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Protein

Forkhead box protein P2

Gene

Foxp2

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

Functioni

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.2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri345 – 37026C2H2-typeAdd
BLAST
DNA bindingi503 – 59391Fork-headPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. DNA binding Source: UniProtKB
  2. metal ion binding Source: UniProtKB-KW
  3. protein heterodimerization activity Source: MGI
  4. protein homodimerization activity Source: UniProtKB
  5. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  6. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Source: NTNU_SB
  7. sequence-specific DNA binding transcription factor activity Source: MGI

GO - Biological processi

  1. camera-type eye development Source: MGI
  2. caudate nucleus development Source: UniProtKB
  3. cerebellum development Source: MGI
  4. cerebral cortex development Source: Ensembl
  5. growth Source: MGI
  6. lung alveolus development Source: MGI
  7. lung development Source: MGI
  8. negative regulation of transcription, DNA-templated Source: MGI
  9. negative regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  10. positive regulation of epithelial cell proliferation Source: MGI
  11. positive regulation of epithelial cell proliferation involved in lung morphogenesis Source: MGI
  12. positive regulation of mesenchymal cell proliferation Source: MGI
  13. post-embryonic development Source: MGI
  14. putamen development Source: UniProtKB
  15. righting reflex Source: MGI
  16. skeletal muscle tissue development Source: MGI
  17. smooth muscle tissue development Source: MGI
  18. vocal learning Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein P2
Gene namesi
Name:Foxp2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 6

Organism-specific databases

MGIiMGI:2148705. Foxp2.

Subcellular locationi

Nucleus Curated

GO - Cellular componenti

  1. nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi399 – 3991Missing: Loss of dimerization. Almost complete loss of DNA-binding. Reduced transcriptional repression activity. 1 Publication
Mutagenesisi407 – 4082HL → AA: Severely reduced transcriptional repression activity. 1 Publication
Mutagenesisi408 – 4081L → A: Severely reduced transcriptional repression activity. 1 Publication
Mutagenesisi421 – 4255PLNLV → AANAA: No significant effect on transcriptional repression activity. 1 Publication
Mutagenesisi552 – 5521R → H: No change in synaptic density. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 714714Forkhead box protein P2PRO_0000091882Add
BLAST

Proteomic databases

PRIDEiP58463.

PTM databases

PhosphoSiteiP58463.

Expressioni

Tissue specificityi

Highest expression in lung. Lower expression in spleen, skeletal muscle, brain, kidney and small intestine.

Developmental stagei

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.2 Publications

Gene expression databases

BgeeiP58463.
CleanExiMM_FOXP2.
ExpressionAtlasiP58463. baseline and differential.
GenevestigatoriP58463.

Interactioni

Subunit structurei

Forms homodimers and heterodimers with FOXP1 and FOXP4. Dimerization is required for DNA-binding. Interacts with CTBP1.1 Publication

Protein-protein interaction databases

BioGridi227578. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliP58463.
SMRiP58463. Positions 350-408, 502-583.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni387 – 40822Leucine-zipperAdd
BLAST
Regioni421 – 4255CTBP1-binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi53 – 267215Gln-richAdd
BLAST

Domaini

The leucine-zipper is required for dimerization and transcriptional repression.1 Publication

