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Gene Review

SAR1  -  Arf family GTPase SAR1

Saccharomyces cerevisiae S288c

Synonyms: GTP-binding protein SAR1, Secretion-associated RAS-related protein 1, Small COPII coat GTPase SAR1, YPL218W
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Disease relevance of SAR1

  • The analysis of Sar1p partially purified by E. coli expression suggests that GTP hydrolysis is essential for Sar1p to execute its function [1].
  • Traffic-independent function of the Sar1p/COPII machinery in proteasomal sorting of the cystic fibrosis transmembrane conductance regulator [2].

High impact information on SAR1

  • The Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization [3].
  • The five core COPII proteins (Sar1p, Sec23/24p, and Sec13/31p) act in concert to capture cargo proteins and sculpt the ER membrane into vesicles of defined geometry [4].
  • Replacement of bulky hydrophobic residues in the alpha helix with alanine yields Sar1p mutants that are unable to generate highly curved membranes and are defective in vesicle formation from native ER membranes despite normal recruitment of coat and cargo proteins [4].
  • Here we show that the small GTPase Sar1p directly initiates membrane curvature during vesicle biogenesis [4].
  • COPII vesicle formation requires only three coat assembly subunits: Sar1p, Sec13/31p, and Sec23/24p [5].

Biological context of SAR1

  • 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 [1].
  • Gene disruption experiments show that SAR1 is essential for cell growth [6].
  • To test its function further, SAR1 has been placed under control of the GAL1 promoter and introduced into a haploid cell that had its chromosomal SAR1 copy disrupted [6].
  • Using this complementation system, we analyzed the phenotypes of several mutations in plant SAR1 cDNAs in yeast cells [7].
  • The predicted amino acid sequences of Sec13p, Sec17p, Sec18p and Sar1p show strong conservation in the two yeasts [8].

Anatomical context of SAR1


Associations of SAR1 with chemical compounds

  • Purified Sar1p binds guanine nucleotides specifically and exhibits GTPase activity (0.001 min-1) [11].
  • Sar1p prebound with GTP gamma S inhibits Sar1p function in the vesicle formation assay [11].
  • We have purified Sar1p to apparent homogeneity from cells harboring a galactose-regulated recombinant SAR1 [11].
  • The GTPase-activating protein (GAP) activity of Sec23 involves an arginine side chain inserted into the Sar1 active site [13].
  • The isolated Sec23p subunit and the oligomeric complex stimulated guanosine triphosphatase (GTPase) activity of Sar1p 10- to 15-fold but did not activate two other small GTP-binding proteins involved in vesicle traffic (Ypt1p and ARF) [14].

Physical interactions of SAR1

  • Sec12p is an ER type II membrane protein that mediates the membrane attachment of the GTP-binding Sar1 protein [10].
  • We propose that Sec16p nucleates a Sar1-GTP-dependent initiation of COPII assembly and serves to stabilize the coat to premature disassembly after Sar1p hydrolyzes GTP [15].
  • Both motifs participate in the Sar1-dependent binding of Sec23p-Sec24p complex to the CTs during early steps of cargo selection [16].

Regulatory relationships of SAR1

  • In vivo, the elevation of the SAR1 dosage suppresses temperature sensitivity of the sec12 mutant [1].
  • The membranes and cytosol from the sec23 mutant show only a partial defect in vesicle formation and this defect is also suppressed by the increase of Sar1p [17].
  • Sec16p binds to major-minor mix liposomes and facilitates the recruitment of COPII proteins and vesicle budding in a reaction that is stimulated by Sar1p and GMP-PNP [15].

Other interactions of SAR1

  • The SAR1 gene is a multi-copy suppressor of a thermosensitive sec12 mutation [10].
  • The cytoplasmic domain of Sed4p weakly inhibits the GTPase-activating (GAP) activity of Sec23p toward Sar1p [18].
  • RESULTS: Although deletion of sed4 alone shows no growth defect, sar1 delta(sed4) double mutant cells are inviable [18].
  • They also suppressed yeast sec12 and sec16 temperature-sensitive mutations as yeast SAR1 does [7].
  • The overexpression of EKS1/HRD3, which stabilizes Hmg2p, did not affect the stability of wild-type or mutant Sar1p or any early Sec proteins we examined [9].

