ID   FOXN1_MOUSE             Reviewed;         648 AA.
AC   Q61575;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   27-MAR-2024, entry version 181.
DE   RecName: Full=Forkhead box protein N1;
DE   AltName: Full=Hepatocyte nuclear factor 3 forkhead homolog 11;
DE            Short=HFH-11;
DE            Short=HNF-3/forkhead homolog 11;
DE   AltName: Full=Winged-helix transcription factor nude;
GN   Name=Foxn1; Synonyms=Fkh19, Hfh11, Whn;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND INVOLVEMENT IN NUDE PHENOTYPE.
RC   STRAIN=BALB/cJ; TISSUE=Skin;
RX   PubMed=7969402; DOI=10.1038/372103a0;
RA   Nehls M., Pfeifer D., Schorpp M., Hedrich H., Boehm T.;
RT   "New member of the winged-helix protein family disrupted in mouse and rat
RT   nude mutations.";
RL   Nature 372:103-107(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ; TISSUE=Skin, and Thymus;
RX   PubMed=9321431; DOI=10.1007/s002510050312;
RA   Schorpp M., Hofmann M., Dear T.N., Boehm T.;
RT   "Characterization of mouse and human nude genes.";
RL   Immunogenetics 46:509-515(1997).
RN   [3]
RP   INVOLVEMENT IN NUDE PHENOTYPE.
RX   PubMed=2288204; DOI=10.1159/000146996;
RA   Kopf-Maier P., Mboneko V.F., Merker H.J.;
RT   "Nude mice are not hairless. A morphological study.";
RL   Cells Tissues Organs 139:178-190(1990).
RN   [4]
RP   REVIEW.
RX   PubMed=16232301; DOI=10.1111/j.1600-0625.2005.00362.x;
RA   Mecklenburg L., Tychsen B., Paus R.;
RT   "Learning from nudity: lessons from the nude phenotype.";
RL   Exp. Dermatol. 14:797-810(2005).
RN   [5]
RP   FUNCTION.
RX   PubMed=17459087; DOI=10.1111/j.1432-0436.2007.00176.x;
RA   Li J., Baxter R.M., Weiner L., Goetinck P.F., Calautti E., Brissette J.L.;
RT   "Foxn1 promotes keratinocyte differentiation by regulating the activity of
RT   protein kinase C.";
RL   Differentiation 75:694-701(2007).
RN   [6]
RP   FUNCTION.
RX   PubMed=19853842; DOI=10.1016/j.cellimm.2009.09.007;
RA   Mori K., Itoi M., Tsukamoto N., Amagai T.;
RT   "Foxn1 is essential for vascularization of the murine thymus anlage.";
RL   Cell. Immunol. 260:66-69(2010).
RN   [7]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=19955175; DOI=10.1074/jbc.m109.072124;
RA   Cheng L., Guo J., Sun L., Fu J., Barnes P.F., Metzger D., Chambon P.,
RA   Oshima R.G., Amagai T., Su D.M.;
RT   "Postnatal tissue-specific disruption of transcription factor FoxN1
RT   triggers acute thymic atrophy.";
RL   J. Biol. Chem. 285:5836-5847(2010).
RN   [8]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=21109991; DOI=10.1007/s00109-010-0700-8;
RA   Guo J., Rahman M., Cheng L., Zhang S., Tvinnereim A., Su D.M.;
RT   "Morphogenesis and maintenance of the 3D thymic medulla and prevention of
RT   nude skin phenotype require FoxN1 in pre- and post-natal K14 epithelium.";
RL   J. Mol. Med. 89:263-277(2011).
RN   [9]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=22072979; DOI=10.1371/journal.pgen.1002348;
RA   Nowell C.S., Bredenkamp N., Tetelin S., Jin X., Tischner C., Vaidya H.,
RA   Sheridan J.M., Stenhouse F.H., Heussen R., Smith A.J., Blackburn C.C.;
RT   "Foxn1 regulates lineage progression in cortical and medullary thymic
RT   epithelial cells but is dispensable for medullary sublineage divergence.";
RL   PLoS Genet. 7:E1002348-E1002348(2011).
RN   [10]
RP   REVIEW.
RX   PubMed=23091413; DOI=10.7150/ijbs.5033;
RA   Zhang Z., Burnley P., Coder B., Su D.M.;
RT   "Insights on FoxN1 biological significance and usages of the 'nude' mouse
RT   in studies of T-lymphopoiesis.";
RL   Int. J. Biol. Sci. 8:1156-1167(2012).
RN   [11]
RP   REVIEW.
RX   PubMed=23874334; DOI=10.3389/fimmu.2013.00187;
RA   Romano R., Palamaro L., Fusco A., Giardino G., Gallo V., Del Vecchio L.,
RA   Pignata C.;
RT   "FOXN1: a master regulator gene of thymic epithelial development program.";
RL   Front. Immunol. 4:187-187(2013).
