P08753
SS
Gene name |
Gnai3 (Gnai-3) |
Protein name |
Guanine nucleotide-binding protein G |
Names |
i subunit alpha-3 , G, i alpha-3 |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:25643 |
EC number |
|
Protein Class |
|
Descriptions
The Gα subunits of heterotrimeric G proteins are GTP hydrolyases which, upon receptor activation, bind to GTP and regulate effector molecules. Gα-catalyzed hydrolysis of GTP to GDP releases the Gα-GDP product complex from effector and allows its sequestration by inhibitory Gβγ subunits. In Gia1-GppNHp complex, Gln204 of Gia1 interacts with nucleophilic water (Wnuc), participating directly in the Gia1-GTP ground state but must reorient to stabilize the transition state. RGS4, a member of the RGS family of G protein stimulatory factors, accelerates hydrolysis of GTP by Gia1 by destabilizing the ground-state conformation of Gln204. Insertion of Asn128 of RGS4 into the active site enhances catalysis by aiding in binding, orienting, and polarizing Wnuc in the pre-transition state complex. Asn128 of RGS4 displaces the side chain of Gln204 from its anti-catalytic position in the ground state, freeing it to participate in stabilization of the transition state.
Autoinhibitory domains (AIDs)
Target domain |
179-349 (P-loop containing nucleoside triphosphate hydrolase domain) |
Relief mechanism |
Partner binding |
Assay |
|
Target domain |
184-348 (Ras-like domain) |
Relief mechanism |
Ligand binding, Partner binding |
Assay |
|
Accessory elements
No accessory elements
References
- Coleman DE et al. (1999) "Structure of Gialpha1.GppNHp, autoinhibition in a galpha protein-substrate complex", The Journal of biological chemistry, 274, 16669-72
- Lutz S et al. (2007) "Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs", Science (New York, N.Y.), 318, 1923-7
- Goricanec D et al. (2016) "Conformational dynamics of a G-protein α subunit is tightly regulated by nucleotide binding", Proceedings of the National Academy of Sciences of the United States of America, 113, E3629-38
Autoinhibited structure
Activated structure
3 structures for P08753
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 6MHE | X-ray | 220 A | A | 26-354 | PDB |
| 6MHF | X-ray | 200 A | A | 26-354 | PDB |
| AF-P08753-F1 | Predicted | AlphaFoldDB |
No variants for P08753
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P08753 | |||||
No associated diseases with P08753
7 regional properties for P08753
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | EF-hand domain | 182 - 233 | IPR002048 |
| domain | FAD-binding 8 | 562 - 678 | IPR013112 |
| domain | Ferric reductase, NAD binding domain | 685 - 849 | IPR013121 |
| domain | Ferric reductase transmembrane component-like domain | 363 - 518 | IPR013130 |
| domain | NADPH oxidase Respiratory burst | 103 - 201 | IPR013623 |
| domain | FAD-binding domain, ferredoxin reductase-type | 558 - 681 | IPR017927 |
| binding_site | EF-Hand 1, calcium-binding site | 211 - 223 | IPR018247 |
Functions
8 GO annotations of cellular component
| Name | Definition |
|---|---|
| centrosome | A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| Golgi apparatus | A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways. |
| Golgi membrane | The lipid bilayer surrounding any of the compartments of the Golgi apparatus. |
| heterotrimeric G-protein complex | Any of a family of heterotrimeric GTP-binding and hydrolyzing proteins; they belong to a superfamily of GTPases that includes monomeric proteins such as EF-Tu and RAS. Heterotrimeric G-proteins consist of three subunits; the alpha subunit contains the guanine nucleotide binding site and possesses GTPase activity; the beta and gamma subunits are tightly associated and function as a beta-gamma heterodimer; extrinsic plasma membrane proteins (cytoplasmic face) that function as a complex to transduce signals from G protein-coupled receptors to an effector protein. |
| midbody | A thin cytoplasmic bridge formed between daughter cells at the end of cytokinesis. The midbody forms where the contractile ring constricts, and may persist for some time before finally breaking to complete cytokinesis. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| zymogen granule | A membrane-bounded, cytoplasmic secretory granule found in enzyme-secreting cells and visible by light microscopy. Contain zymogen, an inactive enzyme precursor, often of a digestive enzyme. |
9 GO annotations of molecular function
| Name | Definition |
|---|---|
| G protein-coupled receptor binding | Binding to a G protein-coupled receptor. |
| G protein-coupled serotonin receptor binding | Binding to a metabotropic serotonin receptor. |
