Atoh8

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

activating transcription factor binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 18560595
DNA-binding transcription factor activity
Source: UniProtKB
Inferred from direct assayⁱ
- 23938248
E-box binding Source: UniProtKB
protein dimerization activity Source: InterPro
transcription factor binding
Source: UniProtKB
Inferred from physical interactionⁱ

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

cell differentiation Source: UniProtKB-KW
formation of primary germ layer
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 18560595
myoblast proliferation
Source: UniProtKB
Inferred from direct assayⁱ
- 24186058
negative regulation of endothelial cell proliferation Source: UniProtKB
negative regulation of gene expression Source: MGI
negative regulation of transcription, DNA-templated
Source: UniProtKB
Inferred from direct assayⁱ
- 18560595
- 23938248
nervous system development Source: UniProtKB-KW
positive regulation of endothelial cell differentiation Source: UniProtKB
positive regulation of endothelial cell migration Source: UniProtKB
positive regulation of gene expression Source: MGI
positive regulation of transcription, DNA-templated Source: UniProtKB
SMAD protein signal transduction Source: UniProtKB
tube formation Source: UniProtKB

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Developmental protein, DNA-binding
Biological process	Differentiation, 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
Organismⁱ	Mus musculus (Mouse)
Taxonomic identifierⁱ	10090 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesⁱ	UP000000589 Componentⁱ: Chromosome 6

Organism-specific databases

MGIⁱ	MGI:1918343 Atoh8

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 key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000323752	1 – 322	Protein atonal homolog 8Add BLAST		322

Proteomic databases

PaxDbⁱ	Q99NA2
PRIDEⁱ	Q99NA2

PTM databases

iPTMnetⁱ	Q99NA2
PhosphoSitePlusⁱ	Q99NA2

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

Bgeeⁱ	ENSMUSG00000037621 Expressed in 108 organ(s), highest expression level in head
CleanExⁱ	MM_ATOH8
ExpressionAtlasⁱ	Q99NA2 baseline and differential
Genevisibleⁱ	Q99NA2 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
Inferred from physical interactionⁱ
- 18560595
protein dimerization activity Source: InterPro
transcription factor binding
Source: UniProtKB
Inferred from physical interactionⁱ

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	214472, 1 interactor
IntActⁱ	Q99NA2, 1 interactor
Molecular INTeraction database More...MINTⁱ	Q99NA2

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q99NA2
SMRⁱ	Q99NA2
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	231 – 283	bHLHPROSITE-ProRule annotationAdd BLAST		53

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	231 – 244	Basic motif; degeneratePROSITE-ProRule annotationAdd BLAST		14
Regionⁱ	245 – 283	Helix-loop-helix motifPROSITE-ProRule annotationAdd BLAST		39

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	121 – 188	Pro-richPROSITE-ProRule annotationAdd BLAST		68

Domainⁱ

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

Phylogenomic databases

eggNOGⁱ	ENOG410IQ4D Eukaryota ENOG4111P2D LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00680000099860
HOGENOMⁱ	HOG000034181
HOVERGENⁱ	HBG095605
InParanoidⁱ	Q99NA2
KEGG Orthology (KO) More...KOⁱ	K09084
OMAⁱ	ETQPFRE
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G167Y
PhylomeDBⁱ	Q99NA2
TreeFamⁱ	TF324848

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00083 HLH, 1 hit
Gene3Dⁱ	4.10.280.10, 1 hit
InterProⁱ	View protein in InterPro IPR032660 ATOH8 IPR011598 bHLH_dom IPR036638 HLH_DNA-bd_sf
PANTHERⁱ	PTHR19290:SF102 PTHR19290:SF102, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00010 HLH, 1 hit
SMARTⁱ	View protein in SMART SM00353 HLH, 1 hit
SUPFAMⁱ	SSF47459 SSF47459, 1 hit
PROSITEⁱ	View 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 all Align All

Q99NA2-1 [UniParc]FASTA Add 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.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation

	A0A0U1RP16	A0A0U1RP16_MOUSE		Protein atonal homolog 8 Protein atonal homolog 8	Atoh8	114	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	213	K → E in BAC25499 (PubMed:16141072).Curated		1

