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O08574

- MESP2_MOUSE

UniProt

O08574 - MESP2_MOUSE

Protein

Mesoderm posterior protein 2

Gene

Mesp2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 85 (01 Oct 2014)
      Sequence version 1 (01 Jul 1997)
      Previous versions | rss
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    Functioni

    Transcription factor with important role in somitogenesis. Defines the rostrocaudal patterning of the somite by participating in distinct Notch pathways. Regulates also the FGF signaling pathway. Specifies the rostral half of the somites. Generates rostro-caudal polarity of somites by down-regulating in the presumptive rostral domain DLL1, a Notch ligand. Participates in the segment border formation by activating in the anterior presomitic mesoderm LFNG, a negative regulator of DLL1-Notch signaling. Acts as a strong suppressor of Notch activity. Together with MESP1 is involved in the epithelialization of somitic mesoderm and in the development of cardiac mesoderm. May play a role with Tcf15 in the differentiation of myotomal and sclerotomal cells by regulating Pax family genes. Controls also the expression of the protocadherin PCDH8/PAPC, EPHA4, RIPPLY2, NOTCH2, FGFR1, and CER1. Binds to the E-boxes within the EPH4A and RIPPLY2 enhancers.10 Publications

    GO - Molecular functioni

    1. DNA binding Source: MGI
    2. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
    3. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
    4. sequence-specific DNA binding transcription factor activity Source: MGI

    GO - Biological processi

    1. mesodermal cell migration Source: MGI
    2. Notch signaling pathway Source: MGI
    3. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
    4. signal transduction involved in regulation of gene expression Source: MGI
    5. somite rostral/caudal axis specification Source: MGI
    6. somitogenesis Source: MGI

    Keywords - Molecular functioni

    Developmental protein

    Keywords - Biological processi

    Notch signaling pathway, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mesoderm posterior protein 2
    Gene namesi
    Name:Mesp2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:1096325. Mesp2.

    Subcellular locationi

    Nucleus 2 PublicationsPROSITE-ProRule annotation

    GO - Cellular componenti

    1. nucleus Source: MGI

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Mice die shortly after birth and show caudal truncation and severe skeletal malformations. Lack of segmentation and impaired segment polarity of the paraxial mesoderm are the primarly defects. Mutants show altered expression of MEOX1, Pax1, and DLL1 and lack of expression of Notch1, Notch2, and FGFR1. Mice lacking Mesp1 and Mesp2 die around 9.5 dpc. The major defect is the apparent lack of any mesodermal layer between endoderm and ectoderm and a defect in the migratory activity of mesodermal cells.3 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi70 – 734RRTR → AATA: Localizes in nucleus and cytoplasm. Localizes mainly in cytoplasm; when associated with 145-A--A-150. 1 Publication
    Mutagenesisi145 – 1506RRRRRR → AAAAAA: Localizes in nucleus and cytoplasm. Localizes mainly in cytoplasm; when associated with 70-A--A-73. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 370370Mesoderm posterior protein 2PRO_0000296302Add
    BLAST

    Post-translational modificationi

    Degraded by the proteasome.
    Phosphorylated.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiO08574.

    PTM databases

    PhosphoSiteiO08574.

    Expressioni

    Developmental stagei

    First transiently detected in the nascent mesoderm at the onset of gastrulation. A second site of expression is detected at 8 dpc in the rostral region of the presomitic mesoderm inmediately before segmentation. Down-regulated immediately after the formation of the segmented somites before 13.5 dpc. Initially expressed throughout the length of one somite, and then quickly repressed in the presumptive caudal region. Mesp2 is involved in the rapid down-regulation of its own expression in the presumptive caudal half of the somite.4 Publications

    Inductioni

    Down-regulated in NOTCH1, DLL1, RBPJ and FOXC1/FOXC2 mutant mices. Expression in the anterior presomitic mesoderm is periodic, dissipating once the segmental border is established. Negatively regulated by RIPPLY2. Positively regulated by TBX6 and Notch signaling.5 Publications

    Gene expression databases

    CleanExiMM_MESP2.
    GenevestigatoriO08574.