Analytical, diagnostic and therapeutic context of SAR1

  • This assay employs membranes prepared from wild-type cells and cytosol fractions depleted of Sar1p due to overproduction of Sec12p or by gel filtration chromatography [11].
  • In this study, we used a PCR approach to examine the complexity of SAR1-related sequences expressed in mammalian cells that possess multiple secretory pathways [12].
  • By random and site-directed mutagenesis of the SAR1 gene, we have obtained three temperature-sensitive mutants, N132I, E112K, and D32G [19].
  • First, overexpression of the Sar1p-specific guanosine nucleotide exchange factor Sec12p was shown to result in the titration of the GTPase Sar1p, which is essential for COPII-coated vesicle formation [20].
  • Genomic Southern blot analysis, using the 3'-gene-specific regions of the Bsar1 cDNAs as probes, revealed that the two cDNA clones are members of a B. campestris Sar1 family that consists of 2 to 3 genes [21].


  1. Reconstitution of GTP-binding Sar1 protein function in ER to Golgi transport. Oka, T., Nishikawa, S., Nakano, A. J. Cell Biol. (1991) [Pubmed]
  2. Traffic-independent function of the Sar1p/COPII machinery in proteasomal sorting of the cystic fibrosis transmembrane conductance regulator. Fu, L., Sztul, E. J. Cell Biol. (2003) [Pubmed]
  3. Small GTP-binding proteins. Takai, Y., Sasaki, T., Matozaki, T. Physiol. Rev. (2001) [Pubmed]
  4. Sar1p N-terminal helix initiates membrane curvature and completes the fission of a COPII vesicle. Lee, M.C., Orci, L., Hamamoto, S., Futai, E., Ravazzola, M., Schekman, R. Cell (2005) [Pubmed]
  5. COPII-coated vesicle formation reconstituted with purified coat proteins and chemically defined liposomes. Matsuoka, K., Orci, L., Amherdt, M., Bednarek, S.Y., Hamamoto, S., Schekman, R., Yeung, T. Cell (1998) [Pubmed]
  6. A novel GTP-binding protein, Sar1p, is involved in transport from the endoplasmic reticulum to the Golgi apparatus. Nakańo, A., Muramatsu, M. J. Cell Biol. (1989) [Pubmed]
  7. Isolation of a tobacco cDNA encoding Sar1 GTPase and analysis of its dominant mutations in vesicular traffic using a yeast complementation system. Takeuchi, M., Tada, M., Saito, C., Yashiroda, H., Nakano, A. Plant Cell Physiol. (1998) [Pubmed]
  8. Isolation of Pichia pastoris genes involved in ER-to-Golgi transport. Payne, W.E., Kaiser, C.A., Bevis, B.J., Soderholm, J., Fu, D., Sears, I.B., Glick, B.S. Yeast (2000) [Pubmed]
  9. Identification of SEC12, SED4, truncated SEC16, and EKS1/HRD3 as multicopy suppressors of ts mutants of Sar1 GTPase. Saito, Y., Yamanushi, T., Oka, T., Nakano, A. J. Biochem. (1999) [Pubmed]
  10. 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]
  11. 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]
  12. Molecular analysis of SAR1-related cDNAs from a mouse pituitary cell line. Shen, K.A., Hammond, C.M., Moore, H.P. FEBS Lett. (1993) [Pubmed]
  13. Structure of the Sec23/24-Sar1 pre-budding complex of the COPII vesicle coat. Bi, X., Corpina, R.A., Goldberg, J. Nature (2002) [Pubmed]
  14. Requirement for a GTPase-activating protein in vesicle budding from the endoplasmic reticulum. Yoshihisa, T., Barlowe, C., Schekman, R. Science (1993) [Pubmed]
  15. Sec16p potentiates the action of COPII proteins to bud transport vesicles. Supek, F., Madden, D.T., Hamamoto, S., Orci, L., Schekman, R. J. Cell Biol. (2002) [Pubmed]
  16. Endoplasmic reticulum export of glycosyltransferases depends on interaction of a cytoplasmic dibasic motif with Sar1. Giraudo, C.G., Maccioni, H.J. Mol. Biol. Cell (2003) [Pubmed]
  17. Inhibition of GTP hydrolysis by Sar1p causes accumulation of vesicles that are a functional intermediate of the ER-to-Golgi transport in yeast. Oka, T., Nakano, A. J. Cell Biol. (1994) [Pubmed]
  18. 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]
  19. Characterization of yeast sar1 temperature-sensitive mutants, which are defective in protein transport from the endoplasmic reticulum. Yamanushi, T., Hirata, A., Oka, T., Nakano, A. J. Biochem. (1996) [Pubmed]
  20. 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]
  21. The presence of a Sar1 gene family in Brassica campestris that suppresses a yeast vesicular transport mutation Sec12-1. Kim, W.Y., Cheong, N.E., Je, D.Y., Kim, M.G., Lim, C.O., Bahk, J.D., Cho, M.J., Lee, S.Y. Plant Mol. Biol. (1997) [Pubmed]
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