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P58463 (FOXP2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Forkhead box protein P2
Gene names
Name:Foxp2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length714 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.6 Ref.7

Subunit structure

Forms homodimers and heterodimers with FOXP1 and FOXP4. Dimerization is required for DNA-binding. Interacts with CTBP1. Ref.6

Subcellular location

Nucleus Probable.

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. Ref.1 Ref.5

Domain

The leucine-zipper is required for dimerization and transcriptional repression. Ref.6

Sequence similarities

Contains 1 C2H2-type zinc finger.

Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionRepressor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcamera-type eye development

Inferred from mutant phenotype PubMed 17619227. Source: MGI

caudate nucleus development

Inferred from sequence or structural similarity. Source: UniProtKB

cerebellum development

Inferred from mutant phenotype PubMed 15983371PubMed 17619227. Source: MGI

cerebral cortex development

Inferred from Biological aspect of Ancestor. Source: RefGenome

growth

Inferred from mutant phenotype PubMed 17619227. Source: MGI

lung alveolus development

Inferred from mutant phenotype PubMed 17428829. Source: MGI

lung development

Inferred from genetic interaction PubMed 17428829. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.6PubMed 17428829. Source: MGI

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.1. Source: MGI

pattern specification process

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of epithelial cell proliferation

Inferred from genetic interaction PubMed 17428829. Source: MGI

positive regulation of epithelial cell proliferation involved in lung morphogenesis

Inferred from genetic interaction PubMed 17428829. Source: MGI

positive regulation of mesenchymal cell proliferation

Inferred from genetic interaction PubMed 17428829. Source: MGI

post-embryonic development

Inferred from mutant phenotype PubMed 17619227. Source: MGI

putamen development

Inferred from sequence or structural similarity. Source: UniProtKB

righting reflex

Inferred from mutant phenotype PubMed 17619227. Source: MGI

skeletal muscle tissue development

Inferred from genetic interaction PubMed 17428829. Source: MGI

smooth muscle tissue development

Inferred from genetic interaction PubMed 17428829. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

vocal learning

Inferred from mutant phenotype PubMed 15983371. Source: MGI

   Cellular_componentcytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionDNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

DNA binding, bending

Inferred from Biological aspect of Ancestor. Source: RefGenome

chromatin binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.6. Source: UniProtKB

protein heterodimerization activity

Inferred from physical interaction Ref.6. Source: MGI

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 17428829. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P58463-1)

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.
Isoform 2 (identifier: P58463-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 714714Forkhead box protein P2
PRO_0000091882

Regions

Zinc finger345 – 37026C2H2-type
DNA binding503 – 59391Fork-head
Region387 – 40822Leucine-zipper
Region421 – 4255CTBP1-binding
Compositional bias53 – 267215Gln-rich

Natural variations

Alternative sequence134 – 15421Missing in isoform 2.
VSP_011540

Experimental info

Mutagenesis3991Missing: Loss of dimerization. Almost complete loss of DNA-binding. Reduced transcriptional repression activity. Ref.6
Mutagenesis407 – 4082HL → AA: Severely reduced transcriptional repression activity. Ref.6
Mutagenesis4081L → A: Severely reduced transcriptional repression activity. Ref.6
Mutagenesis421 – 4255PLNLV → AANAA: No significant effect on transcriptional repression activity. Ref.6
Mutagenesis5521R → H: No change in synaptic density. Ref.7
Sequence conflict61A → V in AAK69651. Ref.1
Sequence conflict5431N → S in AAK69651. Ref.1
Sequence conflict6631P → R in BAC38477. Ref.3
Sequence conflict6751E → D in BAC38477. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 31, 2004. Version 2.
Checksum: EB02D66B5AA452D0

FASTA71479,819
        10         20         30         40         50         60 
MMQESATETI SNSSMNQNGM STLSSQLDAG SRDGRSSGDT SSEVSTVELL HLQQQQALQA 

        70         80         90        100        110        120 
ARQLLLQQQT SGLKSPKSSE KQRPLQVPVS VAMMTPQVIT PQQMQQILQQ QVLSPQQLQA 

