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Forkhead box protein P2

 FOXP2_MOUSE             Reviewed;         714 AA.
P58463; Q6PD37; Q8C4F0; Q8R441;
05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
31-AUG-2004, sequence version 2.
20-JUN-2018, entry version 151.
RecName: Full=Forkhead box protein P2;
Name=Foxp2;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND DEVELOPMENTAL STAGE.
STRAIN=C57BL/6J; TISSUE=Lung;
PubMed=11358962; DOI=10.1074/jbc.M100636200;
Shu W., Yang H., Zhang L., Lu M.M., Morrisey E.E.;
"Characterization of a new subfamily of winged-helix/forkhead (Fox)
genes that are expressed in the lung and act as transcriptional
repressors.";
J. Biol. Chem. 276:27488-27497(2001).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
STRAIN=BALB/cJ;
PubMed=12192408; DOI=10.1038/nature01025;
Enard W., Przeworski M., Fisher S.E., Lai C.S.L., Wiebe V., Kitano T.,
Monaco A.P., Paeaebo S.;
"Molecular evolution of FOXP2, a gene involved in speech and
language.";
Nature 418:869-872(2002).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
STRAIN=C57BL/6J; TISSUE=Cerebellum;
PubMed=16141072; DOI=10.1126/science.1112014;
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
Hayashizaki Y.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
STRAIN=C57BL/6J; TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
DEVELOPMENTAL STAGE.
PubMed=14516685; DOI=10.1016/S0925-4773(03)00116-3;
Lu M.M., Li S., Yang H., Morrisey E.E.;
"Foxp4: a novel member of the Foxp subfamily of winged-helix genes co-
expressed with Foxp1 and Foxp2 in pulmonary and gut tissues.";
Mech. Dev. 119:S197-S202(2002).
[6]
FUNCTION, DIMERIZATION, INTERACTION WITH CTBP1, DOMAIN, AND
MUTAGENESIS OF GLU-399; 407-HIS-LEU-408; LEU-408 AND 421-PRO--VAL-425.
PubMed=14701752; DOI=10.1128/MCB.24.2.809-822.2004;
Li S., Weidenfeld J., Morrisey E.E.;
"Transcriptional and DNA binding activity of the Foxp1/2/4 family is
modulated by heterotypic and homotypic protein interactions.";
Mol. Cell. Biol. 24:809-822(2004).
[7]
FUNCTION, AND MUTAGENESIS OF ARG-552.
PubMed=24179158; DOI=10.1126/science.1245079;
Sia G.M., Clem R.L., Huganir R.L.;
"The human language-associated gene SRPX2 regulates synapse formation
and vocalization in mice.";
Science 342:987-991(2013).
-!- FUNCTION: Transcriptional repressor that may play a role in the
specification and differentiation of lung epithelium. May also
play a role in developing neural, gastrointestinal and
cardiovascular tissues. Can act with CTBP1 to synergistically
repress transcription but CTPBP1 is not essential. Plays a role in
synapse formation by regulating SRPX2 levels.
{ECO:0000269|PubMed:14701752, ECO:0000269|PubMed:24179158}.
-!- SUBUNIT: Forms homodimers and heterodimers with FOXP1 and FOXP4.
Dimerization is required for DNA-binding (By similarity).
Interacts with CTBP1 (PubMed:14701752). Interacts with FOXP1 (By
similarity). {ECO:0000250|UniProtKB:O15409,
ECO:0000269|PubMed:14701752}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=P58463-1; Sequence=Displayed;
Name=2;
IsoId=P58463-2; Sequence=VSP_011540;
Note=May be due to a competing acceptor splice site. No
experimental confirmation available.;
-!- TISSUE SPECIFICITY: Highest expression in lung. Lower expression
in spleen, skeletal muscle, brain, kidney and small intestine.
