O08967
Gene name |
Cyth3 (Grp1, Pscd3) |
Protein name |
Cytohesin-3 |
Names |
ARF nucleotide-binding site opener 3, Protein ARNO3, General receptor of phosphoinositides 1, Grp1, PH, SEC7 and coiled-coil domain-containing protein 3, CLM3, SEC7 homolog C, mSec7-3 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:19159 |
EC number |
|
Protein Class |
GUANYL-NUCLEOTIDE EXCHANGE FACTOR (PTHR10663) |
Descriptions
Cyth3 regulates membrane trafficking and actin dynamics. Sec7-PH tandem reveals a pseudosubstrate mechanism of autoinhibition in which the linker region between domains and a C-terminal amphipathic helix physically block the docking sites for the switch regions of Arf GTPases. Truncation of the polybasic motif (383-395) increases the activity of Cyth3 by 20- to 100-fold. The deletion of the Sec-PH linker region (251-265) also increases the Cyth3 activity.
Autoinhibitory domains (AIDs)
Target domain |
63-250 (Sec7 domain) |
Relief mechanism |
Partner binding, PTM |
Assay |
Deletion assay, Mutagenesis experiment, Structural analysis |
Target domain |
63-250 (Sec7 domain) |
Relief mechanism |
Partner binding, PTM |
Assay |
Deletion assay, Mutagenesis experiment, Structural analysis |
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
10 structures for O08967
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 1FGY | X-ray | 150 A | A | 261-387 | PDB |
| 1FGZ | X-ray | 205 A | A | 261-387 | PDB |
| 1FHW | X-ray | 190 A | A/B | 264-391 | PDB |
| 1FHX | X-ray | 250 A | A/B | 264-391 | PDB |
| 1U2B | X-ray | 180 A | A | 261-387 | PDB |
| 2R09 | X-ray | 190 A | A/B | 63-399 | PDB |
| 2R0D | X-ray | 204 A | A/B | 63-399 | PDB |
| 6BBP | EM | 3500 A | A | 63-399 | PDB |
| 6BBQ | EM | 3500 A | A | 63-399 | PDB |
| AF-O08967-F1 | Predicted | AlphaFoldDB |
No variants for O08967
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for O08967 | |||||
No associated diseases with O08967
Functions
| Description | ||
|---|---|---|
| EC Number | ||
| Subcellular Localization |
|
|
| PANTHER Family | PTHR10663 | GUANYL-NUCLEOTIDE EXCHANGE FACTOR |
| PANTHER Subfamily | PTHR10663:SF320 | CYTOHESIN-3 |
| PANTHER Protein Class |
guanyl-nucleotide exchange factor
G-protein modulator protein-binding activity modulator |
|
| PANTHER Pathway Category | No pathway information available | |
8 GO annotations of cellular component
| Name | Definition |
|---|---|
| adherens junction | A cell-cell junction composed of the epithelial cadherin-catenin complex. The epithelial cadherins, or E-cadherins, of each interacting cell extend through the plasma membrane into the extracellular space and bind to each other. The E-cadherins bind to catenins on the cytoplasmic side of the membrane, where the E-cadherin-catenin complex binds to cytoskeletal components and regulatory and signaling molecules. |
| bicellular tight junction | An occluding cell-cell junction that is composed of a branching network of sealing strands that completely encircles the apical end of each cell in an epithelial sheet; the outer leaflets of the two interacting plasma membranes are seen to be tightly apposed where sealing strands are present. Each sealing strand is composed of a long row of transmembrane adhesion proteins embedded in each of the two interacting plasma membranes. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| extrinsic component of cytoplasmic side of plasma membrane | The component of a plasma membrane consisting of gene products and protein complexes that are loosely bound to its cytoplasmic surface, but not integrated into the hydrophobic region. |
