SEC4/YFL005W Summary Help

Standard Name SEC4 1, 2
Systematic Name YFL005W
Alias SRO6
Feature Type ORF, Verified
Description Rab family GTPase; essential for vesicle-mediated exocytic secretion and autophagy; associates with the exocyst component Sec15p and may regulate polarized delivery of transport vesicles to the exocyst at the plasma membrane (3, 4 and see Summary Paragraph)
Name Description SECretory 5
Chromosomal Location
ChrVI:130334 to 130981 | ORF Map | GBrowse
Gbrowse
Genetic position: -6 cM
Gene Ontology Annotations All SEC4 GO evidence and references
  View Computational GO annotations for SEC4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 5 genes
Resources
Classical genetics
conditional
dominant negative
overexpression
unspecified
Large-scale survey
null
overexpression
reduction of function
repressible
Resources
247 total interaction(s) for 108 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 15
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 26
  • Biochemical Activity: 10
  • Co-crystal Structure: 3
  • Co-fractionation: 1
  • Co-purification: 2
  • PCA: 10
  • Reconstituted Complex: 11
  • Two-hybrid: 16

Genetic Interactions
  • Dosage Growth Defect: 3
  • Dosage Lethality: 3
  • Dosage Rescue: 33
  • Negative Genetic: 46
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 1
  • Synthetic Growth Defect: 7
  • Synthetic Haploinsufficiency: 1
  • Synthetic Lethality: 53
  • Synthetic Rescue: 2

Resources
Expression Summary
histogram
Resources
Length (a.a.) 215
Molecular Weight (Da) 23,506
Isoelectric Point (pI) 7.11
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVI:130334 to 130981 | ORF Map | GBrowse
SGD ORF map
Genetic position: -6 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..648 130334..130981 2011-02-03 1996-07-31
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 SGDIDS000001889
SUMMARY PARAGRAPH for SEC4

SEC4 encodes an essential GTPase that is required during vesicular transport and fusion from the Golgi to the plasma membrane, the last steps of exocytic secretion (6, 7, and reviewed in 8). In addition to exocytosis, Sec4p is also involved in the processes of autophagy and endocytosis (4, 9). Sec4p is a member of a family of Ras-related GTP-binding proteins that includes S. cerevisiae Ypt1p and the mammalian Rab proteins (7, 10, 11, 12, 13). Other SEC4 homologs include those found in various fungi such as A. niger, C. lindemuthianum, P. pastoris, C. albicans, Y. lipolytica, and S. pombe (14, 15, 16, 17, 18, 19), as well as non-fungal organisms such as D. discoideum (20, 21). Cells that are defective for Sec4p function are impaired in secretion (7), accumulate secretory vesicles and plasma membrane components (22), and cannot form spores (23).

The GTPase activity of Sec4p, and as a result exocytosis, is also regulated by several GTPase activating proteins (GAPs) including Gyp1p, Gyp5p, Msb3p, and Msb4p (24, 25, 26). Other identified effectors of Sec4p include the exocyst complex, mediated by a Sec4p interaction with the Sec15p subunit (27, 3); the SNAP25-like SNARE Sec9p (28); and Sro7p, a member of the lgl (lethal giant larvae) family of tumor suppressors (29, 30). It was demonstrated that Sec4p-Sec9p-Sro7p are able to form a ternary complex (30).

Sec4p is located at bud tips, exocytic sites of the plasma membrane, and on post-Golgi secretory vesicles (31, 32). Sec4p delivery to polarized sites is mediated by the type V myosin motor Myo2p (33). The localization of Sec4p is also influenced by regulatory factors such as the Osh proteins (34), the Rab GTPase binding protein Mrs6p (35), by a post-translational modification of dual prenylation via the geranylgeranyltransferase complex of Bet2p/Bet4p (36, 37), and by whether Sec4p is in its GDP- or GTP- bound state (38). The nucleotide bound state of Sec4p is regulated by its guanine nucleotide exchange factor (GEF) Sec2p (39, 40), by its guanine nucleotide dissociation stimulator Dss4p (41, 42), and by the GDP dissociation inhibitor Gdi1p (43).

