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 (PubMed:24236640). Regulates endothelial cell proliferation, migration and tube-like structures formation (PubMed:24463812). Modulates endothelial cell differentiation through NOS3 (PubMed:24463812). May be implicated in specification and differentiation of neuronal cell lineages in the brain (By similarity). May participate in kidney development and may be involved in podocyte differentiation (By similarity). 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 (By similarity). During myogenesis, may play a role during the transition of myoblasts from the proliferative phase to the differentiation phase (By similarity). 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 (PubMed:24236640). 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 (By similarity).By similarity2 Publications

Caution

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

GO - Molecular functionⁱ

activating transcription factor binding Source: Ensembl
DNA-binding transcription factor activity
Source: UniProtKB
Inferred from direct assayⁱ
- 24236640
DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
E-box binding
Source: UniProtKB
Inferred from direct assayⁱ
- 24236640
protein dimerization activity Source: InterPro

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

cell differentiation Source: UniProtKB-KW
formation of primary germ layer Source: UniProtKB
myoblast proliferation Source: UniProtKB
negative regulation of endothelial cell proliferation
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 24463812
negative regulation of gene expression
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 27780851
negative regulation of transcription, DNA-templated Source: UniProtKB
nervous system development Source: UniProtKB-KW
positive regulation of endothelial cell differentiation
Source: UniProtKB
Inferred from direct assayⁱ
- 24463812
positive regulation of endothelial cell migration
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 24463812
positive regulation of gene expression
Source: BHF-UCL
Inferred from genetic interactionⁱ
- 27780851
positive regulation of transcription, DNA-templated
Source: UniProtKB
Inferred from direct assayⁱ
- 24236640
SMAD protein signal transduction
Source: UniProtKB
Inferred from direct assayⁱ
- 24236640
tube formation
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 24463812

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 8 Alternative name(s): Class A basic helix-loop-helix protein 21 Short name: bHLHa21 Helix-loop-helix protein hATH-6Imported Short name: hATH61 Publication
Gene namesⁱ	Name:ATOH8Imported Synonyms:ATH6, BHLHA21
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [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 › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 2

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000168874.12
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:24126 ATOH8
neXtProtⁱ	NX_Q96SQ7

Keywords - Cellular componentⁱ

Cytoplasm, Nucleus

Pathology & Biotechⁱ

Organism-specific databases

DisGeNET More...DisGeNETⁱ	84913
Open Targets More...OpenTargetsⁱ	ENSG00000168874
PharmGKBⁱ	PA134904746

Polymorphism and mutation databases

BioMutaⁱ	ATOH8
DMDMⁱ	224471820

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000323751	1 – 321	Protein atonal homolog 8Add BLAST		321

Proteomic databases

PaxDbⁱ	Q96SQ7
PeptideAtlas More...PeptideAtlasⁱ	Q96SQ7
PRIDEⁱ	Q96SQ7
ProteomicsDBⁱ	78136 78137 [Q96SQ7-2]

PTM databases

iPTMnetⁱ	Q96SQ7
PhosphoSitePlusⁱ	Q96SQ7

Expressionⁱ

Tissue specificityⁱ

Expressed in lung, liver, kidney, heart and pancreas. Expressed in endothel of umbilical vessels.1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000168874 Expressed in 184 organ(s), highest expression level in left lobe of thyroid gland
CleanExⁱ	HS_ATOH8
Genevisibleⁱ	Q96SQ7 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA028406

HPAⁱ

HPA028406

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 similarity

GO - Molecular functionⁱ

activating transcription factor binding Source: Ensembl
protein dimerization activity Source: InterPro

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	124350, 2 interactors
IntActⁱ	Q96SQ7, 1 interactor
STRINGⁱ	9606.ENSP00000304676

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q96SQ7
SMRⁱ	Q96SQ7
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	230 – 282	bHLHPROSITE-ProRule annotationAdd BLAST		53

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	230 – 243	Basic motif; degeneratePROSITE-ProRule annotationAdd BLAST		14
Regionⁱ	244 – 282	Helix-loop-helix motifPROSITE-ProRule annotationAdd BLAST		39

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	69 – 187	Pro-richPROSITE-ProRule annotationAdd BLAST		119

Domainⁱ

The bHLH domain mediates transcriptional repression by inhibiting TCF3 transcriptional activity through heterodimerization.By similarity

