P27601
SS
Gene name |
Gna13 (Gna-13) |
Protein name |
Guanine nucleotide-binding protein subunit alpha-13 |
Names |
G alpha-13 , G-protein subunit alpha-13 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:14674 |
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 |
206-371 (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
14 variants for P27601
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3389216355 | 113 | N>S | No | EVA | |
| rs3389212248 | 127 | T>I | No | EVA | |
| rs3389182657 | 129 | A>S | No | EVA | |
| rs3389225036 | 131 | M>I | No | EVA | |
| rs3389225058 | 132 | A>T | No | EVA | |
| rs3389207507 | 133 | A>D | No | EVA | |
| rs3389146883 | 133 | A>P | No | EVA | |
| rs3389225000 | 171 | G>S | No | EVA | |
| rs3389146865 | 258 | E>K | No | EVA | |
| rs3389226786 | 285 | S>P | No | EVA | |
| rs3389213376 | 311 | E>Q | No | EVA | |
| rs3389188615 | 327 | V>M | No | EVA | |
| rs3389210223 | 334 | R>C | No | EVA | |
| rs1132733554 | 365 | T>M | No | EVA |
2 associated diseases with P27601
[MIM: 614893]: Immunodeficiency 32A (IMD32A)
An immunologic disorder characterized by abnormal peripheral blood myeloid phenotype with a marked loss of CD11C-positive/CD1C dendritic cells, resulting in selective susceptibility to mycobacterial infections. {ECO:0000269|PubMed:21524210}. Note=The disease is caused by variants affecting the gene represented in this entry.
[MIM: 226990]: Immunodeficiency 32B (IMD32B)
An autosomal recessive primary immunodeficiency characterized by monocyte and dendritic cell deficiency, myeloproliferation, and susceptibility to severe opportunistic infections, including disseminated BCG infection and oral candidiasis. {ECO:0000269|PubMed:21524210, ECO:0000269|PubMed:25122610}. Note=The disease is caused by variants affecting the gene represented in this entry.
Without disease ID
- An immunologic disorder characterized by abnormal peripheral blood myeloid phenotype with a marked loss of CD11C-positive/CD1C dendritic cells, resulting in selective susceptibility to mycobacterial infections. {ECO:0000269|PubMed:21524210}. Note=The disease is caused by variants affecting the gene represented in this entry.
- An autosomal recessive primary immunodeficiency characterized by monocyte and dendritic cell deficiency, myeloproliferation, and susceptibility to severe opportunistic infections, including disseminated BCG infection and oral candidiasis. {ECO:0000269|PubMed:21524210, ECO:0000269|PubMed:25122610}. Note=The disease is caused by variants affecting the gene represented in this entry.
5 regional properties for P27601
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Ras-associating domain | 779 - 866 | IPR000159 |
| domain | Ras-like guanine nucleotide exchange factor, N-terminal | 111 - 239 | IPR000651 |
| domain | Ras guanine-nucleotide exchange factors catalytic domain | 363 - 630 | IPR001895 |
| domain | Ral guanine nucleotide dissociation stimulator, RA domain | 779 - 864 | IPR015758 |
| conserved_site | Ras guanine-nucleotide exchange factor, conserved site | 545 - 575 | IPR019804 |
Functions
7 GO annotations of cellular component
| Name | Definition |
|---|---|
| brush border membrane | The portion of the plasma membrane surrounding the brush border. |
| 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. |
| 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. |
| melanosome | A tissue-specific, membrane-bounded cytoplasmic organelle within which melanin pigments are synthesized and stored. Melanosomes are synthesized in melanocyte cells. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
5 GO annotations of molecular function
| Name | Definition |
|---|---|
| D5 dopamine receptor binding | Binding to a D5 dopamine 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. |
16 GO annotations of biological process
| Name | Definition |
|---|---|
