ATOH7_HUMAN
ID ATOH7_HUMAN Reviewed; 152 AA.
AC Q8N100;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Transcription factor ATOH7 {ECO:0000305};
DE AltName: Full=Atonal bHLH transcription factor 7 {ECO:0000312|HGNC:HGNC:13907};
DE AltName: Full=Class A basic helix-loop-helix protein 13 {ECO:0000312|HGNC:HGNC:13907};
DE Short=bHLHa13 {ECO:0000312|HGNC:HGNC:13907};
DE AltName: Full=Protein atonal homolog 7 {ECO:0000312|HGNC:HGNC:13907};
GN Name=ATOH7 {ECO:0000312|HGNC:HGNC:13907}; Synonyms=ATH5, BHLHA13;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11889557; DOI=10.1007/s00335-001-2101-3;
RA Brown N.L., Dagenais S.L., Chen C.-M., Glaser T.;
RT "Molecular characterization and mapping of ATOH7, a human atonal homolog
RT with a predicted role in retinal ganglion cell development.";
RL Mamm. Genome 13:95-101(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION.
RX PubMed=14516699; DOI=10.1016/s0925-4773(03)00130-8;
RA McLellan A.S., Langlands K., Kealey T.;
RT "Exhaustive identification of human class II basic helix-loop-helix
RT proteins by virtual library screening.";
RL Mech. Dev. 119:S285-S291(2002).
RN [4]
RP INVOLVEMENT IN PHPVAR.
RX PubMed=21441919; DOI=10.1038/nn.2798;
RA Ghiasvand N.M., Rudolph D.D., Mashayekhi M., Brzezinski J.A., Goldman D.,
RA Glaser T.;
RT "Deletion of a remote enhancer near ATOH7 disrupts retinal neurogenesis,
RT causing NCRNA disease.";
RL Nat. Neurosci. 14:578-586(2011).
RN [5]
RP VARIANTS THR-47 AND GLY-65.
RX PubMed=20395239; DOI=10.1093/hmg/ddq144;
RA Macgregor S., Hewitt A.W., Hysi P.G., Ruddle J.B., Medland S.E.,
RA Henders A.K., Gordon S.D., Andrew T., McEvoy B., Sanfilippo P.G.,
RA Carbonaro F., Tah V., Li Y.J., Bennett S.L., Craig J.E., Montgomery G.W.,
RA Tran-Viet K.N., Brown N.L., Spector T.D., Martin N.G., Young T.L.,
RA Hammond C.J., Mackey D.A.;
RT "Genome-wide association identifies ATOH7 as a major gene determining human
RT optic disc size.";
RL Hum. Mol. Genet. 19:2716-2724(2010).
RN [6]
RP VARIANT PHPVAR VAL-49.
RX PubMed=22068589; DOI=10.1093/hmg/ddr509;
RA Khan K., Logan C.V., McKibbin M., Sheridan E., Elcioglu N.H., Yenice O.,
RA Parry D.A., Fernandez-Fuentes N., Abdelhamed Z.I., Al-Maskari A.,
RA Poulter J.A., Mohamed M.D., Carr I.M., Morgan J.E., Jafri H., Raashid Y.,
RA Taylor G.R., Johnson C.A., Inglehearn C.F., Toomes C., Ali M.;
RT "Next generation sequencing identifies mutations in Atonal homolog 7
RT (ATOH7) in families with global eye developmental defects.";
RL Hum. Mol. Genet. 21:776-783(2012).
RN [7]
RP VARIANT PHPVAR HIS-46, CHARACTERIZATION OF VARIANT PHPVAR HIS-46, VARIANTS
RP THR-47 AND GLY-65, CHARACTERIZATION OF VARIANTS THR-47 AND GLY-65, AND
RP MUTAGENESIS OF LEU-56.
