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Protein

Protein atonal homolog 8

Gene

Atoh8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor that binds a palindromic (canonical) core consensus DNA sequence 5'-CANNTG- 3' known as an E-box element, possibly as a heterodimer with other bHLH proteins (By similarity). Regulates endothelial cell proliferation, migration and tube-like structures formation (By similarity). Modulates endothelial cell differentiation through NOS3 (By similarity). May be implicated in specification and differentiation of neuronal cell lineages in the brain (PubMed:11733035). May participate in kidney development and may be involved in podocyte differentiation (PubMed:16937370). During early embryonic development is involved in tissue-specific differentiation processes that are dependent on class II bHLH factors and namely modulates the differentiation program initiated by the pro-endocrine factor NEUROG3 (PubMed:18560595). During myogenesis, may play a role during the transition of myoblasts from the proliferative phase to the differentiation phase (PubMed:24186058). Positively regulates HAMP transcription in two ways, firstly by acting directly on the HAMP promoter via E-boxes binding and indirectly through increased phosphorylation of SMAD protein complex (By similarity). Repress NEUROG3-dependent gene activation in a gene-specific manner through at least two mechanisms; requires only either the sequestering of a general partner such as TCF3 through heterodimerization, either also requires binding of the bHLH domain to DNA via a basic motif (PubMed:23938248).By similarity4 Publications

GO - Molecular functioni

  • activating transcription factor binding Source: UniProtKB
  • E-box binding Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Protein atonal homolog 8Imported
Alternative name(s):
Helix-loop-helix protein mATH-61 Publication
Short name:
mATH61 Publication
Okadin1 Publication
Gene namesi
Name:Atoh8Imported
Synonyms:Ath6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1918343. Atoh8.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nuclear speck Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice heterozygous survive to adulthood and present no phenotype (PubMed:18560595). Mice homozygous are lethal (PubMed:18560595).1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 322322Protein atonal homolog 8PRO_0000323752Add
BLAST

Proteomic databases

PaxDbiQ99NA2.
PRIDEiQ99NA2.

Expressioni

Tissue specificityi

Expressed by subsets of mature neurons (PubMed:11733035). Expressed in kidney (podocytes) (PubMed:16937370). Expression is restricted to the atria, lung mesenchyme, and vascular smooth muscle (PubMed:23836893).3 Publications

Developmental stagei

Expressed at high levels at E8.5 and its expression level gradually decreases during embryogenesis. At E12.5, is expressed throughout the developing nervous system. It is expressed in both the ventricular zone and the mantle layer of the developing brain. At E14.5, expressed in the cortical plate as well as in other regions of the brain. Also expressed at a high level in the spinal cord and dorsal root ganglia. Expressed by almost all cells in the spinal cord and dorsal root ganglia at this stage. At later stages, expression is gradually restricted to several regions such as the hippocampus, cerebellum and retina. In the hippocampus, a high level of expression continues during embryogenesis until adulthood. Expressed in the CA1-CA3 regions and the dentate gyrus. At E18.5, expressed in cerebellum by Purkinje cells and granule cell precursors in the external granular layer (EGL). By postnatal day 4, expressed by aligned Purkinje cells and by the EGL and internal granular layer (IGL) cells. In the adult cerebellum, expressed at a high level by Purkinje cells and weakly by granule cells in the IGL. In developing retina, expressed in both the ganglion cell layer and the ventricular zone at E11.5 and E17.5. Expression becomes very weak in the adult retina. Early in metanephric development, expressed in metanephric mesenchyme but not ureteric bud-derived cells, with overall expression being most abundant in the nephrogenic zone. From E14.5 to birth, expressed at constant levels. By day 13, corresponding to the end of new nephron induction, expression levels begin to decline. By day 19, expression returned to fetal levels, and by day 40, the low level of expression that persisted into adulthood is established. In adult kidney, expression is restricted to podocytes. Expressed in pancreatic tissue from E12.5 until E17.5. Is still detectable at low level,at postnatal day 1 and in isolated pancreatic islets in adult (PubMed:18560595).3 Publications

Inductioni

Specifically activated by bHLH factors.1 Publication

Gene expression databases

BgeeiQ99NA2.
CleanExiMM_ATOH8.
GenevisibleiQ99NA2. MM.

