| SMART accession number: | SM00222
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| Description: |
Domain named after the S. cerevisiae SEC7 gene product, which is required for proper protein transport through the Golgi. The domain facilitates guanine nucleotide exchange on the small GTPases, ARFs (ADP ribosylation factors). |
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| Interpro abstract (IPR000904): |
The SEC7 domain was named after the first protein found to contain such a region [(PUBMED:3042778)]. It has been shown to be linked with guanine nucleotide exchange function [(PUBMED:9072969), (PUBMED:9442017)]. The 3D structure of the domain displays several alpha-helices [(PUBMED:9653114)]. It was found to be associated with other domains involved in guanine nucleotide exchange (e.g., CDC25, Dbl) in mammalian factors [(PUBMED:9868368)].
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| GO process: | regulation of ARF protein signal transduction (GO:0032012) |
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| GO component: | intracellular (GO:0005622) |
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| GO function: | ARF guanyl-nucleotide exchange factor activity (GO:0005086) |
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| Family alignment: |
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Click on the following links for more information.
- Evolution (species in which this domain is found)
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- Literature (relevant references for this domain)
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Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Beraud-Dufour S et al.
- A glutamic finger in the guanine nucleotide exchange factor ARNO displaces Mg2+ and the beta-phosphate to destabilize GDP on ARF1.
- EMBO J. 1998; 17: 3651-9
- Display abstract
The Sec7 domain of the guanine nucleotide exchange factor ARNO (ARNO-Sec7) is responsible for the exchange activity on the small GTP-binding protein ARF1. ARNO-Sec7 forms a stable complex with the nucleotide-free form of [Delta17]ARF1, a soluble truncated form of ARF1. The crystal structure of ARNO-Sec7 has been solved recently, and a site-directed mutagenesis approach identified a hydrophobic groove and an adjacent hydrophilic loop as the ARF1-binding site. We show that Glu156 in the hydrophilic loop of ARNO-Sec7 is involved in the destabilization of Mg2+ and GDP from ARF1. The conservative mutation E156D and the charge reversal mutation E156K reduce the exchange activity of ARNO-Sec7 by several orders of magnitude. Moreover, [E156K]ARNO-Sec7 forms a complex with the Mg2+-free form of [Delta17]ARF1-GDP without inducing the release of GDP. Other mutations in ARNO-Sec7 and in [Delta17]ARF1 suggest that prominent hydrophobic residues of the switch I region of ARF1 insert into the groove of the Sec7 domain, and that Lys73 of the switch II region of ARF1 forms an ion pair with Asp183 of ARNO-Sec7.
- Betz SF et al.
- Solution structure of the cytohesin-1 (B2-1) Sec7 domain and its interaction with the GTPase ADP ribosylation factor 1.
- Proc Natl Acad Sci U S A. 1998; 95: 7909-14
- Display abstract
Cytohesin-1 (B2-1) is a guanine nucleotide exchange factor for human ADP ribosylation factor (Arf) GTPases, which are important for vesicular protein trafficking and coatamer assembly in the cell. Cytohesin-1 also has been reported to promote cellular adhesion via binding to the beta2 integrin cytoplasmic domain. The solution structure of the Sec7 domain of cytohesin-1, which is responsible for both the protein's guanine nucleotide exchange factor function and beta2 integrin binding, was determined by NMR spectroscopy. The structure consists of 10 alpha-helices that form a unique tertiary fold. The binding between the Sec7 domain and a soluble, truncated version of human Arf-1 was investigated by examining 1H-15N and 1H-13C chemical shift changes between the native protein and the Sec7/Arf-1 complex. We show that the binding to Arf-1 occurs through a large surface on the C-terminal subdomain that is composed of both hydrophobic and polar residues. Structure-based mutational analysis of the cytohesin-1 Sec7 domain has been used to identify residues important for binding to Arf and for mediating nucleotide exchange. Investigations into the interaction between the Sec7 domain and the beta2 integrin cytoplasmic domain suggest that the two proteins do not interact in the solution phase.
