ID FOXN4_DANRE Reviewed; 550 AA. AC A2BGM5; Q8UVH2; Q90X68; Q9DG30; Q9PT94; DT 14-MAY-2014, integrated into UniProtKB/Swiss-Prot. DT 20-FEB-2007, sequence version 1. DT 10-FEB-2021, entry version 106. DE RecName: Full=Forkhead box protein N4; GN Name=foxn4; Synonyms=sli, slipjig; OS Danio rerio (Zebrafish) (Brachydanio rerio). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes; OC Danionidae; Danioninae; Danio. OX NCBI_TaxID=7955; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=11054532; DOI=10.1016/s0378-1119(00)00344-9; RA Schlake T., Schorpp M., Boehm T.; RT "Formation of regulator/target gene relationships during evolution."; RL Gene 256:29-34(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), DEVELOPMENTAL STAGE, AND RP TISSUE SPECIFICITY. RC STRAIN=Tuebingen; TISSUE=Thymus; RX PubMed=15464224; DOI=10.1016/j.devbrainres.2004.05.014; RA Danilova N., Visel A., Willett C.E., Steiner L.A.; RT "Expression of the winged helix/forkhead gene, foxn4, during zebrafish RT development."; RL Brain Res. Dev. Brain Res. 153:115-119(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Tuebingen; RX PubMed=23594743; DOI=10.1038/nature12111; RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M., RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I., RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J., RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y., RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B., RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S., RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M., RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J., RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G., RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P., RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S., RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N., RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J., RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J., RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D., RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S., RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E., RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A., RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P., RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J., RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E., RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C., RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C., RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M., RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G., RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F., RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M., RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M., RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C., RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.; RT "The zebrafish reference genome sequence and its relationship to the human RT genome."; RL Nature 496:498-503(2013). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Kidney; RG NIH - Zebrafish Gene Collection (ZGC) project; RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases. RN [5] RP FUNCTION IN HEART DEVELOPMENT, DISRUPTION PHENOTYPE, AND DNA-BINDING. RX PubMed=18347092; DOI=10.1101/gad.1629408; RA Chi N.C., Shaw R.M., De Val S., Kang G., Jan L.Y., Black B.L., RA Stainier D.Y.; RT "Foxn4 directly regulates tbx2b expression and atrioventricular canal RT formation."; RL Genes Dev. 22:734-739(2008). CC -!- FUNCTION: Transcription factor essential for neural and some non-neural CC tissues development. Binds to an 11-bp consensus sequence containing CC the invariant tetranucleotide 5'-ACGC-3'. During development of the CC central nervous system, required to specify the amacrine and horizontal CC cell fates from multipotent retinal progenitors while suppressing the CC alternative photoreceptor cell fates. Drives commitment of p2 CC progenitors to the V2b interneuron fates during spinal cord CC neurogenesis. In development of non-neural tissues, plays an essential CC role in the specification of the atrioventricular canal. CC {ECO:0000269|PubMed:18347092}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00089}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage; Named isoforms=3; CC Name=1; CC IsoId=A2BGM5-1; Sequence=Displayed; CC Name=2; CC IsoId=A2BGM5-2; Sequence=VSP_054327; CC Name=3; CC IsoId=A2BGM5-3; Sequence=VSP_054326; CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed mainly in adult thymus. CC Isoform 2 is detected in adult skin. Isoform 3 is expressed in adult CC brain and embryo. Prominent expression sites include the olfactory CC placode, the basal layer of the olfactory epithelium, the CC neuroepithelium of the developing retina, the germinal zone of the CC differentiated eye, regions of motoneuron development in the neural CC tube and periventricular regions of the brain. CC {ECO:0000269|PubMed:15464224}. CC -!