FOXN4_MOUSE
ID FOXN4_MOUSE Reviewed; 521 AA.
AC Q8K3Q3; Q0VGP0; Q920C0;
DT 27-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Forkhead box protein N4;
GN Name=Foxn4;
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 DEVELOPMENTAL STAGE.
RA Visel A., Eichele G.;
RT "Cloning of mouse FoxN4, a predicted forkhead/winged-helix transcription
RT factor.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Eye;
RX PubMed=11520680; DOI=10.1016/s0925-4773(01)00465-8;
RA Gouge A., Holt J., Hardy A.P., Sowden J.C., Smith H.K.;
RT "Foxn4 - a new member of the forkhead gene family is expressed in the
RT retina.";
RL Mech. Dev. 107:203-206(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION IN RETINA DEVELOPMENT, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE,
RP AND TISSUE SPECIFICITY.
RX PubMed=15363391; DOI=10.1016/j.neuron.2004.08.041;
RA Li S., Mo Z., Yang X., Price S.M., Shen M.M., Xiang M.;
RT "Foxn4 controls the genesis of amacrine and horizontal cells by retinal
RT progenitors.";
RL Neuron 43:795-807(2004).
RN [5]
RP FUNCTION IN NEUROGENESIS, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=16020526; DOI=10.1073/pnas.0504799102;
RA Li S., Misra K., Matise M.P., Xiang M.;
RT "Foxn4 acts synergistically with Mash1 to specify subtype identity of V2
RT interneurons in the spinal cord.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:10688-10693(2005).
RN [6]
RP FUNCTION IN NEUROGENESIS, AND DEVELOPMENTAL STAGE.
RX PubMed=17728344; DOI=10.1242/dev.005868;
RA Del Barrio M.G., Taveira-Marques R., Muroyama Y., Yuk D.I., Li S.,
RA Wines-Samuelson M., Shen J., Smith H.K., Xiang M., Rowitch D.,
RA Richardson W.D.;
RT "A regulatory network involving Foxn4, Mash1 and delta-like 4/Notch1
RT generates V2a and V2b spinal interneurons from a common progenitor pool.";
RL Development 134:3427-3436(2007).
RN [7]
RP FUNCTION IN LUNG DEVELOPMENT, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=21438071; DOI=10.1002/dvdy.22610;
RA Li S., Xiang M.;
RT "Foxn4 influences alveologenesis during lung development.";
RL Dev. Dyn. 240:1512-1517(2011).
RN [8]
RP FUNCTION AS TRANSCRIPTION FACTOR, AND SUBCELLULAR LOCATION.
RX PubMed=22323600; DOI=10.1073/pnas.1115767109;
RA Luo H., Jin K., Xie Z., Qiu F., Li S., Zou M., Cai L., Hozumi K.,
RA Shima D.T., Xiang M.;
RT "Forkhead box N4 (Foxn4) activates Dll4-Notch signaling to suppress
RT photoreceptor cell fates of early retinal progenitors.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E553-E562(2012).
RN [9]
RP FUNCTION AS TRANSCRIPTION FACTOR, AND DNA-BINDING.
RX PubMed=23652001; DOI=10.1038/ncomms2793;
RA Liu H., Kim S.Y., Fu Y., Wu X., Ng L., Swaroop A., Forrest D.;
RT "An isoform of retinoid-related orphan receptor beta directs
RT differentiation of retinal amacrine and horizontal interneurons.";
RL Nat. Commun. 4:1813-1813(2013).
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. {ECO:0000269|PubMed:15363391, ECO:0000269|PubMed:16020526,
CC ECO:0000269|PubMed:17728344, ECO:0000269|PubMed:21438071,
CC ECO:0000269|PubMed:22323600, ECO:0000269|PubMed:23652001}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00089,
CC ECO:0000269|PubMed:22323600}.
CC -!- TISSUE SPECIFICITY: Mainly expressed in proliferator progenitor cells
CC in brain and retina rather than differentiated cells. In contrast, is
CC expressed only in postmitotic epithelial cells rather than in
CC proliferative progenitors in the proximal airway.
CC {ECO:0000269|PubMed:15363391, ECO:0000269|PubMed:16020526,
CC ECO:0000269|PubMed:21438071}.
CC -!- DEVELOPMENTAL STAGE: Expressed in both neural and non-neural tissues of
CC the embryo. In the nervous system, its expression is detected only in a
CC few selected central nervous system tissues including the midbrain,
CC hindbrain, spinal cord and retina while absent from the peripheral
CC nervous system. At about 9.5 dpc-10.5 dpc, commences its expression in
CC the dorsal mesenphalon, ventral rhombencephalon and ventral spinal
CC cord. In the spinal cord, is found in p2 progenitor cells but not in
CC mature V2a and V2b cells, in other interneuron subtypes or in
CC motoneurons. The expression in the brain and spinal cord becomes weak
CC at 12.5 dpc and disappears by 13.5 dpc. In the central eye, expression
CC starts in the central retina at 11.5 dpc, then gradually becomes
CC abundant in the entire retinal outer neuroblastic layer by 13.5 dpc,
CC but is absent from the inner neuroblastic layer. Starting from P1 and
CC by P7, the expression in the retina gradually disappears from the
CC center to the periphery. In airway system, expression turns on at 14.5
CC dpc in a small set of cells in the epithelia of the trachea and
CC esophagus, then spreads to the epithelia of bronchi and bronchioles by
CC 15.5 dpc, the expression persists until at least P8 (at protein level).
CC {ECO:0000269|PubMed:15363391, ECO:0000269|PubMed:16020526,
CC ECO:0000269|PubMed:17728344, ECO:0000269|PubMed:21438071,
CC ECO:0000269|Ref.1}.
