FOXP2_MOUSE
ID FOXP2_MOUSE Reviewed; 714 AA.
AC P58463; Q6PD37; Q8C4F0; Q8R441;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 31-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Forkhead box protein P2;
GN Name=Foxp2;
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] (ISOFORM 1), AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J; TISSUE=Lung;
RX PubMed=11358962; DOI=10.1074/jbc.m100636200;
RA Shu W., Yang H., Zhang L., Lu M.M., Morrisey E.E.;
RT "Characterization of a new subfamily of winged-helix/forkhead (Fox) genes
RT that are expressed in the lung and act as transcriptional repressors.";
RL J. Biol. Chem. 276:27488-27497(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=BALB/cJ;
RX PubMed=12192408; DOI=10.1038/nature01025;
RA Enard W., Przeworski M., Fisher S.E., Lai C.S.L., Wiebe V., Kitano T.,
RA Monaco A.P., Paeaebo S.;
RT "Molecular evolution of FOXP2, a gene involved in speech and language.";
RL Nature 418:869-872(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=14516685; DOI=10.1016/s0925-4773(03)00116-3;
RA Lu M.M., Li S., Yang H., Morrisey E.E.;
RT "Foxp4: a novel member of the Foxp subfamily of winged-helix genes co-
RT expressed with Foxp1 and Foxp2 in pulmonary and gut tissues.";
RL Mech. Dev. 119:S197-S202(2002).
RN [6]
RP FUNCTION, DIMERIZATION, INTERACTION WITH CTBP1, DOMAIN, AND MUTAGENESIS OF
RP GLU-399; 407-HIS-LEU-408; LEU-408 AND 421-PRO--VAL-425.
RX PubMed=14701752; DOI=10.1128/mcb.24.2.809-822.2004;
RA Li S., Weidenfeld J., Morrisey E.E.;
RT "Transcriptional and DNA binding activity of the Foxp1/2/4 family is
RT modulated by heterotypic and homotypic protein interactions.";
RL Mol. Cell. Biol. 24:809-822(2004).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF ARG-552.
RX PubMed=24179158; DOI=10.1126/science.1245079;
RA Sia G.M., Clem R.L., Huganir R.L.;
RT "The human language-associated gene SRPX2 regulates synapse formation and
RT vocalization in mice.";
RL Science 342:987-991(2013).
CC -!- FUNCTION: Transcriptional repressor that may play a role in the
CC specification and differentiation of lung epithelium. May also play a
CC role in developing neural, gastrointestinal and cardiovascular tissues.
CC Can act with CTBP1 to synergistically repress transcription but CTPBP1
CC is not essential. Plays a role in synapse formation by regulating SRPX2
CC levels. {ECO:0000269|PubMed:14701752, ECO:0000269|PubMed:24179158}.
CC -!- SUBUNIT: Forms homodimers and heterodimers with FOXP1 and FOXP4.
CC Dimerization is required for DNA-binding (By similarity). Interacts
CC with CTBP1 (PubMed:14701752). Interacts with FOXP1 (By similarity).
CC Interacts with TBR1 (By similarity). Interacts with ZMYM2 (By
CC similarity). {ECO:0000250|UniProtKB:O15409,
CC ECO:0000269|PubMed:14701752}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P58463-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P58463-2; Sequence=VSP_011540;
CC -!- TISSUE SPECIFICITY: Highest expression in lung. Lower expression in
CC spleen, skeletal muscle, brain, kidney and small intestine.
CC -!- DEVELOPMENTAL STAGE: Expressed in developing lung, neural, intestinal
CC and cardiovascular tissues. Expressed at a high level in the distal
CC airway epithelium and at a low level in the proximal airway epithelium
CC at 12.5 dpc, and restricted to the distal airway epithelium by 14.5
CC dpc. In the spinal cord, at 12.5 dpc, expressed in a subset of
CC interneurons dorsal to motor neurons. At 16.5 dpc, expression in the
CC brain is observed in the inner intermediate zone of the neopallial
CC cortex and in the developing cerebral hemispheres. In the
CC gastrointestinal system, at 12.5 expressed in the outer mesodermal
CC layer and in the intestinal epithelium. By 16.5 dpc, expression is
CC restricted to the outer longitudinal muscle layer of the intestine and
CC stomach. In the cardiovascular system, at 14.5 dpc, expressed in the
CC outflow tract region of the developing heart. By 16.5 dpc, observed in
CC the outflow tract and atrium, but not in the ventricles.
