Bone morphogenetic protein 4

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Bone morphogenetic protein 4
Image:PBB Protein BMP4 image.jpg
PDB rendering based on 1reu.
Available structures:
For the file format that describes the 3D structures of molecules found in the Protein Data Bank, see Protein Data Bank (file format).

The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free.

Contents

History

Founded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB).

The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community.

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When the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off.

The growth rate of the PDB has been the subject of fairly extensive analysis.

Contents

As of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose.

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Statistics

As of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:

Proteins Nucleic Acids Protein/NA complexes Other Total
X-ray diffraction 36223 983 1684 24 38914
NMR 5665 781 134 7 6587
Electron microscopy 105 10 38 0 153
Other 80 4 4 2 90
Total 42073 1778 1860 33 45744

Note that theoretical models are no longer accepted in the PDB.

22461 structures in the PDB have a structure factor file. 3138 structures in the PDB have an NMR restraint file.

The current breakdown of holdings is updated weekly.

File format

Through the years the PDB file format has undergone many, many changes and revisions. Its original format was dictated by the width of computer punch cards.

This legacy format has caused many problems with the format, and consequently there are 'clean-up' projects;

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References

Printed

  • H.M. Berman, K. Henrick, H. Nakamura (2003): Announcing the worldwide Protein Data Bank. Nature Structural Biology 10 (12), p. 980 PMID 14634627.
  • H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I.N. Shindyalov, P.E. Bourne: The Protein Data Bank. Nucleic Acids Research, 28 pp. 235-242 (2000). PMID 10592235
  • Bernstein FC, Koetzle TF, Williams GJ, Meyer Jr EF, Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol 1977;112:535-542. PMID 875032.
  • E.F. Meyer “The First Years of the Protein Data Bank“, Protein Science 6:1591-1597 (1997)
  • Sussman, JL, Lin, D, Jiang, J, Manning, NO, Prilusky, J, Ritter, O & Abola, EE. Protein data bank (PDB): a database of 3D structural information of biological macromolecules. Acta Cryst 1998; D54:1078-1084. PMID 10089483.

Online

Other external links

Links to enzyme database data

  • [1] The best mapping is provided by Kim Henrick's group at EBI as part of the MSD SIFTS initiative.
  • [2] PDB provide a mapping on their beta site, but it is at the whole PDB level not chain level.
  • [3] Search at BRENDA enzyme database portal.
  • [4] PDBSProtEC:

Molecular graphic visualisation tools

Identifiers
Symbol(s) BMP4; BMP2B; BMP2B1; ZYME
External IDs OMIM: 112262 MGI: 88180 Homologene: 7247
RNA expression pattern

Image:PBB GE BMP4 211518 s at tn.png

More reference expression data

Orthologs
Human Mouse
Entrez 652 12159
Ensembl ENSG00000125378 ENSMUSG00000021835
Uniprot P12644 Q3ULR1
Refseq NM_001202 (mRNA)
NP_001193 (protein) 		NM_007554 (mRNA)
NP_031580 (protein)
Location Chr 14: 53.49 - 53.49 Mb Chr 14: 45.31 - 45.31 Mb
Pubmed search [5] [6]

Bone morphogenetic protein 4, also known as BMP4, is a human gene.


The protein encoded by this gene is a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfamily. The superfamily includes large families of growth and differentiation factors. Bone morphogenetic proteins were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site. This particular family member plays an important role in the onset of endochondral bone formation in humans, and a reduction in expression has been associated with a variety of bone diseases, including the heritable disorder Fibrodysplasia Ossificans Progressiva. Alternative splicing in the 5' untranslated region of this gene has been described and three variants are described, all encoding an identical protein.[1]


BMP4 is a polypeptide belonging to the TGF-β superfamily of proteins. It, like other bone morphogenetic proteins, is involved in bone and cartilage development, specifically tooth and limb development and fracture repair. It has been shown to be involved in muscle development, bone mineralization, and uteric bud development. BMP4 has also been implicated in Fibrodysplasia Ossificans Progressiva in which it is underexpressed.

In human embryonic development, BMP4 is a critical signaling molecule required for the early differentiation of the embryo and establishing of a dorsal-ventral axis. BMP4 is secreted from the dorsal portion of the notochord, and it acts in concert with sonic hedgehog (released from the ventral portion of the notochord) to establish a dorsal-ventral axis for the differentiation of later structures.

BMP4 stimulates differentiation of overlying ectodermal tissue. Inhibition of the BMP4 signal (by chordin, noggin, or follistatin) causes the ectoderm to differentiate into the neural plate. If these cells also receive signals from FGF, they will differentiate into the spinal cord; in the absence of FGF the cells become brain tissue.

