MESP2_MOUSE
ID MESP2_MOUSE Reviewed; 370 AA.
AC O08574; Q3UIV5;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Mesoderm posterior protein 2;
GN Name=Mesp2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=ICR;
RX PubMed=9242490; DOI=10.1101/gad.11.14.1827;
RA Saga Y., Hata N., Koseki H., Taketo M.M.;
RT "Mesp2: a novel mouse gene expressed in the presegmented mesoderm and
RT essential for segmentation initiation.";
RL Genes Dev. 11:1827-1839(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 107-370.
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP INDUCTION.
RX PubMed=10330372; DOI=10.1016/s0960-9822(99)80212-7;
RA del Barco Barrantes I., Elia A.J., Wuensch K., De Angelis M.H., Mak T.W.,
RA Rossant J., Conlon R.A., Gossler A., de la Pompa J.L.;
RT "Interaction between Notch signalling and Lunatic fringe during somite
RT boundary formation in the mouse.";
RL Curr. Biol. 9:470-480(1999).
RN [4]
RP FUNCTION IN DEVELOPMENT OF CARDIAC MESODERM, DEVELOPMENTAL STAGE, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=10887078; DOI=10.1242/dev.127.15.3215;
RA Kitajima S., Takagi A., Inoue T., Saga Y.;
RT "MesP1 and MesP2 are essential for the development of cardiac mesoderm.";
RL Development 127:3215-3226(2000).
RN [5]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=10932180; DOI=10.1038/78062;
RA Takahashi Y., Koizumi K., Takagi A., Kitajima S., Inoue T., Koseki H.,
RA Saga Y.;
RT "Mesp2 initiates somite segmentation through the Notch signalling
RT pathway.";
RL Nat. Genet. 25:390-396(2000).
RN [6]
RP INDUCTION.
RX PubMed=11562355; DOI=10.1101/gad.907301;
RA Kume T., Jiang H., Topczewska J.M., Hogan B.L.;
RT "The murine winged helix transcription factors, Foxc1 and Foxc2, are both
RT required for cardiovascular development and somitogenesis.";
RL Genes Dev. 15:2470-2482(2001).
RN [7]
RP FUNCTION.
RX PubMed=12900443; DOI=10.1242/dev.00629;
RA Takahashi Y., Inoue T., Gossler A., Saga Y.;
RT "Feedback loops comprising Dll1, Dll3 and Mesp2, and differential
RT involvement of Psen1 are essential for rostrocaudal patterning of
RT somites.";
RL Development 130:4259-4268(2003).
RN [8]
RP FUNCTION.
RX PubMed=12591245; DOI=10.1016/s0012-1606(02)00085-4;
RA Rhee J., Takahashi Y., Saga Y., Wilson-Rawls J., Rawls A.;
RT "The protocadherin papc is involved in the organization of the epithelium
RT along the segmental border during mouse somitogenesis.";
RL Dev. Biol. 254:248-261(2003).
RN [9]
RP FUNCTION.
RX PubMed=15677726; DOI=10.1242/dev.01597;
RA Takahashi Y., Kitajima S., Inoue T., Kanno J., Saga Y.;
RT "Differential contributions of Mesp1 and Mesp2 to the epithelialization and
RT rostro-caudal patterning of somites.";
RL Development 132:787-796(2005).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=15902259; DOI=10.1038/nature03591;
RA Morimoto M., Takahashi Y., Endo M., Saga Y.;
RT "The Mesp2 transcription factor establishes segmental borders by
RT suppressing Notch activity.";
RL Nature 435:354-359(2005).
RN [11]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=16728472; DOI=10.1242/dev.02422;
RA Nakajima Y., Morimoto M., Takahashi Y., Koseki H., Saga Y.;
RT "Identification of Epha4 enhancer required for segmental expression and the
RT regulation by Mesp2.";
RL Development 133:2517-2525(2006).
RN [12]
RP SUBCELLULAR LOCATION, DEGRADATION, PHOSPHORYLATION, AND MUTAGENESIS OF
RP 70-ARG--ARG-73 AND 145-ARG--ARG-150.
RX PubMed=16996494; DOI=10.1016/j.ydbio.2006.08.043;
RA Morimoto M., Kiso M., Sasaki N., Saga Y.;
RT "Cooperative Mesp activity is required for normal somitogenesis along the
RT anterior-posterior axis.";
RL Dev. Biol. 300:687-698(2006).
RN [13]
RP INDUCTION BY TBX6 AND NOTCH SIGNALING.
