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   29-OCT-2014, entry version 66.
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_005165099.1. [A2BGM5-1]
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; ENSGT00760000118794; -.
DR   HOGENOM; HOG000232153; -.
DR   HOVERGEN; HBG051655; -.
DR   InParanoid; A2BGM5; -.
DR   KO; K09407; -.
DR   OMA; PSPQEYR; -.
DR   OrthoDB; EOG77T146; -.
DR   TreeFam; TF329867; -.
DR   NextBio; 20806754; -.
DR   PRO; PR:A2BGM5; -.
DR   Bgee; Q90X68; -.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005667; C:transcription factor complex; IBA:RefGenome.
DR   GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR   GO; GO:0008301; F:DNA binding, bending; IBA:RefGenome.
DR   GO; GO:0003690; F:double-stranded DNA binding; IBA:RefGenome.
DR   GO; GO:0001158; F:enhancer sequence-specific DNA binding; ISS:UniProtKB.
DR   GO; GO:0003705; F:RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity; IBA:RefGenome.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:ZFIN.
DR   GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; ISS:UniProtKB.
DR   GO; GO:0008134; F:transcription factor binding; IBA:RefGenome.
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:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IBA:RefGenome.
DR   GO; GO:0048513; P:organ development; IBA:RefGenome.
DR   GO; GO:0007389; P:pattern specification process; IBA:RefGenome.
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:0051090; P:regulation of sequence-specific DNA binding transcription factor activity; IBA:RefGenome.
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:0009888; P:tissue development; IBA:RefGenome.
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
//