B2RSH2
Gene name |
Gnai1 (Gnai-1) |
Protein name |
Guanine nucleotide-binding protein G |
Names |
i subunit alpha-1 , Adenylate cyclase-inhibiting G alpha protein |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:14677 |
EC number |
|
Protein Class |
|
Descriptions
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
14 variants for B2RSH2
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3388747170 | 59 | A>D | No | EVA | |
| rs3388747149 | 89 | G>R | No | EVA | |
| rs3388738844 | 113 | A>V | No | EVA | |
| rs3388738889 | 116 | E>K | No | EVA | |
| rs3388741377 | 118 | F>Y | No | EVA | |
| rs3388743977 | 119 | M>V | No | EVA | |
| rs3388734550 | 140 | F>L | No | EVA | |
| rs3388747152 | 151 | S>* | No | EVA | |
| rs3388741406 | 155 | Y>* | No | EVA | |
| rs3388750876 | 161 | R>S | No | EVA | |
| rs3388741327 | 162 | I>K | No | EVA | |
| rs3394954054 | 171 | Q>E | No | EVA | |
| rs3388745036 | 185 | V>E | No | EVA | |
| rs3388736950 | 233 | V>I | No | EVA |
3 associated diseases with B2RSH2
[MIM: 114290]: Campomelic dysplasia (CMD1)
A rare, often lethal, osteochondrodysplasia characterized by congenital bowing and angulation of long bones. Other skeletal defects include unusually small scapula, deformed pelvis and spine, and a missing pair of ribs. Craniofacial and ear defects are common. Most patients die soon after birth due to respiratory distress which has been attributed to hypoplasia of the tracheobronchial cartilage and small thoracic cage. Up to two-thirds of affected XY individuals have genital defects or may develop as phenotypic females. {ECO:0000269|PubMed:10446171, ECO:0000269|PubMed:10951468, ECO:0000269|PubMed:11323423, ECO:0000269|PubMed:11754051, ECO:0000269|PubMed:12783851, ECO:0000269|PubMed:19033726, ECO:0000269|PubMed:19921652, ECO:0000269|PubMed:20513132, ECO:0000269|PubMed:24038782, ECO:0000269|PubMed:7485151, ECO:0000269|PubMed:7990924, ECO:0000269|PubMed:8001137, ECO:0000269|PubMed:9002675, ECO:0000269|PubMed:9452059}. Note=The disease is caused by variants affecting the gene represented in this entry.
[MIM: 278850]: 46,XX sex reversal 2 (SRXX2)
A condition in which male gonads develop in a genetic female (female to male sex reversal). {ECO:0000269|PubMed:21208124}. Note=The disease is caused by variants affecting the gene represented in this entry.
[MIM: 616425]: 46,XY sex reversal 10 (SRXY10)
A disorder of sex development. Affected individuals have a 46,XY karyotype, show gonadal dysgenesis with streak gonads, look like normal females at birth, do not develop secondary sexual characteristics at puberty and do not menstruate. {ECO:0000269|PubMed:25604083}. Note=The disease is caused by variants affecting the gene represented in this entry.
Without disease ID
- A rare, often lethal, osteochondrodysplasia characterized by congenital bowing and angulation of long bones. Other skeletal defects include unusually small scapula, deformed pelvis and spine, and a missing pair of ribs. Craniofacial and ear defects are common. Most patients die soon after birth due to respiratory distress which has been attributed to hypoplasia of the tracheobronchial cartilage and small thoracic cage. Up to two-thirds of affected XY individuals have genital defects or may develop as phenotypic females. {ECO:0000269|PubMed:10446171, ECO:0000269|PubMed:10951468, ECO:0000269|PubMed:11323423, ECO:0000269|PubMed:11754051, ECO:0000269|PubMed:12783851, ECO:0000269|PubMed:19033726, ECO:0000269|PubMed:19921652, ECO:0000269|PubMed:20513132, ECO:0000269|PubMed:24038782, ECO:0000269|PubMed:7485151, ECO:0000269|PubMed:7990924, ECO:0000269|PubMed:8001137, ECO:0000269|PubMed:9002675, ECO:0000269|PubMed:9452059}. Note=The disease is caused by variants affecting the gene represented in this entry.
