ID ATOH8_MOUSE Reviewed; 322 AA.
AC Q99NA2; Q8C1I7;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 27-MAR-2024, entry version 143.
DE RecName: Full=Transcription factor Atoh8 {ECO:0000305};
DE AltName: Full=Helix-loop-helix protein mATH-6 {ECO:0000305|PubMed:11733035};
DE Short=mATH6 {ECO:0000303|PubMed:11733035};
DE AltName: Full=Okadin {ECO:0000303|Ref.1};
DE AltName: Full=Protein atonal homolog 8 {ECO:0000312|MGI:MGI:1918343};
GN Name=Atoh8 {ECO:0000312|MGI:MGI:1918343}; Synonyms=Ath6;
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 [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cecum;
RA Yoshida S., Okada T., Nabeshima Y.;
RT "Okadin, a putative transcription factor cDNA type II.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP FUNCTION.
RX PubMed=11733035; DOI=10.1046/j.1365-2443.2001.00476.x;
RA Inoue C., Bae S.K., Takatsuka K., Inoue T., Bessho Y., Kageyama R.;
RT "Math6, a bHLH gene expressed in the developing nervous system, regulates
RT neuronal versus glial differentiation.";
RL Genes Cells 6:977-986(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP FUNCTION.
RC STRAIN=FVB/N;
RX PubMed=16937370; DOI=10.1002/dvdy.20934;
RA Ross M.D., Martinka S., Mukherjee A., Sedor J.R., Vinson C.,
RA Bruggeman L.A.;
RT "Math6 expression during kidney development and altered expression in a
RT mouse model of glomerulosclerosis.";
RL Dev. Dyn. 235:3102-3109(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 213-322.
RC STRAIN=C57BL/6J; TISSUE=Testis;
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 [6]
RP DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, INTERACTION WITH NEUROG3 AND
RP NEUROD1, FUNCTION, AND INDUCTION.
RX PubMed=18560595; DOI=10.1371/journal.pone.0002430;
RA Lynn F.C., Sanchez L., Gomis R., German M.S., Gasa R.;
RT "Identification of the bHLH factor Math6 as a novel component of the
RT embryonic pancreas transcriptional network.";
RL PLoS ONE 3:E2430-E2430(2008).
RN [7]
RP INTERACTION WITH TCF3, FUNCTION, AND DOMAIN.
RX PubMed=23938248; DOI=10.1016/j.bbagrm.2013.08.003;
RA Ejarque M., Altirriba J., Gomis R., Gasa R.;
RT "Characterization of the transcriptional activity of the basic helix-loop-
RT helix (bHLH) transcription factor Atoh8.";
RL Biochim. Biophys. Acta 1829:1175-1183(2013).
RN [8]
RP INTERACTION WITH ZFPM2, AND TISSUE SPECIFICITY.
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).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=24186058; DOI=10.1007/s00418-013-1155-0;
RA Balakrishnan-Renuka A., Morosan-Puopolo G., Yusuf F., Abduelmula A.,
RA Chen J., Zoidl G., Philippi S., Dai F., Brand-Saberi B.;
RT "ATOH8, a regulator of skeletal myogenesis in the hypaxial myotome of the
RT trunk.";
RL Histochem. Cell Biol. 141:289-300(2014).
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 Regulates endothelial cell proliferation, migration and tube-like
CC structures formation (By similarity). Modulates endothelial cell
CC differentiation through NOS3 (By similarity). May be implicated in
CC specification and differentiation of neuronal cell lineages in the
CC brain (PubMed:11733035). May participate in kidney development and may
CC be involved in podocyte differentiation (PubMed:16937370). During early
CC embryonic development is involved in tissue-specific differentiation
CC processes that are dependent on class II bHLH factors and namely
CC modulates the differentiation program initiated by the pro-endocrine
CC factor NEUROG3 (PubMed:18560595). During myogenesis, may play a role
CC during the transition of myoblasts from the proliferative phase to the
CC differentiation phase (PubMed:24186058). Positively regulates HAMP
CC transcription in two ways, firstly by acting directly on the HAMP
CC promoter via E-boxes binding and indirectly through increased
CC phosphorylation of SMAD protein complex (By similarity). Repress
CC NEUROG3-dependent gene activation in a gene-specific manner through at
CC least two mechanisms; requires only either the sequestering of a
CC general partner such as TCF3 through heterodimerization, either also
CC requires binding of the bHLH domain to DNA via a basic motif
CC (PubMed:23938248). {ECO:0000250|UniProtKB:Q96SQ7,
CC ECO:0000269|PubMed:11733035, ECO:0000269|PubMed:16937370,
CC ECO:0000269|PubMed:18560595, ECO:0000269|PubMed:23938248}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Interacts with NEUROG3 and NEUROD1. Interacts with ZFPM2;
CC mediates indirect interaction with GATA4. Forms a heterodimer with
CC TCF3; repress transcription of TCF3 and TCF3/NEUROG3 dimer-induced
CC transactivation of E box-dependent promoters. {ECO:0000250,
CC ECO:0000269|PubMed:18560595, ECO:0000269|PubMed:23836893,
CC ECO:0000269|PubMed:23938248}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24186058}. Nucleus
CC speckle {ECO:0000250|UniProtKB:Q96SQ7}. Cytoplasm
CC {ECO:0000269|PubMed:24186058}.