| G-protein beta/gamma-subunit complex binding | Binding to a complex of G-protein beta/gamma subunits. |
| GDP binding | Binding to GDP, guanosine 5'-diphosphate. |
| GTP binding | Binding to GTP, guanosine triphosphate. |
| GTPase activating protein binding | Binding to a GTPase activating protein. |
| GTPase activity | Catalysis of the reaction |
| metal ion binding | Binding to a metal ion. |
| protein domain specific binding | Binding to a specific domain of a protein. |
12 GO annotations of biological process
| Name | Definition |
|---|---|
| adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | A G protein-coupled receptor signaling pathway in which the signal is transmitted via the inhibition of adenylyl cyclase activity and a subsequent decrease in the intracellular concentration of cyclic AMP (cAMP). |
| adenylate cyclase-modulating G protein-coupled receptor signaling pathway | A G protein-coupled receptor signaling pathway in which the signal is transmitted via the activation or inhibition of adenylyl cyclase activity and a subsequent change in the intracellular concentration of cyclic AMP (cAMP). |
| cell cycle | The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division. |
| cell division | The process resulting in division and partitioning of components of a cell to form more cells; may or may not be accompanied by the physical separation of a cell into distinct, individually membrane-bounded daughter cells. |
| dopamine receptor signaling pathway | The series of molecular signals generated as a consequence of a dopamine receptor binding to one of its physiological ligands. |
| GTP metabolic process | The chemical reactions and pathways involving GTP, guanosine triphosphate. |
| negative regulation of apoptotic signaling pathway | Any process that stops, prevents or reduces the frequency, rate or extent of apoptotic signaling pathway. |
| negative regulation of secretion | Any process that stops, prevents, or reduces the frequency, rate or extent of the controlled release of a substance from a cell or a tissue. |
| positive regulation of macroautophagy | Any process, such as recognition of nutrient depletion, that activates or increases the rate of macroautophagy to bring cytosolic macromolecules to the vacuole/lysosome for degradation. |
| positive regulation of superoxide anion generation | Any process that activates or increases the frequency, rate or extent of enzymatic generation of superoxide by a cell. |
| positive regulation of vascular associated smooth muscle cell proliferation | Any process that activates or increases the frequency, rate or extent of vascular smooth muscle cell proliferation. |
| vesicle fusion | Fusion of the membrane of a transport vesicle with its target membrane. |
62 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P63097 | GNAI1 | Guanine nucleotide-binding protein G | Bos taurus (Bovine) | SS |
| P0C7Q4 | GNAT3 | Guanine nucleotide-binding protein G | Bos taurus (Bovine) | SS |
| P04696 | GNAT2 | Guanine nucleotide-binding protein G | Bos taurus (Bovine) | SS |
| P04695 | GNAT1 | Guanine nucleotide-binding protein G | Bos taurus (Bovine) | SS |
| P08239 | GNAO1 | Guanine nucleotide-binding protein G | Bos taurus (Bovine) | SS |
| P50147 | GNAI2 | Guanine nucleotide-binding protein G | Gallus gallus (Chicken) | SS |
| P50146 | GNAI1 | Guanine nucleotide-binding protein G | Gallus gallus (Chicken) | SS |
| P16378 | Galphao | G protein alpha o subunit | Drosophila melanogaster (Fruit fly) | SS |
| P25157 | cta | Guanine nucleotide-binding protein subunit alpha homolog | Drosophila melanogaster (Fruit fly) | SS |
| P20353 | Galphai | G protein alpha i subunit | Drosophila melanogaster (Fruit fly) | SS |
| P11488 | GNAT1 | Guanine nucleotide-binding protein G | Homo sapiens (Human) | SS |
| P19087 | GNAT2 | Guanine nucleotide-binding protein G | Homo sapiens (Human) | SS |
| P09471 | GNAO1 | Guanine nucleotide-binding protein G | Homo sapiens (Human) | SS |
| Q03113 | GNA12 | Guanine nucleotide-binding protein subunit alpha-12 | Homo sapiens (Human) | SS |
| P04899 | GNAI2 | Guanine nucleotide-binding protein G | Homo sapiens (Human) | SS |
| P63096 | GNAI1 | Guanine nucleotide-binding protein G | Homo sapiens (Human) | EV |
| A8MTJ3 | GNAT3 | Guanine nucleotide-binding protein G | Homo sapiens (Human) | SS |
| Q14344 | GNA13 | Guanine nucleotide-binding protein subunit alpha-13 | Homo sapiens (Human) | SS |
| P19086 | GNAZ | Guanine nucleotide-binding protein G | Homo sapiens (Human) | SS |
| P08754 | GNAI3 | Guanine nucleotide-binding protein G | Homo sapiens (Human) | SS |
| P27600 | Gna12 | Guanine nucleotide-binding protein subunit alpha-12 | Mus musculus (Mouse) | SS |