| nucleoplasm | That part of the nuclear content other than the chromosomes or the nucleolus. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| ruffle | Projection at the leading edge of a crawling cell; the protrusions are supported by a microfilament meshwork. |
2 GO annotations of molecular function
| Name | Definition |
|---|---|
| guanyl-nucleotide exchange factor activity | Stimulates the exchange of GDP to GTP on a signaling GTPase, changing its conformation to its active form. Guanine nucleotide exchange factors (GEFs) act by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP), which is more abundant in the cell under normal cellular physiological conditions. |
| phosphatidylinositol-3,4,5-trisphosphate binding | Binding to phosphatidylinositol-3,4,5-trisphosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 3', 4' and 5' positions. |
4 GO annotations of biological process
| Name | Definition |
|---|---|
| establishment of epithelial cell polarity | The specification and formation of anisotropic intracellular organization of an epithelial cell. |
| Golgi vesicle transport | The directed movement of substances into, out of or within the Golgi apparatus, mediated by vesicles. |
| positive regulation of cell adhesion | Any process that activates or increases the frequency, rate or extent of cell adhesion. |
| regulation of ARF protein signal transduction | Any process that modulates the frequency, rate or extent of ARF protein signal transduction. |
16 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q2KI41 | CYTH2 | Cytohesin-2 | Bos taurus (Bovine) | SS |
| Q15438 | CYTH1 | Cytohesin-1 | Homo sapiens (Human) | SS |
| Q99418 | CYTH2 | Cytohesin-2 | Homo sapiens (Human) | SS |
| Q9UIA0 | CYTH4 | Cytohesin-4 | Homo sapiens (Human) | SS |
| O43739 | CYTH3 | Cytohesin-3 | Homo sapiens (Human) | EV |
| Q80YW0 | Cyth4 | Cytohesin-4 | Mus musculus (Mouse) | SS |
| Q3TES0 | Iqsec3 | IQ motif and SEC7 domain-containing protein 3 | Mus musculus (Mouse) | SS |
| G3X9K3 | Arfgef1 | Brefeldin A-inhibited guanine nucleotide-exchange protein 1 | Mus musculus (Mouse) | PR |
| A2A5R2 | Arfgef2 | Brefeldin A-inhibited guanine nucleotide-exchange protein 2 | Mus musculus (Mouse) | PR |
| Q8R0S2 | Iqsec1 | IQ motif and SEC7 domain-containing protein 1 | Mus musculus (Mouse) | SS |
| P63034 | Cyth2 | Cytohesin-2 | Mus musculus (Mouse) | SS |
| Q9QX11 | Cyth1 | Cytohesin-1 | Mus musculus (Mouse) | SS |
| Q5DU25 | Iqsec2 | IQ motif and SEC7 domain-containing protein 2 | Mus musculus (Mouse) | SS |
| P97694 | Cyth1 | Cytohesin-1 | Rattus norvegicus (Rat) | SS |
| P63035 | Cyth2 | Cytohesin-2 | Rattus norvegicus (Rat) | SS |
| P97696 | Cyth3 | Cytohesin-3 | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MDEGGGGEGG | SVPEDLSLEE | REELLDIRRR | KKELIDDIER | LKYEIAEVMT | EIDNLTSVEE |
| 70 | 80 | 90 | 100 | 110 | 120 |
| SKTTQRNKQI | AMGRKKFNMD | PKKGIQFLIE | NDLLQSSPED | VAQFLYKGEG | LNKTVIGDYL |
| 130 | 140 | 150 | 160 | 170 | 180 |
| GERDDFNIKV | LQAFVELHEF | ADLNLVQALR | QFLWSFRLPG | EAQKIDRMME | AFASRYCLCN |
| 190 | 200 | 210 | 220 | 230 | 240 |
| PGVFQSTDTC | YVLSFAIIML | NTSLHNHNVR | DKPTAERFIT | MNRGINEGGD | LPEELLRNLY |
| 250 | 260 | 270 | 280 | 290 | 300 |
| ESIKNEPFKI | PEDDGNDLTH | TFFNPDREGW | LLKLGGRVKT | WKRRWFILTD | NCLYYFEYTT |
| 310 | 320 | 330 | 340 | 350 | 360 |
| DKEPRGIIPL | ENLSIREVED | PRKPNCFELY | NPSHKGQVIK | ACKTEADGRV | VEGNHVVYRI |
| 370 | 380 | 390 | |||
| SAPSPEEKEE | WMKSIKASIS | RDPFYDMLAT | RKRRIANKK |