ATOH8_HUMAN
ID ATOH8_HUMAN Reviewed; 321 AA.
AC Q96SQ7; Q504S2; Q659B0;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Transcription factor ATOH8 {ECO:0000305};
DE AltName: Full=Class A basic helix-loop-helix protein 21 {ECO:0000312|HGNC:HGNC:24126};
DE Short=bHLHa21 {ECO:0000312|HGNC:HGNC:24126};
DE AltName: Full=Helix-loop-helix protein hATH-6 {ECO:0000312|EMBL:AAO85773.1};
DE Short=hATH6 {ECO:0000303|PubMed:24463812};
DE AltName: Full=Protein atonal homolog 8 {ECO:0000312|HGNC:HGNC:24126};
GN Name=ATOH8 {ECO:0000312|HGNC:HGNC:24126}; Synonyms=ATH6, BHLHA21;
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 [MRNA] (ISOFORM 1), VARIANT PRO-150, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Umbilical vein;
RX PubMed=12419857; DOI=10.1152/physiolgenomics.00102.2002;
RA Wasserman S.M., Mehraban F., Komuves L.G., Yang R.B., Tomlinson J.E.,
RA Zhang Y., Spriggs F., Topper J.N.;
RT "Gene expression profile of human endothelial cells exposed to sustained
RT fluid shear stress.";
RL Physiol. Genomics 12:13-23(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-150.
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-150.
RC TISSUE=Muscle, and Retinal pigment epithelium;
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 154-321 (ISOFORM 2).
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP FUNCTION.
RX PubMed=24236640; DOI=10.1111/bjh.12649;
RA Patel N., Varghese J., Masaratana P., Latunde-Dada G.O., Jacob M.,
RA Simpson R.J., McKie A.T.;
RT "The transcription factor ATOH8 is regulated by erythropoietic activity and
RT regulates HAMP transcription and cellular pSMAD1,5,8 levels.";
RL Br. J. Haematol. 164:586-596(2014).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24463812; DOI=10.1242/jcs.136358;
RA Fang F., Wasserman S.M., Torres-Vazquez J., Weinstein B., Cao F., Li Z.,
RA Wilson K.D., Yue W., Wu J.C., Xie X., Pei X.;
RT "The role of Hath6, a newly identified shear-stress-responsive
RT transcription factor, in endothelial cell differentiation and function.";
RL J. Cell Sci. 127:1428-1440(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 (PubMed:24236640).
CC Regulates endothelial cell proliferation, migration and tube-like
CC structures formation (PubMed:24463812). Modulates endothelial cell
CC differentiation through NOS3 (PubMed:24463812). May be implicated in
CC specification and differentiation of neuronal cell lineages in the
CC brain (By similarity). May participate in kidney development and may be
CC involved in podocyte differentiation (By similarity). 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 (By similarity). During myogenesis, may play a role
CC during the transition of myoblasts from the proliferative phase to the
CC differentiation phase (By similarity). 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 (PubMed:24236640). 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 (By
CC similarity). {ECO:0000250|UniProtKB:Q99NA2,
CC ECO:0000269|PubMed:24236640, ECO:0000269|PubMed:24463812}.
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.
CC {ECO:0000250|UniProtKB:Q99NA2}.
CC -!- INTERACTION:
CC Q96SQ7-1; P16298-4: PPP3CB; NbExp=5; IntAct=EBI-26429573, EBI-26442038;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24463812}. Nucleus
CC speckle {ECO:0000269|PubMed:24463812}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q99NA2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96SQ7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96SQ7-2; Sequence=VSP_032118;
CC -!- TISSUE SPECIFICITY: Expressed in lung, liver, kidney, heart and
CC pancreas. Expressed in endothel of umbilical vessels.
CC {ECO:0000269|PubMed:12419857}.
CC -!- DOMAIN: The bHLH domain mediates transcriptional repression by
CC inhibiting TCF3 transcriptional activity through heterodimerization.
CC {ECO:0000250|UniProtKB:Q99NA2}.
CC -!- CAUTION: Contains a degenerate basic motif not likely to bind DNA.
CC {ECO:0000255|PROSITE-ProRule:PRU00981}.
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DR EMBL; AF529205; AAO85773.1; -; mRNA.
DR EMBL; AK027614; BAB55233.1; -; mRNA.
DR EMBL; AK074681; BAC11135.1; -; mRNA.
DR EMBL; AC012454; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC021207; AAH21207.1; -; mRNA.
DR EMBL; BC094832; AAH94832.1; -; mRNA.
DR EMBL; AL831857; CAH56263.1; -; mRNA.
DR CCDS; CCDS1985.1; -. [Q96SQ7-1]
DR RefSeq; NP_116216.2; NM_032827.6. [Q96SQ7-1]
DR AlphaFoldDB; Q96SQ7; -.
