR   SMR; D2CLZ9; -.
DR   STRING; 7955.ENSDARP00000054688; -.
DR   PaxDb; D2CLZ9; -.
DR   Ensembl; ENSDART00000054689; ENSDARP00000054688; ENSDARG00000037555.
DR   GeneID; 561606; -.
DR   KEGG; dre:561606; -.
DR   CTD; 84913; -.
DR   ZFIN; ZDB-GENE-061215-7; atoh8.
DR   eggNOG; KOG3898; Eukaryota.
DR   GeneTree; ENSGT00940000161151; -.
DR   HOGENOM; CLU_057987_0_0_1; -.
DR   InParanoid; D2CLZ9; -.
DR   OMA; HRSEIIT; -.
DR   OrthoDB; 1014108at2759; -.
DR   PhylomeDB; D2CLZ9; -.
DR   TreeFam; TF324848; -.
DR   PRO; PR:D2CLZ9; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 14.
DR   Bgee; ENSDARG00000037555; Expressed in spleen and 22 other tissues.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
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:0007507; P:heart development; IGI:ZFIN.
DR   GO; GO:0001947; P:heart looping; IMP:UniProtKB.
DR   GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR   GO; GO:0061074; P:regulation of neural retina development; IMP:ZFIN.
DR   GO; GO:2001014; P:regulation of skeletal muscle cell differentiation; IMP:ZFIN.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0048797; P:swim bladder formation; IMP:UniProtKB.
DR   Gene3D; 4.10.280.10; -; 1.
DR   InterPro; IPR032660; ATOH8.
DR   InterPro; IPR011598; bHLH_dom.
DR   InterPro; IPR036638; HLH_DNA-bd_sf.
DR   PANTHER; PTHR19290:SF102; PTHR19290:SF102; 1.
DR   Pfam; PF00010; HLH; 1.
DR   SMART; SM00353; HLH; 1.
DR   SUPFAM; SSF47459; SSF47459; 1.
DR   PROSITE; PS50888; BHLH; 1.
PE   2: Evidence at transcript level;
KW   Cytoplasm; Developmental protein; Differentiation; DNA-binding;
KW   Neurogenesis; Nucleus; Reference proteome; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..266
FT                   /note="Transcription factor atoh8"
FT                   /id="PRO_0000433566"
FT   DOMAIN          175..227
FT                   /note="bHLH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT   REGION          140..164
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          175..188
FT                   /note="Basic motif; degenerate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT   REGION          189..227
FT                   /note="Helix-loop-helix motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
SQ   SEQUENCE   266 AA;  29804 MW;  0679730255481602 CRC64;
     MKNPHLNSPC KILNTVSGDK KMKRKAREPI KHVSEDHYPY FKLYKNPHLM AETLGDGSPQ
     ETHRSEIITS RDDSVRNDVL NTAVDMRINT ITAAEVPDSK LRSVSEKTVN SKIVQASPQV
     SVLSAPQVFP LERVVLSQRA ASQAPAGGSE RAESPRKRAG EPSGVVTEIK AIQQTRRLLA
     NARERTRVHT ISAAFEALRK QVPCYSYGQK LSKLAILRIA CNYILSLAQL ADLDYTPDHR
     NMSFRECVEQ CTRTLQAEGR SKKRKE
 
 
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