ATOH7_MOUSE
ID ATOH7_MOUSE Reviewed; 149 AA.
AC Q9Z2E5;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Transcription factor Atoh7 {ECO:0000305};
DE AltName: Full=Atonal bHLH transcription factor 7 {ECO:0000312|MGI:MGI:1355553};
DE AltName: Full=Helix-loop-helix protein mATH-5 {ECO:0000303|PubMed:9806930};
DE Short=mATH5 {ECO:0000303|PubMed:9806930};
DE AltName: Full=Protein atonal homolog 7 {ECO:0000312|MGI:MGI:1355553};
GN Name=Atoh7 {ECO:0000312|MGI:MGI:1355553}; Synonyms=Ath5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC STRAIN=129/SvJ; TISSUE=Retina;
RX PubMed=9806930; DOI=10.1242/dev.125.23.4821;
RA Brown N.L., Kanekar S., Vetter M.L., Tucker P.K., Gemza D.L., Glaser T.;
RT "Math5 encodes a murine basic helix-loop-helix transcription factor
RT expressed during early stages of retinal neurogenesis.";
RL Development 125:4821-4833(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129S4/SvJae;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; 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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11493566; DOI=10.1242/dev.128.13.2497;
RA Brown N.L., Patel S., Brzezinski J., Glaser T.;
RT "Math5 is required for retinal ganglion cell and optic nerve formation.";
RL Development 128:2497-2508(2001).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11156601; DOI=10.1101/gad.855301;
RA Wang S.W., Kim B.S., Ding K., Wang H., Sun D., Johnson R.L., Klein W.H.,
RA Gan L.;
RT "Requirement for math5 in the development of retinal ganglion cells.";
RL Genes Dev. 15:24-29(2001).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12451142; DOI=10.1523/jneurosci.22-23-10427.2002;
RA Wee R., Castrucci A.M., Provencio I., Gan L., Van Gelder R.N.;
RT "Loss of photic entrainment and altered free-running circadian rhythms in
RT math5-/- mice.";
RL J. Neurosci. 22:10427-10433(2002).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=17977745; DOI=10.1016/j.mcn.2007.09.006;
RA Saul S.M., Brzezinski J.A. IV, Altschuler R.A., Shore S.E., Rudolph D.D.,
RA Kabara L.L., Halsey K.E., Hufnagel R.B., Zhou J., Dolan D.F., Glaser T.;
RT "Math5 expression and function in the central auditory system.";
RL Mol. Cell. Neurosci. 37:153-169(2008).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=26392540; DOI=10.1073/pnas.1516259112;
RA Buhr E.D., Yue W.W., Ren X., Jiang Z., Liao H.W., Mei X., Vemaraju S.,
RA Nguyen M.T., Reed R.R., Lang R.A., Yau K.W., Van Gelder R.N.;
RT "Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators
RT in mammalian retina and cornea.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:13093-13098(2015).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=33712461; DOI=10.1126/sciadv.abe4983;
RA Brodie-Kommit J., Clark B.S., Shi Q., Shiau F., Kim D.W., Langel J.,
RA Sheely C., Ruzycki P.A., Fries M., Javed A., Cayouette M., Schmidt T.,
RA Badea T., Glaser T., Zhao H., Singer J., Blackshaw S., Hattar S.;
RT "Atoh7-independent specification of retinal ganglion cell identity.";
RL Sci. Adv. 7:0-0(2021).
CC -!- FUNCTION: Transcription factor that binds to DNA at the consensus
CC sequence 5'-CAG[GC]TG-3' (PubMed:33712461). Dimerization with TCF3
CC isoform E47 may be required in certain situations (By similarity).
CC Binds to gene promoters and enhancer elements, and thereby regulates a
CC transcriptional program of retinal ganglion cell (RGC) determinant
CC genes (PubMed:33712461). 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 (PubMed:11493566, PubMed:11156601,
CC PubMed:12451142, PubMed:33712461). Binds to its own promoter and
CC enhancer sequences, suggesting autoregulation of ATOH7 transcription
CC (PubMed:33712461). Required for retinal circadian rhythm
CC photoentrainment (PubMed:12451142, PubMed:26392540). Plays a role in
CC brainstem auditory signaling and binaural processing (PubMed:17977745).
