Gene Symbol: Bmp1
Description: bone morphogenetic protein 1
Alias: Pcp, Tld, bone morphogenetic protein 1, mammalian tolloid protein, procollagen C-proteinase
Species: mouse
Products:     Bmp1

Top Publications

  1. Ge G, Greenspan D. BMP1 controls TGFbeta1 activation via cleavage of latent TGFbeta-binding protein. J Cell Biol. 2006;175:111-20 pubmed
    ..The latter target LLCs to the extracellular matrix (ECM). Bone morphogenetic protein 1 (BMP1)-like metalloproteinases play key roles in ECM formation, by converting precursors into mature ..
  2. Kessler E, Takahara K, Biniaminov L, Brusel M, Greenspan D. Bone morphogenetic protein-1: the type I procollagen C-proteinase. Science. 1996;271:360-2 pubmed
    ..Procollagen C-proteinase (PCP) cleaves the COOH-propeptides of procollagens I, II, and III to yield the major fibrous components of vertebrate ..
  3. Ge G, Fernandez C, Moses M, Greenspan D. Bone morphogenetic protein 1 processes prolactin to a 17-kDa antiangiogenic factor. Proc Natl Acad Sci U S A. 2007;104:10010-5 pubmed
    ..Here we show that PRL and GH are bound and processed by members of the bone morphogenetic protein 1 (BMP1) subgroup of extracellular metalloproteinases, previously shown to play key roles in forming ..
  4. Takahara K, Lyons G, Greenspan D. Bone morphogenetic protein-1 and a mammalian tolloid homologue (mTld) are encoded by alternatively spliced transcripts which are differentially expressed in some tissues. J Biol Chem. 1994;269:32572-8 pubmed
    ..humans, it has a domain structure similar to that of the Drosophila dorsal-ventral patterning gene-product tolloid (Tld), but is considerably shorter...
  5. Takahara K, Brevard R, Hoffman G, Suzuki N, Greenspan D. Characterization of a novel gene product (mammalian tolloid-like) with high sequence similarity to mammalian tolloid/bone morphogenetic protein-1. Genomics. 1996;34:157-65 pubmed
    ..due to a domain structure identical to that of the Drosophila dorsal-ventral patterning gene product tolloid (Tld)...
  6. Clark T, Conway S, Scott I, Labosky P, Winnier G, Bundy J, et al. The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation and positioning of the heart. Development. 1999;126:2631-42 pubmed
    ..Tll1 expression was also high in the developing interventricular septum, where expression of the BMP-1 gene, Bmp1, was not observed...
  7. Pappano W, Steiglitz B, Scott I, Keene D, Greenspan D. Use of Bmp1/Tll1 doubly homozygous null mice and proteomics to identify and validate in vivo substrates of bone morphogenetic protein 1/tolloid-like metalloproteinases. Mol Cell Biol. 2003;23:4428-38 pubmed
    b>Bone morphogenetic protein 1 (BMP-1) and mammalian Tolloid (mTLD), two proteinases encoded by Bmp1, provide procollagen C-proteinase (pCP) activity that converts procollagens I to III into the major fibrous components of mammalian ..
  8. Suzuki N, Labosky P, Furuta Y, Hargett L, Dunn R, Fogo A, et al. Failure of ventral body wall closure in mouse embryos lacking a procollagen C-proteinase encoded by Bmp1, a mammalian gene related to Drosophila tolloid. Development. 1996;122:3587-95 pubmed
    The mouse bone morphogenetic protein1 (Bmp1) gene encodes a secreted astacin metalloprotease that cleaves the COOH-propeptide of procollagen I, II and III...
  9. Scott I, Blitz I, Pappano W, Imamura Y, Clark T, Steiglitz B, et al. Mammalian BMP-1/Tolloid-related metalloproteinases, including novel family member mammalian Tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis. Dev Biol. 1999;213:283-300 pubmed
    Vertebrate bone morphogenetic protein 1 (BMP-1) and Drosophila Tolloid (TLD) are prototypes of a family of metalloproteases with important roles in various developmental events...

More Information


  1. Keller B, Yang T, Chen Y, Munivez E, Bertin T, Zabel B, et al. Interaction of TGF? and BMP signaling pathways during chondrogenesis. PLoS ONE. 2011;6:e16421 pubmed publisher
    ..We also found evidence of direct interaction between the two signaling pathways in a cell model of chondrogenesis in vitro. ..
