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smad2

MAD homolog 2 (Drosophila)

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GeneInformationForm
GeneName smad2
Aliases ENSDARG:ENSDARG00000006389; madh2; fj43c06; wu:fj43c06
Description MAD homolog 2 (Drosophila)
GenomicLocation chromosome 10 14899576-14971855 reverse strand
ExternalIDs Entrez:30639; EMBL:BC044338; UniGene:79140; ZFIN:ZDB-GENE-990603-7;
TranscriptID ENSDART:ENSDART00000128579; ENSDART:ENSDART00000121892; ENSDART:ENSDART00000044756; ENSDART:ENSDART00000147653; ENSDART:ENSDART00000143608; ENSDART:ENSDART00000137430
mRNA NCBI:NM_131366
GeneDescription Smad genes encode transcription factors involved in the signal transduction of members of the TGFbeta superfamily.
GeneFunction Dick et al. (2000) reported the characterization and genomic mapping of smad2 in Zebrafish. Full-length zebrafish smad2, although functionally active in Xenopus explants, has no effect when overexpressed in zebrafish embryos. In contrast, an N-terminally truncated, constitutively active version of Smad2 protein causes severe dorsalization or partial secondary axis formation, pointing to a role of Smad2 during mesoderm and axis formation. Smad2 shows strong and ubiquitous maternal expression. Zygotic expression is weak and ubiquitous in the case of smad2, These data suggest that Smad2 acts as a mediator of Nodal signals during zebrafish midline signaling, while Smad3 might be involved in later steps of eye field separation. Randall et al. (2002) experimentally shown in Xenopus and Zebrafish ,that transforming growth factor-b (TGF-b)/activin induced Smad2/Smad4 complexes are recruited to different promoter elements by transcription factors, such as Fast-1 or the Mix family proteins Mixer and Milk, through a direct interaction between Smad2 and a common Smad interaction motif (SIM) in the transcription factors.Using whole zebrafish embryos, and mammalian cell lines, Batut et al. (2007) shown phosphorylation and nuclear accumulation of Smad2 required an intact microtubule network and the ATPase activity of the kinesin motor. Smad2 interacted directly with the kinesin-1 light chain subunit (KLC2), and interfered with kinesin activity in Xenopus and zebrafish embryos which phenocopied loss of Nodal signaling.Jia et al. (2007) studied the role of smad2 protein/gene in Zebrafish development. The transforming growth factor-ligands Nodal, activin, and Vg1 play important roles in mesendoderm induction and patterning during vertebrate embryogenesis. These ligands are believed to transduce the signal through the receptor-activated transcription factors Smad2 and Smad3. However, the roles of smad2/3 genes in development of zebrafish embryos are largely unknown because the presence of multiple smad2/3 genes and their maternal expression have hampered the investigation of their developmental roles.Choi et al. (2007) found that smad2 gene is downregulated by the overexpression of FoxH1 gene which has a negative effect on vascular formation in zebrafish embryos.Esguerra et al. (2007) studied the role of Smad proteins in mediating Nodal signaling pathway. During vertebrate development, signaling by the TGF Beta ligand Nodal is critical for mesoderm formation. Stimulation of Alk4/EGF-CFC receptor complexes by Nodal activates Smad2/3, leading to left-sided expression of target genes that promote asymmetric placement of certain internal organs. Thus, although the role of Smad proteins in mediating Nodal signaling is well-documented, the functional characterization of Ttrap provides insight into a novel Smad partner that plays an essential role in the fine-tuning of this signal transduction cascade.Pezeron et al. (2008) experimentally confirmed that, transcript level increase of the intermediate Nodal pathway members downstream of Smad2, i.e. mixer, gata5 and mezzo, in Zoep or Zoep-like embryos injected with rasl11b MOATG. Altogether, these results demonstrate that rasl11b does not act upstream of Smad2 and confirm that Rasl11b does not influence the activation level of the Nodal pathway but rather acts on mesendoderm formation in a Nodal-independent way.Liu et.al. (2011) reported that SMAD2 target genes have a role for multiple co-regulatory facto[[rs in zebrafish early gastrulas. Smad2/3 signals play pivotal roles in mesendoderm induction and axis determination during late blastulation and early gastrulation in vertebrate embryos. However, Smad2/3 direct target genes during those critical developmental stages have not been systematically identified. Here, through ChIP-chip a[[ssay, it is shown that the promoter/enhancer regions of 679 genes are bound by Smad2 in the zebrafish early gastrulas. Expression analyses confirm that a significant proportion of Smad2 targets are indeed subjected to Nodal/Smad2 regulation at the onset of gastrulation.