Sequence similaritiesi

Contains 1 C2H2-type zinc finger.Curated
Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri345 – 37026C2H2-typeAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiCOG5025.
GeneTreeiENSGT00780000121840.
HOGENOMiHOG000092089.
HOVERGENiHBG051657.
InParanoidiP58463.
KOiK09409.
OrthoDBiEOG7M6D7G.
PhylomeDBiP58463.
TreeFamiTF326978.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
IPR015880. Znf_C2H2-like.
[Graphical view]
PfamiPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
SM00355. ZnF_C2H2. 1 hit.
[Graphical view]
PROSITEiPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P58463-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MMQESATETI SNSSMNQNGM STLSSQLDAG SRDGRSSGDT SSEVSTVELL
60 70 80 90 100
HLQQQQALQA ARQLLLQQQT SGLKSPKSSE KQRPLQVPVS VAMMTPQVIT
110 120 130 140 150
PQQMQQILQQ QVLSPQQLQA LLQQQQAVML QQQQLQEFYK KQQEQLHLQL
160 170 180 190 200
LQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QHPGKQAKEQ
210 220 230 240 250
QQQQQQQQLA AQQLVFQQQL LQMQQLQQQQ HLLSLQRQGL ISIPPGQAAL
260 270 280 290 300
PVQSLPQAGL SPAEIQQLWK EVTGVHSMED NGIKHGGLDL TTNNSSSTTS
310 320 330 340 350
STTSKASPPI THHSIVNGQS SVLNARRDSS SHEETGASHT LYGHGVCKWP
360 370 380 390 400
GCESICEDFG QFLKHLNNEH ALDDRSTAQC RVQMQVVQQL EIQLSKERER
410 420 430 440 450
LQAMMTHLHM RPSEPKPSPK PLNLVSSVTM SKNMLETSPQ SLPQTPTTPT
460 470 480 490 500
APVTPITQGP SVITPASVPN VGAIRRRHSD KYNIPMSSEI APNYEFYKNA
510 520 530 540 550
DVRPPFTYAT LIRQAIMESS DRQLTLNEIY SWFTRTFAYF RRNAATWKNA
560 570 580 590 600
VRHNLSLHKC FVRVENVKGA VWTVDEVEYQ KRRSQKITGS PTLVKNIPTS
610 620 630 640 650
LGYGAALNAS LQAALAESSL PLLSNPGLIN NASSGLLQAV HEDLNGSLDH
660 670 680 690 700
IDSNGNSSPG CSPQPHIHSI HVKEEPVIAE DEDCPMSLVT TANHSPELED
710
DREIEEEPLS EDLE
Length:714
Mass (Da):79,819
Last modified:August 31, 2004 - v2
Checksum:iEB02D66B5AA452D0
GO
Isoform 2 (identifier: P58463-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     134-154: Missing.

Note: May be due to a competing acceptor splice site. No experimental confirmation available.

Show »
Length:693
Mass (Da):77,138
Checksum:i5A9582A3C4DB2E09
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti6 – 61A → V in AAK69651. (PubMed:11358962)Curated
Sequence conflicti543 – 5431N → S in AAK69651. (PubMed:11358962)Curated
Sequence conflicti663 – 6631P → R in BAC38477. (PubMed:16141072)Curated
Sequence conflicti675 – 6751E → D in BAC38477. (PubMed:16141072)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei134 – 15421Missing in isoform 2. 1 PublicationVSP_011540Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF339106 mRNA. Translation: AAK69651.1.
AY079003 mRNA. Translation: AAL85482.1.
AK082361 mRNA. Translation: BAC38477.1.
BC058960 mRNA. Translation: AAH58960.1.
BC062926 mRNA. Translation: AAH62926.1.
CCDSiCCDS19918.1. [P58463-1]
CCDS71726.1. [P58463-2]
RefSeqiNP_001273536.1. NM_001286607.1. [P58463-2]
NP_444472.2. NM_053242.4. [P58463-1]
NP_997600.1. NM_212435.1. [P58463-1]
UniGeneiMm.332919.

Genome annotation databases

EnsembliENSMUST00000031545; ENSMUSP00000031545; ENSMUSG00000029563. [P58463-1]
ENSMUST00000115472; ENSMUSP00000111132; ENSMUSG00000029563. [P58463-2]
ENSMUST00000115477; ENSMUSP00000111137; ENSMUSG00000029563. [P58463-1]
GeneIDi114142.
KEGGimmu:114142.
UCSCiuc009ayy.1. mouse. [P58463-1]
uc012eie.1. mouse. [P58463-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF339106 mRNA. Translation: AAK69651.1.
AY079003 mRNA. Translation: AAL85482.1.
AK082361 mRNA. Translation: BAC38477.1.
BC058960 mRNA. Translation: AAH58960.1.
BC062926 mRNA. Translation: AAH62926.1.
CCDSiCCDS19918.1. [P58463-1]
CCDS71726.1. [P58463-2]
RefSeqiNP_001273536.1. NM_001286607.1. [P58463-2]
NP_444472.2. NM_053242.4. [P58463-1]
NP_997600.1. NM_212435.1. [P58463-1]
UniGeneiMm.332919.