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS39511.1
NCBI Reference Sequences More...RefSeqⁱ	NP_722473.1, NM_153778.3
UniGeneⁱ	Mm.87449

Genome annotation databases

Ensemblⁱ	ENSMUST00000042646; ENSMUSP00000036981; ENSMUSG00000037621
GeneIDⁱ	71093
KEGGⁱ	mmu:71093
UCSC genome browser More...UCSCⁱ	uc009cic.2 mouse

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q99NA2	Uncharacterized protein		NEOLE		345	UniRef90_Q99NA2
Atonal bHLH transcription factor 8		RAT		322
protein atonal homolog 8		MESAU		320
UPI000B4F9035		MERUN		322
UPI000A30419D		MUSPA		322
+4

Protein	Similar proteins		Species	Score	Length	Source
Q99NA2	Protein atonal homolog 8		HUMAN		321	UniRef50_Q96SQ7
Uncharacterized protein		RHIRO		326
Uncharacterized protein		FELCA		326
Protein atonal homolog 8 (Fragment)		NEOVI		143
protein atonal homolog 8		NEOSC		325
+191

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
CCDSⁱ	CCDS39511.1
RefSeqⁱ	NP_722473.1, NM_153778.3
UniGeneⁱ	Mm.87449

3D structure databases

ProteinModelPortalⁱ	Q99NA2
SMRⁱ	Q99NA2
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	214472, 1 interactor
IntActⁱ	Q99NA2, 1 interactor
MINTⁱ	Q99NA2

PTM databases

iPTMnetⁱ	Q99NA2
PhosphoSitePlusⁱ	Q99NA2

Proteomic databases

PaxDbⁱ	Q99NA2
PRIDEⁱ	Q99NA2

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENSMUST00000042646; ENSMUSP00000036981; ENSMUSG00000037621
GeneIDⁱ	71093
KEGGⁱ	mmu:71093
UCSCⁱ	uc009cic.2 mouse

Organism-specific databases

CTDⁱ	84913
MGIⁱ	MGI:1918343 Atoh8

Phylogenomic databases

eggNOGⁱ	ENOG410IQ4D Eukaryota ENOG4111P2D LUCA
GeneTreeⁱ	ENSGT00680000099860
HOGENOMⁱ	HOG000034181
HOVERGENⁱ	HBG095605
InParanoidⁱ	Q99NA2
KOⁱ	K09084
OMAⁱ	ETQPFRE
OrthoDBⁱ	EOG091G167Y
PhylomeDBⁱ	Q99NA2
TreeFamⁱ	TF324848

Miscellaneous databases

ChiTaRSⁱ	Atoh8 mouse
Protein Ontology More...PROⁱ	PR:Q99NA2
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000037621 Expressed in 108 organ(s), highest expression level in head
CleanExⁱ	MM_ATOH8
ExpressionAtlasⁱ	Q99NA2 baseline and differential
Genevisibleⁱ	Q99NA2 MM

Family and domain databases

CDDⁱ	cd00083 HLH, 1 hit
Gene3Dⁱ	4.10.280.10, 1 hit
InterProⁱ	View protein in InterPro IPR032660 ATOH8 IPR011598 bHLH_dom IPR036638 HLH_DNA-bd_sf
PANTHERⁱ	PTHR19290:SF102 PTHR19290:SF102, 1 hit
Pfamⁱ	View protein in Pfam PF00010 HLH, 1 hit
SMARTⁱ	View protein in SMART SM00353 HLH, 1 hit
SUPFAMⁱ	SSF47459 SSF47459, 1 hit
PROSITEⁱ	View protein in PROSITE PS50888 BHLH, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	ATOH8_MOUSE
Accessionⁱ	Q99NA2Primary (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 7, 2018
	This is version 115 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q99NA2 (ATOH8_MOUSE)

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Protein atonal homolog 8

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Caution

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Other locations

Nucleus

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Compositional bias

Phylogenomic databases

Family and domain databases

Experimental Info

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