P08239
SS
Gene name |
GNAO1 |
Protein name |
Guanine nucleotide-binding protein G |
Names |
o subunit alpha , GTP-binding protein G39 |
Species |
Bos taurus (Bovine) |
KEGG Pathway |
bta:281792 |
EC number |
|
Protein Class |
|
Descriptions
Gαi1 is a G-protein alpha subunit that plays a crucial role in signal transduction pathway initiated by G-protein-coupled receptor (GPCR) activation. G proteins function as transducers downstream of GPCRs in numerous signaling cascades. The alpha subunit contains the guanine nucleotide binding site and alternates between an active (GTP-bound state) and an inactive (GDP-bound state). Activated GPCR induces conformational change in Gαi1, which allows for GDP-to-GTP exchange by binding to the GPCR-binding site within a Ras-like domain, leading to dissociation of the Gαi1 subunit and initiation of downstream signaling.
Autoinhibitory domains (AIDs)
Target domain |
185-348 (Ras-like domain) |
Relief mechanism |
Ligand binding, Partner binding |
Assay |
|
Accessory elements
No accessory elements
References
- 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
- 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
Autoinhibited structure
Activated structure
1 structures for P08239
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P08239-F1 | Predicted | AlphaFoldDB |
77 variants for P08239
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs444433923 | 2 | G>A | No | EVA | |
| rs444433923 | 2 | G>V | No | EVA | |
| rs452662556 | 5 | L>V | No | EVA | |
| rs467188013 | 7 | A>P | No | EVA | |
| rs436696234 | 9 | E>D | No | EVA | |
| rs455094336 | 9 | E>G | No | EVA | |
| rs450459458 | 16 | S>I | No | EVA | |
| rs476129554 | 41 | A>P | No | EVA | |
| rs457601674 | 51 | K>E | No | EVA | |
| rs433349711 | 77 | T>P | No | EVA | |
| rs460628179 | 79 | Q>K | No | EVA | |
| rs472824675 | 101 | K>R | No | EVA | |
| rs3423447923 | 103 | D>N | No | EVA | |
| rs475229113 | 105 | K>T | No | EVA | |
| rs438446011 | 107 | V>E | No | EVA | |
| rs463214576 | 107 | V>L | No | EVA | |
| rs471354454 | 108 | C>R | No | EVA | |
| rs453080826 | 111 | V>G | No | EVA | |
| rs474087349 | 114 | M>L | No | EVA | |
| rs474087349 | 114 | M>V | No | EVA | |
| rs455572278 | 123 | E>D | No | EVA | |
| rs469356805 | 125 | L>P | No | EVA | |
| rs432443662 | 128 | M>I | No | EVA | |
| rs450957296 | 128 | M>R | No | EVA | |
| rs465425404 | 129 | M>L | No | EVA | |
| rs480084453 | 132 | W>G | No | EVA | |
| rs461629362 | 133 | G>S | No | EVA | |
| rs449473537 | 135 | S>A | No | EVA | |
| rs463175958 | 136 | G>E | No | EVA | |
| rs482359556 | 136 | G>R | No | EVA | |
| rs471458929 | 138 | Q>P | No | EVA | |
| rs459390148 | 139 | E>* | No | EVA | |
| rs440960908 | 139 | E>G | No | EVA | |
| rs473985875 | 140 | C>S | No | EVA | |
| rs455560405 | 141 | F>L | No | EVA | |
| rs443532720 | 142 | N>K | No | EVA | |
| rs476550952 | 143 | R>G | No | EVA | |
| rs457280382 | 145 | R>W | No | EVA | |
| rs432355753 | 146 | E>K | No | EVA | |
| rs432355753 | 146 | E>Q | No | EVA | |
| rs453360428 | 148 | Q>P | No | EVA | |
| rs434905963 | 149 | L>P | No | EVA | |
| rs467927435 | 150 | N>K | No | EVA | |
| rs449434842 | 151 | D>A | No | EVA | |
| rs482324576 | 151 | D>E | No | EVA | |
| rs477874258 | 154 | K>N | No | EVA | |
| rs444761382 | 154 | K>T | No | EVA | |
| rs459374560 | 155 | Y>C | No | EVA | |
| rs455448086 | 200 | F>V | No | EVA | |
| rs436954223 | 201 | D>H | No | EVA | |
| rs470007744 | 202 | V>F | No | EVA | |
| rs451446875 | 202 | V>G | No | EVA | |
| rs465313031 | 204 | G>R | No | EVA | |
| rs479637489 | 207 | S>A | No | EVA | |
| rs467670896 | 215 | C>F | No | EVA | |
| rs449306416 | 218 | D>H | No | EVA | |
| rs482435340 | 224 | F>I | No | EVA | |
| rs464012378 | 225 | C>G | No | EVA | |
