SED4/YCR067C Summary Help

Standard Name SED4 1
Systematic Name YCR067C
Feature Type ORF, Verified
Description Integral ER membrane protein that stimulates Sar1p GTPase activity; involved in COPII vesicle budding through disassociation of coat proteins from membranes onto liposomes; binds Sec16p; SED4 has a paralog, SEC12, that arose from the whole genome duplication (1, 2, 3, 4 and see Summary Paragraph)
Name Description Suppressor of Erd2 Deletion 1
Chromosomal Location
ChrIII:236322 to 233125 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All SED4 GO evidence and references
  View Computational GO annotations for SED4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Mutant phenotypes All SED4 Phenotype evidence and references
Classical genetics
null
Large-scale survey
null
Resources
interactions All SED4 Interaction evidence and references
58 total interaction(s) for 32 unique genes/features.
Physical Interactions
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 1
  • Protein-RNA: 1
  • Reconstituted Complex: 1
  • Two-hybrid: 2
Genetic Interactions
  • Dosage Lethality: 1
  • Dosage Rescue: 3
  • Negative Genetic: 18
  • Phenotypic Enhancement: 4
  • Phenotypic Suppression: 16
  • Positive Genetic: 4
  • Synthetic Growth Defect: 5
  • Synthetic Lethality: 1
Resources
Expression Summary
histogram
Resources
Protein Information All SED4 Protein evidence and references
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIII:236322 to 233125 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..3198 236322..233125 2011-02-03 1997-01-28
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000663
SUMMARY PARAGRAPH for SED4

Transport of proteins from the endoplasmic reticulum (ER) to the Golgi is mediated by COPII vesicles (5). The COPII vesicle coat is minimally comprised of 5 subunits: the GTPase Sar1p, the Sec23p-Sec24p heterodimer, and the Sec13p-Sec31p complex (6, 7, 8, 9). COPII vesicle coats can also contain heterodimers of Sec23p complexed with either of the Sec24p homologs, Sfb2p or Sfb3p (10, 11, 12). In S. cerevisiae, COPII vesicle formation occurs throughout the ER (13). In most other eukaryotes, COPII vesicle-mediated protein export is localized to specialized regions termed transitional ER (tER) or ER exit sites (ERES) (7).

COPII vesicle formation requires the assembly of the COPII vesicle coat and cargo selection and is regulated by cycles of GTP hydrolysis. The GTP exchange factor (GEF) Sec12p, an ER membrane protein, activates Sar1p by exchanging GDP for GTP. Sar1p-GTP recruits the Sec23p-Sec24p heterodimer. Sec23p is a GTPase activating protein (GAP) for the Sar1p GTPase activity (14, 15, and reviewed in 7). Sec24p, Sfb2p, and Sfb3p, are involved in cargo selection (16, 12, 11). Sar1p, the Sec23p-Sec24p heterodimer, and cargo form the prebudding complex. Improper cargo selection results in GTP hydrolysis and diassembly of the prebudding complex (17). However, once the pre-budding complex is assembled, Sec13p and Sec31p polymerize to form the outer layer or scaffold of the COPII vesicle coat. The Sec13p-Sec31p complex further stimulates the GTPase activity of Sar1p (reviewed in 7).

Although Sar1p, Sec23p, Sec24p, Sec13p, and Sec31p are necessary and sufficient for vesicle formation, additional factors such as Sec16p and Sed4p are also involved in this process. Through interactions with other COPII proteins, Sec16p is thought to facilitate the assembly of the vesicle coat by stabilizing the pre-budding complex (18) while Sed4p regulates the vesicle budding process by stimulating the GTPase activity of Sar1p (4).

Mutations in genes involved in COPII vesicle formation are also impaired in other processes such as ERAD (ER-associated degradation) and autophagy, suggesting that ER to the Golgi transport is a prerequisite for these processes to occur (19, 20, 21, 22).