References

Further reading

  • Wozney JM, Rosen V, Celeste AJ, et al. (1989). "Novel regulators of bone formation: molecular clones and activities.". Science 242 (4885): 1528-34. PMID 3201241.
  • van den Wijngaard A, Weghuis DO, Boersma CJ, et al. (1995). "Fine mapping of the human bone morphogenetic protein-4 gene (BMP4) to chromosome 14q22-q23 by in situ hybridization.". Genomics 27 (3): 559-60. PMID 7558046.
  • Oida S, Iimura T, Maruoka Y, et al. (1995). "Cloning and sequence of bone morphogenetic protein 4 (BMP-4) from a human placental cDNA library.". DNA Seq. 5 (5): 273-5. PMID 7579580.
  • Rosenzweig BL, Imamura T, Okadome T, et al. (1995). "Cloning and characterization of a human type II receptor for bone morphogenetic proteins.". Proc. Natl. Acad. Sci. U.S.A. 92 (17): 7632-6. PMID 7644468.
  • Nohno T, Ishikawa T, Saito T, et al. (1995). "Identification of a human type II receptor for bone morphogenetic protein-4 that forms differential heteromeric complexes with bone morphogenetic protein type I receptors.". J. Biol. Chem. 270 (38): 22522-6. PMID 7673243.
  • Yamaji N, Celeste AJ, Thies RS, et al. (1995). "A mammalian serine/threonine kinase receptor specifically binds BMP-2 and BMP-4.". Biochem. Biophys. Res. Commun. 205 (3): 1944-51. doi:10.1006/bbrc.1994.2898. PMID 7811286.
  • Harris SE, Harris MA, Mahy P, et al. (1994). "Expression of bone morphogenetic protein messenger RNAs by normal rat and human prostate and prostate cancer cells.". Prostate 24 (4): 204-11. PMID 8146069.
  • van den Wijngaard A, van Kraay M, van Zoelen EJ, et al. (1996). "Genomic organization of the human bone morphogenetic protein-4 gene: molecular basis for multiple transcripts.". Biochem. Biophys. Res. Commun. 219 (3): 789-94. doi:10.1006/bbrc.1996.0312. PMID 8645259.
  • Nishitoh H, Ichijo H, Kimura M, et al. (1996). "Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5.". J. Biol. Chem. 271 (35): 21345-52. PMID 8702914.
  • Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791-806. PMID 8889548.
  • Shore EM, Xu M, Shah PB, et al. (1998). "The human bone morphogenetic protein 4 (BMP-4) gene: molecular structure and transcriptional regulation.". Calcif. Tissue Int. 63 (3): 221-9. PMID 9701626.
  • Tucker AS, Matthews KL, Sharpe PT (1998). "Transformation of tooth type induced by inhibition of BMP signaling.". Science 282 (5391): 1136-8. PMID 9804553.
  • Van den Wijngaard A, Pijpers MA, Joosten PH, et al. (1999). "Functional characterization of two promoters in the human bone morphogenetic protein-4 gene.". J. Bone Miner. Res. 14 (8): 1432-41. PMID 10457277.
  • Li W, LoTurco JJ (2000). "Noggin is a negative regulator of neuronal differentiation in developing neocortex.". Dev. Neurosci. 22 (1-2): 68-73. PMID 10657699.
  • Raatikainen-Ahokas A, Hytönen M, Tenhunen A, et al. (2000). "BMP-4 affects the differentiation of metanephric mesenchyme and reveals an early anterior-posterior axis of the embryonic kidney.". Dev. Dyn. 217 (2): 146-58. doi:<146::AID-DVDY2>3.0.CO;2-I 10.1002/(SICI)1097-0177(200002)217:2<146::AID-DVDY2>3.0.CO;2-I. PMID 10706139.
  • van den Wijngaard A, Mulder WR, Dijkema R, et al. (2000). "Antiestrogens specifically up-regulate bone morphogenetic protein-4 promoter activity in human osteoblastic cells.". Mol. Endocrinol. 14 (5): 623-33. PMID 10809227.
  • Ying Y, Liu XM, Marble A, et al. (2000). "Requirement of Bmp8b for the generation of primordial germ cells in the mouse.". Mol. Endocrinol. 14 (7): 1053-63. PMID 10894154.
  • Nakade O, Takahashi K, Takuma T, et al. (2001). "Effect of extracellular calcium on the gene expression of bone morphogenetic protein-2 and -4 of normal human bone cells.". J. Bone Miner. Metab. 19 (1): 13-9. PMID 11156467.
  • Hatta T, Konishi H, Katoh E, et al. (2001). "Identification of the ligand-binding site of the BMP type IA receptor for BMP-4.". Biopolymers 55 (5): 399-406. doi:<399::AID-BIP1014>3.0.CO;2-9 10.1002/1097-0282(2000)55:5<399::AID-BIP1014>3.0.CO;2-9. PMID 11241215.
  • Aoki H, Fujii M, Imamura T, et al. (2001). "Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction.". J. Cell. Sci. 114 (Pt 8): 1483-9. PMID 11282024.

External links

v • d • e
Cell signaling: TGF beta signaling pathway
TGF beta superfamily of ligandsTGF beta family (TGF-β1, TGF-β2, TGF-β3)
Bone morphogenetic proteins (BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a, BMP8b, BMP10 , BMP15)
Growth differentiation factors (GDF1, GDF2, GDF3, GDF5, GDF6, GDF7, Myostatin/GDF8, GDF9, GDF10, GDF11, GDF15)
Other (Activin A and B/Inhibin A and B, Anti-müllerian hormone, Nodal)
TGF beta receptorsTGFBR1: Activin type 1 receptors (ACVR1, ACVR1B, ACVR1C) - ACVRL1 - BMPR1 (BMPR1A - BMPR1B)
TGFBR2: Activin type 2 receptors (ACVR2A, ACVR2B) - AMHR2 - BMPR2
TGFBR3: betaglycan
Transducers/SMADR-SMAD (SMAD1, SMAD2, SMAD3, SMAD5, SMAD9) - I-SMAD (SMAD6, SMAD7) - SMAD4
Ligand InhibitorsCerberus - Chordin - DAN - Decorin - Follistatin - Gremlin - Lefty - LTBP1 - Noggin - THBS1
CoreceptorsBAMBI - Cripto
OtherSARA
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