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Gene Review

SEC12  -  Sec12p

Saccharomyces cerevisiae S288c

Synonyms: Guanine nucleotide-exchange factor SEC12, N3244, Protein transport protein SEC12, SED2, YNR026C
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High impact information on SEC12

  • 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) [1].
  • SEC12 encodes a guanine-nucleotide-exchange factor essential for transport vesicle budding from the ER [1].
  • 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 [1].
  • Large liposomes containing bound cytoplasmic domains of the v-SNAREs, Sec22p or Bos1p, or of the ER resident proteins, Sec12p and Ufe1p, were exposed to COPII proteins and GMP-PNP. v-SNAREs but not resident proteins were concentrated in synthetic COPII vesicles generated from donor liposomes [2].
  • Furthermore, mitotic exit was sufficient to cause Chs2p neck localization specifically by triggering the Sec12p-dependent transport of Chs2p out of the ER [3].

Biological context of SEC12

  • In the yeast secretory pathway, two genes SEC12 and SAR1, which encode a 70-kD integral membrane protein and a 21-kD GTP-binding protein, respectively, cooperate in protein transport from the ER to the Golgi apparatus [4].
  • Second, Sec12p was shown to be essential for autophagy but not for the cytoplasm to vacuole-targeting (Cvt) (pathway, which shares mostly the same machinery with autophagy [5].
  • This sorting is not blocked by a temperature-sensitive mutation in SEC12, which inhibits ER to Golgi transport, a null mutation in VPS8, which inhibits Golgi to PVC transport, or temperature-sensitive and null mutations in END4, which inhibit endocytosis from the plasma membrane [6].
  • Glycosylation of Sec12p during biogenesis is indicated by an electrophoretic mobility shift of the protein that is influenced by tunicamycin and by imposition of an independent secretory pathway block [7].
  • The formation of diffusible vesicles from the ER requires ATP, Sec12p, Sec23p, and GTP hydrolysis [8].

Anatomical context of SEC12


Associations of SEC12 with chemical compounds

  • Both proteins have NH2-terminal cytoplasmic domains which resemble that of Sec12p: they are similar in size and present a significant degree of amino acid identity with the cytoplasmic domain of Sec12p [11].
  • Heat inactivation and trypsin treatment of cytosol, as well as addition of ATP gamma S to the chase incubations, led to a stabilization of p alpha F. ERAD was observed in sec12 microsomes, indicating that export of p alpha F via transport vesicles was not required [12].
  • When the exit of vesicles from the endoplasmic reticulum or entry into the cis-Golgi were blocked in sec12 or sec18 cells, all anchors contained a side chain consisting of a single alpha 1,2-linked mannose [13].

Physical interactions of SEC12

  • Sec12p is an ER type II membrane protein that mediates the membrane attachment of the GTP-binding Sar1 protein [11].
  • We present the first evidence that Rer1p directly interacts with the transmembrane domain (TMD) of Sec12p which contains a retrieval signal [14].

Regulatory relationships of SEC12

  • In vivo, the elevation of the SAR1 dosage suppresses temperature sensitivity of the sec12 mutant [4].
  • To investigate whether Emp47p undergoes retrograde transport from the Golgi to the ER like other di-lysine-tagged proteins we developed an assay to measure this step after block of forward transport in a sec12 mutant [15].

Other interactions of SEC12

  • The SAR1 gene is a multi-copy suppressor of a thermosensitive sec12 mutation [11].
  • Sec12p, a close homologue of Sed4p, also acts early in the assembly of transport vesicles [16].
  • In the delta(sed4) background, the suppression activity of SAR1 towards sec12 and sec16 is lost [17].
  • In contrast, the lumenal domains of Sec12p, Stl1p and Stl2p are very different in size and do not show any appreciable homology [11].
  • Pulse-chase experiments using these mutants show that alpha-COP and Rer1p function together in a very early Golgi compartment to initiate the recycling of Sec12p-derived hybrid proteins [18].

