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Protein

Forkhead box protein N1

Gene

Foxn1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional regulator which regulates the development, differentiation, and function of thymic epithelial cells (TECs) both in the prenatal and postnatal thymus. Acts as a master regulator of the TECs lineage development and is required from the onset of differentiation in progenitor TECs in the developing fetus to the final differentiation steps through which TECs mature to acquire their full functionality. Regulates, either directly or indirectly the expression of a variety of genes that mediate diverse aspects of thymus development and function, including MHC Class II, DLL4, CCL25, CTSL, CD40 and PAX1. Regulates the differentiation of the immature TECs into functional cortical TECs (cTECs) and medullary TECs (mTECs) (PubMed:22072979). Essential for maintenance of mTECs population in the postnatal thymus (PubMed:19955175). Involved in the morphogenesis and maintenance of the three-dimensional thymic microstructure which is necessary for a fully functional thymus (PubMed:21109991). Plays an important role in the maintenance of hematopoiesis and particularly T lineage progenitors within the bone marrow niche with age (PubMed:24184560). Essential for the vascularization of the thymus anlage (PubMed:19853842). Promotes the terminal differentiation of epithelial cells in the epidermis and hair follicles, partly by negatively regulating the activity of protein kinase C (PubMed:17459087).6 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi271 – 36797Fork-headPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. sequence-specific DNA binding Source: InterPro
  2. sequence-specific DNA binding RNA polymerase II transcription factor activity Source: GO_Central

GO - Biological processi

  1. blood vessel morphogenesis Source: UniProtKB
  2. cell proliferation Source: UniProtKB
  3. epidermis development Source: MGI
  4. epithelial cell proliferation Source: UniProtKB
  5. hair follicle development Source: MGI
  6. hemopoiesis Source: UniProtKB
  7. keratinocyte differentiation Source: MGI
  8. lymphocyte homeostasis Source: MGI
  9. lymphoid lineage cell migration into thymus Source: UniProtKB
  10. nail development Source: MGI
  11. positive regulation of hair follicle development Source: UniProtKB
  12. regulation of gene expression Source: MGI
  13. regulation of positive thymic T cell selection Source: UniProtKB
  14. regulation of T cell differentiation in thymus Source: MGI
  15. regulation of transcription from RNA polymerase II promoter Source: GO_Central
  16. T cell homeostasis Source: UniProtKB
  17. T cell lineage commitment Source: UniProtKB
  18. thymus development Source: MGI
  19. thymus epithelium morphogenesis Source: UniProtKB
  20. transcription from RNA polymerase II promoter Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein N1
Alternative name(s):
Hepatocyte nuclear factor 3 forkhead homolog 11
Short name:
HFH-11
Short name:
HNF-3/forkhead homolog 11
Winged-helix transcription factor nude
Gene namesi
Name:Foxn1
Synonyms:Fkh19, Hfh11, Whn
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 11

Organism-specific databases

MGIiMGI:102949. Foxn1.

Subcellular locationi

GO - Cellular componenti

  1. nucleus Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in FOXN1 are the cause of the nude/severe combined immunodeficiency (SCID) phenotype which is characterized by athymia and hairlessness. Mice develop largely normal hair follicles and produce hair shafts. However, presumably because of a lack of certain hair keratins, the hair shafts that are generated twist and coil in the hair follicle infundibulum, which becomes dilated. Since hair shafts fail to penetrate the epidermis, macroscopic nudity results and generates the grossly misleading impression that nude mice are hairless.

Disruption phenotypei

Mice exhibit nude skin phenotype and acute thymic atrophy with a severe early block in thymic epithelial cells (TECs) differentiation. A more severe deterioration seen in medullary thymic epithelial cells (mTECs) than in cortical thymic epithelial cells (cTECs).3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 648648Forkhead box protein N1PRO_0000091867Add
BLAST

Proteomic databases

MaxQBiQ61575.
PRIDEiQ61575.

PTM databases

PhosphoSiteiQ61575.