    Structurei

    3D structure databases

    ProteinModelPortaliO08574.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini79 – 13355bHLHPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni326 – 3305May contain a degradation domain

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi145 – 1506Poly-Arg

    Sequence similaritiesi

    Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG320808.
    HOVERGENiHBG096371.
    KOiK09076.
    PhylomeDBiO08574.

    Family and domain databases

    Gene3Di4.10.280.10. 1 hit.
    InterProiIPR011598. bHLH_dom.
    [Graphical view]
    PfamiPF00010. HLH. 1 hit.
    [Graphical view]
    SMARTiSM00353. HLH. 1 hit.
    [Graphical view]
    SUPFAMiSSF47459. SSF47459. 1 hit.
    PROSITEiPS50888. BHLH. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O08574-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAQSSPPQSL QGLVPLGLLP GLGLGSAIGL HVSGLVLRFV RFLPFYATRR    50
    PSQPAGPARS TRTTQATAPR RTRPAPAGGQ RQSASEREKL RMRTLARALQ 100
    ELRRFLPPSV APAGQSLTKI ETLRLAIRYI GHLSALLGLS EDSLRRRRRR 150
    SADAAFSHRC PQCPDGGSPS QAQMLGPSLG SAMSSGVSWG CPPACPGPLI 200
    SPENLGNRIS NVDPRVTPPY CPQIQSPLHQ SLERAADSSP WAPPQACPGM 250
    QMSPEPRNKT GHWTQSTEPA ELTKVYQSLS VSPEPRLSLG SPLLLPRPSC 300
    QRLQPQPQPQ PQWGCWGHDA EVLSTSEDQG SSPALQLPVA SPTPSSGLQL 350
    SGCPELWQED LEGPPLNIFY 370
    Length:370
    Mass (Da):39,789
    Last modified:July 1, 1997 - v1
    Checksum:i31CAB72E2398150D
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti107 – 1071P → G in BAE27401. (PubMed:16141072)Curated
    Sequence conflicti215 – 2151R → W in BAE27401. (PubMed:16141072)Curated
    Sequence conflicti286 – 2861R → C in BAE27401. (PubMed:16141072)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U71125 mRNA. Translation: AAB51199.1.
    AK146740 mRNA. Translation: BAE27401.1.
    RefSeqiNP_032615.2. NM_008589.2.
    UniGeneiMm.31472.

    Genome annotation databases

    GeneIDi17293.
    KEGGimmu:17293.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U71125 mRNA. Translation: AAB51199.1 .
    AK146740 mRNA. Translation: BAE27401.1 .
    RefSeqi NP_032615.2. NM_008589.2.
    UniGenei Mm.31472.

    3D structure databases

    ProteinModelPortali O08574.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei O08574.

    Proteomic databases

    PRIDEi O08574.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 17293.
    KEGGi mmu:17293.

    Organism-specific databases

    CTDi 145873.
    MGIi MGI:1096325. Mesp2.

    Phylogenomic databases

    eggNOGi NOG320808.
    HOVERGENi HBG096371.
    KOi K09076.
    PhylomeDBi O08574.

    Miscellaneous databases

    NextBioi 291818.
    PROi O08574.
    SOURCEi Search...

    Gene expression databases

    CleanExi MM_MESP2.
    Genevestigatori O08574.