Last updated: 2010-05-13 Contact SGD

References cited on this page View Complete Literature Guide for SEC4
1) Novick P, et al.  (1980) Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell 21(1):205-15
2) Fields, C. and Schekman, R.  (1985) Personal Communication, Mortimer Map Edition 9
3) Guo W, et al.  (1999) The exocyst is an effector for Sec4p, targeting secretory vesicles to sites of exocytosis. EMBO J 18(4):1071-80
4) Geng J, et al.  (2010) Post-golgi sec proteins are required for autophagy in Saccharomyces cerevisiae. Mol Biol Cell 21(13):2257-69
5) Novick P and Schekman R  (1979) Secretion and cell-surface growth are blocked in a temperature-sensitive mutant of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 76(4):1858-62
6) Kabcenell AK, et al.  (1990) Binding and hydrolysis of guanine nucleotides by Sec4p, a yeast protein involved in the regulation of vesicular traffic. J Biol Chem 265(16):9366-72
7) Salminen A and Novick PJ  (1987) A ras-like protein is required for a post-Golgi event in yeast secretion. Cell 49(4):527-38
8) Novick P, et al.  (2006) Interactions between Rabs, tethers, SNAREs and their regulators in exocytosis. Biochem Soc Trans 34(Pt 5):683-6
9) Kean LS, et al.  (1993) Retrograde lipid traffic in yeast: identification of two distinct pathways for internalization of fluorescent-labeled phosphatidylcholine from the plasma membrane. J Cell Biol 123(6 Pt 1):1403-19
10) Brennwald P and Novick P  (1993) Interactions of three domains distinguishing the Ras-related GTP-binding proteins Ypt1 and Sec4. Nature 362(6420):560-3
11) Dunn B, et al.  (1993) Specificity domains distinguish the Ras-related GTPases Ypt1 and Sec4. Nature 362(6420):563-5
12) Chavrier P, et al.  (1990) Molecular cloning of YPT1/SEC4-related cDNAs from an epithelial cell line. Mol Cell Biol 10(12):6578-85
13) Zahraoui A, et al.  (1989) The human Rab genes encode a family of GTP-binding proteins related to yeast YPT1 and SEC4 products involved in secretion. J Biol Chem 264(21):12394-401
14) Punt PJ, et al.  (2001) Identification and characterization of a family of secretion-related small GTPase-encoding genes from the filamentous fungus Aspergillus niger: a putative SEC4 homologue is not essential for growth. Mol Microbiol 41(2):513-25
15) Dumas B, et al.  (2001) Molecular characterization of CLPT1, a SEC4-like Rab/GTPase of the phytopathogenic fungus Colletotrichum lindemuthianum which is regulated by the carbon source. Gene 272(1-2):219-25
16) Huynh TT, et al.  (2001) The genes of two G-proteins involved in protein transport in Pichia pastoris. Biochem Biophys Res Commun 280(2):454-9
17) Clement M, et al.  (1998) Isolation and characterization of the Candida albicans SEC4 gene. Yeast 14(7):675-80
18) Pertuiset B, et al.  (1995) Molecular cloning of Rab-related genes in the yeast Yarrowia lipolytica. Analysis of RYL1, an essential gene encoding a SEC4 homologue. Curr Genet 27(2):123-30
19) Haubruck H, et al.  (1990) Structural and functional analysis of ypt2, an essential ras-related gene in the fission yeast Schizosaccharomyces pombe encoding a Sec4 protein homologue. EMBO J 9(6):1957-62
20) Saxe SA and Kimmel AR  (1990) SAS1 and SAS2, GTP-binding protein genes in Dictyostelium discoideum with sequence similarities to essential genes in Saccharomyces cerevisiae. Mol Cell Biol 10(5):2367-78
21) Saxe SA and Kimmel AR  (1988) Genes encoding novel GTP-binding proteins in Dictyostelium. Dev Genet 9(4-5):259-65
