FOXN4_HUMAN
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 03-AUG-2022, entry version 162.
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; Q96NZ1; -.
DR PeptideAtlas; Q96NZ1; -.
DR PRIDE; Q96NZ1; -.
DR ProteomicsDB; 77580; -. [Q96NZ1-1]
DR Antibodypedia; 30846; 200 antibodies from 23 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 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; 438804at2759; -.
DR PhylomeDB; Q96NZ1; -.
DR TreeFam; TF329867; -.
DR PathwayCommons; Q96NZ1; -.
DR SignaLink; Q96NZ1; -.
DR SIGNOR; Q96NZ1; -.
DR BioGRID-ORCS; 121643; 17 hits in 1090 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 88 other tissues.
DR ExpressionAtlas; Q96NZ1; baseline and differential.
DR Genevisible; Q96NZ1; HS.
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:0008016; P:regulation of heart contraction; ISS: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:0021514; P:ventral spinal cord interneuron differentiation; 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 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