  2. See J, Mamontov P, Ahn K, Wine Lee L, Crenshaw E, Grinspan J. BMP signaling mutant mice exhibit glial cell maturation defects. Mol Cell Neurosci. 2007;35:171-82 pubmed
  3. Oganesian A, Au S, Horst J, Holzhausen L, Macy A, Pace J, et al. The NH2-terminal propeptide of type I procollagen acts intracellularly to modulate cell function. J Biol Chem. 2006;281:38507-18 pubmed
    ..Our findings suggest that N-propeptide performs an important feedback regulatory function and provides a rationale for the prominence of a homotrimeric form of type I procollagen (alpha1 trimer) during vertebrate development. ..
  4. Muir A, Ren Y, Butz D, Davis N, Blank R, Birk D, et al. Induced ablation of Bmp1 and Tll1 produces osteogenesis imperfecta in mice. Hum Mol Genet. 2014;23:3085-101 pubmed publisher
    ..Recently, mutations in the gene for the proteinase bone morphogenetic 1 (BMP1) were reported in two recessive OI families...
  5. Scott I, Imamura Y, Pappano W, Troedel J, Recklies A, Roughley P, et al. Bone morphogenetic protein-1 processes probiglycan. J Biol Chem. 2000;275:30504-11 pubmed
    ..fibroblasts (MEFs) produce only fully processed biglycan, whereas MEFs derived from embryos homozygous null for the Bmp1 gene, which encodes both BMP-1 and mammalian Tolloid, produce predominantly unprocessed probiglycan, and MEFs ..
  6. Darwich R, Li W, Yamak A, Komati H, Andelfinger G, Sun K, et al. KLF13 is a genetic modifier of the Holt-Oram syndrome gene TBX5. Hum Mol Genet. 2017;26:942-954 pubmed publisher
    ..The data also suggest that, in human, KLF13 may be a genetic modifier of the Holt-Oram Syndrome gene TBX5. ..
  7. Lee Y, Lee S. Regulation of GDF-11 and myostatin activity by GASP-1 and GASP-2. Proc Natl Acad Sci U S A. 2013;110:E3713-22 pubmed publisher
    ..All of these findings suggest that both GASP-1 and GASP-2 are important modulators of GDF-11 and MSTN activity in vivo. ..
  8. Muir A, Massoudi D, Nguyen N, Keene D, Lee S, Birk D, et al. BMP1-like proteinases are essential to the structure and wound healing of skin. Matrix Biol. 2016;56:114-131 pubmed publisher
    Closely related extracellular metalloproteinases bone morphogenetic protein 1 (BMP1) and mammalian Tolloid-like 1 (mTLL1) are co-expressed in various tissues and have been suggested to have overlapping roles in the biosynthetic processing ..
  9. Fukagawa M, Suzuki N, Hogan B, Jones C. Embryonic expression of mouse bone morphogenetic protein-1 (BMP-1), which is related to the Drosophila dorsoventral gene tolloid and encodes a putative astacin metalloendopeptidase. Dev Biol. 1994;163:175-83 pubmed
    ..5 days p.c. in the floorplate region of the developing neural tube. Potential therefore exists for the interaction of BMP-1 protein with products of TGF-beta-related genes expressed during embryogenesis. ..
  10. Ceci J, Kingsley D, Silan C, Copeland N, Jenkins N. An interspecific backcross linkage map of the proximal half of mouse chromosome 14. Genomics. 1990;6:673-8 pubmed
    ..This interspecific backcross map will be valuable for establishing linkage relationships of additional loci to mouse chromosome 14. ..
  11. Steiglitz B, Keene D, Greenspan D. PCOLCE2 encodes a functional procollagen C-proteinase enhancer (PCPE2) that is a collagen-binding protein differing in distribution of expression and post-translational modification from the previously described PCPE1. J Biol Chem. 2002;277:49820-30 pubmed
    ..The latter observations may provide insights into the ways PCPEs affect the kinetics of the C-proteinase reaction and into the physical interactions that occur between procollagen C-proteinases and their substrates. ..