RX PubMed=22645276; DOI=10.1093/hmg/dds197;
RA Prasov L., Masud T., Khaliq S., Mehdi S.Q., Abid A., Oliver E.R.,
RA Silva E.D., Lewanda A., Brodsky M.C., Borchert M., Kelberman D.,
RA Sowden J.C., Dattani M.T., Glaser T.;
RT "ATOH7 mutations cause autosomal recessive persistent hyperplasia of the
RT primary vitreous.";
RL Hum. Mol. Genet. 21:3681-3694(2012).
RN [8]
RP VARIANTS PHPVAR 41-ARG--ARG-48 DEL AND 134-GLU--THR-152 DEL.
RX PubMed=26933893; DOI=10.3109/13816810.2015.1120316;
RA Kondo H., Matsushita I., Tahira T., Uchio E., Kusaka S.;
RT "Mutations in ATOH7 gene in patients with nonsyndromic congenital retinal
RT nonattachment and familial exudative vitreoretinopathy.";
RL Ophthalmic Genet. 37:462-464(2016).
RN [9]
RP VARIANT PHPVAR PRO-42.
RX PubMed=28192794; DOI=10.1167/iovs.16-20281;
RA Keser V., Khan A., Siddiqui S., Lopez I., Ren H., Qamar R., Nadaf J.,
RA Majewski J., Chen R., Koenekoop R.K.;
RT "The Genetic Causes of Nonsyndromic Congenital Retinal Detachment: A
RT Genetic and Phenotypic Study of Pakistani Families.";
RL Invest. Ophthalmol. Vis. Sci. 58:1028-1036(2017).
RN [10]
RP VARIANTS VAL-59 AND THR-59, CHARACTERIZATION OF VARIANTS HIS-46; VAL-59 AND
RP THR-59, FUNCTION, INTERACTION WITH TCF3, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF ALA-59.
RX PubMed=31696227; DOI=10.1093/hmg/ddz268;
RA Atac D., Koller S., Hanson J.V.M., Feil S., Tiwari A., Bahr A., Baehr L.,
RA Magyar I., Kottke R., Gerth-Kahlert C., Berger W.;
RT "Atonal homolog 7 (ATOH7) loss-of-function mutations in predominant
RT bilateral optic nerve hypoplasia.";
RL Hum. Mol. Genet. 29:132-148(2020).
CC -!- FUNCTION: Transcription factor that binds to DNA at the consensus
CC sequence 5'-CAG[GC]TG-3' (PubMed:31696227). Dimerization with TCF3
CC isoform E47 may be required in certain situations (PubMed:31696227).
CC Binds to gene promoters and enhancer elements, and thereby regulates a
CC transcriptional program of retinal ganglion cell (RGC) determinant
CC genes (By similarity). Although the exact mechanism is not certain,
CC retinal transcription regulation by ATOH7 has a role in RGC
CC determination and survival, photoreceptor population development,
CC targeting of RGC axons to the optic nerve and development of the
CC retino-hypothalamic tract (By similarity). Binds to its own promoter
CC and enhancer sequences, suggesting autoregulation of ATOH7
CC transcription (By similarity). Required for retinal circadian rhythm
CC photoentrainment (By similarity). Plays a role in brainstem auditory
CC signaling and binaural processing (By similarity).
CC {ECO:0000250|UniProtKB:Q9Z2E5, ECO:0000269|PubMed:31696227}.
CC -!- SUBUNIT: Forms a heterodimer with TCF3 isoform E47; interaction may be
CC required for DNA-binding in certain situations.
CC {ECO:0000269|PubMed:31696227}.
CC -!- INTERACTION:
CC Q8N100; P15884-3: TCF4; NbExp=3; IntAct=EBI-11976887, EBI-13636688;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:31696227}. Perikaryon
CC {ECO:0000250|UniProtKB:Q9Z2E5}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q9Z2E5}.
CC -!- DISEASE: Persistent hyperplastic primary vitreous, autosomal recessive
CC (PHPVAR) [MIM:221900]: A developmental eye malformation associated with
CC microphthalmia, cataract, glaucoma, and congenital retinal non-
CC attachment. It is due to failure of the primary vitreous to regress in
CC utero, resulting in the presence of a retrolental fibrovascular
CC membrane with persistence of the posterior portion of the tunica
CC vasculosa lentis and hyaloid artery. Disease manifestations range from
CC a trivial remnant of hyaloid vessels to a dense fibrovascular mass
CC causing lens opacity and retinal detachment.