CC -!- TISSUE SPECIFICITY: Expressed by subsets of mature neurons
CC (PubMed:11733035). Expressed in kidney (podocytes) (PubMed:16937370).
CC Expression is restricted to the atria, lung mesenchyme, and vascular
CC smooth muscle (PubMed:23836893). {ECO:0000269|PubMed:11733035,
CC ECO:0000269|PubMed:16937370, ECO:0000269|PubMed:23836893}.
CC -!- DEVELOPMENTAL STAGE: Expressed at high levels at 8.5 dpc and its
CC expression level gradually decreases during embryogenesis. At 12.5 dpc,
CC is expressed throughout the developing nervous system. It is expressed
CC in both the ventricular zone and the mantle layer of the developing
CC brain. At 14.5 dpc, expressed in the cortical plate as well as in other
CC regions of the brain. Also expressed at a high level in the spinal cord
CC and dorsal root ganglia. Expressed by almost all cells in the spinal
CC cord and dorsal root ganglia at this stage. At later stages, expression
CC is gradually restricted to several regions such as the hippocampus,
CC cerebellum and retina. In the hippocampus, a high level of expression
CC continues during embryogenesis until adulthood. Expressed in the CA1-
CC CA3 regions and the dentate gyrus. At 18.5 dpc, expressed in cerebellum
CC by Purkinje cells and granule cell precursors in the external granular
CC layer (EGL). By postnatal day 4, expressed by aligned Purkinje cells
CC and by the EGL and internal granular layer (IGL) cells. In the adult
CC cerebellum, expressed at a high level by Purkinje cells and weakly by
CC granule cells in the IGL. In developing retina, expressed in both the
CC ganglion cell layer and the ventricular zone at 11.5 dpc and 17.5 dpc.
CC Expression becomes very weak in the adult retina. Early in metanephric
CC development, expressed in metanephric mesenchyme but not ureteric bud-
CC derived cells, with overall expression being most abundant in the
CC nephrogenic zone. From 14.5 dpc to birth, expressed at constant levels.
CC By day 13, corresponding to the end of new nephron induction,
CC expression levels begin to decline. By day 19, expression returned to
CC fetal levels, and by day 40, the low level of expression that persisted
CC into adulthood is established. In adult kidney, expression is
CC restricted to podocytes. Expressed in pancreatic tissue from 12.5 dpc
CC until 17.5 dpc. Is still detectable at low level,at postnatal day 1 and
CC in isolated pancreatic islets in adult (PubMed:18560595).
CC {ECO:0000269|PubMed:11733035, ECO:0000269|PubMed:16937370,
CC ECO:0000269|PubMed:18560595}.
CC -!- INDUCTION: Specifically activated by bHLH factors.
CC {ECO:0000269|PubMed:18560595}.
CC -!- DOMAIN: The bHLH domain mediates transcriptional repression by
CC inhibiting TCF3 transcriptional activity through heterodimerization.
CC {ECO:0000269|PubMed:23938248}.
CC -!- DISRUPTION PHENOTYPE: Mice heterozygous survive to adulthood and
CC present no phenotype (PubMed:18560595). The homozygous knockout of
CC Atoh8 is embryonic lethal (PubMed:18560595).
CC {ECO:0000269|PubMed:18560595}.
CC -!- CAUTION: Contains a degenerate basic motif not likely to bind DNA.