Expressioni

Tissue specificityi

Bone marrow (at protein level). Expressed in thymus and skin.1 Publication

Gene expression databases

BgeeiQ61575.
CleanExiMM_FOXN1.
ExpressionAtlasiQ61575. baseline and differential.
GenevestigatoriQ61575.

Structurei

3D structure databases

ProteinModelPortaliQ61575.
SMRiQ61575. Positions 271-351.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi573 – 5764Poly-Pro

Sequence similaritiesi

Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG5025.
GeneTreeiENSGT00780000121868.
HOGENOMiHOG000059593.
HOVERGENiHBG051653.
InParanoidiQ61575.
KOiK09407.
OMAiGHSFKTP.
OrthoDBiEOG75F4D8.
PhylomeDBiQ61575.
TreeFamiTF329867.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
PROSITEiPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q61575-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVSLLPPQSD VTLPGSTRLE GEPQGDLMQA PGLPDSPAPQ NKHANFSCSS
60 70 80 90 100
FVPDGPPERT PSLPPHSPSI ASPDPEQIQG HCTAGPGPGS FRLSPSEKYP
110 120 130 140 150
GFGFEEGPAG SPGRFLKGNH MPFHPYKRHF HEDIFSEAQT AMALDGHSFK
160 170 180 190 200
TQGALEAFEE IPVDMGDAEA FLPSFPAEAW CNKLPYPSQE HNQILQGSEV
210 220 230 240 250
KVKPQALDSG PGMYCYQPPL QHMYCSSQPA FHQYSPGGGS YPVPYLGSPH
260 270 280 290 300
YPYQRIAPQA NAEGHQPLFP KPIYSYSILI FMALKNSKTG SLPVSEIYNF
310 320 330 340 350
MTEHFPYFKT APDGWKNSVR HNLSLNKCFE KVENKSGSSS RKGCLWALNP
360 370 380 390 400
SKIDKMQEEL QKWKRKDPIA VRKSMAKPEE LDSLIGDKRE KLGSPLLGCP
410 420 430 440 450
PPGLAGPGPI RPMAPSAGLS QPLHPMHPAP GPMPGKNPLQ DLLGGHAPSC
460 470 480 490 500
YGQTYPHLSP SLAPSGHQQP LFPQPDGHLE LQAQPGTPQD SPLPAHTPPS
510 520 530 540 550
HGAKLMAEPS SARTMHDTLL PDGDLGTDLD AINPSLTDFD FQGNLWEQLK
560 570 580 590 600
DDSLALDPLV LVTSSPTSSS MLPPPPAAHC FPPGPCLAET GNEAGELAPP
610 620 630 640
GSGGSGALGD MHLSTLYSAF VELESTPSSA AAGPAVYLSP GSKPLALA
Length:648
Mass (Da):69,245
Last modified:November 1, 1996 - v1
Checksum:i7A75411BDE2B23E5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X81593 mRNA. Translation: CAA57279.1.
CCDSiCCDS25102.1.
RefSeqiNP_032264.1. NM_008238.2.
XP_006532329.1. XM_006532266.1.
UniGeneiMm.392151.
Mm.4496.

Genome annotation databases

EnsembliENSMUST00000108294; ENSMUSP00000103929; ENSMUSG00000002057.
GeneIDi15218.
KEGGimmu:15218.
UCSCiuc007kjd.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X81593 mRNA. Translation: CAA57279.1.
CCDSiCCDS25102.1.
RefSeqiNP_032264.1. NM_008238.2.
XP_006532329.1. XM_006532266.1.
UniGeneiMm.392151.
Mm.4496.

3D structure databases

ProteinModelPortaliQ61575.
SMRiQ61575. Positions 271-351.
ModBaseiSearch...
MobiDBiSearch...

PTM databases

PhosphoSiteiQ61575.

Proteomic databases

MaxQBiQ61575.
PRIDEiQ61575.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000108294; ENSMUSP00000103929; ENSMUSG00000002057.
GeneIDi15218.
KEGGimmu:15218.
UCSCiuc007kjd.1. mouse.