Mutations in the human homolog of SEC23, Sec23A, cause the autosomal recessive disorder Cranio-lenticulo sutural dysplasia (CLSD), while mutation of Sar1B, one of the two human isoforms of S. cerevisiae Sar1p, cause defects in lipoprotein metabolism including the diseases that are known as the chylomicron retention diseases (CMRDs) (reviewed in 7).

Last updated: 2010-01-07

References cited on this page View Complete Literature Guide for SED4
1) Hardwick KG, et al.  (1992) Genes that allow yeast cells to grow in the absence of the HDEL receptor. EMBO J 11(11):4187-95
2) Gimeno RE, et al.  (1995) SED4 encodes a yeast endoplasmic reticulum protein that binds Sec16p and participates in vesicle formation. J Cell Biol 131(2):325-38
3) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
4) Kodera C, et al.  (2011) Sed4p stimulates sar1p GTP hydrolysis and promotes limited coat disassembly. Traffic 12(5):591-9
5) Bonifacino JS and Glick BS  (2004) The mechanisms of vesicle budding and fusion. Cell 116(2):153-66
6) Lee MC and Miller EA  (2007) Molecular mechanisms of COPII vesicle formation. Semin Cell Dev Biol 18(4):424-34
7) Hughes H and Stephens DJ  (2008) Assembly, organization, and function of the COPII coat. Histochem Cell Biol 129(2):129-51
8) Barlowe C, et al.  (1994) COPII: a membrane coat formed by Sec proteins that drive vesicle budding from the endoplasmic reticulum. Cell 77(6):895-907
9) Fath S, et al.  (2007) Structure and organization of coat proteins in the COPII cage. Cell 129(7):1325-36
10) Peng R, et al.  (2000) Evidence for overlapping and distinct functions in protein transport of coat protein Sec24p family members. J Biol Chem 275(15):11521-8
11) Miller E, et al.  (2002) Cargo selection into COPII vesicles is driven by the Sec24p subunit. EMBO J 21(22):6105-13
12) Miller EA, et al.  (2003) Multiple cargo binding sites on the COPII subunit Sec24p ensure capture of diverse membrane proteins into transport vesicles. Cell 114(4):497-509
13) Rossanese OW, et al.  (1999) Golgi structure correlates with transitional endoplasmic reticulum organization in Pichia pastoris and Saccharomyces cerevisiae. J Cell Biol 145(1):69-81
14) Barlowe C, et al.  (1993) Purification and characterization of SAR1p, a small GTP-binding protein required for transport vesicle formation from the endoplasmic reticulum. J Biol Chem 268(2):873-9
15) Yoshihisa T, et al.  (1993) Requirement for a GTPase-activating protein in vesicle budding from the endoplasmic reticulum. Science 259(5100):1466-8
16) Shimoni Y, et al.  (2000) Lst1p and Sec24p cooperate in sorting of the plasma membrane ATPase into COPII vesicles in Saccharomyces cerevisiae. J Cell Biol 151(5):973-84
17) Sato K and Nakano A  (2005) Dissection of COPII subunit-cargo assembly and disassembly kinetics during Sar1p-GTP hydrolysis. Nat Struct Mol Biol 12(2):167-74
18) Supek F, et al.  (2002) Sec16p potentiates the action of COPII proteins to bud transport vesicles. J Cell Biol 158(6):1029-38
19) Taxis C, et al.  (2002) ER-golgi traffic is a prerequisite for efficient ER degradation. Mol Biol Cell 13(6):1806-18
20) Hamasaki M, et al.  (2003) The early secretory pathway contributes to autophagy in yeast. Cell Struct Funct 28(1):49-54
21) Fu L and Sztul E  (2003) Traffic-independent function of the Sar1p/COPII machinery in proteasomal sorting of the cystic fibrosis transmembrane conductance regulator. J Cell Biol 160(2):157-63
22) Ishihara N, et al.  (2001) Autophagosome requires specific early Sec proteins for its formation and NSF/SNARE for vacuolar fusion. Mol Biol Cell 12(11):3690-702