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bone morphogenetic protein 4


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GeneName bmp4
Aliases ENSDARG:ENSDARG00000019995; bmp-4; zbmp-4; MGC100779; zgc:100779
Description bone morphogenetic protein 4
GenomicLocation chromosome 17 51094184-51116252 forward strand
ExternalIDs Entrez:30612; EMBL:U90122; UniGene:567; ZFIN:ZDB-GENE-980528-2059;
TranscriptID ENSDART:ENSDART00000075150; ENSDART:ENSDART00000126820
mRNA NCBI:NM_131342
GeneDescription Bone morphogenetic proteins (BMPs) are known to play roles in inner ear development of higher vertebrates.BMP4 also plays an important role in the development of protrusions to form semicircular canals during Zebrafish development.
GeneFunction Hwang et al. (1997) isolated zebrafish BMP4 gene from a zebrafish genomic DNA library. The size of the isolated BMP4 gene was approximately 14.9 kb. The isolated gene contained two exons which formed the complete coding region together with part of the 3'-noncoding region. The deduced BMP4 protein sequence contained 400 amino acids. Sequence comparison showed that it shared 73% amino acid sequence identity with that of human and mouse BMP4. An intron with a size of 8,963 bp was present between two coding exons. Danio retroposon A (DANA)-like retroposon was located in the intron. It contained four conserved boxes and was flanked by a pair of direct repeats of 9 nucleotide sequence (GTTTTAATA). During embryonic development of the zebrafish, a 3.8-kb BMP4 mRNA was detected from gastrula stage up to a month-old hatching larvae via Northern blot analysis. The results suggest that the zebrafish BMP4 gene may play important roles during zebrafish development.Thisse et al. (1999) studied phylogenetic relation between antivin (novel TGF- beta family gene) and TGF-beta super family genes including bmp4.
GeneCloning Martinez-Barbera et al. (1997) described the cloning and expression of bmp4 Zebrafish gene. To study the evolution of Bmps, Martinez-Barbera et al. (1997) isolated cDNAs for three members of the zebrafish Bmp gene family: Bmp2a, Bmp2b and Bmp4. The deduced Bmp2b aa sequence consists of 411 aa and the mature protein shows 88% and 86% identities to zebrafish Bmp2a and Bmp4, respectively. The expression of the mRNA of these three genes has been analyzed by whole mount in situ hybridization and RT-PCR. Areas of zebrafish Bmp2 and Bmp4 expression suggest evolutionary conserved mechanisms of Bmp2/4 dependent differentiation between lower and higher vertebrates.Nikaido et al. (1997) studied the conservation of bmp2 and bmp4 genes which are responsible for mesodermal patterning between zebrafish and Xenopus. Nikaido et al 1997 isolated two cDNA clones encoding bone morphogenetic protein (BMP)-related proteins from a zebrafish cDNA library. Based on their predicted amino acid sequences, these two clones were designated as zbmp-2 and zbmp-4. Chin et al. (1997) cloned and examined the expression pattern of zebrafish bone morphogenetic protein-4(BMP4) as a start to evaluating signals which might participate in the fashioning of organ systems in this genetically tractable species. The predicted sequence of the mature zebrafish protein is more than 75% identical to that of other vertebrates and 66% identical to Drosophila decapentaplegic (Dpp).
GeneStructure This gene encodes for two transcripts.The transcript ENSDART00000075150 consists of 4 exons and is 2.994 bps in length. The protein product ENSDARP00000069635 consists of 400 residues.The transcript ENSDART00000126820 consists of 7 exons and is 1.511 bps in length. The protein product ENSDARP00000107113 consists of 391 residues
Protein ENSDARP:ENSDARP00000069635; ENSDARP:ENSDARP00000107113
ProteinDomainandFamilies has domain InterPro:IPR001111; InterPro:IPR015615; InterPro:IPR001839; InterPro:IPR017948; InterPro:IPR002405;
Motifs has motif Prosite:PS00250; PFAM:PF00019; PFAM:PF00688; PRINTS:PR00669;
Expression ArrayExpress:ENSDARG00000019995;
GeneOntology GO:0005576; GO:0040007; GO:0045165; GO:0001707; GO:0042664; GO:0035162; GO:0048264; GO:0007507; GO:0008083;
Orthologs Entrez:652;
VariationAndRepeats RSID:rs41084681; RSID:rs41084681; RSID:rs40925936; RSID:rs40925936; RSID:rs180097470; RSID:rs180097470; RSID:rs180097471; RSID:rs180097471; RSID:rs40673277; RSID:rs40673277; RSID:rs180097472; RSID:rs180097472; RSID:rs40753291; RSID:rs40753291; RSID:rs179895091; RSID:rs179895091; RSID:rs41067900; RSID:rs41067900; RSID:rs40724126; RSID:rs40724126; RSID:rs180097473; RSID:rs180097473; RSID:rs40875119; RSID:rs40875119; RSID:rs179895121; RSID:rs179895121; RSID:rs179895138; RSID:rs179895138; RSID:rs179895103; RSID:rs179895103; RSID:rs179895116; RSID:rs179895116; RSID:rs179895089; RSID:rs179895089; RSID:rs179895098; RSID:rs179895098; RSID:rs179895069; RSID:rs179895069; RSID:rs41081284; RSID:rs41081284; RSID:rs41156953; RSID:rs41156953; RSID:rs179895083; RSID:rs179895083; RSID:rs179895075; RSID:rs179895075; RSID:rs179895080; RSID:rs179895080; RSID:rs180165739