| P20612 | Gnat1 | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| P27601 | Gna13 | Guanine nucleotide-binding protein subunit alpha-13 | Mus musculus (Mouse) | SS |
| Q3V3I2 | Gnat3 | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| O70443 | Gnaz | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| P50149 | Gnat2 | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| P08752 | Gnai2 | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| B2RSH2 | Gnai1 | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| P18872 | Gnao1 | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| Q9DC51 | Gnai3 | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| P93564 | GPA1 | Guanine nucleotide-binding protein alpha-1 subunit | Solanum tuberosum (Potato) | SS |
| P04897 | Gnai2 | Guanine nucleotide-binding protein G | Rattus norvegicus (Rat) | SS |
| P19627 | Gnaz | Guanine nucleotide-binding protein G | Rattus norvegicus (Rat) | SS |
| P29348 | Gnat3 | Guanine nucleotide-binding protein G | Rattus norvegicus (Rat) | SS |
| Q63210 | Gna12 | Guanine nucleotide-binding protein subunit alpha-12 | Rattus norvegicus (Rat) | SS |
| Q6Q7Y5 | Gna13 | Guanine nucleotide-binding protein subunit alpha-13 | Rattus norvegicus (Rat) | SS |
| Q9JID2 | Gna11 | Guanine nucleotide-binding protein subunit alpha-11 | Rattus norvegicus (Rat) | SS |
| O88302 | Gna15 | Guanine nucleotide-binding protein subunit alpha-15 | Rattus norvegicus (Rat) | SS |
| P82471 | Gnaq | Guanine nucleotide-binding protein G | Rattus norvegicus (Rat) | SS |
| P38406 | Gnal | Guanine nucleotide-binding protein G | Rattus norvegicus (Rat) | SS |
| P10824 | Gnai1 | Guanine nucleotide-binding protein G subunit alpha-1 | Rattus norvegicus (Rat) | EV |
| P59215 | Gnao1 | Guanine nucleotide-binding protein G | Rattus norvegicus (Rat) | SS |
| Q63803 | Gnas | Guanine nucleotide-binding protein G | Rattus norvegicus (Rat) | SS |
| Q0DJ33 | GPA1 | Guanine nucleotide-binding protein alpha-1 subunit | Oryza sativa subsp. japonica (Rice) | SS |
| P51875 | goa-1 | Guanine nucleotide-binding protein G | Caenorhabditis elegans | SS |
| Q18434 | odr-3 | Guanine nucleotide-binding protein alpha-17 subunit | Caenorhabditis elegans | SS |
| Q9BIG4 | gpa-10 | Guanine nucleotide-binding protein alpha-10 subunit | Caenorhabditis elegans | PR |
| P28052 | gpa-3 | Guanine nucleotide-binding protein alpha-3 subunit | Caenorhabditis elegans | SS |
| Q9XTB2 | gpa-13 | Guanine nucleotide-binding protein alpha-13 subunit | Caenorhabditis elegans | SS |
| Q9BIG5 | gpa-4 | Guanine nucleotide-binding protein alpha-4 subunit | Caenorhabditis elegans | SS |
| P28051 | gpa-1 | Guanine nucleotide-binding protein alpha-1 subunit | Caenorhabditis elegans | SS |
| P91907 | gpa-15 | Guanine nucleotide-binding protein alpha-15 subunit | Caenorhabditis elegans | SS |
| Q20907 | gpa-8 | Guanine nucleotide-binding protein alpha-8 subunit | Caenorhabditis elegans | PR |
| Q21917 | gpa-7 | Guanine nucleotide-binding protein alpha-7 subunit | Caenorhabditis elegans | SS |
| Q93743 | gpa-6 | Guanine nucleotide-binding protein alpha-6 subunit | Caenorhabditis elegans | SS |
| Q9N2V6 | gpa-16 | Guanine nucleotide-binding protein alpha-16 subunit | Caenorhabditis elegans | SS |
| O76584 | gpa-11 | Guanine nucleotide-binding protein alpha-11 subunit | Caenorhabditis elegans | SS |
| P49084 | GPA1 | Guanine nucleotide-binding protein alpha-1 subunit | Glycine max (Soybean) (Glycine hispida) | SS |
| P93163 | GPA2 | Guanine nucleotide-binding protein alpha-2 subunit | Glycine max (Soybean) (Glycine hispida) | SS |
| O80462 | XLG1 | Extra-large guanine nucleotide-binding protein 1 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| P18064 | GPA1 | Guanine nucleotide-binding protein alpha-1 subunit | Arabidopsis thaliana (Mouse-ear cress) | SS |
| P26981 | GPA1 | Guanine nucleotide-binding protein alpha-1 subunit | Solanum lycopersicum (Tomato) (Lycopersicon esculentum) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MGCTLSAEDK | AAVERSKMID | RNLREDGEKA | AKEVKLLLLG | AGESGKSTIV | KQMKIIHEDG |
| 70 | 80 | 90 | 100 | 110 | 120 |
| YSEDECKQYK | VVVYSNTIQS | IIAIIRAMGR | LKIDFGEAAR | ADDARQLFVL | AGSAEEGVMT |
| 130 | 140 | 150 | 160 | 170 | 180 |
| SELAGVIKRL | WRDGGVQACF | SRSREYQLND | SASYYLNDLD | RISQTNYIPT | QQDVLRTRVK |
| 190 | 200 | 210 | 220 | 230 | 240 |
| TTGIVETHFT | FKELYFKMFD | VGGQRSERKK | WIHCFEGVTA | IIFCVALSDY | DLVLAEDEEM |
| 250 | 260 | 270 | 280 | 290 | 300 |
| NRMHESMKLF | DSICNNKWFT | DTSIILFLNK | KDLFEEKIKR | SPLTICYPEY | TGSNTYEEAA |
| 310 | 320 | 330 | 340 | 350 | |
| AYIQCQFEDL | NRRKDTKEVY | THFTCATDTK | NVQFVFDAVT | DVIIKNNLKE | CGLY |