-!- DEVELOPMENTAL STAGE: Expressed in developing lung, neural,
intestinal and cardiovascular tissues. Expressed at a high level
in the distal airway epithelium and at a low level in the proximal
airway epithelium at 12.5 dpc, and restricted to the distal airway
epithelium by 14.5 dpc. In the spinal cord, at 12.5 dpc, expressed
in a subset of interneurons dorsal to motor neurons. At 16.5 dpc,
expression in the brain is observed in the inner intermediate zone
of the neopallial cortex and in the developing cerebral
hemispheres. In the gastrointestinal system, at 12.5 expressed in
the outer mesodermal layer and in the intestinal epithelium. By
16.5 dpc, expression is restricted to the outer longitudinal
muscle layer of the intestine and stomach. In the cardiovascular
system, at 14.5 dpc, expressed in the outflow tract region of the
developing heart. By 16.5 dpc, observed in the outflow tract and
atrium, but not in the ventricles. {ECO:0000269|PubMed:11358962,
ECO:0000269|PubMed:14516685}.
-!- DOMAIN: The leucine-zipper is required for dimerization and
transcriptional repression. {ECO:0000269|PubMed:14701752}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution (CC BY 4.0) License
-----------------------------------------------------------------------
EMBL; AF339106; AAK69651.1; -; mRNA.
EMBL; AY079003; AAL85482.1; -; mRNA.
EMBL; AK082361; BAC38477.1; -; mRNA.
EMBL; BC058960; AAH58960.1; -; mRNA.
EMBL; BC062926; AAH62926.1; -; mRNA.
CCDS; CCDS19918.1; -. [P58463-1]
CCDS; CCDS71726.1; -. [P58463-2]
RefSeq; NP_001273536.1; NM_001286607.1. [P58463-2]
RefSeq; NP_444472.2; NM_053242.4. [P58463-1]
RefSeq; NP_997600.1; NM_212435.1. [P58463-1]
UniGene; Mm.332919; -.
ProteinModelPortal; P58463; -.
SMR; P58463; -.
BioGrid; 227578; 2.
IntAct; P58463; 1.
STRING; 10090.ENSMUSP00000031545; -.
iPTMnet; P58463; -.
PhosphoSitePlus; P58463; -.
MaxQB; P58463; -.
PaxDb; P58463; -.
PRIDE; P58463; -.
Ensembl; ENSMUST00000031545; ENSMUSP00000031545; ENSMUSG00000029563. [P58463-1]
Ensembl; ENSMUST00000115472; ENSMUSP00000111132; ENSMUSG00000029563. [P58463-2]
Ensembl; ENSMUST00000115477; ENSMUSP00000111137; ENSMUSG00000029563. [P58463-1]
GeneID; 114142; -.
KEGG; mmu:114142; -.
UCSC; uc009ayy.1; mouse. [P58463-1]
UCSC; uc012eie.1; mouse. [P58463-2]
CTD; 93986; -.
MGI; MGI:2148705; Foxp2.
eggNOG; KOG4385; Eukaryota.
eggNOG; COG5025; LUCA.
GeneTree; ENSGT00920000148947; -.
HOGENOM; HOG000092089; -.
HOVERGEN; HBG051657; -.
InParanoid; P58463; -.
KO; K09409; -.
PhylomeDB; P58463; -.
TreeFam; TF326978; -.
ChiTaRS; Foxp2; mouse.
PRO; PR:P58463; -.
Proteomes; UP000000589; Chromosome 6.
Bgee; ENSMUSG00000029563; -.
CleanEx; MM_FOXP2; -.
ExpressionAtlas; P58463; baseline and differential.
Genevisible; P58463; MM.
GO; GO:0005634; C:nucleus; IBA:GO_Central.
GO; GO:0050681; F:androgen receptor binding; IEA:Ensembl.
GO; GO:0003677; F:DNA binding; IDA:MGI.
GO; GO:0003700; F:DNA binding transcription factor activity; IDA:MGI.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0046982; F:protein heterodimerization activity; IPI:MGI.
