ID   FOXN4_HUMAN             Reviewed;         517 AA.
AC   Q96NZ1; Q6ZMR4; Q96NZ0;
DT   27-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2005, sequence version 2.
DT   27-MAR-2024, entry version 171.
DE   RecName: Full=Forkhead box protein N4;
GN   Name=FOXN4;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16541075; DOI=10.1038/nature04569;
RA   Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA   Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA   Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA   Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA   Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA   Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA   Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA   Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA   Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA   Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA   Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA   Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA   Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA   Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA   Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA   Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA   Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA   David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA   D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA   Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA   Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA   Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA   LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA   Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA   Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA   Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA   Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA   Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA   Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA   Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA   Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA   Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA   Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA   Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA   Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA   Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA   Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA   Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA   Gibbs R.A.;
RT   "The finished DNA sequence of human chromosome 12.";
RL   Nature 440:346-351(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 41-517 (ISOFORMS 1 AND 2).
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 MRNA] (ISOFORM 3).
RC   TISSUE=Brain;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
CC   -!- FUNCTION: Transcription factor essential for neural and some non-neural
CC       tissues development, such as retina and lung respectively. Binds to an
CC       11-bp consensus sequence containing the invariant tetranucleotide 5'-
CC       ACGC-3'. During development of the central nervous system, is required
CC       to specify the amacrine and horizontal cell fates from multipotent
CC       retinal progenitors while suppressing the alternative photoreceptor
CC       cell fates through activating DLL4-NOTCH signaling. Also acts
CC       synergistically with ASCL1/MASH1 to activate DLL4-NOTCH signaling and
CC       drive commitment of p2 progenitors to the V2b interneuron fates during
CC       spinal cord neurogenesis. In development of non-neural tissues, plays
CC       an essential role in the specification of the atrioventricular canal
CC       and is indirectly required for patterning the distal airway during lung
CC       development (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q96NZ1; P54253: ATXN1; NbExp=3; IntAct=EBI-11749712, EBI-930964;
CC       Q96NZ1; Q13643: FHL3; NbExp=4; IntAct=EBI-11749712, EBI-741101;
CC       Q96NZ1; P48378: RFX2; NbExp=3; IntAct=EBI-11749712, EBI-746731;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00089}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q96NZ1-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q96NZ1-2; Sequence=VSP_017227, VSP_017228, VSP_017229;
CC       Name=3;
CC         IsoId=Q96NZ1-3; Sequence=VSP_054325;
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DR   EMBL; AC012384; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AF425596; AAL23949.1; -; mRNA.
DR   EMBL; AF425597; AAL23950.1; -; mRNA.
DR   EMBL; AK131519; BAD18661.1; -; mRNA.
DR   CCDS; CCDS9126.2; -. [Q96NZ1-1]
DR   RefSeq; NP_998761.2; NM_213596.2. [Q96NZ1-1]
DR   AlphaFoldDB; Q96NZ1; -.
DR   SMR; Q96NZ1; -.
DR   BioGRID; 125742; 30.
DR   IntAct; Q96NZ1; 6.
DR   STRING; 9606.ENSP00000299162; -.
DR   iPTMnet; Q96NZ1; -.
DR   PhosphoSitePlus; Q96NZ1; -.
DR   BioMuta; FOXN4; -.
DR   DMDM; 71153520; -.
DR   MassIVE; Q96NZ1; -.
DR   MaxQB; Q96NZ1; -.
DR   PaxDb; 9606-ENSP00000299162; -.
DR   PeptideAtlas; Q96NZ1; -.
DR   ProteomicsDB; 77580; -. [Q96NZ1-1]
DR   Antibodypedia; 30846; 231 antibodies from 24 providers.
DR   DNASU; 121643; -.
DR   Ensembl; ENST00000299162.10; ENSP00000299162.5; ENSG00000139445.18. [Q96NZ1-1]
DR   Ensembl; ENST00000355216.5; ENSP00000347354.1; ENSG00000139445.18. [Q96NZ1-3]
DR   GeneID; 121643; -.
DR   KEGG; hsa:121643; -.
DR   MANE-Select; ENST00000299162.10; ENSP00000299162.5; NM_213596.3; NP_998761.2.
DR   UCSC; uc001toe.5; human. [Q96NZ1-1]
DR   AGR; HGNC:21399; -.
DR   CTD; 121643; -.
DR   DisGeNET; 121643; -.
DR   GeneCards; FOXN4; -.
DR   HGNC; HGNC:21399; FOXN4.
DR   HPA; ENSG00000139445; Tissue enriched (testis).
DR   MIM; 609429; gene.
DR   neXtProt; NX_Q96NZ1; -.
DR   OpenTargets; ENSG00000139445; -.
DR   PharmGKB; PA134982965; -.
DR   VEuPathDB; HostDB:ENSG00000139445; -.
DR   eggNOG; KOG2294; Eukaryota.
DR   GeneTree; ENSGT00940000158984; -.
DR   HOGENOM; CLU_031768_0_0_1; -.
DR   InParanoid; Q96NZ1; -.
DR   OMA; QCPTSVY; -.
DR   OrthoDB; 5385885at2759; -.
DR   PhylomeDB; Q96NZ1; -.
DR   TreeFam; TF329867; -.
DR   PathwayCommons; Q96NZ1; -.
DR   SignaLink; Q96NZ1; -.
DR   SIGNOR; Q96NZ1; -.
DR   BioGRID-ORCS; 121643; 18 hits in 1169 CRISPR screens.
