FOXN4_DANRE
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 03-AUG-2022, entry version 110.
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}.
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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 AlphaFoldDB; A2BGM5; -.
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; QCPTSVY; -.
DR OrthoDB; 438804at2759; -.
DR PhylomeDB; A2BGM5; -.
DR TreeFam; TF329867; -.
DR PRO; PR:A2BGM5; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 5.
DR Bgee; ENSDARG00000010591; Expressed in face and 29 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 REGION 402..437
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 422..437
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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