RN   [12]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=24184560; DOI=10.4049/jimmunol.1202278;
RA   Zook E.C., Zhang S., Gerstein R.M., Witte P.L., Le P.T.;
RT   "Enhancing T lineage production in aged mice: a novel function of Foxn1 in
RT   the bone marrow niche.";
RL   J. Immunol. 191:5583-5593(2013).
CC   -!- FUNCTION: Transcriptional regulator which regulates the development,
CC       differentiation, and function of thymic epithelial cells (TECs) both in
CC       the prenatal and postnatal thymus. Acts as a master regulator of the
CC       TECs lineage development and is required from the onset of
CC       differentiation in progenitor TECs in the developing fetus to the final
CC       differentiation steps through which TECs mature to acquire their full
CC       functionality. Regulates, either directly or indirectly the expression
CC       of a variety of genes that mediate diverse aspects of thymus
CC       development and function, including MHC Class II, DLL4, CCL25, CTSL,
CC       CD40 and PAX1. Regulates the differentiation of the immature TECs into
CC       functional cortical TECs (cTECs) and medullary TECs (mTECs)
CC       (PubMed:22072979). Essential for maintenance of mTECs population in the
CC       postnatal thymus (PubMed:19955175). Involved in the morphogenesis and
CC       maintenance of the three-dimensional thymic microstructure which is
CC       necessary for a fully functional thymus (PubMed:21109991). Plays an
CC       important role in the maintenance of hematopoiesis and particularly T
CC       lineage progenitors within the bone marrow niche with age
CC       (PubMed:24184560). Essential for the vascularization of the thymus
CC       anlage (PubMed:19853842). Promotes the terminal differentiation of
CC       epithelial cells in the epidermis and hair follicles, partly by
CC       negatively regulating the activity of protein kinase C
CC       (PubMed:17459087). {ECO:0000269|PubMed:17459087,
CC       ECO:0000269|PubMed:19853842, ECO:0000269|PubMed:19955175,
CC       ECO:0000269|PubMed:21109991, ECO:0000269|PubMed:22072979,
CC       ECO:0000269|PubMed:24184560}.
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- TISSUE SPECIFICITY: Bone marrow (at protein level). Expressed in thymus
CC       and skin. {ECO:0000269|PubMed:24184560}.
CC   -!- DISEASE: Note=Defects in FOXN1 are the cause of the nude/severe
CC       combined immunodeficiency (SCID) phenotype which is characterized by
CC       athymia and hairlessness. Mice develop largely normal hair follicles
CC       and produce hair shafts. However, presumably because of a lack of
CC       certain hair keratins, the hair shafts that are generated twist and
CC       coil in the hair follicle infundibulum, which becomes dilated. Since
CC       hair shafts fail to penetrate the epidermis, macroscopic nudity results
CC       and generates the grossly misleading impression that nude mice are
CC       hairless. {ECO:0000269|PubMed:2288204, ECO:0000269|PubMed:7969402}.
CC   -!- DISRUPTION PHENOTYPE: Mice exhibit nude skin phenotype and acute thymic
CC       atrophy with a severe early block in thymic epithelial cells (TECs)
CC       differentiation. A more severe deterioration seen in medullary thymic
CC       epithelial cells (mTECs) than in cortical thymic epithelial cells
CC       (cTECs). {ECO:0000269|PubMed:19955175, ECO:0000269|PubMed:21109991,
CC       ECO:0000269|PubMed:22072979}.
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DR   EMBL; X81593; CAA57279.1; -; mRNA.
DR   CCDS; CCDS25102.1; -.
DR   RefSeq; NP_032264.1; NM_008238.2.
DR   RefSeq; XP_006532327.2; XM_006532264.2.
DR   RefSeq; XP_006532329.1; XM_006532266.3.
DR   RefSeq; XP_017169774.1; XM_017314285.1.
DR   RefSeq; XP_017169775.1; XM_017314286.1.
DR   RefSeq; XP_017169776.1; XM_017314287.1.
DR   RefSeq; XP_017169777.1; XM_017314288.1.
DR   RefSeq; XP_017169778.1; XM_017314289.1.
DR   RefSeq; XP_017169779.1; XM_017314290.1.
DR   RefSeq; XP_017169780.1; XM_017314291.1.
DR   RefSeq; XP_017169781.1; XM_017314292.1.
DR   AlphaFoldDB; Q61575; -.
DR   SMR; Q61575; -.
DR   STRING; 10090.ENSMUSP00000103929; -.
DR   iPTMnet; Q61575; -.
DR   PhosphoSitePlus; Q61575; -.
DR   MaxQB; Q61575; -.
DR   PaxDb; 10090-ENSMUSP00000103929; -.
DR   ProteomicsDB; 267400; -.
DR   Pumba; Q61575; -.
DR   Antibodypedia; 14085; 319 antibodies from 36 providers.
DR   DNASU; 15218; -.
DR   Ensembl; ENSMUST00000108294.2; ENSMUSP00000103929.2; ENSMUSG00000002057.5.
DR   GeneID; 15218; -.
DR   KEGG; mmu:15218; -.