| rs464012378 | 225 | C>S | No | EVA | |
| rs439077219 | 228 | L>R | No | EVA | |
| rs459316759 | 234 | V>G | No | EVA | |
| rs440810639 | 240 | T>A | No | EVA | |
| rs440810639 | 240 | T>P | No | EVA | |
| rs473806239 | 241 | T>P | No | EVA | |
| rs447946922 | 260 | F>S | No | EVA | |
| rs479451917 | 291 | Y>S | No | EVA | |
| rs446139121 | 293 | G>A | No | EVA | |
| rs478995224 | 294 | S>P | No | EVA | |
| rs467030242 | 295 | N>H | No | EVA | |
| rs448614071 | 297 | Y>H | No | EVA | |
| rs481487165 | 297 | Y>S | No | EVA | |
| rs443969103 | 302 | A>P | No | EVA | |
| rs477089563 | 305 | Q>P | No | EVA | |
| rs449432707 | 337 | D>N | No | EVA | |
| rs454696365 | 348 | L>I | No | EVA | |
| rs442662197 | 348 | L>R | No | EVA | |
| rs457178814 | 355 | Y>W | No | EVA |
1 associated diseases with P08239
[MIM: 618667]: Hydrocephalus, congenital communicating, 1 (HYDCC1)
A form of congenital hydrocephalus, a disease characterized by onset in utero of enlarged ventricles due to accumulation of ventricular cerebrospinal fluid. Affected individuals may have neurologic impairment. HYDCC1 inheritance is autosomal dominant. {ECO:0000269|PubMed:29983323}. Note=The disease is caused by variants affecting the gene represented in this entry.
Without disease ID
- A form of congenital hydrocephalus, a disease characterized by onset in utero of enlarged ventricles due to accumulation of ventricular cerebrospinal fluid. Affected individuals may have neurologic impairment. HYDCC1 inheritance is autosomal dominant. {ECO:0000269|PubMed:29983323}. Note=The disease is caused by variants affecting the gene represented in this entry.
12 regional properties for P08239
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | B-box-type zinc finger | 194 - 243 | IPR000315-1 |
| domain | B-box-type zinc finger | 273 - 314 | IPR000315-2 |
| repeat | NHL repeat | 593 - 636 | IPR001258-1 |
| repeat | NHL repeat | 640 - 683 | IPR001258-2 |
| repeat | NHL repeat | 687 - 730 | IPR001258-3 |
| repeat | NHL repeat | 734 - 777 | IPR001258-4 |
| repeat | NHL repeat | 781 - 824 | IPR001258-5 |
| repeat | NHL repeat | 828 - 868 | IPR001258-6 |
| repeat | Filamin/ABP280 repeat | 483 - 583 | IPR001298 |
| domain | Zinc finger, RING-type | 12 - 95 | IPR001841 |
| repeat | Filamin/ABP280 repeat-like | 479 - 580 | IPR017868 |
| conserved_site | Zinc finger, RING-type, conserved site | 61 - 70 | IPR017907 |
2 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| 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. |
7 GO annotations of molecular function
| Name | Definition |
|---|---|
| corticotropin-releasing hormone receptor 1 binding | Binding to a corticotropin-releasing hormone receptor 1 (CRHR1). CRHR1 is the major subtype in the pituitary corticotroph, and mediates the stimulatory actions of corticotropin-releasing hormone on corticotropin hormone secretion. CRHR1 are also located in cortical areas of the brain, cerebellum and limbic system. |
| 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. |
| GTP binding | Binding to GTP, guanosine triphosphate. |
| GTPase activity | Catalysis of the reaction |
| metal ion binding | Binding to a metal ion. |
| mu-type opioid receptor binding | Binding to a mu-type opioid receptor. |
2 GO annotations of biological process
| Name | Definition |
|---|---|
| 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). |
| dopamine receptor signaling pathway | The series of molecular signals generated as a consequence of a dopamine receptor binding to one of its physiological ligands. |
58 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P04695 | GNAT1 | Guanine nucleotide-binding protein G | Bos taurus (Bovine) | SS |
| P04696 | GNAT2 | Guanine nucleotide-binding protein G | Bos taurus (Bovine) | SS |