CC {ECO:0000269|PubMed:21441919, ECO:0000269|PubMed:22068589,
CC ECO:0000269|PubMed:22645276, ECO:0000269|PubMed:26933893,
CC ECO:0000269|PubMed:28192794}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. A 6.5 kb deletion that
CC spans a remote cis regulatory element 20 kb upstream from ATOH7 has
CC been found in PHPVAR patients (PubMed:21441919).
CC {ECO:0000269|PubMed:21441919}.
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DR EMBL; AF418922; AAL11911.1; -; Genomic_DNA.
DR EMBL; BC032621; AAH32621.1; -; mRNA.
DR EMBL; BK000277; DAA01057.1; -; mRNA.
DR CCDS; CCDS7276.1; -.
DR RefSeq; NP_660161.1; NM_145178.3.
DR AlphaFoldDB; Q8N100; -.
DR SMR; Q8N100; -.
DR BioGRID; 128637; 1.
DR IntAct; Q8N100; 2.
DR STRING; 9606.ENSP00000362777; -.
DR iPTMnet; Q8N100; -.
DR PhosphoSitePlus; Q8N100; -.
DR BioMuta; ATOH7; -.
DR DMDM; 74750873; -.
DR PaxDb; Q8N100; -.
DR PeptideAtlas; Q8N100; -.
DR PRIDE; Q8N100; -.
DR Antibodypedia; 28437; 223 antibodies from 26 providers.
DR DNASU; 220202; -.
DR Ensembl; ENST00000373673.5; ENSP00000362777.3; ENSG00000179774.9.
DR GeneID; 220202; -.
DR KEGG; hsa:220202; -.
DR MANE-Select; ENST00000373673.5; ENSP00000362777.3; NM_145178.4; NP_660161.1.
DR UCSC; uc001jnq.4; human.
DR CTD; 220202; -.
DR DisGeNET; 220202; -.
DR GeneCards; ATOH7; -.
DR HGNC; HGNC:13907; ATOH7.
DR HPA; ENSG00000179774; Tissue enhanced (brain, liver).
DR MalaCards; ATOH7; -.
DR MIM; 221900; phenotype.
DR MIM; 609875; gene.
DR neXtProt; NX_Q8N100; -.
DR OpenTargets; ENSG00000179774; -.
DR Orphanet; 289499; Congenital cataract microcornea with corneal opacity.
DR Orphanet; 91495; Persistent hyperplastic primary vitreous.
DR PharmGKB; PA38369; -.
DR VEuPathDB; HostDB:ENSG00000179774; -.
DR eggNOG; KOG4395; Eukaryota.
DR GeneTree; ENSGT00940000161556; -.
DR HOGENOM; CLU_145503_0_0_1; -.
DR InParanoid; Q8N100; -.
DR OMA; WVSLHCE; -.
DR OrthoDB; 1453771at2759; -.
DR PhylomeDB; Q8N100; -.
DR TreeFam; TF315153; -.
DR PathwayCommons; Q8N100; -.
DR SignaLink; Q8N100; -.
DR SIGNOR; Q8N100; -.
DR BioGRID-ORCS; 220202; 2 hits in 1082 CRISPR screens.
DR GenomeRNAi; 220202; -.
DR Pharos; Q8N100; Tbio.
DR PRO; PR:Q8N100; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q8N100; protein.
DR Bgee; ENSG00000179774; Expressed in prefrontal cortex and 69 other tissues.
DR ExpressionAtlas; Q8N100; baseline and differential.
DR Genevisible; Q8N100; HS.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR GO; GO:0003407; P:neural retina development; IMP:MGI.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0021554; P:optic nerve development; IMP:MGI.
