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Protein

Protein atonal homolog 8

Gene

Atoh8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Caution

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, DNA-binding
Biological processDifferentiation, Neurogenesis, Transcription, Transcription regulation

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1918343 Atoh8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
ChainiPRO_00003237521 – 322Protein atonal homolog 8Add BLAST322

Proteomic databases

PaxDbiQ99NA2
PRIDEiQ99NA2

PTM databases

iPTMnetiQ99NA2
PhosphoSitePlusiQ99NA2

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

BgeeiENSMUSG00000037621 Expressed in 108 organ(s), highest expression level in head
CleanExiMM_ATOH8
ExpressionAtlasiQ99NA2 baseline and differential
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

Protein-protein interaction databases

BioGridi214472, 1 interactor
IntActiQ99NA2, 1 interactor
MINTiQ99NA2

Structurei

3D structure databases

ProteinModelPortaliQ99NA2
SMRiQ99NA2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini231 – 283bHLHPROSITE-ProRule annotationAdd BLAST53

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni231 – 244Basic motif; degeneratePROSITE-ProRule annotationAdd BLAST14
Regioni245 – 283Helix-loop-helix motifPROSITE-ProRule annotationAdd BLAST39

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi121 – 188Pro-richPROSITE-ProRule annotationAdd BLAST68

Domaini

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

Phylogenomic databases

eggNOGiENOG410IQ4D Eukaryota
ENOG4111P2D LUCA
GeneTreeiENSGT00680000099860
HOGENOMiHOG000034181
HOVERGENiHBG095605
InParanoidiQ99NA2
KOiK09084
OMAiETQPFRE
OrthoDBiEOG091G167Y
PhylomeDBiQ99NA2
TreeFamiTF324848

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR032660 ATOH8
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
PANTHERiPTHR19290:SF102 PTHR19290:SF102, 1 hit
PfamiView protein in Pfam
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0U1RP16A0A0U1RP16_MOUSE
Protein atonal homolog 8
Atoh8
114Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti213K → E in BAC25499 (PubMed:16141072).Curated1

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

Similar proteinsi

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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi214472, 1 interactor
IntActiQ99NA2, 1 interactor
MINTiQ99NA2

PTM databases

iPTMnetiQ99NA2
PhosphoSitePlusiQ99NA2

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
GeneTreeiENSGT00680000099860
HOGENOMiHOG000034181
HOVERGENiHBG095605
InParanoidiQ99NA2
KOiK09084
OMAiETQPFRE
OrthoDBiEOG091G167Y
PhylomeDBiQ99NA2
TreeFamiTF324848

Miscellaneous databases

ChiTaRSiAtoh8 mouse
PROiPR:Q99NA2
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000037621 Expressed in 108 organ(s), highest expression level in head
CleanExiMM_ATOH8
ExpressionAtlasiQ99NA2 baseline and differential
GenevisibleiQ99NA2 MM

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR032660 ATOH8
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
PANTHERiPTHR19290:SF102 PTHR19290:SF102, 1 hit
PfamiView protein in Pfam
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiATOH8_MOUSE
AccessioniPrimary (citable) accession number: Q99NA2
Secondary accession number(s): Q8C1I7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: June 1, 2001
Last modified: November 7, 2018
This is version 115 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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