| P0C7Q4 | GNAT3 | Guanine nucleotide-binding protein G | Bos taurus (Bovine) | SS |
| P63097 | GNAI1 | Guanine nucleotide-binding protein G | Bos taurus (Bovine) | SS |
| P38408 | GNA14 | Guanine nucleotide-binding protein subunit alpha-14 | Bos taurus (Bovine) | PR |
| P04896 | GNAS | Guanine nucleotide-binding protein G(s) subunit alpha isoforms short | Bos taurus (Bovine) | PR |
| P50147 | GNAI2 | Guanine nucleotide-binding protein G | Gallus gallus (Chicken) | SS |
| P50146 | GNAI1 | Guanine nucleotide-binding protein G | Gallus gallus (Chicken) | SS |
| P20353 | Galphai | G protein alpha i subunit | Drosophila melanogaster (Fruit fly) | SS |
| P25157 | cta | Guanine nucleotide-binding protein subunit alpha homolog | Drosophila melanogaster (Fruit fly) | SS |
| P16378 | Galphao | G protein alpha o 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 |
| 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 |
| P08754 | GNAI3 | Guanine nucleotide-binding protein G | Homo sapiens (Human) | SS |
| 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 |
| P09471 | GNAO1 | Guanine nucleotide-binding protein G | Homo sapiens (Human) | SS |
| Q9DC51 | Gnai3 | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | 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 |
| P93564 | GPA1 | Guanine nucleotide-binding protein alpha-1 subunit | Solanum tuberosum (Potato) | SS |
| Q63210 | Gna12 | Guanine nucleotide-binding protein subunit alpha-12 | 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 |
| P04897 | Gnai2 | Guanine nucleotide-binding protein G | Rattus norvegicus (Rat) | SS |
| P08753 | Gnai3 | Guanine nucleotide-binding protein G | Rattus norvegicus (Rat) | SS |
| Q6Q7Y5 | Gna13 | Guanine nucleotide-binding protein subunit alpha-13 | Rattus norvegicus (Rat) | SS |
| P59215 | Gnao1 | Guanine nucleotide-binding protein G | Rattus norvegicus (Rat) | SS |
| Q0DJ33 | GPA1 | Guanine nucleotide-binding protein alpha-1 subunit | Oryza sativa subsp. japonica (Rice) | SS |
| O76584 | gpa-11 | Guanine nucleotide-binding protein alpha-11 subunit | Caenorhabditis elegans | SS |
| Q93743 | gpa-6 | Guanine nucleotide-binding protein alpha-6 subunit | Caenorhabditis elegans | SS |
| Q20907 | gpa-8 | Guanine nucleotide-binding protein alpha-8 subunit | Caenorhabditis elegans | PR |
| P91907 | gpa-15 | Guanine nucleotide-binding protein alpha-15 subunit | Caenorhabditis elegans | SS |
| Q21917 | gpa-7 | Guanine nucleotide-binding protein alpha-7 subunit | Caenorhabditis elegans | SS |
| Q9BIG5 | gpa-4 | Guanine nucleotide-binding protein alpha-4 subunit | Caenorhabditis elegans | SS |
| Q9N2V6 | gpa-16 | Guanine nucleotide-binding protein alpha-16 subunit | Caenorhabditis elegans | SS |
| P28051 | gpa-1 | Guanine nucleotide-binding protein alpha-1 subunit | Caenorhabditis elegans | SS |
| P28052 | gpa-3 | Guanine nucleotide-binding protein alpha-3 subunit | Caenorhabditis elegans | 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 |
| Q9XTB2 | gpa-13 | Guanine nucleotide-binding protein alpha-13 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 |
| MGCTLSAEER | AALERSKAIE | KNLKEDGISA | AKDVKLLLLG | AGESGKSTIV | KQMKIIHEDG |
| 70 | 80 | 90 | 100 | 110 | 120 |
| FSGEDVKQYK | PVVYSNTIQS | LAAIVRAMDT | LGIEYGDKER | KADAKMVCDV | VSRMEDTEPF |
| 130 | 140 | 150 | 160 | 170 | 180 |
| SPELLSAMMR | LWGDSGIQEC | FNRSREYQLN | DSAKYYLDSL | DRIGAADYQP | TEQDILRTRV |
| 190 | 200 | 210 | 220 | 230 | 240 |
| KTTGIVETHF | TFKNLHFRLF | DVGGQRSERK | KWIHCFEDVT | AIIFCVALSG | YDQVLHEDET |
| 250 | 260 | 270 | 280 | 290 | 300 |
| TNRMHESLML | FDSICNNKFF | IDTSIILFLN | KKDLFGEKIK | KSPLTICFPE | YTGSNTYEDA |
| 310 | 320 | 330 | 340 | 350 | |
| AAYIQAQFES | KNRSPNKEIY | CHMTCATDTN | NIQVVFDAVT | DIIIANNLRG | CGLY |