Interactioni

Subunit structurei

Efficient DNA binding requires dimerization with another bHLH protein. Interacts with NEUROG3 AND NEUROD1. Interacts with ZFPM2; mediates indirect interaction with GATA4. Forms a heterodimer with TCF3; repress transcription of TCF3 and TCF3/NEUROG3 dimer-induced transactivation of E box-dependent promoters.By similarity3 Publications

GO - Molecular functioni

  • activating transcription factor binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi214472. 1 interaction.
IntActiQ99NA2. 1 interaction.
MINTiMINT-4124565.
STRINGi10090.ENSMUSP00000036981.

Structurei

3D structure databases

ProteinModelPortaliQ99NA2.
SMRiQ99NA2. Positions 232-286.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini231 – 28353bHLHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni231 – 24414Basic motif; degeneratePROSITE-ProRule annotationAdd
BLAST
Regioni245 – 28339Helix-loop-helix motifPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi121 – 18868Pro-richPROSITE-ProRule annotationAdd
BLAST

Domaini

The bHLH domain mediates transcriptional repression by inhibiting TCF3 transcriptional activity through heterodimerization.1 Publication

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IQ4D. Eukaryota.
ENOG4111P2D. LUCA.
GeneTreeiENSGT00440000034222.
HOGENOMiHOG000034181.
HOVERGENiHBG095605.
InParanoidiQ99NA2.
KOiK09084.
OMAiETQPFRE.
OrthoDBiEOG73NG5F.
PhylomeDBiQ99NA2.
TreeFamiTF324848.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR032660. ATOH8.
IPR011598. bHLH_dom.
[Graphical view]
PANTHERiPTHR19290:SF102. PTHR19290:SF102. 1 hit.
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q99NA2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKHIPVLEDG PWKTVCVKEL NGLKKLKRKG KEPVRRANGY KTFRLDLEAP
60 70 80 90 100
ELGATVSTTA ATNGLRDRTQ PFPIATPVPA SVAPAVPPGG GTDTAREFRG
110 120 130 140 150
IRAPEVSDAR KRGFALGTVG PGLPTPPPPP ASQSLAPGDP EAHSFREQAL
160 170 180 190 200
RPRILLCAPP ARPTQSAPLA PPAAPQESPV RPAPPTRPGE SSYSSISHVI
210 220 230 240 250
YNNHPDSSAS PRKRPGEATA ASTEIKALQQ TRRLLANARE RTRVHTISAA
260 270 280 290 300
FEALRKQVPC YSYGQKLSKL AILRIACNYI LSLARLADLD YSADHSNLSF
310 320
SECVQRCTRT LQAEGRAKKR KE
Length:322
Mass (Da):34,785
Last modified:June 1, 2001 - v1
Checksum:i561D5BEAF50A2410
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti213 – 2131K → E in BAC25499 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB046527 mRNA. Translation: BAC57617.1.
AB046528 mRNA. Translation: BAC57618.1.
AB049066 mRNA. Translation: BAB39468.1.
AY349615 mRNA. Translation: AAQ54689.1.
BC023684 mRNA. Translation: AAH23684.1.
AK016909 mRNA. Translation: BAC25499.1.
CCDSiCCDS39511.1.
RefSeqiNP_722473.1. NM_153778.3.
UniGeneiMm.87449.

Genome annotation databases

EnsembliENSMUST00000042646; ENSMUSP00000036981; ENSMUSG00000037621.
GeneIDi71093.
KEGGimmu:71093.
UCSCiuc009cic.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB046527 mRNA. Translation: BAC57617.1.
AB046528 mRNA. Translation: BAC57618.1.
AB049066 mRNA. Translation: BAB39468.1.
AY349615 mRNA. Translation: AAQ54689.1.
BC023684 mRNA. Translation: AAH23684.1.
AK016909 mRNA. Translation: BAC25499.1.
CCDSiCCDS39511.1.
RefSeqiNP_722473.1. NM_153778.3.
UniGeneiMm.87449.

