Characterization of a novel gene product (mammalian tolloid-like) with high sequence similarity to mammalian tolloid/bone morphogenetic protein-1

Genomics. 1996 Jun 1;34(2):157-65. doi: 10.1006/geno.1996.0260.


Bone morphogenetic protein-1 (BMP-1), a metalloprotease isolated from osteogenic extracts of demineralized bone, is capable of cleaving the C-propeptides of procollagen types I, II, and III. A single mammalian gene produces alternatively spliced RNA transcripts for BMP-1 and for a second longer protein, designated mammalian tolloid (mTld) due to a domain structure identical to that of the Drosophila dorsal-ventral patterning gene product tolloid (Tld). Here we report the use of a cDNA library, prepared from BMP-1/mTld-null mouse embryos, to isolate cDNA clones for a novel mammalian protein with a domain structure identical to that of mTld. The new protein, designated mammalian tolloid-like (mTll), has 76% identity with mTld for amino acid residues in all domains downstream of, and including, the protease domain. In contrast, the N-terminal activation domains of the two proteins show little similarity. In situ hybridizations show the distribution of mTll RNA to overlap extensively that previously shown for the BMP-1 and mTld RNA forms. However, mTll shows additional strong expression in structures of the developing, neonatal, and adult brain in which expression of BMP-1 and mTld has not been observed. The murine mTll gene (Tll) is mapped to central chromosome 8, which is a different chromosomal location than that of the BMP-1/mTld gene. Loci for some developmental abnormalities map to the same general chromosomal location as Tll.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Bone Morphogenetic Protein 1
  • Bone Morphogenetic Proteins / biosynthesis
  • Bone Morphogenetic Proteins / chemistry*
  • Chromosome Mapping
  • DNA Primers
  • Drosophila
  • Drosophila Proteins*
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Gene Expression
  • Gene Library
  • Growth Substances / chemistry*
  • In Situ Hybridization
  • Mammals
  • Metalloendopeptidases*
  • Metalloproteases
  • Mice
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Protein Biosynthesis*
  • Proteins / chemistry*
  • Proteins / genetics
  • Restriction Mapping
  • Sequence Homology, Amino Acid
  • Tolloid-Like Metalloproteinases
  • Transcription, Genetic


  • Bone Morphogenetic Proteins
  • DNA Primers
  • Drosophila Proteins
  • Growth Substances
  • Proteins
  • Metalloproteases
  • Tolloid-Like Metalloproteinases
  • Metalloendopeptidases
  • Tll1 protein, mouse
  • Tok protein, Drosophila
  • Bmp1 protein, mouse
  • Bone Morphogenetic Protein 1

Associated data

  • GENBANK/U34042