Phylogenomic databases

eggNOGⁱ	ENOG410IQ4E Eukaryota ENOG4111WSZ LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00680000099860
HOGENOMⁱ	HOG000034181
HOVERGENⁱ	HBG095605
InParanoidⁱ	Q96SQ7
KEGG Orthology (KO) More...KOⁱ	K09084
OMAⁱ	ETQPFRE
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G167Y
PhylomeDBⁱ	Q96SQ7
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

Sequences (2)ⁱ

Sequence statusⁱ: Complete.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align Add to basket

Isoform 1 (identifier: Q96SQ7-1) [UniParc]FASTA Add to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKHIPVLEDG PWKTVCVKEL NGLKKLKRKG KEPARRANGY KTFRLDLEAP 
        60         70         80         90        100
EPRAVATNGL RDRTHRLQPV PVPVPVPVPV APAVPPRGGT DTAGERGGSR 
       110        120        130        140        150
APEVSDARKR CFALGAVGPG LPTPPPPPPP APQSQAPGGP EAQPFREPGL 
       160        170        180        190        200
RPRILLCAPP ARPAPSAPPA PPAPPESTVR PAPPTRPGES SYSSISHVIY 
       210        220        230        240        250
NNHQDSSASP RKRPGEATAA SSEIKALQQT RRLLANARER TRVHTISAAF 
       260        270        280        290        300
EALRKQVPCY SYGQKLSKLA ILRIACNYIL SLARLADLDY SADHSNLSFS 
       310        320 
ECVQRCTRTL QAEGRAKKRK E

Length:321

Mass (Da):34,644

Last modified:March 3, 2009 - v2

Checksum:ⁱ6AEC8043AD8D2075

GO

Isoform 2 (identifier: Q96SQ7-2) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
321-321: E → SLIITQDTTA...PPLRARRPPH

« Hide

        10         20         30         40         50
MKHIPVLEDG PWKTVCVKEL NGLKKLKRKG KEPARRANGY KTFRLDLEAP 
        60         70         80         90        100
EPRAVATNGL RDRTHRLQPV PVPVPVPVPV APAVPPRGGT DTAGERGGSR 
       110        120        130        140        150
APEVSDARKR CFALGAVGPG LPTPPPPPPP APQSQAPGGP EAQPFREPGL 
       160        170        180        190        200
RPRILLCAPP ARPAPSAPPA PPAPPESTVR PAPPTRPGES SYSSISHVIY 
       210        220        230        240        250
NNHQDSSASP RKRPGEATAA SSEIKALQQT RRLLANARER TRVHTISAAF 
       260        270        280        290        300
EALRKQVPCY SYGQKLSKLA ILRIACNYIL SLARLADLDY SADHSNLSFS 
       310        320        330        340        350
ECVQRCTRTL QAEGRAKKRK SLIITQDTTA RAAGLEAAGK TVQKVLCERG 
       360        370        380        390        400
NSLMNNRTGR RKSWRLEFLF LRRRCFLLTF YLWFLFFSRF LLMLFLPLLT 
       410 
SVVTFLPPLR ARRPPH

Note: No experimental confirmation available.

Show »

Length:416

Mass (Da):45,801

Checksum:ⁱAF58E6215A2DB518

GO

Natural variant

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_039582	150	L → P3 PublicationsCorresponds to variant dbSNP:rs17851881Ensembl.		1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_032118	321	E → SLIITQDTTARAAGLEAAGK TVQKVLCERGNSLMNNRTGR RKSWRLEFLFLRRRCFLLTF YLWFLFFSRFLLMLFLPLLT SVVTFLPPLRARRPPH in isoform 2. 1 Publication		1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF529205 mRNA Translation: AAO85773.1 AK027614 mRNA Translation: BAB55233.1 AK074681 mRNA Translation: BAC11135.1 AC012454 Genomic DNA No translation available. BC021207 mRNA Translation: AAH21207.1 BC094832 mRNA Translation: AAH94832.1 AL831857 mRNA Translation: CAH56263.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS1985.1 [Q96SQ7-1]
NCBI Reference Sequences More...RefSeqⁱ	NP_116216.2, NM_032827.6 [Q96SQ7-1]
UniGeneⁱ	Hs.135569