       130        140        150        160        170        180 
LLQQQQAVML QQQQLQEFYK KQQEQLHLQL LQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ 

       190        200        210        220        230        240 
QQQQQQQQQQ QHPGKQAKEQ QQQQQQQQLA AQQLVFQQQL LQMQQLQQQQ HLLSLQRQGL 

       250        260        270        280        290        300 
ISIPPGQAAL PVQSLPQAGL SPAEIQQLWK EVTGVHSMED NGIKHGGLDL TTNNSSSTTS 

       310        320        330        340        350        360 
STTSKASPPI THHSIVNGQS SVLNARRDSS SHEETGASHT LYGHGVCKWP GCESICEDFG 

       370        380        390        400        410        420 
QFLKHLNNEH ALDDRSTAQC RVQMQVVQQL EIQLSKERER LQAMMTHLHM RPSEPKPSPK 

       430        440        450        460        470        480 
PLNLVSSVTM SKNMLETSPQ SLPQTPTTPT APVTPITQGP SVITPASVPN VGAIRRRHSD 

       490        500        510        520        530        540 
KYNIPMSSEI APNYEFYKNA DVRPPFTYAT LIRQAIMESS DRQLTLNEIY SWFTRTFAYF 

       550        560        570        580        590        600 
RRNAATWKNA VRHNLSLHKC FVRVENVKGA VWTVDEVEYQ KRRSQKITGS PTLVKNIPTS 

       610        620        630        640        650        660 
LGYGAALNAS LQAALAESSL PLLSNPGLIN NASSGLLQAV HEDLNGSLDH IDSNGNSSPG 

       670        680        690        700        710 
CSPQPHIHSI HVKEEPVIAE DEDCPMSLVT TANHSPELED DREIEEEPLS EDLE 

« Hide

Isoform 2 [UniParc].

Checksum: 5A9582A3C4DB2E09
Show »

FASTA69377,138

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS19918.1. [P58463-1]
CCDS71726.1. [P58463-2]
RefSeqNP_001273536.1. NM_001286607.1. [P58463-2]
NP_444472.2. NM_053242.4. [P58463-1]
NP_997600.1. NM_212435.1. [P58463-1]
UniGeneMm.332919.

3D structure databases

ProteinModelPortalP58463.
SMRP58463. Positions 350-408, 502-583.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid227578. 1 interaction.

PTM databases

PhosphoSiteP58463.

Proteomic databases

PRIDEP58463.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000031545; ENSMUSP00000031545; ENSMUSG00000029563. [P58463-1]
ENSMUST00000115472; ENSMUSP00000111132; ENSMUSG00000029563. [P58463-2]
ENSMUST00000115477; ENSMUSP00000111137; ENSMUSG00000029563. [P58463-1]
GeneID114142.
KEGGmmu:114142.
UCSCuc009ayy.1. mouse. [P58463-1]
uc012eie.1. mouse. [P58463-2]

Organism-specific databases

CTD93986.
MGIMGI:2148705. Foxp2.

Phylogenomic databases

eggNOGCOG5025.
GeneTreeENSGT00750000117475.
HOGENOMHOG000092089.
HOVERGENHBG051657.
KOK09409.
OrthoDBEOG7M6D7G.
PhylomeDBP58463.
TreeFamTF326978.

Gene expression databases

ArrayExpressP58463.
BgeeP58463.
CleanExMM_FOXP2.
GenevestigatorP58463.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
IPR015880. Znf_C2H2-like.
[Graphical view]
PfamPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSPR00053. FORKHEAD.
SMARTSM00339. FH. 1 hit.
SM00355. ZnF_C2H2. 1 hit.
[Graphical view]
PROSITEPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFOXP2. mouse.
NextBio368137.
PROP58463.
SOURCESearch...

Entry information

Entry nameFOXP2_MOUSE
AccessionPrimary (citable) accession number: P58463
Secondary accession number(s): Q6PD37, Q8C4F0, Q8R441
Entry history
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: August 31, 2004
Last modified: July 9, 2014
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot