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   27-MAR-2024, entry version 129.
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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
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   DNASU; 17293; -.
DR   GeneID; 17293; -.
DR   KEGG; mmu:17293; -.
DR   AGR; MGI:1096325; -.
DR   CTD; 145873; -.
DR   MGI; MGI:1096325; Mesp2.
DR   eggNOG; KOG4029; Eukaryota.
DR   InParanoid; O08574; -.
DR   OrthoDB; 5354298at2759; -.
DR   PhylomeDB; O08574; -.
DR   BioGRID-ORCS; 17293; 1 hit in 78 CRISPR screens.
DR   PRO; PR:O08574; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; O08574; Protein.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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   CDD; cd18938; bHLH_TS_Mesp; 1.
DR   Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1.
DR   InterPro; IPR011598; bHLH_dom.
DR   InterPro; IPR036638; HLH_DNA-bd_sf.
DR   InterPro; IPR040259; Mesogenin/MesP.
DR   PANTHER; PTHR20937; IP14615P; 1.
DR   PANTHER; PTHR20937:SF6; MESODERM POSTERIOR PROTEIN 2; 1.
DR   Pfam; PF00010; HLH; 1.
DR   SMART; SM00353; HLH; 1.
DR   SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 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
FT                   145-A--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
FT                   70-A--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
//