| adenylate cyclase-activating G protein-coupled receptor signaling pathway | A G protein-coupled receptor signaling pathway in which the signal is transmitted via the activation of adenylyl cyclase activity and a subsequent increase 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). |
| angiogenesis | Blood vessel formation when new vessels emerge from the proliferation of pre-existing blood vessels. |
| branching involved in blood vessel morphogenesis | The process of coordinated growth and sprouting of blood vessels giving rise to the organized vascular system. |
| cell differentiation | The cellular developmental process in which a relatively unspecialized cell, e.g. embryonic or regenerative cell, acquires specialized structural and/or functional features that characterize a specific cell. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state. |
| 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. |
| in utero embryonic development | The process whose specific outcome is the progression of the embryo in the uterus over time, from formation of the zygote in the oviduct, to birth. An example of this process is found in Mus musculus. |
| intracellular signal transduction | The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell. |
| negative regulation of vascular associated smooth muscle cell migration | Any process that stops, prevents or reduces the frequency, rate or extent of vascular associated smooth muscle cell migration. |
| negative regulation of vascular associated smooth muscle cell proliferation | Any process that stops, prevents or reduces the frequency, rate or extent of vascular smooth muscle cell proliferation. |
| platelet activation | A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. |
| positive regulation of cytosolic calcium ion concentration | Any process that increases the concentration of calcium ions in the cytosol. |
| regulation of blood pressure | Any process that modulates the force with which blood travels through the circulatory system. The process is controlled by a balance of processes that increase pressure and decrease pressure. |
| regulation of cell shape | Any process that modulates the surface configuration of a cell. |
| regulation of fibroblast migration | Any process that modulates the rate, frequency or extent of fibroblast cell migration. Fibroblast cell migration is accomplished by extension and retraction of a pseudopodium. |
| Rho protein signal transduction | The series of molecular signals within the cell that are mediated by a member of the Rho family of proteins switching to a GTP-bound active state. |
58 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 |
| P20353 | Galphai | G protein alpha i subunit | Drosophila melanogaster (Fruit fly) | 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 |
| 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 |
| P08754 | GNAI3 | Guanine nucleotide-binding protein G | Homo sapiens (Human) | SS |
| A8MTJ3 | GNAT3 | Guanine nucleotide-binding protein G | Homo sapiens (Human) | SS |
| P19086 | GNAZ | Guanine nucleotide-binding protein G | Homo sapiens (Human) | SS |
| Q14344 | GNA13 | Guanine nucleotide-binding protein subunit alpha-13 | Homo sapiens (Human) | SS |
| B2RSH2 | Gnai1 | Guanine nucleotide-binding protein G | Mus musculus (Mouse) | SS |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| MADFLPSRSV | LSVCFPGCVL | TNGEAEQQRK | SKEIDKCLSR | EKTYVKRLVK | ILLLGAGESG |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KSTFLKQMRI | IHGQDFDQRA | REEFRPTIYS | NVIKGMRVLV | DAREKLHIPW | GDNKNQLHGD |
| 130 | 140 | 150 | 160 | 170 | 180 |
| KLMAFDTRAP | MAAQGMVETR | VFLQYLPAIR | ALWEDSGIQN | AYDRRREFQL | GESVKYFLDN |
| 190 | 200 | 210 | 220 | 230 | 240 |
| LDKLGVPDYI | PSQQDILLAR | RPTKGIHEYD | FEIKNVPFKM | VDVGGQRSER | KRWFECFDSV |
| 250 | 260 | 270 | 280 | 290 | 300 |
| TSILFLVSSS | EFDQVLMEDR | QTNRLTESLN | IFETIVNNRV | FSNVSIILFL | NKTDLLEEKV |
| 310 | 320 | 330 | 340 | 350 | 360 |
| QVVSIKDYFL | EFEGDPHCLR | DVQKFLVECF | RGKRRDQQQR | PLYHHFTTAI | NTENIRLVFR |
| 370 | |||||
| DVKDTILHDN | LKQLMLQ |