SEC12 encodes a guanine-nucleotide-exchange factor essential for transport vesicle budding from the ER

Nature. 1993 Sep 23;365(6444):347-9. doi: 10.1038/365347a0.


In yeast a type II integral membrane glycoprotein that is essential for transport vesicle budding from the endoplasmic reticulum (ER) is encoded by SEC12 (refs 1-3). SAR1 was discovered as a multicopy suppressor of the sec12-1ts strain and encodes a GTPase of M(r) 21,000 (21K) also essential for vesicle budding from the ER. Sar1 is a peripherally associated membrane protein which shows enhanced membrane binding in cells containing elevated levels of Sec12 protein (refs 6, 7). We show here that a purified fragment of Sec12 promotes guanine-nucleotide dissociation from Sar1 whereas the purified mutant Sec12-1 has only 15% of the wild-type activity. GTP hydrolysis by Sar1 is not enhanced by Sec12, but is stimulated more than 50-fold by a mixture of Sec12 and Sec23, a GTPase-activating protein specific for Sar1 (ref. 8). We propose that Sec12 catalyses Sar1 guanine-nucleotide exchange in a process that recruits Sar1 to a vesicle formation site on the ER membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors
  • Biological Transport
  • Endoplasmic Reticulum / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Proteins / metabolism*
  • Genes, Fungal
  • Guanine Nucleotide Exchange Factors
  • Guanine Nucleotides / metabolism*
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Intracellular Membranes / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Monomeric GTP-Binding Proteins*
  • Peptide Fragments / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Vesicular Transport Proteins


  • Fungal Proteins
  • Guanine Nucleotide Exchange Factors
  • Guanine Nucleotides
  • Membrane Glycoproteins
  • Peptide Fragments
  • SEC12 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Vesicular Transport Proteins
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • ADP-Ribosylation Factors
  • Monomeric GTP-Binding Proteins
  • SAR1 protein, S cerevisiae