CC {ECO:0000255|PROSITE-ProRule:PRU00981}.
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DR EMBL; AB046527; BAC57617.1; -; mRNA.
DR EMBL; AB046528; BAC57618.1; -; mRNA.
DR EMBL; AB049066; BAB39468.1; -; mRNA.
DR EMBL; AY349615; AAQ54689.1; -; mRNA.
DR EMBL; BC023684; AAH23684.1; -; mRNA.
DR EMBL; AK016909; BAC25499.1; -; mRNA.
DR CCDS; CCDS39511.1; -.
DR RefSeq; NP_722473.1; NM_153778.3.
DR AlphaFoldDB; Q99NA2; -.
DR SMR; Q99NA2; -.
DR BioGRID; 214472; 1.
DR IntAct; Q99NA2; 1.
DR STRING; 10090.ENSMUSP00000036981; -.
DR iPTMnet; Q99NA2; -.
DR PhosphoSitePlus; Q99NA2; -.
DR PaxDb; 10090-ENSMUSP00000036981; -.
DR Pumba; Q99NA2; -.
DR Antibodypedia; 17011; 158 antibodies from 26 providers.
DR DNASU; 71093; -.
DR Ensembl; ENSMUST00000042646.8; ENSMUSP00000036981.8; ENSMUSG00000037621.9.
DR GeneID; 71093; -.
DR KEGG; mmu:71093; -.
DR UCSC; uc009cic.2; mouse.
DR AGR; MGI:1918343; -.
DR CTD; 84913; -.
DR MGI; MGI:1918343; Atoh8.
DR VEuPathDB; HostDB:ENSMUSG00000037621; -.
DR eggNOG; KOG3898; Eukaryota.
DR GeneTree; ENSGT00940000161151; -.
DR HOGENOM; CLU_057987_0_0_1; -.
DR InParanoid; Q99NA2; -.
DR OMA; QKVLCER; -.
DR OrthoDB; 2883823at2759; -.
DR PhylomeDB; Q99NA2; -.
DR TreeFam; TF324848; -.
DR BioGRID-ORCS; 71093; 0 hits in 76 CRISPR screens.
DR ChiTaRS; Atoh8; mouse.
DR PRO; PR:Q99NA2; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q99NA2; Protein.
DR Bgee; ENSMUSG00000037621; Expressed in spermatid and 102 other cell types or tissues.
DR ExpressionAtlas; Q99NA2; baseline and differential.
DR Genevisible; Q99NA2; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0001704; P:formation of primary germ layer; IMP:UniProtKB.
DR GO; GO:0051450; P:myoblast proliferation; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB.
DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISS:UniProtKB.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060395; P:SMAD protein signal transduction; ISS:UniProtKB.
DR GO; GO:0035148; P:tube formation; ISS:UniProtKB.
DR CDD; cd11421; bHLH_TS_ATOH8; 1.
DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1.
DR InterPro; IPR032660; ATOH8_bHLH.
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:SF102; TRANSCRIPTION FACTOR ATOH8; 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; Differentiation; DNA-binding;
KW Neurogenesis; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..322
FT /note="Transcription factor Atoh8"
FT /id="PRO_0000323752"
FT DOMAIN 231..283
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 77..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 101..144
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 159..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 231..244
FT /note="Basic motif; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 245..283
FT /note="Helix-loop-helix motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT COMPBIAS 121..135
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 164..186
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 188..209
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 213
FT /note="K -> E (in Ref. 5; BAC25499)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 322 AA; 34785 MW; 561D5BEAF50A2410 CRC64;
MKHIPVLEDG PWKTVCVKEL NGLKKLKRKG KEPVRRANGY KTFRLDLEAP ELGATVSTTA
ATNGLRDRTQ PFPIATPVPA SVAPAVPPGG GTDTAREFRG IRAPEVSDAR KRGFALGTVG
PGLPTPPPPP ASQSLAPGDP EAHSFREQAL RPRILLCAPP ARPTQSAPLA PPAAPQESPV
RPAPPTRPGE SSYSSISHVI YNNHPDSSAS PRKRPGEATA ASTEIKALQQ TRRLLANARE
RTRVHTISAA FEALRKQVPC YSYGQKLSKL AILRIACNYI LSLARLADLD YSADHSNLSF
SECVQRCTRT LQAEGRAKKR KE
//