3D structure databases

ProteinModelPortaliQ99NA2.
SMRiQ99NA2. Positions 232-286.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi214472. 1 interaction.
IntActiQ99NA2. 1 interaction.
MINTiMINT-4124565.
STRINGi10090.ENSMUSP00000036981.

Proteomic databases

PaxDbiQ99NA2.
PRIDEiQ99NA2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000042646; ENSMUSP00000036981; ENSMUSG00000037621.
GeneIDi71093.
KEGGimmu:71093.
UCSCiuc009cic.2. mouse.

Organism-specific databases

CTDi84913.
MGIiMGI:1918343. Atoh8.

Phylogenomic databases

eggNOGiENOG410IQ4D. Eukaryota.
ENOG4111P2D. LUCA.
GeneTreeiENSGT00440000034222.
HOGENOMiHOG000034181.
HOVERGENiHBG095605.
InParanoidiQ99NA2.
KOiK09084.
OMAiETQPFRE.
OrthoDBiEOG73NG5F.
PhylomeDBiQ99NA2.
TreeFamiTF324848.

Miscellaneous databases

ChiTaRSiAtoh8. mouse.
NextBioi333009.
PROiQ99NA2.
SOURCEiSearch...

Gene expression databases

BgeeiQ99NA2.
CleanExiMM_ATOH8.
GenevisibleiQ99NA2. MM.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR032660. ATOH8.
IPR011598. bHLH_dom.
[Graphical view]
PANTHERiPTHR19290:SF102. PTHR19290:SF102. 1 hit.
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Okadin, a putative transcription factor cDNA type II."
    Yoshida S., Okada T., Nabeshima Y.
    Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
    Tissue: Cecum.
  2. "Math6, a bHLH gene expressed in the developing nervous system, regulates neuronal versus glial differentiation."
    Inoue C., Bae S.K., Takatsuka K., Inoue T., Bessho Y., Kageyama R.
    Genes Cells 6:977-986(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, FUNCTION.
  3. "Math6 expression during kidney development and altered expression in a mouse model of glomerulosclerosis."
    Ross M.D., Martinka S., Mukherjee A., Sedor J.R., Vinson C., Bruggeman L.A.
    Dev. Dyn. 235:3102-3109(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, FUNCTION.
    Strain: FVB/N.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Mammary tumor.
  5. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 213-322.
    Strain: C57BL/6J.
    Tissue: Testis.
  6. "Identification of the bHLH factor Math6 as a novel component of the embryonic pancreas transcriptional network."
    Lynn F.C., Sanchez L., Gomis R., German M.S., Gasa R.
    PLoS ONE 3:E2430-E2430(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, INTERACTION WITH NEUROG3 AND NEUROD1, FUNCTION, INDUCTION.
  7. "Characterization of the transcriptional activity of the basic helix-loop-helix (bHLH) transcription factor Atoh8."
    Ejarque M., Altirriba J., Gomis R., Gasa R.
    Biochim. Biophys. Acta 1829:1175-1183(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TCF3, FUNCTION, DOMAIN.
  8. "The transcription factor Atonal homolog 8 regulates Gata4 and Friend of Gata-2 during vertebrate development."
    Rawnsley D.R., Xiao J., Lee J.S., Liu X., Mericko-Ishizuka P., Kumar V., He J., Basu A., Lu M., Lynn F.C., Pack M., Gasa R., Kahn M.L.
    J. Biol. Chem. 288:24429-24440(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ZFPM2, TISSUE SPECIFICITY.
  9. Cited for: SUBCELLULAR LOCATION.

Entry informationi

Entry nameiATOH8_MOUSE
AccessioniPrimary (citable) accession number: Q99NA2
Secondary accession number(s): Q8C1I7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: June 1, 2001
Last modified: November 11, 2015
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Contains a degenerate basic motif not likely to bind DNA.PROSITE-ProRule annotation

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.