MDC9, a widely expressed cellular disintegrin containing cytoplasmic SH3 ligand domains

J Cell Biol. 1996 Feb;132(4):717-26. doi: 10.1083/jcb.132.4.717.

Abstract

Cellular disintegrins are a family of proteins that are related to snake venom integrin ligands and metalloproteases. We have cloned and sequenced the mouse and human homologue of a widely expressed cellular disintegrin, which we have termed MDC9 (for metalloprotease/disintegrin/cysteine-rich protein 9). The deduced mouse and human protein sequences are 82% identical. MDC9 contains several distinct protein domains: a signal sequence is followed by a prodomain and a domain with sequence similarity to snake venom metalloproteases, a disintegrin domain, a cysteine-rich region, an EGF repeat, a membrane anchor, and a cytoplasmic tail. The cytoplasmic tail of MDC9 has two proline-rich sequences which can bind the SH3 domain of Src, and may therefore function as SH3 ligand domains. Western blot analysis shows that MDC9 is an approximately 84-kD glycoprotein in all mouse tissues examined, and in NIH 3T3 fibroblast and C2C12 myoblast mouse cell lines. MDC9 can be both cell surface biotinylated and 125I-labeled in NIH 3T3 mouse fibroblasts, indicating that the protein is present on the plasma membrane. Expression of MDC9 in COS-7 cells yields an 84-kD protein, and immunofluorescence analysis of COS-7 cells expressing MDC9 shows a staining pattern that is consistent with a plasma membrane localization. The apparent molecular mass of 84 kD suggests that MDC9 contains a membrane-anchored metalloprotease and disintegrin domain. We propose that MDC9 might function as a membrane-anchored integrin ligand or metalloprotease, or that MDC9 may combine both activities in one protein.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • ADAM Proteins
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • DNA, Complementary / isolation & purification
  • Disintegrins
  • Humans
  • Membrane Proteins
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / isolation & purification
  • Mice
  • Molecular Sequence Data
  • Peptides / genetics*
  • Peptides / isolation & purification
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • src Homology Domains*

Substances

  • DNA, Complementary
  • Disintegrins
  • Membrane Proteins
  • Peptides
  • ADAM Proteins
  • ADAM9 protein, human
  • Adam9 protein, mouse
  • Metalloendopeptidases

Associated data

  • GENBANK/U41765
  • GENBANK/U41766