CC {ECO:0000250|UniProtKB:Q8N100, ECO:0000269|PubMed:11156601,
CC ECO:0000269|PubMed:11493566, ECO:0000269|PubMed:12451142,
CC ECO:0000269|PubMed:17977745, ECO:0000269|PubMed:26392540,
CC ECO:0000269|PubMed:33712461}.
CC -!- SUBUNIT: Forms a heterodimer with TCF3 isoform E47; interaction may be
CC required for DNA-binding in certain situations.
CC {ECO:0000250|UniProtKB:Q8N100}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:33712461}. Perikaryon
CC {ECO:0000269|PubMed:17977745}. Cell projection, axon
CC {ECO:0000269|PubMed:17977745}.
CC -!- TISSUE SPECIFICITY: Expressed in retinal ganglion cells
CC (PubMed:26392540). Expressed in the cerebellum, trapezoid body, ventral
CC nucleus of the lateral lamniscus and in areas of the auditory hindbrain
CC such as the cochlear nucleus, lateral superior olive and medial nucleus
CC of the trapezoid body (PubMed:17977745). Expressed in the modiolar
CC nerve root and in the cochlear in a small group of bushy neurons within
CC the acoustic nerve (PubMed:17977745). Expressed weakly in the sensory
CC epithelia of the saccule and utricle (PubMed:17977745).
CC {ECO:0000269|PubMed:17977745, ECO:0000269|PubMed:26392540}.
CC -!- DEVELOPMENTAL STAGE: Expression initiates at 11 dpc in the central
CC optic cup and is detected in retinal progenitor cells until birth
CC (PubMed:9806930). In addition to the eye, only expressed in the
CC developing tenth cranial ganglion between 13.5 dpc and 15.5 dpc
CC (PubMed:9806930). Expressed in the retina and faintly expressed in the
CC caudal rhombic lip and rostral rhombic lip at 12.5 dpc
CC (PubMed:17977745). Expressed in the presumptive ventral cochlear
CC nucleus and in initial axons emerging from the cochlear nucleus and
CC extending via the trapezoid body towards the ipsilateral lateral
CC superior olive at 14.5 dpc (PubMed:17977745). Expressed in the cochlear
CC duct epithelium between 14.5 dpc and 17.5 dpc (PubMed:17977745).
CC Expressed in the retina at 16.5 dpc (PubMed:17977745). Expressed in the
CC cochlear nucleus at 16.5 dpc and P8 (PubMed:17977745). Abundantly
CC expressed in the ventral cochlear nucleus and axons originating from
CC these cells that form branches in the lateral superior olive at 18.5dpc
CC (PubMed:17977745). {ECO:0000269|PubMed:17977745,
CC ECO:0000269|PubMed:9806930}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile but display multiple
CC optic abnormalities resulting in blindness (PubMed:11493566,
CC PubMed:11156601, PubMed:12451142, PubMed:26392540, PubMed:33712461).
CC Normal hindbrain morphology, however mice show disruption of brainstem
CC auditory signaling and binaural processing (PubMed:17977745). Loss of
CC retinal circadian rhythm photoentrainment, and decreased expression of
CC Opn5 (PubMed:12451142, PubMed:26392540). Loss of the retinohypothalamic
CC tract connecting the retina to the suprachiasmatic nuclei
CC (PubMed:12451142). Loss of axon bundles, optic nerves and chiasmata,
CC with a decreased thickness of the retinal inner plexiform layer and
CC inner nuclear layer (PubMed:11493566). Increase in cone photoreceptors
CC and decrease in dopaminergic amacrine cells in the ganglion cell layer
CC (PubMed:11493566, PubMed:33712461). Loss of retinal Pou4f2-expressing
CC retinal ganglion cells resulting in a decrease in the thickness of the
CC retinal cell layer and loss of the nerve fiber layer (PubMed:11493566,
CC PubMed:11156601). Significant reduction in RGCs and compensatory
CC increase in cone photoreceptors and neurogenic progenitor cells at 14.5
CC dpc (PubMed:33712461). The 1% of RGCs that survive into adulthood show
CC severe axon guidance defects and extend into the retina instead of
CC targeting the optic disk with only a few forming a rudimentary optic
CC nerve (PubMed:33712461). No observable RGC axonal terminals in the
CC brain and persistent retinal hyaloid vasculature into adulthood
CC (PubMed:33712461). In Atoh7 and Bax double knockout mice, significant
CC reduction in RGCs and compensatory increase in cone photoreceptor cells
CC and neurogenic retinal progenitor cells at 14.5 dpc, however there is
CC no difference in the number of RGCs derived from Atoh7-expressing cells
CC and cone photoreceptors during adulthood (PubMed:33712461). Reduced
CC light spatial receptive fields, slower light-driven responses and
CC reduced pupillary light response (PubMed:33712461).