- DEVELOPMENTAL STAGE: In embryo, expressed ubiquitously, but with CC decreasing intensity, from the one-cell through gastrula stages. CC {ECO:0000269|PubMed:15464224}. CC -!- DISRUPTION PHENOTYPE: At 36-48 hpf, mutants exhibit pericardial edema CC due to dysmorphic hearts that fail to loop and form and CC atrioventricular (AV) canal. Hearts show continues peristatic pumping CC rather than coordinated and sequential beating of atrial and CC ventricular chambers. Endocardial cells remain squamous and AV CC myocardial cell shape fail to occur. {ECO:0000269|PubMed:18347092}. 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; AJ252024; CAB64948.1; -; mRNA. DR EMBL; AF198446; AAG27086.2; -; mRNA. DR EMBL; AF424786; AAL17865.1; -; mRNA. DR EMBL; AF443870; AAL38028.1; -; mRNA. DR EMBL; BX510366; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BX510917; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC128811; AAI28812.1; -; mRNA. DR RefSeq; NP_571174.1; NM_131099.2. DR RefSeq; XP_005165156.1; XM_005165099.3. [A2BGM5-1] DR RefSeq; XP_009299558.1; XM_009301283.1. [A2BGM5-3] DR SMR; A2BGM5; -. DR STRING; 7955.ENSDARP00000020367; -. DR PaxDb; A2BGM5; -. DR PeptideAtlas; A2BGM5; -. DR Ensembl; ENSDART00000008994; ENSDARP00000020367; ENSDARG00000010591. [A2BGM5-1] DR Ensembl; ENSDART00000163771; ENSDARP00000130721; ENSDARG00000010591. [A2BGM5-2] DR GeneID; 30315; -. DR KEGG; dre:30315; -. DR CTD; 121643; -. DR ZFIN; ZDB-GENE-990415-277; foxn4. DR eggNOG; KOG2294; Eukaryota. DR GeneTree; ENSGT00940000158984; -. DR InParanoid; A2BGM5; -. DR OMA; HPSPQDY; -. DR OrthoDB; 438804at2759; -. DR TreeFam; TF329867; -. DR PRO; PR:A2BGM5; -. DR Proteomes; UP000000437; Chromosome 5. DR Bgee; ENSDARG00000010591; Expressed in eye and 28 other tissues. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB. DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:ZFIN. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:ZFIN. DR GO; GO:0035881; P:amacrine cell differentiation; ISS:UniProtKB. DR GO; GO:0036302; P:atrioventricular canal development; IMP:UniProtKB. DR GO; GO:0001947; P:heart looping; IMP:UniProtKB. DR GO; GO:0003170; P:heart valve development; IMP:ZFIN. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:ZFIN. DR GO; GO:0008016; P:regulation of heart contraction; IMP:UniProtKB. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB. DR GO; GO:0010842; P:retina layer formation; ISS:UniProtKB. DR GO; GO:0060579; P:ventral spinal cord interneuron fate commitment; ISS:UniProtKB. DR CDD; cd00059; FH; 1. DR Gene3D; 1.10.10.10; -; 1. DR InterPro; IPR001766; Fork_head_dom. DR InterPro; IPR030456; TF_fork_head_CS_2. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. DR Pfam; PF00250; Forkhead; 1. DR PRINTS; PR00053; FORKHEAD. DR SMART; SM00339; FH; 1. DR SUPFAM; SSF46785; SSF46785; 1. DR PROSITE; PS00658; FORK_HEAD_2; 1. DR PROSITE; PS50039; FORK_HEAD_3; 1. PE 1: Evidence at protein level; KW Alternative promoter usage; Developmental protein; DNA-binding; KW Neurogenesis; Nucleus; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1..550 FT /note="Forkhead box protein N4" FT /id="PRO_0000428907" FT DNA_BIND 231..327 FT /note="Fork-head" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089" FT VAR_SEQ 1..139 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15464224" FT /id="VSP_054326" FT VAR_SEQ 1..134 FT /note="MTVQSKLQGRGKFKKRFFRAGQQVPRPTLELSSVWLSKIFYNPEQHHNKQKM FT IESGITTRMSGIHENPGQSHHTSAQDYRLLTTDPSQLKDELPGDLQSLSWLTSVDVPRL FT QQIGGGRPDFTSSAQSSLLERQT -> MAP (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15464224" FT /id="VSP_054327" FT CONFLICT 8 FT /note="Q -> H (in Ref. 1; CAB64948, 2; AAG27086 and 4; FT AAI28812)" FT /evidence="ECO:0000305" FT CONFLICT 39 FT /note="I -> V (in Ref. 1; CAB64948)" FT /evidence="ECO:0000305" SQ SEQUENCE 550 AA; 60968 MW; D030E6C2022B33C0 CRC64; MTVQSKLQGR GKFKKRFFRA GQQVPRPTLE LSSVWLSKIF YNPEQHHNKQ KMIESGITTR MSGIHENPGQ SHHTSAQDYR LLTTDPSQLK DELPGDLQSL SWLTSVDVPR LQQIGGGRPD FTSSAQSSLL ERQTAQLNSM TVAGGAGSAI HLQSEMQHSP LAINSMPQFS PGFPCAASVY QTAPQQVLTF TQANQQCSPG GLYGNYNSQN LFPQPRITAH SQDLQPKCFP KPIYSYSCLI AMALKNSKTG SLPVSEIYSF MKEHFPYFKT APDGWKNSVR HNLSLNKCFE KVENKMSGSS RKGCLWALNP AKIDKMEEEM QKWKRKDLPA IRRSMANPDE LDKLITDRPE SCRQKSVDPG MTRLPSCPPG QTLPLAAQMQ PQPVVTLSLQ CLPMHQHLQL QLQNQSRLAP SSPAPAQTPP LHTVPDMTNS SLPQHPAKQH TDFYTVHTDV NSEVDALDPS IMDFAWQGNL WEEMKDDSFN LEALGTLSNS PLRLSDCDLD TSSVTPVSSA GGLPYPDLQV TGLYSSYSAI DALSNQYMNT QGGTKPIVLL //