DR   ChiTaRS; FOXN4; human.
DR   GenomeRNAi; 121643; -.
DR   Pharos; Q96NZ1; Tbio.
DR   PRO; PR:Q96NZ1; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q96NZ1; Protein.
DR   Bgee; ENSG00000139445; Expressed in ventricular zone and 90 other cell types or tissues.
DR   ExpressionAtlas; Q96NZ1; baseline and differential.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
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; IDA:UniProtKB.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR   GO; GO:0035881; P:amacrine cell differentiation; ISS:UniProtKB.
DR   GO; GO:0036302; P:atrioventricular canal development; ISS:UniProtKB.
DR   GO; GO:0001947; P:heart looping; ISS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0008016; P:regulation of heart contraction; ISS:UniProtKB.
DR   GO; GO:0010842; P:retina layer formation; ISS:UniProtKB.
DR   GO; GO:0021514; P:ventral spinal cord interneuron differentiation; ISS:UniProtKB.
DR   GO; GO:0060579; P:ventral spinal cord interneuron fate commitment; ISS:UniProtKB.
DR   CDD; cd20057; FH_FOXN4; 1.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1.
DR   InterPro; IPR001766; Fork_head_dom.
DR   InterPro; IPR049624; FOXN1_4.
DR   InterPro; IPR030456; TF_fork_head_CS_2.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   InterPro; IPR036390; WH_DNA-bd_sf.
DR   PANTHER; PTHR46721:SF3; FORK-HEAD DOMAIN-CONTAINING PROTEIN; 1.
DR   PANTHER; PTHR46721; FORKHEAD BOX PROTEIN N1; 1.
DR   Pfam; PF00250; Forkhead; 1.
DR   PRINTS; PR00053; FORKHEAD.
DR   SMART; SM00339; FH; 1.
DR   SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
DR   PROSITE; PS00658; FORK_HEAD_2; 1.
DR   PROSITE; PS50039; FORK_HEAD_3; 1.
DR   Genevisible; Q96NZ1; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Developmental protein; DNA-binding; Neurogenesis;
KW   Nucleus; Reference proteome; Transcription; Transcription regulation.
FT   CHAIN           1..517
FT                   /note="Forkhead box protein N4"
FT                   /id="PRO_0000091870"
FT   DNA_BIND        193..289
FT                   /note="Fork-head"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT   REGION          365..398
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          497..517
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        376..398
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..198
FT                   /note="MIESDTSSIMSGIIRNSGQNHHPSPQEYRLLATTSDDDLPGDLQSLSWLTAV
FT                   DVPRLQQMASGRVDLGGPCVPHPHPGALAGVADLHVGATPSPLLHGPAGMAPRGMPGLG
FT                   PITGHRDSMSQFPVGGQPSSGLQDPPHLYSPATQPQFPLPPGAQQCPPVGLYGPPFGVR
FT                   PPYPQPHVAVHSSQELHPKHYPKPIYSY -> MPGLPCPALPCPAPPPAP (in
FT                   isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_054325"
FT   VAR_SEQ         119
FT                   /note="S -> SQ (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15464224"
FT                   /id="VSP_017227"
FT   VAR_SEQ         157..257
FT                   /note="CPPVGLYGPPFGVRPPYPQPHVAVHSSQELHPKHYPKPIYSYSCLIAMALKN
FT                   SKTGSLPVSEIYSFMKEHFPYFKTAPDGWKNSVRHNLSLNKCFEKVENK -> LSDRHG
FT                   PEEQQDRQPACERDLQLHEGALPLLQDGPRRVEELGAAQPVSEQVLREGGEQDERLLPQ
FT                   GLPVGSEPGPHRQDGGGDAQVEEEGPGCHPPEYGQP (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15464224"
FT                   /id="VSP_017228"
FT   VAR_SEQ         258..517
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15464224"
FT                   /id="VSP_017229"
FT   VARIANT         137
FT                   /note="P -> L (in dbSNP:rs11609341)"
FT                   /id="VAR_059300"
SQ   SEQUENCE   517 AA;  55215 MW;  D4150E6C4F1363EF CRC64;
     MIESDTSSIM SGIIRNSGQN HHPSPQEYRL LATTSDDDLP GDLQSLSWLT AVDVPRLQQM
     ASGRVDLGGP CVPHPHPGAL AGVADLHVGA TPSPLLHGPA GMAPRGMPGL GPITGHRDSM
     SQFPVGGQPS SGLQDPPHLY SPATQPQFPL PPGAQQCPPV GLYGPPFGVR PPYPQPHVAV
     HSSQELHPKH YPKPIYSYSC LIAMALKNSK TGSLPVSEIY SFMKEHFPYF KTAPDGWKNS
     VRHNLSLNKC FEKVENKMSG SSRKGCLWAL NLARIDKMEE EMHKWKRKDL AAIHRSMANP
     EELDKLISDR PESCRRPGKP GEPEAPVLTH ATTVAVAHGC LAVSQLPPQP LMTLSLQSVP
     LHHQVQPQAH LAPDSPAPAQ TPPLHALPDL SPSPLPHPAM GRAPVDFINI STDMNTEVDA
     LDPSIMDFAL QGNLWEEMKD EGFSLDTLGA FADSPLGCDL GASGLTPASG GSDQSFPDLQ
     VTGLYTAYST PDSVAASGTS SSSQYLGAQG NKPIALL
//