DR   UCSC; uc007kjd.2; mouse.
DR   AGR; MGI:102949; -.
DR   CTD; 8456; -.
DR   MGI; MGI:102949; Foxn1.
DR   VEuPathDB; HostDB:ENSMUSG00000002057; -.
DR   eggNOG; KOG2294; Eukaryota.
DR   GeneTree; ENSGT00940000158029; -.
DR   HOGENOM; CLU_031768_1_0_1; -.
DR   InParanoid; Q61575; -.
DR   OMA; SHSLCEP; -.
DR   OrthoDB; 5385885at2759; -.
DR   PhylomeDB; Q61575; -.
DR   TreeFam; TF329867; -.
DR   BioGRID-ORCS; 15218; 3 hits in 80 CRISPR screens.
DR   ChiTaRS; Foxn1; mouse.
DR   PRO; PR:Q61575; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; Q61575; Protein.
DR   Bgee; ENSMUSG00000002057; Expressed in pharyngeal epithelium and 54 other cell types or tissues.
DR   ExpressionAtlas; Q61575; baseline and differential.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:NTNU_SB.
DR   GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR   GO; GO:0048514; P:blood vessel morphogenesis; IMP:UniProtKB.
DR   GO; GO:0008544; P:epidermis development; IMP:MGI.
DR   GO; GO:0001942; P:hair follicle development; IMP:MGI.
DR   GO; GO:0030097; P:hemopoiesis; IMP:UniProtKB.
DR   GO; GO:0030216; P:keratinocyte differentiation; IDA:MGI.
DR   GO; GO:0002260; P:lymphocyte homeostasis; IMP:MGI.
DR   GO; GO:0097535; P:lymphoid lineage cell migration into thymus; IMP:UniProtKB.
DR   GO; GO:0035878; P:nail development; IMP:MGI.
DR   GO; GO:0030858; P:positive regulation of epithelial cell differentiation; ISO:MGI.
DR   GO; GO:0051798; P:positive regulation of hair follicle development; IMP:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:NTNU_SB.
DR   GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR   GO; GO:1902232; P:regulation of positive thymic T cell selection; IMP:UniProtKB.
DR   GO; GO:0033081; P:regulation of T cell differentiation in thymus; IMP:MGI.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0043029; P:T cell homeostasis; IMP:UniProtKB.
DR   GO; GO:0002360; P:T cell lineage commitment; IMP:UniProtKB.
DR   GO; GO:0048538; P:thymus development; IMP:MGI.
DR   GO; GO:0097536; P:thymus epithelium morphogenesis; IMP:UniProtKB.
DR   CDD; cd20056; FH_FOXN1; 1.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1.
DR   InterPro; IPR047401; FH_FOXN1.
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; FORKHEAD BOX PROTEIN N1; 1.
DR   PANTHER; PTHR46721:SF1; 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; Q61575; MM.
PE   1: Evidence at protein level;
KW   Developmental protein; Differentiation; DNA-binding; Nucleus;
KW   Reference proteome; Transcription; Transcription regulation.
FT   CHAIN           1..648
FT                   /note="Forkhead box protein N1"
FT                   /id="PRO_0000091867"
FT   DNA_BIND        271..367
FT                   /note="Fork-head"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT   REGION          1..95
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          392..432
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          457..521
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          629..648
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..15
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        57..71
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   648 AA;  69245 MW;  7A75411BDE2B23E5 CRC64;
     MVSLLPPQSD VTLPGSTRLE GEPQGDLMQA PGLPDSPAPQ NKHANFSCSS FVPDGPPERT
     PSLPPHSPSI ASPDPEQIQG HCTAGPGPGS FRLSPSEKYP GFGFEEGPAG SPGRFLKGNH
     MPFHPYKRHF HEDIFSEAQT AMALDGHSFK TQGALEAFEE IPVDMGDAEA FLPSFPAEAW
     CNKLPYPSQE HNQILQGSEV KVKPQALDSG PGMYCYQPPL QHMYCSSQPA FHQYSPGGGS
     YPVPYLGSPH YPYQRIAPQA NAEGHQPLFP KPIYSYSILI FMALKNSKTG SLPVSEIYNF
     MTEHFPYFKT APDGWKNSVR HNLSLNKCFE KVENKSGSSS RKGCLWALNP SKIDKMQEEL
     QKWKRKDPIA VRKSMAKPEE LDSLIGDKRE KLGSPLLGCP PPGLAGPGPI RPMAPSAGLS
     QPLHPMHPAP GPMPGKNPLQ DLLGGHAPSC YGQTYPHLSP SLAPSGHQQP LFPQPDGHLE
     LQAQPGTPQD SPLPAHTPPS HGAKLMAEPS SARTMHDTLL PDGDLGTDLD AINPSLTDFD
     FQGNLWEQLK DDSLALDPLV LVTSSPTSSS MLPPPPAAHC FPPGPCLAET GNEAGELAPP
     GSGGSGALGD MHLSTLYSAF VELESTPSSA AAGPAVYLSP GSKPLALA
//