CC {ECO:0000269|PubMed:11358962, ECO:0000269|PubMed:14516685}.
CC -!- DOMAIN: The leucine-zipper is required for dimerization and
CC transcriptional repression. {ECO:0000269|PubMed:14701752}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to a competing acceptor splice
CC site. {ECO:0000305}.
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DR EMBL; AF339106; AAK69651.1; -; mRNA.
DR EMBL; AY079003; AAL85482.1; -; mRNA.
DR EMBL; AK082361; BAC38477.1; -; mRNA.
DR EMBL; BC058960; AAH58960.1; -; mRNA.
DR EMBL; BC062926; AAH62926.1; -; mRNA.
DR CCDS; CCDS19918.1; -. [P58463-1]
DR CCDS; CCDS71726.1; -. [P58463-2]
DR RefSeq; NP_001273536.1; NM_001286607.1. [P58463-2]
DR RefSeq; NP_444472.2; NM_053242.4. [P58463-1]
DR RefSeq; NP_997600.1; NM_212435.1. [P58463-1]
DR AlphaFoldDB; P58463; -.
DR SMR; P58463; -.
DR BioGRID; 227578; 3.
DR IntAct; P58463; 1.
DR STRING; 10090.ENSMUSP00000031545; -.
DR iPTMnet; P58463; -.
DR PhosphoSitePlus; P58463; -.
DR MaxQB; P58463; -.
DR PaxDb; P58463; -.
DR PRIDE; P58463; -.
DR ProteomicsDB; 271601; -. [P58463-1]
DR ProteomicsDB; 271602; -. [P58463-2]
DR Antibodypedia; 672; 475 antibodies from 40 providers.
DR DNASU; 114142; -.
DR Ensembl; ENSMUST00000031545; ENSMUSP00000031545; ENSMUSG00000029563. [P58463-1]
DR Ensembl; ENSMUST00000115472; ENSMUSP00000111132; ENSMUSG00000029563. [P58463-2]
DR Ensembl; ENSMUST00000115477; ENSMUSP00000111137; ENSMUSG00000029563. [P58463-1]
DR GeneID; 114142; -.
DR KEGG; mmu:114142; -.
DR UCSC; uc009ayy.1; mouse. [P58463-1]
DR UCSC; uc012eie.1; mouse. [P58463-2]
DR CTD; 93986; -.
DR MGI; MGI:2148705; Foxp2.
DR VEuPathDB; HostDB:ENSMUSG00000029563; -.
DR eggNOG; KOG4385; Eukaryota.
DR GeneTree; ENSGT00940000155480; -.
DR HOGENOM; CLU_019502_3_1_1; -.
DR InParanoid; P58463; -.
DR OMA; REYPESH; -.
DR PhylomeDB; P58463; -.
DR TreeFam; TF326978; -.
DR BioGRID-ORCS; 114142; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Foxp2; mouse.
DR PRO; PR:P58463; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P58463; protein.
DR Bgee; ENSMUSG00000029563; Expressed in olfactory tubercle and 288 other tissues.
DR ExpressionAtlas; P58463; baseline and differential.
DR Genevisible; P58463; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IMP:NTNU_SB.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050681; F:nuclear androgen receptor binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IMP:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0001221; F:transcription coregulator binding; IPI:UniProtKB.
DR GO; GO:0043010; P:camera-type eye development; IMP:MGI.
DR GO; GO:0021757; P:caudate nucleus development; ISS:UniProtKB.
DR GO; GO:0021702; P:cerebellar Purkinje cell differentiation; IMP:MGI.
DR GO; GO:0021549; P:cerebellum development; IMP:MGI.
DR GO; GO:0060502; P:epithelial cell proliferation involved in lung morphogenesis; IGI:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0098582; P:innate vocalization behavior; ISO:MGI.
DR GO; GO:0048286; P:lung alveolus development; IMP:MGI.
DR GO; GO:0030324; P:lung development; IGI:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IGI:MGI.