GO; GO:0042803; F:protein homodimerization activity; IPI:MGI.
GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; IMP:NTNU_SB.
GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding; IMP:NTNU_SB.
GO; GO:0043010; P:camera-type eye development; IMP:MGI.
GO; GO:0021757; P:caudate nucleus development; ISS:UniProtKB.
GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
GO; GO:0021549; P:cerebellum development; IMP:MGI.
GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
GO; GO:0040007; P:growth; IMP:MGI.
GO; GO:0098582; P:innate vocalization behavior; IEA:Ensembl.
GO; GO:0048286; P:lung alveolus development; IMP:MGI.
GO; GO:0030324; P:lung development; IGI:MGI.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IGI:MGI.
GO; GO:0060501; P:positive regulation of epithelial cell proliferation involved in lung morphogenesis; IGI:MGI.
GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IGI:MGI.
GO; GO:0009791; P:post-embryonic development; IMP:MGI.
GO; GO:0021758; P:putamen development; ISS:UniProtKB.
GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
GO; GO:0060013; P:righting reflex; IMP:MGI.
GO; GO:0007519; P:skeletal muscle tissue development; IGI:MGI.
GO; GO:0048745; P:smooth muscle tissue development; IGI:MGI.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0042297; P:vocal learning; IMP:MGI.
CDD; cd00059; FH; 1.
Gene3D; 1.10.10.10; -; 1.
InterPro; IPR001766; Fork_head_dom.
InterPro; IPR032354; FOXP-CC.
InterPro; IPR030456; TF_fork_head_CS_2.
InterPro; IPR036388; WH-like_DNA-bd_sf.
InterPro; IPR036390; WH_DNA-bd_sf.
Pfam; PF00250; Forkhead; 1.
Pfam; PF16159; FOXP-CC; 1.
PRINTS; PR00053; FORKHEAD.
SMART; SM00339; FH; 1.
SUPFAM; SSF46785; SSF46785; 1.
PROSITE; PS00658; FORK_HEAD_2; 1.
PROSITE; PS50039; FORK_HEAD_3; 1.
PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; DNA-binding; Metal-binding;
Nucleus; Reference proteome; Repressor; Transcription;
Transcription regulation; Zinc; Zinc-finger.
CHAIN 1 714 Forkhead box protein P2.
/FTId=PRO_0000091882.
ZN_FING 345 370 C2H2-type.
DNA_BIND 503 593 Fork-head. {ECO:0000255|PROSITE-
ProRule:PRU00089}.
REGION 387 408 Leucine-zipper.
REGION 421 425 CTBP1-binding.
COMPBIAS 53 267 Gln-rich.
VAR_SEQ 134 154 Missing (in isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_011540.
MUTAGEN 399 399 Missing: Loss of dimerization. Almost
complete loss of DNA-binding. Reduced
transcriptional repression activity.
{ECO:0000269|PubMed:14701752}.
MUTAGEN 407 408 HL->AA: Severely reduced transcriptional
repression activity.
{ECO:0000269|PubMed:14701752}.
MUTAGEN 408 408 L->A: Severely reduced transcriptional
repression activity.
{ECO:0000269|PubMed:14701752}.
MUTAGEN 421 425 PLNLV->AANAA: No significant effect on
transcriptional repression activity.
{ECO:0000269|PubMed:14701752}.
MUTAGEN 552 552 R->H: No change in synaptic density.
{ECO:0000269|PubMed:24179158}.
CONFLICT 6 6 A -> V (in Ref. 1; AAK69651).
{ECO:0000305}.
CONFLICT 543 543 N -> S (in Ref. 1; AAK69651).
{ECO:0000305}.
CONFLICT 663 663 P -> R (in Ref. 3; BAC38477).
{ECO:0000305}.
CONFLICT 675 675 E -> D (in Ref. 3; BAC38477).
{ECO:0000305}.
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


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