3D structure databases

ProteinModelPortaliP58463.
SMRiP58463. Positions 350-408, 502-583.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi227578. 1 interaction.

PTM databases

PhosphoSiteiP58463.

Proteomic databases

PRIDEiP58463.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000031545; ENSMUSP00000031545; ENSMUSG00000029563. [P58463-1]
ENSMUST00000115472; ENSMUSP00000111132; ENSMUSG00000029563. [P58463-2]
ENSMUST00000115477; ENSMUSP00000111137; ENSMUSG00000029563. [P58463-1]
GeneIDi114142.
KEGGimmu:114142.
UCSCiuc009ayy.1. mouse. [P58463-1]
uc012eie.1. mouse. [P58463-2]

Organism-specific databases

CTDi93986.
MGIiMGI:2148705. Foxp2.

Phylogenomic databases

eggNOGiCOG5025.
GeneTreeiENSGT00780000121840.
HOGENOMiHOG000092089.
HOVERGENiHBG051657.
InParanoidiP58463.
KOiK09409.
OrthoDBiEOG7M6D7G.
PhylomeDBiP58463.
TreeFamiTF326978.

Miscellaneous databases

ChiTaRSiFoxp2. mouse.
NextBioi368137.
PROiP58463.
SOURCEiSearch...

Gene expression databases

BgeeiP58463.
CleanExiMM_FOXP2.
ExpressionAtlasiP58463. baseline and differential.
GenevestigatoriP58463.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
IPR015880. Znf_C2H2-like.
[Graphical view]
PfamiPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
SM00355. ZnF_C2H2. 1 hit.
[Graphical view]
PROSITEiPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of a new subfamily of winged-helix/forkhead (Fox) genes that are expressed in the lung and act as transcriptional repressors."
    Shu W., Yang H., Zhang L., Lu M.M., Morrisey E.E.
    J. Biol. Chem. 276:27488-27497(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DEVELOPMENTAL STAGE.
    Strain: C57BL/6.
    Tissue: Lung.
  2. "Molecular evolution of FOXP2, a gene involved in speech and language."
    Enard W., Przeworski M., Fisher S.E., Lai C.S.L., Wiebe V., Kitano T., Monaco A.P., Paeaebo S.
    Nature 418:869-872(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: BALB/c.
  3. "The transcriptional landscape of the mammalian genome."
    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.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: C57BL/6J.
    Tissue: Cerebellum.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6.
    Tissue: Brain.
  5. "Foxp4: a novel member of the Foxp subfamily of winged-helix genes co-expressed with Foxp1 and Foxp2 in pulmonary and gut tissues."
    Lu M.M., Li S., Yang H., Morrisey E.E.
    Mech. Dev. 119:S197-S202(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.
  6. "Transcriptional and DNA binding activity of the Foxp1/2/4 family is modulated by heterotypic and homotypic protein interactions."
    Li S., Weidenfeld J., Morrisey E.E.
    Mol. Cell. Biol. 24:809-822(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DIMERIZATION, INTERACTION WITH CTBP1, DOMAIN, MUTAGENESIS OF GLU-399; 407-HIS-LEU-408; LEU-408 AND 421-PRO--VAL-425.
  7. "The human language-associated gene SRPX2 regulates synapse formation and vocalization in mice."
    Sia G.M., Clem R.L., Huganir R.L.
    Science 342:987-991(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF ARG-552.

Entry informationi

Entry nameiFOXP2_MOUSE
AccessioniPrimary (citable) accession number: P58463
Secondary accession number(s): Q6PD37, Q8C4F0, Q8R441
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: August 31, 2004
Last modified: February 4, 2015
This is version 125 of the entry and version 2 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.