22) Harsay E and Bretscher A  (1995) Parallel secretory pathways to the cell surface in yeast. J Cell Biol 131(2):297-310
23) Neiman AM  (1998) Prospore membrane formation defines a developmentally regulated branch of the secretory pathway in yeast. J Cell Biol 140(1):29-37
24) Du LL, et al.  (1998) Identification of a Sec4p GTPase-activating protein (GAP) as a novel member of a Rab GAP family. J Biol Chem 273(6):3253-6
25) Chesneau L, et al.  (2004) Gyp5p and Gyl1p are involved in the control of polarized exocytosis in budding yeast. J Cell Sci 117(Pt 20):4757-67
26) Gao XD, et al.  (2003) The GAP activity of Msb3p and Msb4p for the Rab GTPase Sec4p is required for efficient exocytosis and actin organization. J Cell Biol 162(4):635-46
27) Lipschutz JH and Mostov KE  (2002) Exocytosis: the many masters of the exocyst. Curr Biol 12(6):R212-4
28) Brennwald P, et al.  (1994) Sec9 is a SNAP-25-like component of a yeast SNARE complex that may be the effector of Sec4 function in exocytosis. Cell 79(2):245-58
29) Grosshans BL and Novick P  (2008) Identification and Verification of Sro7p as an Effector of the Sec4p Rab GTPase. Methods Enzymol 438:95-108
30) Grosshans BL, et al.  (2006) The yeast lgl family member Sro7p is an effector of the secretory Rab GTPase Sec4p. J Cell Biol 172(1):55-66
31) Elkind NB, et al.  (2000) The role of the COOH terminus of Sec2p in the transport of post-Golgi vesicles. J Cell Biol 149(1):95-110
32) Goud B, et al.  (1988) A GTP-binding protein required for secretion rapidly associates with secretory vesicles and the plasma membrane in yeast. Cell 53(5):753-68
33) Pruyne DW, et al.  (1998) Tropomyosin-containing actin cables direct the Myo2p-dependent polarized delivery of secretory vesicles in budding yeast. J Cell Biol 143(7):1931-45
34) Kozminski KG, et al.  (2006) Homologues of oxysterol-binding proteins affect Cdc42p- and Rho1p-mediated cell polarization in Saccharomyces cerevisiae. Traffic 7(9):1224-42
35) Jiang Y and Ferro-Novick S  (1994) Identification of yeast component A: reconstitution of the geranylgeranyltransferase that modifies Ypt1p and Sec4p. Proc Natl Acad Sci U S A 91(10):4377-81
36) Calero M, et al.  (2003) Dual prenylation is required for Rab protein localization and function. Mol Biol Cell 14(5):1852-67
37) Jiang Y, et al.  (1993) Bet2p and Mad2p are components of a prenyltransferase that adds geranylgeranyl onto Ypt1p and Sec4p. Nature 366(6450):84-6
38) Walworth NC, et al.  (1989) Mutational analysis of SEC4 suggests a cyclical mechanism for the regulation of vesicular traffic. EMBO J 8(6):1685-93
39) Ortiz D, et al.  (2002) Ypt32 recruits the Sec4p guanine nucleotide exchange factor, Sec2p, to secretory vesicles; evidence for a Rab cascade in yeast. J Cell Biol 157(6):1005-15
40) Walch-Solimena C, et al.  (1997) Sec2p mediates nucleotide exchange on Sec4p and is involved in polarized delivery of post-Golgi vesicles. J Cell Biol 137(7):1495-509
41) Collins RN, et al.  (1997) Interactions of nucleotide release factor Dss4p with Sec4p in the post-Golgi secretory pathway of yeast. J Biol Chem 272(29):18281-9
42) Moya M, et al.  (1993) DSS4-1 is a dominant suppressor of sec4-8 that encodes a nucleotide exchange protein that aids Sec4p function. Nature 361(6411):460-3
43) Garrett MD, et al.  (1994) GDI1 encodes a GDP dissociation inhibitor that plays an essential role in the yeast secretory pathway. EMBO J 13(7):1718-28