CC -!- DISRUPTION PHENOTYPE: Animals display early postnatal lethality, while
CC survivors exhibit noticeable body size reduction starting at P8. At P8
CC and P20, retinas are reduced in thickness with the inner nuclear layer,
CC inner plexiform layer and ganglion cell layer much thinner than in wild
CC type and lack horizontal cells as well as amacrine cells. In lungs,
CC mutants show dilated alveoli with thin walls.
CC {ECO:0000269|PubMed:15363391, ECO:0000269|PubMed:16020526,
CC ECO:0000269|PubMed:21438071}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY039039; AAK72101.1; -; mRNA.
DR EMBL; AF323488; AAL06288.1; -; mRNA.
DR EMBL; BC092242; AAH92242.1; -; mRNA.
DR EMBL; BC130222; AAI30223.1; -; mRNA.
DR CCDS; CCDS19562.1; -.
DR RefSeq; NP_683737.2; NM_148935.2.
DR RefSeq; XP_006530184.1; XM_006530121.3.
DR AlphaFoldDB; Q8K3Q3; -.
DR SMR; Q8K3Q3; -.
DR STRING; 10090.ENSMUSP00000047951; -.
DR iPTMnet; Q8K3Q3; -.
DR PhosphoSitePlus; Q8K3Q3; -.
DR MaxQB; Q8K3Q3; -.
DR PaxDb; Q8K3Q3; -.
DR PRIDE; Q8K3Q3; -.
DR ProteomicsDB; 267402; -.
DR Antibodypedia; 30846; 200 antibodies from 23 providers.
DR DNASU; 116810; -.
DR Ensembl; ENSMUST00000044790; ENSMUSP00000047951; ENSMUSG00000042002.
DR GeneID; 116810; -.
DR KEGG; mmu:116810; -.
DR UCSC; uc008yzk.1; mouse.
DR CTD; 121643; -.
DR MGI; MGI:2151057; Foxn4.
DR VEuPathDB; HostDB:ENSMUSG00000042002; -.
DR eggNOG; KOG2294; Eukaryota.
DR GeneTree; ENSGT00940000158984; -.
DR HOGENOM; CLU_031768_2_0_1; -.
DR InParanoid; Q8K3Q3; -.
DR OMA; QCPTSVY; -.
DR OrthoDB; 438804at2759; -.
DR PhylomeDB; Q8K3Q3; -.
DR TreeFam; TF329867; -.
DR BioGRID-ORCS; 116810; 5 hits in 75 CRISPR screens.
DR PRO; PR:Q8K3Q3; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8K3Q3; protein.
DR Bgee; ENSMUSG00000042002; Expressed in outer nuclear layer of retina and 55 other tissues.
DR ExpressionAtlas; Q8K3Q3; baseline and differential.
DR Genevisible; Q8K3Q3; MM.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA: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; IDA:GO_Central.
DR GO; GO:0035881; P:amacrine cell differentiation; IMP:UniProtKB.
DR GO; GO:0036302; P:atrioventricular canal development; ISS:UniProtKB.
DR GO; GO:0001947; P:heart looping; ISS:UniProtKB.
DR GO; GO:0048663; P:neuron fate commitment; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:GO_Central.
DR GO; GO:0008016; P:regulation of heart contraction; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0010842; P:retina layer formation; IMP:UniProtKB.
DR GO; GO:0021514; P:ventral spinal cord interneuron differentiation; IMP:UniProtKB.
DR GO; GO:0060579; P:ventral spinal cord interneuron fate commitment; IMP: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 Developmental protein; DNA-binding; Neurogenesis; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..521
FT /note="Forkhead box protein N4"
FT /id="PRO_0000091871"
FT DNA_BIND 197..293
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 371..406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 380..403
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 16
FT /note="S -> G (in Ref. 2; AAL06288)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="L -> C (in Ref. 2; AAL06288)"
FT /evidence="ECO:0000305"
FT CONFLICT 229..231
FT /note="EHF -> TL (in Ref. 2; AAL06288)"
FT /evidence="ECO:0000305"
FT CONFLICT 296
FT /note="A -> S (in Ref. 2; AAL06288)"
FT /evidence="ECO:0000305"
FT CONFLICT 309..310
FT /note="KL -> NV (in Ref. 2; AAL06288)"
FT /evidence="ECO:0000305"
FT CONFLICT 402..415
FT /note="PAMGRVPGDFLNIN -> QHGRSWDFSHH (in Ref. 2; AAL06288)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 521 AA; 56121 MW; A5B895C7ED9B2834 CRC64;
MIESGIWSRM SEMIRSSGHS HHCSPQEYRF LPPVGDDDLP GDLQSLSWLT AVDVPRLQQM
ANGRIDLGSS GVTHPHPGAL AGTADLHVGA APRPLLRRSQ TAVVPRGVLG LSPIGNHRAS
AEQMNQFPAG GQASSGLQEM PQLYSPATQI PFPLPLGSQQ CPPAGLYGSP FSARPSYPQA
HGAMHASQEP HPKHYPKPIY SYSCLIAMAL KNSKTGSLPV SEIYSFMKEH FPYFKTAPDG
WKNSVRHNLS LNKCFEKVET KSSGSSRKGC LWALNLARID KMEEEMHKWK RKDLAAIHRS
MANPEELDKL ISDRPESCRR PGKRGEPKAP MLTHATTVAM AHSCLAISQL PPKPLMTLSL
QSVPLHHQLQ PQAHLAPDSP APAQTPPLHA LPSLSPGPLP QPAMGRVPGD FLNINSDMNT
EVDALDPSIM DFALQGNLWE EMKEDSFSLD TLEAFGDSPL GCDLGAPSLT PVSGNSDQSF
PDVQVTGLYA AYSTAADGVA PSAANSAQYL GTPGNKPIAL L