GeneCloning [BAC] DKEY-126N10 and [BAC] DKEY-88L16. Dick et al.(2000) cloned a full-length cDNA encoding zebrafish Smad2 . Accession Nos: AF229022 (zebrafish smad2). Zebrafish Smad2 shows an amino acid identity of 94.9 and 94.2% with its human and mouse orthologues, respectively. Compared to Drosophila smad2, the mediator of signaling by the Drosophila activin receptor Baboon 2.5. Construct generation, mRNA synthesis, and embryo Smad2 shows 69.7% aa identity, injection whereas it is only 51.4% identical to Drosophila Mad,the mediator of signaling by the Drosophila Bmp2/4 homologue Decapentaplegic.
GeneStructure This gene encodes six transcripts: (ENSDART00000044756) consists of 11 exons and is 1,989 bps in length.The Protein product (ENSDARP00000044755) consists of 468 residues.(ENSDART00000121892) consists of 11 exons and is 1,994 bps in length.The Protein product (ENSDARP00000106756) consists of 469 residues.(ENSDART00000147653) consists of 12 exons and is 1,949 bps in length.The Protein product (ENSDARP00000120507) consists of 469 residues.(ENSDART00000137430) consists of 3 exons and is 555 bps in length.The Protein product (ENSDARP00000117374) consists of 74 residues.(ENSDART00000143608) consists of 5 exons and is 812 bps in length.The Protein product (ENSDARP00000120637) consists of 160 residues.(ENSDART00000128579) consists of 11 exons and is 1,452 bps in length.The Protein product (ENSDARP00000111803) consists of 483 residues.
Protein ENSDARP00000111803 ENSDARP00000106756 ENSDARP00000044755 ENSDARP00000120507 ENSDARP00000120637 ENSDARP00000117374
ProteinDomainandFamilies InterPro:IPR001132; InterPro:IPR003619; InterPro:IPR008984; InterPro:IPR013019; InterPro:IPR013790; InterPro:IPR017855;
Motifs has motif Prosite:PS51075; Prosite:PS51076; PFAM:PF03165; PFAM:PF03166; UniProt:SMAD2_DANRE; UniProtKB:E7EYC2;
Expression ArrayExpress:ENSDARG00000006389;
GeneOntology GO:0005622; GO:0005622; GO:0006355; GO:0016481; GO:0045449; GO:0006353; GO:0006350; GO:0031564; GO:0007242; GO:0009880; GO:0006355; GO:0016481; GO:0045449; GO:0006353; GO:0006350; GO:0031564; GO:0007242; GO:0009880; GO:0003700; GO:0003700;
Orthologs Entrez:4087;
VariationAndRepeats RSID:rs180129976; RSID:rs41040454; RSID:rs41244425; RSID:rs40890076; RSID:rs180129977; RSID:rs180129978; RSID:rs40682261; RSID:rs180129979; RSID:rs180129980; RSID:rs180129981; RSID:rs41016371; RSID:rs180129982; RSID:rs180129983; RSID:rs180129984; RSID:rs180129985; RSID:rs179611712; RSID:rs180129986; RSID:rs40714866; RSID:rs179611718; RSID:rs180129987; RSID:rs41054077; RSID:rs180129988; RSID:rs180129989; RSID:rs180129990
DisordersAndMutations Rebagliati et al. (1998) reported Cyclops mutants of Zebrafish embryo . The Cyclops mutation leads to a loss of medial floor plate and to severe deficits in ventral forebrain development, leading to cyclopia. The cyclops locus encodes the nodal related protein Ndr2, a member of the transforming growth factor type b superfamily of factors. The evidence includes identification of a missense mutation in the initiation codon and rescue of the cyclops phenotype by expression of ndr2 RNA, here renamed ‘‘cyclops.’’ Thus, in interaction with other molecules implicated in these processes such as sonic hedgehog and one-eyed-pinhead, cyclops is required for ventral midline patterning of the embryonic central nervous system.Jia et al. (2007) generated potent and specific dominant-negative forms of zebra fish Smad2, Smad3a, and Smad3b by mutating multiple amino acids. Over expression of these mutants abolished mesendoderm induction by ectopic Nodal signaling in zebrafish embryos. Expression of dominant negative smad2/3 abrogated Smad2/3 activities in wild-type embryos and caused various mesendodermal defects similar to those in Nodal-deficient embryos. Smad2/3-deficient cells transplanted into the blastodermal margin of wild-type hosts preferentially differentiated into ectodermal tissues rather than mesendodermal tissues, supporting the idea that response of cells to mesendoderm inducers requires Smad2/3 activities.Interference with Smad2/3 activities in Zoep, Moep, and MZoep mutant embryos resulted in more severe mesendodermal defects. Thus, our data reveal that Nodal signaling and mesendoderm induction depend on Smad2/3 and suggest that transforming growth factor-signals other than Nodal also contribute to Smad2/3 signaling and embryonic patterning.The sequences of antisense morpholino oligonucleotides were as follows: smad2-MO1, 5'-TTACCCTTCCTACGAAAAGCGTTCT-3' smad2-MO2, 5'-GAACAGACCCAAAGTTCCTAACT- 3'; smad2-cMO1, 5'-TTACCCTTGAATGCAAAAGCGTTCT-3 (which is a mismatch (underlined) control for smad2-MO1); smad3a-MO1, 5'-TTCAGTTCAGCGTTCCTCTATTGC-3'; smad3a-MO2,5'-AGTGAAAGGTAAAATTGACAT-3'; smad3b-MO1, 5'-GCAATATAGACATCTTTAGTTGAT-3'; and smad3b-MO2, 5'-TTGTCCACGAGTCACATCACCGCAT-3'.Embryos Injected with smad2/3 Morpholino Oligonucleotides Develop without Observable Defects—Zebrafish smad2,smad3a, and smad3b transcripts are present in one-cell embryos, were examined the efficacy of these morpholino oligonucleotides by co-injection with a corresponding gene’s 5'-UTRGFP expression construct and found that smad2-MO1, smad3a-MO1, smad3b-MO1, and smad3b-MO2 were effective . Embryos injected with smad2-MO1, smad3a- MO1, smad3b-MO1, or smad3b-MO2 alone displayed different degrees of growth retardation and neural degeneration . When co-injected with smad2-MO1, smad3a-MO1, and smad3b-MO2, embryos showed more severe growth retardation.Ferg et al. (2007) injected smad2 mRNA into zebrafish embryos to check the role of maternally inherited mRNA degradation by TBP Microinjected smad2 mRNA was more efficiently degraded in c MO- than in TBP MO-injected embryos and similar results were obtained by WISH Thus, the apparent increase of smad2 mRNA levels in TBP morphants is not due to premature activation of zygotic smad2 expression, but due to the loss of degradation of smad2 mRNAs.
RelatedPubMedArticles Rebagliati MR, Toyama R, Haffter P, Dawid IB. Cyclops encodes a nodal-related factor involved in midline signaling. Proc Natl Acad Sci U S A. 1998 Aug 18; 95(17):9932-7. PMID:9707578 Dick A, Mayr T, Bauer H, Meier A, Hammerschmidt M .Cloning and characterization of zebrafish smad2, smad3 and smad4. Gene. 2000 Apr 4;246(1-2):69- 80. PMID:10767528 Randall RA, Germain S, Inman GJ, Bates PA, Hill CS.Different Smad2 partners bind a common hydrophobic pocket in Smad2 via a defined proline-rich motif. EMBO J 2002 Jan 15;21(1-2):145-56. PMID:11782434 Batut, J.; Howell, M.; Hill, C. S.Kinesin-mediated transport of Smad2 is required for signaling in response to TGF-beta ligands. Dev. Cell 12: 261-274, 2007. PMID:17276343 Choi J, Dong L, Ahn J, Dao D, Hammerschmidt M, Chen JN. FoxH1 negatively modulates flk1 gene expression and vascular formation in zebrafish. Dev Biol. 2007 Apr 15;304(2):735-44. PMID:17306248 Esguerra CV, Nelles L, Vermeire L, Ibrahimi A, Crawford AD, Derua R, Janssens E, Waelkens E, Carmeliet