Organism-specific databases

CTDi8456.
MGIiMGI:102949. Foxn1.

Phylogenomic databases

eggNOGiCOG5025.
GeneTreeiENSGT00780000121868.
HOGENOMiHOG000059593.
HOVERGENiHBG051653.
InParanoidiQ61575.
KOiK09407.
OMAiGHSFKTP.
OrthoDBiEOG75F4D8.
PhylomeDBiQ61575.
TreeFamiTF329867.

Miscellaneous databases

NextBioi287799.
PROiQ61575.
SOURCEiSearch...

Gene expression databases

BgeeiQ61575.
CleanExiMM_FOXN1.
ExpressionAtlasiQ61575. baseline and differential.
GenevestigatoriQ61575.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
PROSITEiPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "New member of the winged-helix protein family disrupted in mouse and rat nude mutations."
    Nehls M., Pfeifer D., Schorpp M., Hedrich H., Boehm T.
    Nature 372:103-107(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN NUDE PHENOTYPE.
    Strain: BALB/c.
    Tissue: Skin.
  2. "Characterization of mouse and human nude genes."
    Schorpp M., Hofmann M., Dear T.N., Boehm T.
    Immunogenetics 46:509-515(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/c.
    Tissue: Skin and Thymus.
  3. "Nude mice are not hairless. A morphological study."
    Kopf-Maier P., Mboneko V.F., Merker H.J.
    Cells Tissues Organs 139:178-190(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN NUDE PHENOTYPE.
  4. "Learning from nudity: lessons from the nude phenotype."
    Mecklenburg L., Tychsen B., Paus R.
    Exp. Dermatol. 14:797-810(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  5. "Foxn1 promotes keratinocyte differentiation by regulating the activity of protein kinase C."
    Li J., Baxter R.M., Weiner L., Goetinck P.F., Calautti E., Brissette J.L.
    Differentiation 75:694-701(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Foxn1 is essential for vascularization of the murine thymus anlage."
    Mori K., Itoi M., Tsukamoto N., Amagai T.
    Cell. Immunol. 260:66-69(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Postnatal tissue-specific disruption of transcription factor FoxN1 triggers acute thymic atrophy."
    Cheng L., Guo J., Sun L., Fu J., Barnes P.F., Metzger D., Chambon P., Oshima R.G., Amagai T., Su D.M.
    J. Biol. Chem. 285:5836-5847(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  8. "Morphogenesis and maintenance of the 3D thymic medulla and prevention of nude skin phenotype require FoxN1 in pre- and post-natal K14 epithelium."
    Guo J., Rahman M., Cheng L., Zhang S., Tvinnereim A., Su D.M.
    J. Mol. Med. 89:263-277(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  9. "Foxn1 regulates lineage progression in cortical and medullary thymic epithelial cells but is dispensable for medullary sublineage divergence."
    Nowell C.S., Bredenkamp N., Tetelin S., Jin X., Tischner C., Vaidya H., Sheridan J.M., Stenhouse F.H., Heussen R., Smith A.J., Blackburn C.C.
    PLoS Genet. 7:E1002348-E1002348(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  10. "Insights on FoxN1 biological significance and usages of the 'nude' mouse in studies of T-lymphopoiesis."
    Zhang Z., Burnley P., Coder B., Su D.M.
    Int. J. Biol. Sci. 8:1156-1167(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  11. "FOXN1: a master regulator gene of thymic epithelial development program."
    Romano R., Palamaro L., Fusco A., Giardino G., Gallo V., Del Vecchio L., Pignata C.
    Front. Immunol. 4:187-187(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  12. "Enhancing T lineage production in aged mice: a novel function of Foxn1 in the bone marrow niche."
    Zook E.C., Zhang S., Gerstein R.M., Witte P.L., Le P.T.
    J. Immunol. 191:5583-5593(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiFOXN1_MOUSE
AccessioniPrimary (citable) accession number: Q61575
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 1, 1996
Last modified: March 4, 2015
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.