- A condition in which male gonads develop in a genetic female (female to male sex reversal). {ECO:0000269|PubMed:21208124}. Note=The disease is caused by variants affecting the gene represented in this entry.
- A disorder of sex development. Affected individuals have a 46,XY karyotype, show gonadal dysgenesis with streak gonads, look like normal females at birth, do not develop secondary sexual characteristics at puberty and do not menstruate. {ECO:0000269|PubMed:25604083}. Note=The disease is caused by variants affecting the gene represented in this entry.
4 regional properties for B2RSH2
Functions
9 GO annotations of cellular component
| Name | Definition |
|---|---|
| cell cortex | The region of a cell that lies just beneath the plasma membrane and often, but not always, contains a network of actin filaments and associated proteins. |
| 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. |
| 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. |
| nucleolus | A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome. |
| 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. |
| protein-containing complex | A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together. |
9 GO annotations of molecular function
| Name | Definition |
|---|---|
| D2 dopamine receptor binding | Binding to a D2 dopamine receptor. |
| 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 |
| magnesium ion binding | Binding to a magnesium (Mg) ion. |
9 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). |
| 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. |
| cellular response to forskolin | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a forskolin stimulus. |
| G protein-coupled receptor signaling pathway | The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane. |
| negative regulation of synaptic transmission | Any process that stops, prevents, or reduces the frequency, rate or extent of synaptic transmission, the process of communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. |
| positive regulation of protein localization to cell cortex | Any process that activates or increases the frequency, rate or extent of protein localization to cell cortex. |
| regulation of cAMP-mediated signaling | Any process which modulates the frequency, rate or extent of cAMP-mediated signaling. |
| regulation of mitotic spindle organization | Any process that modulates the rate, frequency or extent of the assembly, arrangement of constituent parts, or disassembly of the microtubule spindle during a mitotic cell cycle. |
59 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| 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 |
| P63097 | GNAI1 | 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 |
| 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 |
| P63096 | GNAI1 | Guanine nucleotide-binding protein G | Homo sapiens (Human) | EV |
| O70443 | Gnaz | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| P08752 | Gnai2 | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| P20612 | Gnat1 | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| P27600 | Gna12 | Guanine nucleotide-binding protein subunit alpha-12 | Mus musculus (Mouse) | SS |
| P27601 | Gna13 | Guanine nucleotide-binding protein subunit alpha-13 | Mus musculus (Mouse) | SS |
| P50149 | Gnat2 | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| Q3V3I2 | Gnat3 | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| Q9DC51 | Gnai3 | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| P21279 | Gnaq | Guanine nucleotide-binding protein G(q) subunit alpha | Mus musculus (Mouse) | PR |
| P30678 | Gna15 | Guanine nucleotide-binding protein subunit alpha-15 | Mus musculus (Mouse) | PR |
| 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 |
| P59215 | Gnao1 | 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 |
| P10824 | Gnai1 | Guanine nucleotide-binding protein G subunit alpha-1 | Rattus norvegicus (Rat) | EV |
| 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 |
| 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 |
| 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 |
| P28051 | gpa-1 | Guanine nucleotide-binding protein alpha-1 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 |
| 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 | AREVKLLLLG | AGESGKSTIV | KQMKIIHEAG |
| 70 | 80 | 90 | 100 | 110 | 120 |
| YSEEECKQYK | AVVYSNTIQS | IIAIIRAMGR | LKIDFGDSAR | ADDARQLFVL | AGAAEEGFMT |
| 130 | 140 | 150 | 160 | 170 | 180 |
| AELAGVIKRL | WKDSGVQACF | NRSREYQLND | SAAYYLNDLD | RIAQPNYIPT | QQDVLRTRVK |
| 190 | 200 | 210 | 220 | 230 | 240 |
| TTGIVETHFT | FKDLHFKMFD | VGGQRSERKK | WIHCFEGVTA | IIFCVALSDY | DLVLAEDEEM |
| 250 | 260 | 270 | 280 | 290 | 300 |
| NRMHESMKLF | DSICNNKWFT | DTSIILFLNK | KDLFEEKIKK | SPLTICYPEY | AGSNTYEEAA |
| 310 | 320 | 330 | 340 | 350 | |
| AYIQCQFEDL | NKRKDTKEIY | THFTCATDTK | NVQFVFDAVT | DVIIKNNLKD | CGLF |