O08574 (MESP2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mesoderm posterior protein 2

Gene names

Name:

Mesp2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	370 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Notch signaling pathway Transcription Transcription regulation
Cellular component	Nucleus
Ligand	DNA-binding
Molecular function	Developmental protein
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Inferred from genetic interaction Ref.10. Source: MGI mesodermal cell migration Inferred from genetic interaction Ref.4. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.10. Source: MGI signal transduction involved in regulation of gene expression Inferred from direct assay PubMed 18462699. Source: MGI somitogenesis Inferred from mutant phenotype Ref.10. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from direct assay Ref.10. Source: MGI
Molecular_function	DNA binding Inferred from direct assay Ref.10. Source: MGI sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.10. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 370	370	Mesoderm posterior protein 2		PRO_0000296302
Regions
	Domain	79 – 133	55	bHLH
	Region	326 – 330	5	May contain a degradation domain
	Compositional bias	145 – 150	6	Poly-Arg
Experimental info
	Mutagenesis	70 – 73	4	RRTR → AATA: Localizes in nucleus and cytoplasm. Localizes mainly in cytoplasm; when associated with 145-A--A-150. Ref.12
	Mutagenesis	145 – 150	6	RRRRRR → AAAAAA: Localizes in nucleus and cytoplasm. Localizes mainly in cytoplasm; when associated with 70-A--A-73. Ref.12
	Sequence conflict	107	1	P → G in BAE27401. Ref.2
	Sequence conflict	215	1	R → W in BAE27401. Ref.2
	Sequence conflict	286	1	R → C in BAE27401. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O08574 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 31CAB72E2398150D	FASTA	370	39,789
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00114397.
RefSeq	NP_032615.2. NM_008589.2.
UniGene	Mm.31472.
3D structure databases
ProteinModelPortal	O08574.
SMR	O08574. Positions 92-138.
ModBase	Search...
PTM databases
PhosphoSite	O08574.
Proteomic databases
PRIDE	O08574.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	17293.
KEGG	mmu:17293.
Organism-specific databases
CTD	145873.
MGI	MGI:1096325. Mesp2.
Phylogenomic databases
eggNOG	NOG320808.
HOVERGEN	HBG096371.
KO	K09076.
Gene expression databases
CleanEx	MM_MESP2.
Genevestigator	O08574.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. [Graphical view]
Pfam	PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	291818.
SOURCE	Search...

Entry information

Entry name

MESP2_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program