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 24-JAN-2024, entry version 180. 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}. 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; 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.ENSMUSP00000111137; -. DR iPTMnet; P58463; -. DR PhosphoSitePlus; P58463; -. DR MaxQB; P58463; -. DR PaxDb; 10090-ENSMUSP00000031545; -. DR ProteomicsDB; 271601; -. [P58463-1] DR ProteomicsDB; 271602; -. [P58463-2] DR Antibodypedia; 672; 511 antibodies from 40 providers. DR DNASU; 114142; -. DR Ensembl; ENSMUST00000031545.14; ENSMUSP00000031545.8; ENSMUSG00000029563.17. [P58463-1] DR Ensembl; ENSMUST00000115472.8; ENSMUSP00000111132.2; ENSMUSG00000029563.17. [P58463-2] DR Ensembl; ENSMUST00000115477.8; ENSMUSP00000111137.2; ENSMUSG00000029563.17. [P58463-1] DR GeneID; 114142; -. DR KEGG; mmu:114142; -. DR UCSC; uc009ayy.1; mouse. [P58463-1] DR UCSC; uc012eie.1; mouse. [P58463-2] DR AGR; MGI:2148705; -. 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; XHLNNEH; -. DR PhylomeDB; P58463; -. DR TreeFam; TF326978; -. DR BioGRID-ORCS; 114142; 3 hits in 82 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 290 other cell types or tissues. DR ExpressionAtlas; P58463; baseline and differential. 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: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:0045892; P:negative regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; 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; cd20065; FH_FOXP2; 1. DR Gene3D; 1.20.5.340; -; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. DR InterPro; IPR047412; FH_FOXP1_P2. 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 PANTHER; PTHR45796; FORKHEAD BOX P, ISOFORM C; 1. DR PANTHER; PTHR45796:SF1; FORKHEAD BOX PROTEIN P2; 1. DR Pfam; PF00250; Forkhead; 1. DR Pfam; PF16159; FOXP-CC; 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 PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1. DR Genevisible; P58463; MM. 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 //