RX PubMed=16505380; DOI=10.1073/pnas.0508238103;
RA Yasuhiko Y., Haraguchi S., Kitajima S., Takahashi Y., Kanno J., Saga Y.;
RT "Tbx6-mediated Notch signaling controls somite-specific Mesp2 expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:3651-3656(2006).
RN [14]
RP DNA-BINDING, AND INDUCTION BY RIPPLY2.
RX PubMed=17360776; DOI=10.1242/dev.000836;
RA Morimoto M., Sasaki N., Oginuma M., Kiso M., Igarashi K., Aizaki K.,
RA Kanno J., Saga Y.;
RT "The negative regulation of Mesp2 by mouse Ripply2 is required to establish
RT the rostro-caudal patterning within a somite.";
RL Development 134:1561-1569(2007).
RN [15]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17306789; DOI=10.1016/j.ydbio.2007.01.007;
RA Takahashi Y., Yasuhiko Y., Kitajima S., Kanno J., Saga Y.;
RT "Appropriate suppression of Notch signaling by Mesp factors is essential
RT for stripe pattern formation leading to segment boundary formation.";
RL Dev. Biol. 304:593-603(2007).
RN [16]
RP FUNCTION.
RX PubMed=17477400; DOI=10.1002/dvdy.21178;
RA Takahashi Y., Takagi A., Hiraoka S., Koseki H., Kanno J., Rawls A.,
RA Saga Y.;
RT "Transcription factors Mesp2 and Paraxis have critical roles in axial
RT musculoskeletal formation.";
RL Dev. Dyn. 236:1484-1494(2007).
CC -!- FUNCTION: Transcription factor with important role in somitogenesis.
CC Defines the rostrocaudal patterning of the somite by participating in
CC distinct Notch pathways. Regulates also the FGF signaling pathway.
CC Specifies the rostral half of the somites. Generates rostro-caudal
CC polarity of somites by down-regulating in the presumptive rostral
CC domain DLL1, a Notch ligand. Participates in the segment border
CC formation by activating in the anterior presomitic mesoderm LFNG, a
CC negative regulator of DLL1-Notch signaling. Acts as a strong suppressor
CC of Notch activity. Together with MESP1 is involved in the
CC epithelialization of somitic mesoderm and in the development of cardiac
CC mesoderm. May play a role with Tcf15 in the differentiation of myotomal
CC and sclerotomal cells by regulating Pax family genes. Controls also the
CC expression of the protocadherin PCDH8/PAPC, EPHA4, RIPPLY2, NOTCH2,
CC FGFR1, and CER1. Binds to the E-boxes within the EPH4A and RIPPLY2
CC enhancers. {ECO:0000269|PubMed:10887078, ECO:0000269|PubMed:10932180,
CC ECO:0000269|PubMed:12591245, ECO:0000269|PubMed:12900443,
CC ECO:0000269|PubMed:15677726, ECO:0000269|PubMed:15902259,
CC ECO:0000269|PubMed:16728472, ECO:0000269|PubMed:17306789,
CC ECO:0000269|PubMed:17477400, ECO:0000269|PubMed:9242490}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981,
CC ECO:0000269|PubMed:15902259, ECO:0000269|PubMed:16996494}.
CC -!- DEVELOPMENTAL STAGE: First transiently detected in the nascent mesoderm
CC at the onset of gastrulation. A second site of expression is detected
CC at 8 dpc in the rostral region of the presomitic mesoderm inmediately
CC before segmentation. Down-regulated immediately after the formation of
CC the segmented somites before 13.5 dpc. Initially expressed throughout
CC the length of one somite, and then quickly repressed in the presumptive
CC caudal region. Mesp2 is involved in the rapid down-regulation of its
CC own expression in the presumptive caudal half of the somite.
CC {ECO:0000269|PubMed:10887078, ECO:0000269|PubMed:10932180,
CC ECO:0000269|PubMed:15902259, ECO:0000269|PubMed:9242490}.
CC -!- INDUCTION: Down-regulated in NOTCH1, DLL1, RBPJ and FOXC1/FOXC2 mutant
CC mice. Expression in the anterior presomitic mesoderm is periodic,
CC dissipating once the segmental border is established. Negatively
CC regulated by RIPPLY2. Positively regulated by TBX6 and Notch signaling.
CC {ECO:0000269|PubMed:10330372, ECO:0000269|PubMed:11562355,
CC ECO:0000269|PubMed:16505380, ECO:0000269|PubMed:17360776,
CC ECO:0000269|PubMed:9242490}.