DR GO; GO:1902336; P:positive regulation of retinal ganglion cell axon guidance; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0010996; P:response to auditory stimulus; ISS:UniProtKB.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR032663; ATOH7.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR PANTHER; PTHR19290:SF99; PTHR19290:SF99; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Cell projection; Developmental protein; Differentiation; Disease variant;
KW DNA-binding; Neurogenesis; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..152
FT /note="Transcription factor ATOH7"
FT /id="PRO_0000292406"
FT DOMAIN 40..92
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT VARIANT 41..48
FT /note="Missing (in PHPVAR; unknown pathological
FT significance; dbSNP:rs560230254)"
FT /evidence="ECO:0000269|PubMed:26933893"
FT /id="VAR_085727"
FT VARIANT 42
FT /note="R -> P (in PHPVAR; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28192794"
FT /id="VAR_085728"
FT VARIANT 46
FT /note="N -> H (in PHPVAR; loss of function; polypeptide is
FT stable, but does not bind DNA or activate transcription;
FT does not restore retinal ganglion cell development in
FT retinal explants from a mouse Atoh7 null mutant; abolishes
FT heterodimerization with TCF3 E47 isoform; reduces DNA-
FT binding ability and abolishes transcriptional activation;
FT no effect on nuclear localization; dbSNP:rs587777666)"
FT /evidence="ECO:0000269|PubMed:22645276,
FT ECO:0000269|PubMed:31696227"
FT /id="VAR_072398"
FT VARIANT 47
FT /note="A -> T (found in a sporadic case of optic nerve
FT hypoplasia; unknown pathological significance; does not
FT affect DNA-binding activity but reduces transcription
FT activation)"
FT /evidence="ECO:0000269|PubMed:20395239,
FT ECO:0000269|PubMed:22645276"
FT /id="VAR_072399"
FT VARIANT 49
FT /note="E -> V (in PHPVAR; dbSNP:rs587777664)"
FT /evidence="ECO:0000269|PubMed:22068589"
FT /id="VAR_072400"
FT VARIANT 59
FT /note="A -> T (found in patients with bilateral optic nerve
FT hypoplasia; unknown pathological significance; abolishes
FT heterodimerization with TCF3 E47 isoform; reduces DNA-
FT binding ability and abolishes transcriptional activation;
FT no effect on nuclear localization; dbSNP:rs138274069)"
FT /evidence="ECO:0000269|PubMed:31696227"
FT /id="VAR_085729"
FT VARIANT 59
FT /note="A -> V (found in patients with bilateral optic nerve
FT hypoplasia; unknown pathological significance; abolishes
FT heterodimerization with TCF3 E47 isoform; reduces DNA-
FT binding ability and abolishes transcriptional activation;
FT no effect on nuclear localization; dbSNP:rs754494518)"
FT /evidence="ECO:0000269|PubMed:31696227"
FT /id="VAR_085730"
FT VARIANT 65
FT /note="R -> G (does not affect DNA-binding activity or
FT transcription activation; dbSNP:rs111699024)"
FT /evidence="ECO:0000269|PubMed:20395239,
FT ECO:0000269|PubMed:22645276"
FT /id="VAR_072401"
FT VARIANT 134..152
FT /note="Missing (in PHPVAR; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26933893"
FT /id="VAR_085731"
FT MUTAGEN 56
FT /note="L->P: Loss of DNA-binding activity; loss of ability
FT to restore retinal ganglion cell development in retinal
FT explants from a mouse Atoh7 null mutant."
FT /evidence="ECO:0000269|PubMed:22645276"
FT MUTAGEN 59
FT /note="A->G: Abolishes heterodimerization with TCF3 isoform
FT E47; no effect on nuclear localization."
FT /evidence="ECO:0000269|PubMed:31696227"
SQ SEQUENCE 152 AA; 16871 MW; 9E93E9E60E1697C5 CRC64;
MKSCKPSGPP AGARVAPPCA GGTECAGTCA GAGRLESAAR RRLAANARER RRMQGLNTAF
DRLRRVVPQW GQDKKLSKYE TLQMALSYIM ALTRILAEAE RFGSERDWVG LHCEHFGRDH
YLPFPGAKLP GESELYSQRL FGFQPEPFQM AT
