MAGI-1, a membrane-associated guanylate kinase with a unique arrangement of protein-protein interaction domains

J Biol Chem. 1997 Dec 12;272(50):31589-97. doi: 10.1074/jbc.272.50.31589.


Membrane-associated guanylate kinase (MAGUK) proteins participate in the assembly of multiprotein complexes on the inner surface of the plasma membrane at regions of cell-cell contact. MAGUKs are characterized by three types of protein-protein interaction modules: the PDZ domain, the Src homology 3 (SH3) domain, and the guanylate kinase (GuK) domain. The arrangement of these domains is conserved in all previously known MAGUKs: either one or three PDZ domains in the NH2-terminal half, followed by the SH3 domain, followed by a COOH-terminal GuK domain. In this report, we describe the cDNA cloning and subcellular distribution of MAGI-1, a MAGUK with three unique structural features: 1) the GuK domain is at the NH2 terminus, 2) the SH3 domain is replaced by two WW domains, and 3) it contains five PDZ domains. MAGI-1 mRNA was detected in several adult mouse tissues. Sequence analysis of overlapping cDNAs revealed the existence of three splice variants that are predicted to encode MAGI-1 proteins with different COOH termini. The longest variant, MAGI-1c, contains three bipartite nuclear localization signals in its unique COOH-terminal sequence and was found predominantly in the nucleus of Madin-Darby canine kidney cells. A shorter form lacking these signals was found primarily in membrane and cytoplasmic fractions. This distribution, which is reminiscent of that seen for the tight junction protein ZO-1, suggests that MAGI-1 may participate in the transmission of regulatory signals from the cell surface to the nucleus.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cells, Cultured
  • DNA, Complementary / chemistry
  • Dogs
  • Guanylate Kinases
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nucleoside-Phosphate Kinase / chemistry*
  • Nucleoside-Phosphate Kinase / metabolism
  • Protein Binding
  • RNA, Messenger / metabolism
  • Saccharomyces cerevisiae
  • Sequence Alignment
  • Tissue Distribution
  • src Homology Domains*


  • DNA, Complementary
  • Nerve Tissue Proteins
  • RNA, Messenger
  • postsynaptic density proteins
  • Nucleoside-Phosphate Kinase
  • Guanylate Kinases

Associated data

  • GENBANK/AF027503
  • GENBANK/AF027504
  • GENBANK/AF027505