CC -!- PTM: Degraded by the proteasome.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:16996494}.
CC -!- DISRUPTION PHENOTYPE: Mice die shortly after birth and show caudal
CC truncation and severe skeletal malformations. Lack of segmentation and
CC impaired segment polarity of the paraxial mesoderm are the primary
CC defects. Mutants show altered expression of MEOX1, Pax1, and DLL1 and
CC lack of expression of Notch1, Notch2, and FGFR1. Mice lacking Mesp1 and
CC Mesp2 die around 9.5 dpc. The major defect is the apparent lack of any
CC mesodermal layer between endoderm and ectoderm and a defect in the
CC migratory activity of mesodermal cells. {ECO:0000269|PubMed:10887078,
CC ECO:0000269|PubMed:17306789, ECO:0000269|PubMed:9242490}.
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DR EMBL; U71125; AAB51199.1; -; mRNA.
DR EMBL; AK146740; BAE27401.1; -; mRNA.
DR RefSeq; NP_032615.2; NM_008589.2.
DR AlphaFoldDB; O08574; -.
DR SMR; O08574; -.
DR iPTMnet; O08574; -.
DR PhosphoSitePlus; O08574; -.
DR PRIDE; O08574; -.
DR DNASU; 17293; -.
DR GeneID; 17293; -.
DR KEGG; mmu:17293; -.
DR CTD; 145873; -.
DR MGI; MGI:1096325; Mesp2.
DR eggNOG; KOG4029; Eukaryota.
DR InParanoid; O08574; -.
DR OrthoDB; 1072866at2759; -.
DR PhylomeDB; O08574; -.
DR BioGRID-ORCS; 17293; 1 hit in 73 CRISPR screens.
DR PRO; PR:O08574; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O08574; protein.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0003007; P:heart morphogenesis; IBA:GO_Central.
DR GO; GO:0001707; P:mesoderm formation; IBA:GO_Central.
DR GO; GO:0008078; P:mesodermal cell migration; IGI:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IDA:MGI.
DR GO; GO:0032525; P:somite rostral/caudal axis specification; IMP:MGI.
DR GO; GO:0001756; P:somitogenesis; IMP:MGI.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR040259; Mesogenin/MesP.
DR PANTHER; PTHR20937; PTHR20937; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Developmental protein; DNA-binding; Notch signaling pathway; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..370
FT /note="Mesoderm posterior protein 2"
FT /id="PRO_0000296302"
FT DOMAIN 79..133
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 51..89
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 231..265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 325..350
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 326..330
FT /note="May contain a degradation domain"
FT COMPBIAS 54..70
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 70..73
FT /note="RRTR->AATA: Localizes in nucleus and cytoplasm.
FT Localizes mainly in cytoplasm; when associated with 145-A--
FT A-150."
FT /evidence="ECO:0000269|PubMed:16996494"
FT MUTAGEN 145..150
FT /note="RRRRRR->AAAAAA: Localizes in nucleus and cytoplasm.
FT Localizes mainly in cytoplasm; when associated with 70-A--
FT A-73."
FT /evidence="ECO:0000269|PubMed:16996494"
FT CONFLICT 107
FT /note="P -> G (in Ref. 2; BAE27401)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="R -> W (in Ref. 2; BAE27401)"
FT /evidence="ECO:0000305"
FT CONFLICT 286
FT /note="R -> C (in Ref. 2; BAE27401)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 370 AA; 39789 MW; 31CAB72E2398150D CRC64;
MAQSSPPQSL QGLVPLGLLP GLGLGSAIGL HVSGLVLRFV RFLPFYATRR PSQPAGPARS
TRTTQATAPR RTRPAPAGGQ RQSASEREKL RMRTLARALQ ELRRFLPPSV APAGQSLTKI
ETLRLAIRYI GHLSALLGLS EDSLRRRRRR SADAAFSHRC PQCPDGGSPS QAQMLGPSLG
SAMSSGVSWG CPPACPGPLI SPENLGNRIS NVDPRVTPPY CPQIQSPLHQ SLERAADSSP
WAPPQACPGM QMSPEPRNKT GHWTQSTEPA ELTKVYQSLS VSPEPRLSLG SPLLLPRPSC
QRLQPQPQPQ PQWGCWGHDA EVLSTSEDQG SSPALQLPVA SPTPSSGLQL SGCPELWQED
LEGPPLNIFY
