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Protein

Protein atonal homolog 8

Gene

ATOH8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (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

GO - Molecular functioni

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

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • negative regulation of endothelial cell proliferation Source: UniProtKB
  • 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 transcription, DNA-templated Source: UniProtKB
  • SMAD protein signal transduction Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • tube formation Source: UniProtKB
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 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:24126. ATOH8.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134904746.

Polymorphism and mutation databases

BioMutaiATOH8.
DMDMi224471820.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 321321Protein atonal homolog 8PRO_0000323751Add
BLAST

Proteomic databases

PaxDbiQ96SQ7.
PRIDEiQ96SQ7.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ96SQ7.
CleanExiHS_ATOH8.
GenevisibleiQ96SQ7. HS.

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

Protein-protein interaction databases

BioGridi124350. 2 interactions.
IntActiQ96SQ7. 1 interaction.
STRINGi9606.ENSP00000304676.

Structurei

3D structure databases

ProteinModelPortaliQ96SQ7.
SMRiQ96SQ7. Positions 231-285.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini230 – 28253bHLHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni230 – 24314Basic motif; degeneratePROSITE-ProRule annotationAdd
BLAST
Regioni244 – 28239Helix-loop-helix motifPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi69 – 187119Pro-richPROSITE-ProRule annotationAdd
BLAST

Domaini

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

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiNOG311369.
GeneTreeiENSGT00440000034222.
HOGENOMiHOG000034181.
HOVERGENiHBG095605.
InParanoidiQ96SQ7.
KOiK09084.
OMAiETQPFRE.
OrthoDBiEOG73NG5F.
PhylomeDBiQ96SQ7.
TreeFamiTF324848.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

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

Note: No experimental confirmation available.
Show »
Length:416
Mass (Da):45,801
Checksum:iAF58E6215A2DB518
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti150 – 1501L → P.3 Publications
Corresponds to variant rs17851881 [ dbSNP | Ensembl ].
VAR_039582

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei321 – 3211E → SLIITQDTTARAAGLEAAGK TVQKVLCERGNSLMNNRTGR RKSWRLEFLFLRRRCFLLTF YLWFLFFSRFLLMLFLPLLT SVVTFLPPLRARRPPH in isoform 2. 1 PublicationVSP_032118

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.
CCDSiCCDS1985.1. [Q96SQ7-1]
RefSeqiNP_116216.2. NM_032827.6. [Q96SQ7-1]
UniGeneiHs.135569.

Genome annotation databases

EnsembliENST00000306279; ENSP00000304676; ENSG00000168874.
GeneIDi84913.
KEGGihsa:84913.
UCSCiuc002sqm.4. human. [Q96SQ7-2]
uc002sqn.3. human. [Q96SQ7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
CCDSiCCDS1985.1. [Q96SQ7-1]
RefSeqiNP_116216.2. NM_032827.6. [Q96SQ7-1]
UniGeneiHs.135569.

3D structure databases

ProteinModelPortaliQ96SQ7.
SMRiQ96SQ7. Positions 231-285.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124350. 2 interactions.
IntActiQ96SQ7. 1 interaction.
STRINGi9606.ENSP00000304676.

Polymorphism and mutation databases

BioMutaiATOH8.
DMDMi224471820.

Proteomic databases

PaxDbiQ96SQ7.
PRIDEiQ96SQ7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000306279; ENSP00000304676; ENSG00000168874.
GeneIDi84913.
KEGGihsa:84913.
UCSCiuc002sqm.4. human. [Q96SQ7-2]
uc002sqn.3. human. [Q96SQ7-1]

Organism-specific databases

CTDi84913.
GeneCardsiGC02P085978.
HGNCiHGNC:24126. ATOH8.
neXtProtiNX_Q96SQ7.
PharmGKBiPA134904746.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG311369.
GeneTreeiENSGT00440000034222.
HOGENOMiHOG000034181.
HOVERGENiHBG095605.
InParanoidiQ96SQ7.
KOiK09084.
OMAiETQPFRE.
OrthoDBiEOG73NG5F.
PhylomeDBiQ96SQ7.
TreeFamiTF324848.

Miscellaneous databases

GenomeRNAii84913.
NextBioi75304.
PROiQ96SQ7.

Gene expression databases

BgeeiQ96SQ7.
CleanExiHS_ATOH8.
GenevisibleiQ96SQ7. HS.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
[Graphical view]
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. "Gene expression profile of human endothelial cells exposed to sustained fluid shear stress."
    Wasserman S.M., Mehraban F., Komuves L.G., Yang R.B., Tomlinson J.E., Zhang Y., Spriggs F., Topper J.N.
    Physiol. Genomics 12:13-23(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT PRO-150, TISSUE SPECIFICITY.
    Tissue: Umbilical vein.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT PRO-150.
  3. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  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] (ISOFORM 1), VARIANT PRO-150.
    Tissue: Muscle and Retinal pigment epithelium.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 154-321 (ISOFORM 2).
    Tissue: Amygdala.
  6. "The transcription factor ATOH8 is regulated by erythropoietic activity and regulates HAMP transcription and cellular pSMAD1,5,8 levels."
    Patel N., Varghese J., Masaratana P., Latunde-Dada G.O., Jacob M., Simpson R.J., McKie A.T.
    Br. J. Haematol. 164:586-596(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "The role of Hath6, a newly identified shear-stress-responsive transcription factor, in endothelial cell differentiation and function."
    Fang F., Wasserman S.M., Torres-Vazquez J., Weinstein B., Cao F., Li Z., Wilson K.D., Yue W., Wu J.C., Xie X., Pei X.
    J. Cell Sci. 127:1428-1440(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiATOH8_HUMAN
AccessioniPrimary (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: July 22, 2015
This is version 111 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Caution

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.