P, Collen D, Huylebroeck D. Trap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination. Development :2007 Dec;134(24):4381-93. PMID:18039968 Ferg, M., Sanges, R., Gehrig, J., Kiss, J., Bauer, M., Lovas, A., Szabo, M., Yang, L., Straehle, U., Pankratz, M.J., Olasz, F., Stupka, E., and Müller, F. The TATA-binding protein regulates maternal mRNA degradation and differential zygotic transcription in zebrafish . EMBO J. 26(17): 3945-3956 (Journal) 2007. PMID:17703193 Jia S, Ren Z, Li X, Zheng Y, Meng A. smad2 and smad3 are required for mesendoderm induction by transforming growth factor-beta/nodal signals in zebrafish. J Biol Chem. 2008 Jan 25;283(4):2418-26. Epub 2007 Nov 19. PMID:18025082 Pézeron G, Lambert G, Dickmeis T, Strähle U, Rosa FM, Mourrain P.Rasl11b knock down in zebrafish suppresses one-eyed-pinhead mutant phenotype. PLoS ONE 2008 Jan 16;3(1):e1434. PMID:18197245 NCBI Resource Coordinators.: Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. 41(Database issue):D8-D20. 2013. PMID:23193264
Kersey, P. J.; Allen, J. E.; Christensen, M.; et al.: Ensembl Genomes 2013: scaling up access to genome-wide data. Nucleic Acids Res. 2013. PMID:24163254
Sigrist, C. J. A.; de, Castro, E; Cerutti, L; Cuche, B. A.; Hulo, N.; Bridge, A.; Bougueleret, L. Xenarios, I.: New and continuing developments at PROSITE. Nucleic Acids Res. doi: 10.1093/nar/gks1067. 2012. PMID:23161676
Punta, M.; Coggill, P. C.; Eberhardt, et al.: The Pfam protein families database. Nucleic Acids Res. 40(Database Issue):D290-D301. 2012. PMID:22127870
Hunter, S.; Jones P.; Mitchell A.; et al.: Interpro in 2011: new developments in the family and domain prediction database. Nucleic Acids Res. doi: 10.1093/nar/gkr948. 2011. PMID:22096229
Carbon, S.; Ireland, A.; Mungall, C. J.; Shu, S.; Marshall, B.; Lewis, S.; AMIGO Hub; Web Presence Working Group.: AMIGO: online access to ontology and annotation data. Bioinformatics. 25(2):288-9. 2009. PMID:19033274
Ashburner, M.; Ball, C. A.; Blake, J. A.; et al. The Gene Ontology Consortium.: Gene ontology: tool for the unification of biology. Nat. Genet. 25(1):25-9. 2000. PMID:10802651
Sherry, S. T.; Ward, M. H.; Kholodov, M.; Baker, J.; Phan, L.; Smigielski, E. M.; Sirotkin, K.: dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 1;29(1):308-11. 2001. PMID:11125122
Bradford, Y.; Conlin, T.; Dunn, N.; et al.: ZFIN: enhancements and updates to the zebrafish model organism database. Nucleic Acids Res. 39(suppl 1):D822-D829. 2011. PMID:21036866
Kapushesky, M.; Adamusiak, T.; Burdett, T.; et al.: Gene Expression Atlas update--a value-added database of microarray and sequencing-based functional genomics experiments. Nucleic Acids Res. 40(Database isue):D1077-81. 2012. PMID:22064864

Web resources:
NCBI: http://www.ncbi.nlm.nih.gov/
PFAM: http://pfam.sanger.ac.uk/
PROSITE: http://prosite.expasy.org/
Interpro: http://www.ebi.ac.uk/interpro/
ZFIN: http://zfin.org/
Expression Atlas (EMBL): http://www.ebi.ac.uk/gxa/
Ensembl: http://asia.ensembl.org/Danio_rerio/
Database of Single Nucleotide Polymorphisms (dbSNP). Bethesda (MD): National Center for Biotechnology Information, National Library of Medicine.: http://www.ncbi.nlm.nih.gov/SNP/
PRINTS from Genomenet: http://www.genome.jp/
European Nucleotide Archive: http://www.ebi.ac.uk/ena/home
UNIGENE: http://www.ncbi.nlm.nih.gov/unigene/
AMIGO Gene Ontology: http://amigo.geneontology.org
Topic revision: r4 - 2013-08-22 - SubburajK
 
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