DR SMR; Q96SQ7; -.
DR BioGRID; 124350; 2.
DR IntAct; Q96SQ7; 4.
DR STRING; 9606.ENSP00000304676; -.
DR iPTMnet; Q96SQ7; -.
DR PhosphoSitePlus; Q96SQ7; -.
DR BioMuta; ATOH8; -.
DR DMDM; 224471820; -.
DR jPOST; Q96SQ7; -.
DR PaxDb; Q96SQ7; -.
DR PeptideAtlas; Q96SQ7; -.
DR PRIDE; Q96SQ7; -.
DR ProteomicsDB; 78136; -. [Q96SQ7-1]
DR ProteomicsDB; 78137; -. [Q96SQ7-2]
DR Antibodypedia; 17011; 137 antibodies from 26 providers.
DR DNASU; 84913; -.
DR Ensembl; ENST00000306279.4; ENSP00000304676.3; ENSG00000168874.13. [Q96SQ7-1]
DR GeneID; 84913; -.
DR KEGG; hsa:84913; -.
DR MANE-Select; ENST00000306279.4; ENSP00000304676.3; NM_032827.7; NP_116216.2.
DR UCSC; uc002sqn.4; human. [Q96SQ7-1]
DR CTD; 84913; -.
DR DisGeNET; 84913; -.
DR GeneCards; ATOH8; -.
DR HGNC; HGNC:24126; ATOH8.
DR HPA; ENSG00000168874; Tissue enhanced (skeletal).
DR MIM; 619820; gene.
DR neXtProt; NX_Q96SQ7; -.
DR OpenTargets; ENSG00000168874; -.
DR PharmGKB; PA134904746; -.
DR VEuPathDB; HostDB:ENSG00000168874; -.
DR eggNOG; KOG3898; Eukaryota.
DR GeneTree; ENSGT00940000161151; -.
DR HOGENOM; CLU_057987_0_0_1; -.
DR InParanoid; Q96SQ7; -.
DR OMA; VCVQELH; -.
DR OrthoDB; 1014108at2759; -.
DR PhylomeDB; Q96SQ7; -.
DR TreeFam; TF324848; -.
DR PathwayCommons; Q96SQ7; -.
DR SignaLink; Q96SQ7; -.
DR BioGRID-ORCS; 84913; 12 hits in 1089 CRISPR screens.
DR GenomeRNAi; 84913; -.
DR Pharos; Q96SQ7; Tbio.
DR PRO; PR:Q96SQ7; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q96SQ7; protein.
DR Bgee; ENSG00000168874; Expressed in right lobe of thyroid gland and 162 other tissues.
DR Genevisible; Q96SQ7; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IEA:Ensembl.
DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
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:0001704; P:formation of primary germ layer; ISS:UniProtKB.
DR GO; GO:0051450; P:myoblast proliferation; ISS:UniProtKB.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; IDA:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:UniProtKB.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IGI:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060395; P:SMAD protein signal transduction; IDA:UniProtKB.
DR GO; GO:0035148; P:tube 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 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Developmental protein; Differentiation;
KW DNA-binding; Neurogenesis; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..321
FT /note="Transcription factor ATOH8"
FT /id="PRO_0000323751"
FT DOMAIN 230..282
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 59..193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 203..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 230..243
FT /note="Basic motif; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 244..282
FT /note="Helix-loop-helix motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT COMPBIAS 70..84
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 119..137
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 158..182
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 321
FT /note="E -> SLIITQDTTARAAGLEAAGKTVQKVLCERGNSLMNNRTGRRKSWRLE
FT FLFLRRRCFLLTFYLWFLFFSRFLLMLFLPLLTSVVTFLPPLRARRPPH (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_032118"
FT VARIANT 150
FT /note="L -> P (in dbSNP:rs17851881)"
FT /evidence="ECO:0000269|PubMed:12419857,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_039582"
SQ SEQUENCE 321 AA; 34644 MW; 6AEC8043AD8D2075 CRC64;
MKHIPVLEDG PWKTVCVKEL NGLKKLKRKG KEPARRANGY KTFRLDLEAP EPRAVATNGL
RDRTHRLQPV PVPVPVPVPV APAVPPRGGT DTAGERGGSR APEVSDARKR CFALGAVGPG
LPTPPPPPPP APQSQAPGGP EAQPFREPGL RPRILLCAPP ARPAPSAPPA PPAPPESTVR
PAPPTRPGES SYSSISHVIY NNHQDSSASP RKRPGEATAA SSEIKALQQT RRLLANARER
TRVHTISAAF EALRKQVPCY SYGQKLSKLA ILRIACNYIL SLARLADLDY SADHSNLSFS
ECVQRCTRTL QAEGRAKKRK E