  12. Dahn R, Fallon J. Limbiting outgrowth: BMPs as negative regulators in limb development. Bioessays. 1999;21:721-5 pubmed
    ..These studies provide the first insights into how the termination of a limb bud signaling center is accomplished, and intriguingly suggest how distinct aspects of limb morphogenesis are regulated. ..
  13. Hofbauer L, Heufelder A. Updating the metalloprotease nomenclature: bone morphogenetic protein 1 identified as procollagen C proteinase. Eur J Endocrinol. 1996;135:35-6 pubmed
  14. Wozney J, Rosen V, Celeste A, Mitsock L, Whitters M, Kriz R, et al. Novel regulators of bone formation: molecular clones and activities. Science. 1988;242:1528-34 pubmed
    ..Two of the encoded proteins (BMP-2A and BMP-3) are new members of the TGF-beta supergene family, while the third, BMP-1, appears to be a novel regulatory molecule. ..
  15. Kobayashi K, Luo M, Zhang Y, Wilkes D, Ge G, Grieskamp T, et al. Secreted Frizzled-related protein 2 is a procollagen C proteinase enhancer with a role in fibrosis associated with myocardial infarction. Nat Cell Biol. 2009;11:46-55 pubmed publisher
    ..mammalian sFRP, sFRP2, does not affect Chordin processing, but instead, can serve as a direct enhancer of procollagen C proteinase activity of Tolloid-like metalloproteinases...
  16. Ikeya M, Fukushima K, Kawada M, Onishi S, Furuta Y, Yonemura S, et al. Cv2, functioning as a pro-BMP factor via twisted gastrulation, is required for early development of nephron precursors. Dev Biol. 2010;337:405-14 pubmed publisher
    ..These findings revealed the molecular hierarchy between extracellular modifiers that orchestrate local BMP signal peaks in the organogenetic microenvironment. ..
  17. Walton K, Whidden M, Kolterud Ã, Shoffner S, Czerwinski M, Kushwaha J, et al. Villification in the mouse: Bmp signals control intestinal villus patterning. Development. 2016;143:427-36 pubmed publisher
    ..Rather, a complex cocktail of Bmps and Bmp signal modulators secreted from mesenchymal clusters determines the pattern of villi in a manner that mimics the spread of a self-organizing Turing field. ..
  18. Fumoto K, Takigawa Imamura H, Sumiyama K, Kaneiwa T, Kikuchi A. Modulation of apical constriction by Wnt signaling is required for lung epithelial shape transition. Development. 2017;144:151-162 pubmed publisher
  19. Kim B, Huang G, Ho W, Greenspan D. Bone morphogenetic protein-1 processes insulin-like growth factor-binding protein 3. J Biol Chem. 2011;286:29014-25 pubmed publisher
    The bone morphogenetic protein-1 (BMP1)-like metalloproteinases play key roles in extracellular matrix formation, by converting precursors into mature functional proteins involved in forming the extracellular matrix...
  20. Miyauchi H, Ohta H, Nagaoka S, Nakaki F, Sasaki K, Hayashi K, et al. Bone morphogenetic protein and retinoic acid synergistically specify female germ-cell fate in mice. EMBO J. 2017;36:3100-3119 pubmed publisher
    ..Our findings represent a framework for a comprehensive delineation of the sex-determination pathway in mammalian germ cells, including humans. ..
  21. Huang G, Zhang Y, Kim B, Ge G, Annis D, Mosher D, et al. Fibronectin binds and enhances the activity of bone morphogenetic protein 1. J Biol Chem. 2009;284:25879-88 pubmed publisher
    ..fibronectin, the form produced by fibroblasts and various other tissue cell types, and plasma fibronectin bind BMP1 with dissociation constants (KD) of approximately 100 nM, consistent with a physiological role...
  22. Cao X, Chen D. The BMP signaling and in vivo bone formation. Gene. 2005;357:1-8 pubmed
    ..Tissue-specific knockout of a specific BMP ligand, a subtype of BMP receptors or a specific signaling molecule is required to further determine the specific role of a BMP ligand, receptor or signaling molecule in a particular tissue. ..
  23. Ge G, Seo N, Liang X, Hopkins D, Hook M, Greenspan D. Bone morphogenetic protein-1/tolloid-related metalloproteinases process osteoglycin and enhance its ability to regulate collagen fibrillogenesis. J Biol Chem. 2004;279:41626-33 pubmed
    ..We also demonstrate that both pro- and mature OGN can regulate type I collagen fibrillogenesis, and that processing of the prodomain by BMP-1 potentiates the ability of OGN to modulate the formation of collagen fibrils. ..