Genome annotation databases

Ensemblⁱ	ENST00000306279; ENSP00000304676; ENSG00000168874 [Q96SQ7-1]
GeneIDⁱ	84913
KEGGⁱ	hsa:84913
UCSC genome browser More...UCSCⁱ	uc002sqn.4 human [Q96SQ7-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q96SQ7	Uncharacterized protein		RHIRO		326	UniRef90_Q96SQ7
Uncharacterized protein		FELCA		326
Protein atonal homolog 8 (Fragment)		NEOVI		143
protein atonal homolog 8		NEOSC		325
protein atonal homolog 8		Enhydra lutris kenyoni		323
+62
Q96SQ7-2	Uncharacterized protein		CERAT		363	UniRef90_Q96SQ7-2
Uncharacterized protein		RHIRO		353
Uncharacterized protein		PAPAN		346
Uncharacterized protein		MACNE		343
UPI000DC15C0D		THEGE		428
+7

Protein	Similar proteins		Species	Score	Length	Source
Q96SQ7	Protein atonal homolog 8		MOUSE		322	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	AF529205 mRNA Translation: AAO85773.1 AK027614 mRNA Translation: BAB55233.1 AK074681 mRNA Translation: BAC11135.1 AC012454 Genomic DNA No translation available. BC021207 mRNA Translation: AAH21207.1 BC094832 mRNA Translation: AAH94832.1 AL831857 mRNA Translation: CAH56263.1
CCDSⁱ	CCDS1985.1 [Q96SQ7-1]
RefSeqⁱ	NP_116216.2, NM_032827.6 [Q96SQ7-1]
UniGeneⁱ	Hs.135569

3D structure databases

ProteinModelPortalⁱ	Q96SQ7
SMRⁱ	Q96SQ7
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	124350, 2 interactors
IntActⁱ	Q96SQ7, 1 interactor
STRINGⁱ	9606.ENSP00000304676

PTM databases

iPTMnetⁱ	Q96SQ7
PhosphoSitePlusⁱ	Q96SQ7

Polymorphism and mutation databases

BioMutaⁱ	ATOH8
DMDMⁱ	224471820

Proteomic databases

PaxDbⁱ	Q96SQ7
PeptideAtlasⁱ	Q96SQ7
PRIDEⁱ	Q96SQ7
ProteomicsDBⁱ	78136 78137 [Q96SQ7-2]

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENST00000306279; ENSP00000304676; ENSG00000168874 [Q96SQ7-1]
GeneIDⁱ	84913
KEGGⁱ	hsa:84913
UCSCⁱ	uc002sqn.4 human [Q96SQ7-1]

Organism-specific databases

CTDⁱ	84913
DisGeNETⁱ	84913
EuPathDBⁱ	HostDB:ENSG00000168874.12
GeneCardsⁱ	ATOH8
HGNCⁱ	HGNC:24126 ATOH8
HPAⁱ	HPA028406
neXtProtⁱ	NX_Q96SQ7
OpenTargetsⁱ	ENSG00000168874
PharmGKBⁱ	PA134904746
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	ENOG410IQ4E Eukaryota ENOG4111WSZ LUCA
GeneTreeⁱ	ENSGT00680000099860
HOGENOMⁱ	HOG000034181
HOVERGENⁱ	HBG095605
InParanoidⁱ	Q96SQ7
KOⁱ	K09084
OMAⁱ	ETQPFRE
OrthoDBⁱ	EOG091G167Y
PhylomeDBⁱ	Q96SQ7
TreeFamⁱ	TF324848

Miscellaneous databases

GenomeRNAiⁱ	84913
Protein Ontology More...PROⁱ	PR:Q96SQ7

Gene expression databases

Bgeeⁱ	ENSG00000168874 Expressed in 184 organ(s), highest expression level in left lobe of thyroid gland
CleanExⁱ	HS_ATOH8
Genevisibleⁱ	Q96SQ7 HS

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_HUMAN
Accessionⁱ	Q96SQ7Primary (citable) accession number: Q96SQ7 Secondary accession number(s): Q504S2, Q659B0
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
	Last sequence update:	March 3, 2009
	Last modified:	November 7, 2018
	This is version 134 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations

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UniProtKB - Q96SQ7 (ATOH8_HUMAN)

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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

Organism-specific databases

Polymorphism and mutation databases

<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

Organism-specific 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

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<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

Polymorphism and mutation 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

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