Analytical, diagnostic and therapeutic context of SEC12


  1. SEC12 encodes a guanine-nucleotide-exchange factor essential for transport vesicle budding from the ER. Barlowe, C., Schekman, R. Nature (1993) [Pubmed]
  2. Coat assembly directs v-SNARE concentration into synthetic COPII vesicles. Matsuoka, K., Morimitsu, Y., Uchida, K., Schekman, R. Mol. Cell (1998) [Pubmed]
  3. Exit from mitosis triggers Chs2p transport from the endoplasmic reticulum to mother-daughter neck via the secretory pathway in budding yeast. Zhang, G., Kashimshetty, R., Ng, K.E., Tan, H.B., Yeong, F.M. J. Cell Biol. (2006) [Pubmed]
  4. Reconstitution of GTP-binding Sar1 protein function in ER to Golgi transport. Oka, T., Nishikawa, S., Nakano, A. J. Cell Biol. (1991) [Pubmed]
  5. Autophagosome requires specific early Sec proteins for its formation and NSF/SNARE for vacuolar fusion. Ishihara, N., Hamasaki, M., Yokota, S., Suzuki, K., Kamada, Y., Kihara, A., Yoshimori, T., Noda, T., Ohsumi, Y. Mol. Biol. Cell (2001) [Pubmed]
  6. NBD-labeled phosphatidylcholine enters the yeast vacuole via the pre-vacuolar compartment. Hanson, P.K., Grant, A.M., Nichols, J.W. J. Cell. Sci. (2002) [Pubmed]
  7. A membrane glycoprotein, Sec12p, required for protein transport from the endoplasmic reticulum to the Golgi apparatus in yeast. Nakano, A., Brada, D., Schekman, R. J. Cell Biol. (1988) [Pubmed]
  8. Distinct biochemical requirements for the budding, targeting, and fusion of ER-derived transport vesicles. Rexach, M.F., Schekman, R.W. J. Cell Biol. (1991) [Pubmed]
  9. Sec12p-dependent membrane binding of the small GTP-binding protein Sar1p promotes formation of transport vesicles from the ER. d'Enfert, C., Wuestehube, L.J., Lila, T., Schekman, R. J. Cell Biol. (1991) [Pubmed]
  10. Secretory bulk flow of soluble proteins is efficient and COPII dependent. Phillipson, B.A., Pimpl, P., daSilva, L.L., Crofts, A.J., Taylor, J.P., Movafeghi, A., Robinson, D.G., Denecke, J. Plant Cell (2001) [Pubmed]
  11. Fission yeast and a plant have functional homologues of the Sar1 and Sec12 proteins involved in ER to Golgi traffic in budding yeast. d'Enfert, C., Gensse, M., Gaillardin, C. EMBO J. (1992) [Pubmed]
  12. Assembly of ER-associated protein degradation in vitro: dependence on cytosol, calnexin, and ATP. McCracken, A.A., Brodsky, J.L. J. Cell Biol. (1996) [Pubmed]
  13. Biosynthesis of the side chain of yeast glycosylphosphatidylinositol anchors is operated by novel mannosyltransferases located in the endoplasmic reticulum and the Golgi apparatus. Sipos, G., Puoti, A., Conzelmann, A. J. Biol. Chem. (1995) [Pubmed]
  14. Rer1p, a retrieval receptor for endoplasmic reticulum membrane proteins, is dynamically localized to the Golgi apparatus by coatomer. Sato, K., Sato, M., Nakano, A. J. Cell Biol. (2001) [Pubmed]
  15. The Golgi-localization of yeast Emp47p depends on its di-lysine motif but is not affected by the ret1-1 mutation in alpha-COP. Schröder, S., Schimmöller, F., Singer-Krüger, B., Riezman, H. J. Cell Biol. (1995) [Pubmed]
  16. SED4 encodes a yeast endoplasmic reticulum protein that binds Sec16p and participates in vesicle formation. Gimeno, R.E., Espenshade, P., Kaiser, C.A. J. Cell Biol. (1995) [Pubmed]
  17. Sed4p functions as a positive regulator of Sar1p probably through inhibition of the GTPase activation by Sec23p. Saito-Nakano, Y., Nakano, A. Genes Cells (2000) [Pubmed]
  18. Sec12p requires Rer1p for sorting to coatomer (COPI)-coated vesicles and retrieval to the ER. Boehm, J., Letourneur, F., Ballensiefen, W., Ossipov, D., Démollière, C., Schmitt, H.D. J. Cell. Sci. (1997) [Pubmed]
  19. Purification and characterization of SAR1p, a small GTP-binding protein required for transport vesicle formation from the endoplasmic reticulum. Barlowe, C., d'Enfert, C., Schekman, R. J. Biol. Chem. (1993) [Pubmed]
  20. Inhibition of endoplasmic reticulum (ER)-to-Golgi transport induces relocalization of binding protein (BiP) within the ER to form the BiP bodies. Nishikawa, S., Hirata, A., Nakano, A. Mol. Biol. Cell (1994) [Pubmed]
  21. Membrane protein retrieval from the Golgi apparatus to the endoplasmic reticulum (ER): characterization of the RER1 gene product as a component involved in ER localization of Sec12p. Sato, K., Nishikawa, S., Nakano, A. Mol. Biol. Cell (1995) [Pubmed]
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