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 04-FEB-2015, entry version 69. 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 Cyprinidae; 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, RP AND 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., RA Muffato M., Collins J.E., Humphray S., McLaren K., Matthews L., RA McLaren S., Sealy I., Caccamo M., Churcher C., Scott C., Barrett J.C., RA Koch R., Rauch G.J., White S., Chow W., Kilian B., Quintais L.T., RA Guerra-Assuncao J.A., Zhou Y., Gu Y., Yen J., Vogel J.H., Eyre T., RA Redmond S., Banerjee R., Chi J., Fu B., Langley E., Maguire S.F., RA Laird G.K., Lloyd D., Kenyon E., Donaldson S., Sehra H., RA 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., Eliott D., Threadgold G., RA Harden G., Ware D., Mortimer B., Kerry G., Heath P., Phillimore B., RA Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S., Pelan S., RA Griffiths G., Smith M., Glithero R., Howden P., Barker N., Stevens C., RA Harley J., Holt K., Panagiotidis G., Lovell J., Beasley H., RA Henderson C., Gordon D., Auger K., Wright D., Collins J., Raisen C., RA 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., RA Babbage A., Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., RA Wray P., Ellington A., Matthews N., Ellwood M., Woodmansey R., RA Clark G., Cooper J., Tromans A., Grafham D., Skuce C., Pandian R., RA Andrews R., Harrison E., Kimberley A., Garnett J., Fosker N., Hall R., RA Garner P., Kelly D., Bird C., Palmer S., Gehring I., Berger A., RA Dooley C.M., Ersan-Urun Z., Eser C., Geiger H., Geisler M., RA Karotki L., Kirn A., Konantz J., Konantz M., Oberlander M., RA Rudolph-Geiger S., Teucke M., Osoegawa K., Zhu B., Rapp A., Widaa S., RA Langford C., Yang F., Carter N.P., Harrow J., Ning Z., Herrero J., RA Searle S.M., Enright A., Geisler R., Plasterk R.H., Lee C., RA Westerfield M., de Jong P.J., Zon L.I., Postlethwait J.H., RA Nusslein-Volhard C., Hubbard T.J., Roest Crollius H., Rogers J., RA Stemple D.L.; RT "The zebrafish reference genome sequence and its relationship to the RT human 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- CC neural tissues development. Binds to an 11-bp consensus sequence CC containing the invariant tetranucleotide 5'-ACGC-3'. During CC development of the central nervous system, required to specify the CC amacrine and horizontal cell fates from multipotent retinal CC progenitors while suppressing the alternative photoreceptor cell CC fates. Drives commitment of p2 progenitors to the V2b interneuron CC fates during spinal cord neurogenesis. In development of non- CC neural tissues, plays an essential role in the specification of CC the atrioventricular canal. {ECO:0000269|PubMed:18347092}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE- CC 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 CC adult brain and embryo. Prominent expression sites include the CC olfactory placode, the basal layer of the olfactory epithelium, CC the neuroepithelium of the developing retina, the germinal zone of CC the differentiated eye, regions of motoneuron development in the CC neural 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 CC edema due to dysmorphic hearts that fail to loop and form and CC atrioventricular (AV) canal. Hearts show continues peristatic CC pumping rather than coordinated and sequential beating of atrial CC and ventricular chambers. Endocardial cells remain squamous and AV CC myocardial cell shape fail to occur. CC {ECO:0000269|PubMed:18347092}. CC -!- SIMILARITY: Contains 1 fork-head DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00089}. 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_005165099.2. [A2BGM5-1] DR RefSeq; XP_009299558.1; XM_009301283.1. [A2BGM5-3] DR UniGene; Dr.81266; -. DR ProteinModelPortal; A2BGM5; -. DR Ensembl; ENSDART00000008994; ENSDARP00000020367; ENSDARG00000010591. [A2BGM5-1] DR GeneID; 30315; -. DR KEGG; dre:30315; -. DR CTD; 121643; -. DR ZFIN; ZDB-GENE-990415-277; foxn4. DR eggNOG; COG5025; -. DR GeneTree; ENSGT00780000121868; -. DR HOGENOM; HOG000232153; -. DR HOVERGEN; HBG051655; -. DR InParanoid; A2BGM5; -. DR KO; K09407; -. DR OMA; MAVHSSQ; -. DR OrthoDB; EOG77T146; -. DR TreeFam; TF329867; -. DR NextBio; 20806754; -. DR PRO; PR:A2BGM5; -. DR Proteomes; UP000000437; Chromosome 5. DR Bgee; Q90X68; -. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB. DR GO; GO:0001158; F:enhancer sequence-specific DNA binding; ISS:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:ZFIN. DR GO; GO:0000981; F:sequence-specific DNA binding RNA polymerase II transcription factor activity; IBA:GO_Central. DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; ISS:UniProtKB. 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:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB. DR GO; GO:0008016; P:regulation of heart contraction; IMP:UniProtKB. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IBA:GO_Central. 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:0006366; P:transcription from RNA polymerase II promoter; IBA:GOC. DR GO; GO:0060579; P:ventral spinal cord interneuron fate commitment; ISS:UniProtKB. DR Gene3D; 1.10.10.10; -; 1. DR InterPro; IPR001766; TF_fork_head. DR InterPro; IPR018122; TF_fork_head_CS. DR InterPro; IPR011991; WHTH_DNA-bd_dom. DR Pfam; PF00250; Fork_head; 1. DR PRINTS; PR00053; FORKHEAD. DR SMART; SM00339; FH; 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; Complete proteome; Developmental protein; KW DNA-binding; Neurogenesis; Nucleus; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1 550 Forkhead box protein N4. FT /FTId=PRO_0000428907. FT DNA_BIND 231 327 Fork-head. {ECO:0000255|PROSITE- FT ProRule:PRU00089}. FT VAR_SEQ 1 139 Missing (in isoform 3). FT {ECO:0000303|PubMed:15464224}. FT /FTId=VSP_054326. FT VAR_SEQ 1 134 MTVQSKLQGRGKFKKRFFRAGQQVPRPTLELSSVWLSKIFY FT NPEQHHNKQKMIESGITTRMSGIHENPGQSHHTSAQDYRLL FT TTDPSQLKDELPGDLQSLSWLTSVDVPRLQQIGGGRPDFTS FT SAQSSLLERQT -> MAP (in isoform 2). FT {ECO:0000303|PubMed:15464224}. FT /FTId=VSP_054327. FT CONFLICT 8 8 Q -> H (in Ref. 1; CAB64948, 2; AAG27086 FT and 4; AAI28812). {ECO:0000305}. FT CONFLICT 39 39 I -> V (in Ref. 1; CAB64948). FT {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 //