  24. Sasaki H, Hogan B. HNF-3 beta as a regulator of floor plate development. Cell. 1994;76:103-15 pubmed
    ..Ectopic dorsal neuronal differentiation and abnormal dorsal axonal projections are also seen. These results suggest that HNF-3 beta is an important regulator of floor plate development in vivo. ..
  25. Maruhashi T, Kii I, Saito M, Kudo A. Interaction between periostin and BMP-1 promotes proteolytic activation of lysyl oxidase. J Biol Chem. 2010;285:13294-303 pubmed publisher
    ..Thus, we demonstrated that periostin supported BMP-1-mediated proteolytic activation of LOX on the extracellular matrix, which promoted collagen cross-linking. ..
  26. Allen D, Greybeck B, Greyback B, Hanson A, Cleary A, Lindsay S. Skeletal muscle expression of bone morphogenetic protein-1 and tolloid-like-1 extracellular proteases in different fiber types and in response to unloading, food deprivation and differentiation. J Physiol Sci. 2010;60:343-52 pubmed publisher
  27. Williams T, Williams M, Heaton J, Gelehrter T, Innis J. Group 13 HOX proteins interact with the MH2 domain of R-Smads and modulate Smad transcriptional activation functions independent of HOX DNA-binding capability. Nucleic Acids Res. 2005;33:4475-84 pubmed
  28. Wang J, Muir A, Ren Y, Massoudi D, Greenspan D, Feng J. Essential Roles of Bone Morphogenetic Protein-1 and Mammalian Tolloid-like 1 in Postnatal Root Dentin Formation. J Endod. 2017;43:109-115 pubmed publisher
    Mutations in the proteinase bone morphogenetic protein-1 (BMP1) were recently identified in patients with osteogenesis imperfecta, which can be associated with type 1 dentinogenesis imperfecta...
  29. Zhang H, Jani P, Liang T, Lu Y, Qin C. Inactivation of bone morphogenetic protein 1 (Bmp1) and tolloid-like 1 (Tll1) in cells expressing type I collagen leads to dental and periodontal defects in mice. J Mol Histol. 2017;48:83-98 pubmed publisher
    b>Bone morphogenetic protein 1 (BMP1) and tolloid-like 1 (TLL1) belong to the BMP1/tolloid-like proteinase family, which cleaves secretory proteins...
  30. Lee S. Genetic analysis of the role of proteolysis in the activation of latent myostatin. PLoS ONE. 2008;3:e1628 pubmed publisher activated in vitro by cleavage of the propeptide with members of the bone morphogenetic protein-1/tolloid (BMP-1/TLD) family of metalloproteases...
  31. Hoffman M, Kidder B, Steinberg Z, Lakhani S, Ho S, Kleinman H, et al. Gene expression profiles of mouse submandibular gland development: FGFR1 regulates branching morphogenesis in vitro through BMP- and FGF-dependent mechanisms. Development. 2002;129:5767-78 pubmed
    ..Taken together, our results suggest specific FGFs and BMPs play reciprocal roles in regulating branching morphogenesis and FGFR1 signaling plays a central role by regulating both FGF and BMP expression. ..
  32. Jackson I, Chambers D, Tsukamoto K, Copeland N, Gilbert D, Jenkins N, et al. A second tyrosinase-related protein, TRP-2, maps to and is mutated at the mouse slaty locus. EMBO J. 1992;11:527-35 pubmed
    ..Extracts from mice homozygous for the slaty mutation have a 3-fold or more reduction in DT activity, indicating that TRP-2/DT is encoded at the slaty locus, and the missense mutation reduces but does not abolish the enzyme activity. ..
  33. Moore K, D Amore Bruno M, Korfhagen T, Glasser S, Whitsett J, Jenkins N, et al. Chromosomal localization of three pulmonary surfactant protein genes in the mouse. Genomics. 1992;12:388-93 pubmed
    ..The mouse map locations determined in this study for the Sftp genes are consistent with the locations of these genes on the human genetic map and the syntenic relationships between the human and the mouse genomes. ..