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O08574 (MESP2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 84. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mesoderm posterior protein 2
Gene names
Name:Mesp2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length370 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.4 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.15 Ref.16

Subcellular location

Nucleus Ref.10 Ref.12.

Developmental stage

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. Ref.1 Ref.4 Ref.5 Ref.10

Induction

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. Ref.1 Ref.3 Ref.6 Ref.13 Ref.14

Post-translational modification

Degraded by the proteasome.

Phosphorylated. Ref.12

Disruption phenotype

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. Ref.1 Ref.4 Ref.15

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 370370Mesoderm posterior protein 2
PRO_0000296302

Regions

Domain79 – 13355bHLH
Region326 – 3305May contain a degradation domain
Compositional bias145 – 1506Poly-Arg

Experimental info

Mutagenesis70 – 734RRTR → AATA: Localizes in nucleus and cytoplasm. Localizes mainly in cytoplasm; when associated with 145-A--A-150. Ref.12
Mutagenesis145 – 1506RRRRRR → AAAAAA: Localizes in nucleus and cytoplasm. Localizes mainly in cytoplasm; when associated with 70-A--A-73. Ref.12
Sequence conflict1071P → G in BAE27401. Ref.2
Sequence conflict2151R → W in BAE27401. Ref.2
Sequence conflict2861R → C in BAE27401. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O08574 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: 31CAB72E2398150D

FASTA37039,789
        10         20         30         40         50         60 
MAQSSPPQSL QGLVPLGLLP GLGLGSAIGL HVSGLVLRFV RFLPFYATRR PSQPAGPARS 

        70         80         90        100        110        120 
TRTTQATAPR RTRPAPAGGQ RQSASEREKL RMRTLARALQ ELRRFLPPSV APAGQSLTKI 

       130        140        150        160        170        180 
ETLRLAIRYI GHLSALLGLS EDSLRRRRRR SADAAFSHRC PQCPDGGSPS QAQMLGPSLG 

       190        200        210        220        230        240 
SAMSSGVSWG CPPACPGPLI SPENLGNRIS NVDPRVTPPY CPQIQSPLHQ SLERAADSSP 

       250        260        270        280        290        300 
WAPPQACPGM QMSPEPRNKT GHWTQSTEPA ELTKVYQSLS VSPEPRLSLG SPLLLPRPSC 

       310        320        330        340        350        360 
QRLQPQPQPQ PQWGCWGHDA EVLSTSEDQG SSPALQLPVA SPTPSSGLQL SGCPELWQED 

       370 
LEGPPLNIFY 

« Hide

References

« Hide 'large scale' references
[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. 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] 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U71125 mRNA. Translation: AAB51199.1.
AK146740 mRNA. Translation: BAE27401.1.
RefSeqNP_032615.2. NM_008589.2.
UniGeneMm.31472.

3D structure databases

ProteinModelPortalO08574.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteO08574.

Proteomic databases

PRIDEO08574.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID17293.
KEGGmmu:17293.

Organism-specific databases

CTD145873.
MGIMGI:1096325. Mesp2.

Phylogenomic databases

eggNOGNOG320808.
HOVERGENHBG096371.
KOK09076.
PhylomeDBO08574.

Gene expression databases

CleanExMM_MESP2.
GenevestigatorO08574.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
[Graphical view]
PfamPF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio291818.
PROO08574.
SOURCESearch...

Entry information

Entry nameMESP2_MOUSE
AccessionPrimary (citable) accession number: O08574
Secondary accession number(s): Q3UIV5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 24, 2007
Last sequence update: July 1, 1997
Last modified: July 9, 2014
This is version 84 of the entry and version 1 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