DR GO; GO:0060501; P:positive regulation of epithelial cell proliferation involved in lung morphogenesis; IGI:MGI.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IGI:MGI.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0021758; P:putamen development; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060013; P:righting reflex; IMP:MGI.
DR GO; GO:0007519; P:skeletal muscle tissue development; IGI:MGI.
DR GO; GO:0048745; P:smooth muscle tissue development; IGI:MGI.
DR GO; GO:0042297; P:vocal learning; IMP:MGI.
DR GO; GO:0071625; P:vocalization behavior; IMP:MGI.
DR CDD; cd00059; FH; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR032354; FOXP-CC.
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 Pfam; PF16159; FOXP-CC; 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.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA-binding; Metal-binding; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Zinc; Zinc-finger.
FT CHAIN 1..714
FT /note="Forkhead box protein P2"
FT /id="PRO_0000091882"
FT ZN_FING 345..370
FT /note="C2H2-type"
FT DNA_BIND 503..593
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 280..338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 387..408
FT /note="Leucine-zipper"
FT REGION 421..425
FT /note="CTBP1-binding"
FT REGION 437..464
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 648..667
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 677..714
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 287..326
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 649..664
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 700..714
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 134..154
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011540"
FT MUTAGEN 399
FT /note="Missing: Loss of dimerization. Almost complete loss
FT of DNA-binding. Reduced transcriptional repression
FT activity."
FT /evidence="ECO:0000269|PubMed:14701752"
FT MUTAGEN 407..408
FT /note="HL->AA: Severely reduced transcriptional repression
FT activity."
FT /evidence="ECO:0000269|PubMed:14701752"
FT MUTAGEN 408
FT /note="L->A: Severely reduced transcriptional repression
FT activity."
FT /evidence="ECO:0000269|PubMed:14701752"
FT MUTAGEN 421..425
FT /note="PLNLV->AANAA: No significant effect on
FT transcriptional repression activity."
FT /evidence="ECO:0000269|PubMed:14701752"
FT MUTAGEN 552
FT /note="R->H: No change in synaptic density."
FT /evidence="ECO:0000269|PubMed:24179158"
FT CONFLICT 6
FT /note="A -> V (in Ref. 1; AAK69651)"
FT /evidence="ECO:0000305"
FT CONFLICT 543
FT /note="N -> S (in Ref. 1; AAK69651)"
FT /evidence="ECO:0000305"
FT CONFLICT 663
FT /note="P -> R (in Ref. 3; BAC38477)"
FT /evidence="ECO:0000305"
FT CONFLICT 675
FT /note="E -> D (in Ref. 3; BAC38477)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 714 AA; 79819 MW; EB02D66B5AA452D0 CRC64;
MMQESATETI SNSSMNQNGM STLSSQLDAG SRDGRSSGDT SSEVSTVELL HLQQQQALQA
ARQLLLQQQT SGLKSPKSSE KQRPLQVPVS VAMMTPQVIT PQQMQQILQQ QVLSPQQLQA
LLQQQQAVML QQQQLQEFYK KQQEQLHLQL LQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ
QQQQQQQQQQ QHPGKQAKEQ QQQQQQQQLA AQQLVFQQQL LQMQQLQQQQ HLLSLQRQGL
ISIPPGQAAL PVQSLPQAGL SPAEIQQLWK EVTGVHSMED NGIKHGGLDL TTNNSSSTTS
STTSKASPPI THHSIVNGQS SVLNARRDSS SHEETGASHT LYGHGVCKWP GCESICEDFG
QFLKHLNNEH ALDDRSTAQC RVQMQVVQQL EIQLSKERER LQAMMTHLHM RPSEPKPSPK
PLNLVSSVTM SKNMLETSPQ SLPQTPTTPT APVTPITQGP SVITPASVPN VGAIRRRHSD
KYNIPMSSEI APNYEFYKNA DVRPPFTYAT LIRQAIMESS DRQLTLNEIY SWFTRTFAYF
RRNAATWKNA VRHNLSLHKC FVRVENVKGA VWTVDEVEYQ KRRSQKITGS PTLVKNIPTS
LGYGAALNAS LQAALAESSL PLLSNPGLIN NASSGLLQAV HEDLNGSLDH IDSNGNSSPG
CSPQPHIHSI HVKEEPVIAE DEDCPMSLVT TANHSPELED DREIEEEPLS EDLE
