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P58463

- FOXP2_MOUSE

UniProt

P58463 - FOXP2_MOUSE

Protein

Forkhead box protein P2

Gene

Foxp2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 2 (31 Aug 2004)
      Previous versions | rss
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    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 binding Source: UniProtKB
    4. protein heterodimerization activity Source: MGI
    5. protein homodimerization activity Source: UniProtKB
    6. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
    7. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Source: NTNU_SB
    8. 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

    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

    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.
    Mutagenesisi408 – 4081L → A: Severely reduced transcriptional repression activity. 1 Publication
    Mutagenesisi421 – 4255PLNLV → AANAA: No significant effect on transcriptional repression activity.
    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

    ArrayExpressiP58463.
    BgeeiP58463.
    CleanExiMM_FOXP2.
    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.
    GeneTreeiENSGT00750000117475.
    HOGENOMiHOG000092089.
    HOVERGENiHBG051657.
    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

    MMQESATETI SNSSMNQNGM STLSSQLDAG SRDGRSSGDT SSEVSTVELL    50
    HLQQQQALQA ARQLLLQQQT SGLKSPKSSE KQRPLQVPVS VAMMTPQVIT 100
    PQQMQQILQQ QVLSPQQLQA LLQQQQAVML QQQQLQEFYK KQQEQLHLQL 150
    LQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QHPGKQAKEQ 200
    QQQQQQQQLA AQQLVFQQQL LQMQQLQQQQ HLLSLQRQGL ISIPPGQAAL 250
    PVQSLPQAGL SPAEIQQLWK EVTGVHSMED NGIKHGGLDL TTNNSSSTTS 300
    STTSKASPPI THHSIVNGQS SVLNARRDSS SHEETGASHT LYGHGVCKWP 350
    GCESICEDFG QFLKHLNNEH ALDDRSTAQC RVQMQVVQQL EIQLSKERER 400
    LQAMMTHLHM RPSEPKPSPK PLNLVSSVTM SKNMLETSPQ SLPQTPTTPT 450
    APVTPITQGP SVITPASVPN VGAIRRRHSD KYNIPMSSEI APNYEFYKNA 500
    DVRPPFTYAT LIRQAIMESS DRQLTLNEIY SWFTRTFAYF RRNAATWKNA 550
    VRHNLSLHKC FVRVENVKGA VWTVDEVEYQ KRRSQKITGS PTLVKNIPTS 600
    LGYGAALNAS LQAALAESSL PLLSNPGLIN NASSGLLQAV HEDLNGSLDH 650
    IDSNGNSSPG CSPQPHIHSI HVKEEPVIAE DEDCPMSLVT TANHSPELED 700
    DREIEEEPLS EDLE 714
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS19918.1. [P58463-1 ]
    CCDS71726.1. [P58463-2 ]
    RefSeqi NP_001273536.1. NM_001286607.1. [P58463-2 ]
    NP_444472.2. NM_053242.4. [P58463-1 ]
    NP_997600.1. NM_212435.1. [P58463-1 ]
    UniGenei Mm.332919.

    3D structure databases

    ProteinModelPortali P58463.
    SMRi P58463. Positions 350-408, 502-583.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 227578. 1 interaction.

    PTM databases

    PhosphoSitei P58463.

    Proteomic databases

    PRIDEi P58463.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000031545 ; ENSMUSP00000031545 ; ENSMUSG00000029563 . [P58463-1 ]
    ENSMUST00000115472 ; ENSMUSP00000111132 ; ENSMUSG00000029563 . [P58463-2 ]
    ENSMUST00000115477 ; ENSMUSP00000111137 ; ENSMUSG00000029563 . [P58463-1 ]
    GeneIDi 114142.
    KEGGi mmu:114142.
    UCSCi uc009ayy.1. mouse. [P58463-1 ]
    uc012eie.1. mouse. [P58463-2 ]

    Organism-specific databases

    CTDi 93986.
    MGIi MGI:2148705. Foxp2.

    Phylogenomic databases

    eggNOGi COG5025.
    GeneTreei ENSGT00750000117475.
    HOGENOMi HOG000092089.
    HOVERGENi HBG051657.
    KOi K09409.
    OrthoDBi EOG7M6D7G.
    PhylomeDBi P58463.
    TreeFami TF326978.

    Miscellaneous databases

    ChiTaRSi FOXP2. mouse.
    NextBioi 368137.
    PROi P58463.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P58463.
    Bgeei P58463.
    CleanExi MM_FOXP2.
    Genevestigatori P58463.

    Family and domain databases

    Gene3Di 1.10.10.10. 1 hit.
    InterProi IPR001766. TF_fork_head.
    IPR018122. TF_fork_head_CS.
    IPR011991. WHTH_DNA-bd_dom.
    IPR015880. Znf_C2H2-like.
    [Graphical view ]
    Pfami PF00250. Fork_head. 1 hit.
    [Graphical view ]
    PRINTSi PR00053. FORKHEAD.
    SMARTi SM00339. FH. 1 hit.
    SM00355. ZnF_C2H2. 1 hit.
    [Graphical view ]
    PROSITEi PS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    PS00028. ZINC_FINGER_C2H2_1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 121 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