DisordersAndMutations Morpholino Injection studies: Chocron et al. (2007) used morpholino oligonucleotides to study the requirement of bmp4 in Kupffer’s vesicle. Sequence of MOs were: bmp4 splice MO 5'-ggtgtttgattgtctgaccttcatg-3', fluorescein modified bmp4 ATG MO 5'- GTCTCGACAGAAAATAAAGCATGGG-3' , standard control morpholino 5'-CCTCTTACCTCAGTTACAATTTATA-3';. Fluorescein-labeled bmp4 MOs where injected into the yolk at the 512 cell-stage. Injected embryos at 80% epiboly were selected for the specific uptake of the bmp4 MO. Kupffer's vesicle morphogenesis was analyzed at the 10-somite stage using ntl expression. No defect in Kupffer's vesicle morphogenesis was observed when the bmp4 MO was targeted to the dorsal forerunner cells.Waber et al. (2008) reported the first mutation in BMP4 identified in patients with RHD. Waber et al 2008 detected 3 BMP4 mutations in 5 RHD patients. Overexpression assays in zebrafish demonstrated that these mutations affect the function of Bmp4 in vivo. Overexpression of zebrafish bmp4 resulted in ventralization, suggesting opposing roles in mesendoderm formation. When mutant constructs containing the identified ,human mutations were overexpressed instead, these effects were attenuated. Morpholino knockdown of bmp4 affected glomerulogenesis, suggesting specific roles for these genes in the formation of the pronephros. ZFINID:ZDB-GENO-080213-4; ZFINID:ZDB-GENO-080213-2; ZFINID:ZDB-GENO-080213-5; ZFINID:ZDB-GENO-080213-3; ZFINID:ZDB-GENO-080207-5; ZFINID:ZDB-GENO-070803-8; ZFINID:ZDB-GENO-070806-1; ZFINID:ZDB-GENO-110207-4; ZFINID:ZDB-GENO-080213-6; ZFINID:ZDB-GENO-070803-7; ZFINID:ZDB-GENO-080213-1; ZFINID:ZDB-GENO-080213-7;
RelatedPubMedArticles Chen JN, van Eeden FJ, Warren KS, Chin A, Nüsslein-Volhard C, Haffter P, Fishman MC. Left-right pattern of cardiac BMP4 may drive asymmetry of the heart in zebrafish. Development. 1997 Nov;124(21):4373-82. PMID:9334285.Hwang SP, Tsou MF, Lin YC, Liu CH. The zebrafish BMP4 gene: sequence analysis and expression pattern during embryonic development. DNA Cell Biol. 1997 Aug; 16(8):1003-11. PMID:9303442 Martínez-Barberá JP, Toresson H, Da Rocha S, Krauss S. Cloning and expression of three members of the zebrafish Bmp family: Bmp2a, Bmp2b and Bmp4. Gene. 1997 Oct 1;198(1-2):53-9. PMID:9370264 Nikaido M, Tada M, Saji T, Ueno N. Conservation of BMP signaling in zebrafish mesoderm patterning. Mech Dev. 1997 Jan;61(1-2):75-88. PMID:9076679 Thisse C, Thisse B. Antivin, a novel and divergent member of the TGFbeta superfamily, negatively regulates mesoderm induction. Development. 1999 Jan;126(2):229-40. PMID:9847237 Kawahara A, Wilm T, Solnica-Krezel L, Dawid IB. Antagonistic role of vega1 and bozozok/dharma homeobox genes in organizer formation. Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12121-6. PMID:11050240 Gestri G, Carl M, Appolloni I, Wilson SW, Barsacchi G, Andreazzoli M. Six3 functions in anterior neural plate specification by promoting cell proliferation and inhibiting Bmp4 expression. Development. 2005 May;132(10):2401-13. PMID:15843413 Wise SB, Stock DW. Conservation and divergence of Bmp2a, Bmp2b, and Bmp4 expression patterns within and between dentitions of teleost fishes. Evol Dev. 2006 Nov-Dec;8(6):511-23. PMID:17073935 Stickney HL, Imai Y, Draper B, Moens C, Talbot WS. Zebrafish bmp4 functions during late gastrulation to specify ventroposterior cell fates. Dev Biol. 2007 Oct 1;310(1):71-84. Epub 2007 Jul 28. PMID:17727832 Chocron S, Verhoeven MC, Rentzsch F, Hammerschmidt M, Bakkers J. Zebrafish Bmp4 regulates left-right asymmetry at two distinct developmental time points. Dev Biol. 2007 May 15;305(2):577-88. PMID:17395172 Weber S, Taylor JC, Winyard P, Baker KF, Sullivan-Brown J, Schild R, Knüppel T, Zurowska AM, Caldas-Alfonso A, Litwin M, Emre S, Ghiggeri GM, Bakkaloglu A, Mehls O, Antignac C, Network E, Schaefer F, Burdine RD. SIX2 and BMP4 mutations associate with anomalous kidney development. J Am Soc Nephrol. 2008 May;19(5):834-6. PMID:18305125 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: r3 - 2013-09-15 - SrishtiNanda
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