CC {ECO:0000269|PubMed:11156601, ECO:0000269|PubMed:11493566,
CC ECO:0000269|PubMed:12451142, ECO:0000269|PubMed:17977745,
CC ECO:0000269|PubMed:26392540, ECO:0000269|PubMed:33712461,
CC ECO:0000269|PubMed:9806930}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF071223; AAC68868.1; -; mRNA.
DR EMBL; AF418923; AAL11912.1; -; Genomic_DNA.
DR EMBL; BC092234; AAH92234.1; -; mRNA.
DR CCDS; CCDS23896.1; -.
DR RefSeq; NP_058560.1; NM_016864.1.
DR AlphaFoldDB; Q9Z2E5; -.
DR SMR; Q9Z2E5; -.
DR STRING; 10090.ENSMUSP00000039801; -.
DR PhosphoSitePlus; Q9Z2E5; -.
DR PaxDb; Q9Z2E5; -.
DR PRIDE; Q9Z2E5; -.
DR Antibodypedia; 28437; 223 antibodies from 26 providers.
DR DNASU; 53404; -.
DR Ensembl; ENSMUST00000044059; ENSMUSP00000039801; ENSMUSG00000036816.
DR GeneID; 53404; -.
DR KEGG; mmu:53404; -.
DR UCSC; uc007fjv.1; mouse.
DR CTD; 220202; -.
DR MGI; MGI:1355553; Atoh7.
DR VEuPathDB; HostDB:ENSMUSG00000036816; -.
DR eggNOG; KOG4395; Eukaryota.
DR GeneTree; ENSGT00940000161556; -.
DR HOGENOM; CLU_145503_0_0_1; -.
DR InParanoid; Q9Z2E5; -.
DR OMA; WVSLHCE; -.
DR OrthoDB; 1453771at2759; -.
DR PhylomeDB; Q9Z2E5; -.
DR TreeFam; TF315153; -.
DR BioGRID-ORCS; 53404; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Atoh7; mouse.
DR PRO; PR:Q9Z2E5; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9Z2E5; protein.
DR Bgee; ENSMUSG00000036816; Expressed in urethra and 50 other tissues.
DR Genevisible; Q9Z2E5; MM.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IMP:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
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; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IMP:MGI.
DR GO; GO:0009649; P:entrainment of circadian clock; IMP:MGI.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IMP: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; ISO:MGI.
DR GO; GO:1902336; P:positive regulation of retinal ganglion cell axon guidance; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0010996; P:response to auditory stimulus; IMP: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 2: Evidence at transcript level;
KW Cell projection; Developmental protein; Differentiation; DNA-binding;
KW Neurogenesis; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..149
FT /note="Transcription factor Atoh7"
FT /id="PRO_0000292407"
FT DOMAIN 41..93
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
SQ SEQUENCE 149 AA; 16569 MW; DF78A25190B5FD3A CRC64;
MKSACKPHGP PAGARGAPPC AGAAERAVSC AGPGRLESAA RRRLAANARE RRRMQGLNTA
FDRLRRVVPQ WGQDKKLSKY ETLQMALSYI IALTRILAEA ERDWVGLRCE QRGRDHPYLP
FPGARLQVDP EPYGQRLFGF QPEPFPMAS