    Family and domain databases

    Gene3Di 4.10.280.10. 1 hit.
    InterProi IPR011598. bHLH_dom.
    [Graphical view ]
    Pfami PF00010. HLH. 1 hit.
    [Graphical view ]
    SMARTi SM00353. HLH. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47459. SSF47459. 1 hit.
    PROSITEi PS50888. BHLH. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Mesp2: a novel mouse gene expressed in the presegmented mesoderm and essential for segmentation initiation."
      Saga Y., Hata N., Koseki H., Taketo M.M.
      Genes Dev. 11:1827-1839(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, INDUCTION, DISRUPTION PHENOTYPE.
      Strain: ICR.
    2. "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] OF 107-370.
      Strain: C57BL/6J.
      Tissue: Liver.
    3. "Interaction between Notch signalling and Lunatic fringe during somite boundary formation in the mouse."
      del Barco Barrantes I., Elia A.J., Wuensch K., De Angelis M.H., Mak T.W., Rossant J., Conlon R.A., Gossler A., de la Pompa J.L.
      Curr. Biol. 9:470-480(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    4. "MesP1 and MesP2 are essential for the development of cardiac mesoderm."
      Kitajima S., Takagi A., Inoue T., Saga Y.
      Development 127:3215-3226(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEVELOPMENT OF CARDIAC MESODERM, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
    5. "Mesp2 initiates somite segmentation through the Notch signalling pathway."
      Takahashi Y., Koizumi K., Takagi A., Kitajima S., Inoue T., Koseki H., Saga Y.
      Nat. Genet. 25:390-396(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DEVELOPMENTAL STAGE.
    6. "The murine winged helix transcription factors, Foxc1 and Foxc2, are both required for cardiovascular development and somitogenesis."
      Kume T., Jiang H., Topczewska J.M., Hogan B.L.
      Genes Dev. 15:2470-2482(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    7. "Feedback loops comprising Dll1, Dll3 and Mesp2, and differential involvement of Psen1 are essential for rostrocaudal patterning of somites."
      Takahashi Y., Inoue T., Gossler A., Saga Y.
      Development 130:4259-4268(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    8. "The protocadherin papc is involved in the organization of the epithelium along the segmental border during mouse somitogenesis."
      Rhee J., Takahashi Y., Saga Y., Wilson-Rawls J., Rawls A.
      Dev. Biol. 254:248-261(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    9. "Differential contributions of Mesp1 and Mesp2 to the epithelialization and rostro-caudal patterning of somites."
      Takahashi Y., Kitajima S., Inoue T., Kanno J., Saga Y.
      Development 132:787-796(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity."
      Morimoto M., Takahashi Y., Endo M., Saga Y.
      Nature 435:354-359(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
    11. "Identification of Epha4 enhancer required for segmental expression and the regulation by Mesp2."
      Nakajima Y., Morimoto M., Takahashi Y., Koseki H., Saga Y.
      Development 133:2517-2525(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DNA-BINDING.
    12. "Cooperative Mesp activity is required for normal somitogenesis along the anterior-posterior axis."
      Morimoto M., Kiso M., Sasaki N., Saga Y.
      Dev. Biol. 300:687-698(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, DEGRADATION, PHOSPHORYLATION, MUTAGENESIS OF 70-ARG--ARG-73 AND 145-ARG--ARG-150.
    13. "Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression."
      Yasuhiko Y., Haraguchi S., Kitajima S., Takahashi Y., Kanno J., Saga Y.
      Proc. Natl. Acad. Sci. U.S.A. 103:3651-3656(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION BY TBX6 AND NOTCH SIGNALING.
    14. "The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite."
      Morimoto M., Sasaki N., Oginuma M., Kiso M., Igarashi K., Aizaki K., Kanno J., Saga Y.
      Development 134:1561-1569(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: DNA-BINDING, INDUCTION BY RIPPLY2.
    15. "Appropriate suppression of Notch signaling by Mesp factors is essential for stripe pattern formation leading to segment boundary formation."
      Takahashi Y., Yasuhiko Y., Kitajima S., Kanno J., Saga Y.
      Dev. Biol. 304:593-603(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    16. "Transcription factors Mesp2 and Paraxis have critical roles in axial musculoskeletal formation."
      Takahashi Y., Takagi A., Hiraoka S., Koseki H., Kanno J., Rawls A., Saga Y.
      Dev. Dyn. 236:1484-1494(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiMESP2_MOUSE
    AccessioniPrimary (citable) accession number: O08574
    Secondary accession number(s): Q3UIV5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 24, 2007
    Last sequence update: July 1, 1997
    Last modified: October 1, 2014
    This is version 85 of the entry and version 1 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