- Mossessova E, Gulbis JM, Goldberg J
- Structure of the guanine nucleotide exchange factor Sec7 domain of human arno and analysis of the interaction with ARF GTPase.
- Cell. 1998; 92: 415-23
- Display abstract
Sec7-related guanine nucleotide exchange factors (GEFs) initiate vesicle budding from the Golgi membrane surface by converting the GTPase ARF to a GTP-bound, membrane-associated form. Here we report the crystal structure of the catalytic Sec7 homology domain of Arno, a human GEF for ARF1, determined at 2.2 angstroms resolution. The Sec7 domain is an elongated, all-helical protein with a distinctive hydrophobic groove that is phylogenetically conserved. Structure-based mutagenesis identifies the groove and an adjacent conserved loop as the ARF-interacting surface. The sites of Sec7 domain interaction on ARF1 have subsequently been mapped, by protein footprinting experiments, to the switch 1 and switch 2 GTPase regions, leading to a model for the interaction between ARF GTPases and Sec7 domain exchange factors.
- Achstetter T, Franzusoff A, Field C, Schekman R
- SEC7 encodes an unusual, high molecular weight protein required for membrane traffic from the yeast Golgi apparatus.
- J Biol Chem. 1988; 263: 11711-7
- Display abstract
Saccharomyces cerevisiae with mutations at the sec7 locus are pleiotropically deficient in protein transport within the Golgi apparatus and proliferate a large array of Golgi cisternae at a restrictive growth temperature (37 degrees C). The SEC7 gene and its product (Sec7p) have been evaluated by molecular cloning and sequence analysis. Two genes that allow sec7 mutant cells to grow at 37 degrees C are represented in wild-type yeast DNA libraries. A single copy of the authentic SEC7 gene permits growth of mutant cells, whereas the other gene suppresses growth deficiency only when expressed from a multicopy plasmid. The SEC7 gene is contained on a 8.4-kilobase pair SphI restriction fragment, portions of which hybridize to a single 6-kilobase pair mRNA. The gene is essential for yeast vegetative growth. DNA sequence analysis of this region detects a single open reading frame with the potential to encode a 2008-amino acid-long hydrophilic protein of 230 kDa. Putative Sec7p contains an unusual, highly charged acidic domain of 125 amino acids with 29% glutamate, 18% aspartate, and 21% serine. Within this region, stretches of 14 consecutive glutamate residues and 13 consecutive glutamates/aspartates are predicted. This domain in Sec7p may serve a structural role to interact with lipids or proteins on the cytoplasmic surface of the Golgi apparatus.
- Structure (3D structures containing this domain)
3D Structures of Sec7 domains in PDB
| PDB code | Main view | Title | | 1bc9 |  | Cytohesin-1/b2-1 sec7 domain, nmr, minimized average structure |
| 1ku1 |  | Crystal structure of the sec7 domain of yeast gea2 |
| 1pbv |  | Sec7 domain of the exchange factor arno |
| 1r8m |  | Sec7 domain of the arf exchange factor arno with brefeldin a-sensitizing mutations |
| 1r8q |  | Full-length arf1-gdp-mg in complex with brefeldin a and a sec7 domain |
| 1r8s |  | Arf1[delta1-17]-gdp in complex with a sec7 domain carrying the mutation of the catalytic glutamate to lysine |
| 1re0 |  | Structure of arf1-gdp bound to sec7 domain complexed with brefeldin a |
| 1s9d |  | Arf1[delta 1-17]-gdp-mg in complex with brefeldin a and a sec7 domain |
| 1xsz |  | The structure of ralf |
| 1xt0 |  | The structure of n-terminal sec7 domain of ralf |
| 2r09 |  | Crystal structure of autoinhibited form of grp1 arf gtpase exchange factor |
| 2r0d |  | Crystal structure of autoinhibited form of grp1 arf gtpase exchange factor |
- Links (links to other resources describing this domain)
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