Protein: Guanine nucleotide-binding protein G(i) subunit alpha-1 (EC 3.6.5.-) (Adenylate cyclase-inhibiting G alpha protein) (P63096)
Organism: Homo sapiens (Human)
Function: Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (By similarity). The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. Required for normal cytokinesis during mitosis. Required for cortical dynein-dynactin complex recruitment during metaphase.
Subcellular location: Nucleus {ECO:0000250|UniProtKB:P10824}. Cytoplasm {ECO:0000269|PubMed:17635935}. Cell membrane {ECO:0000269|PubMed:17635935, ECO:0000269|PubMed:26766442}; Peripheral membrane protein {ECO:0000250|UniProtKB:P10824}; Cytoplasmic side {ECO:0000250|UniProtKB:P10824}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:17635935}. Cytoplasm, cell cortex {ECO:0000269|PubMed:22327364}. Membrane {ECO:0000250|UniProtKB:P10824}; Lipid-anchor {ECO:0000269|PubMed:20213681, ECO:0000269|PubMed:25255805}. Note=Localizes in the centrosomes of interphase and mitotic cells, but not in centrosomes during cytokinesis. Detected at the cleavage furrow or the midbody (PubMed:17635935). Localized at the plasma membrane throughout mitosis. Colocalizes with RIC8A and RGS14 at the plasma membrane. {ECO:0000250|UniProtKB:P10824, ECO:0000269|PubMed:17635935}.
Sequence: MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAGYSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMTAELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVKTTGIVETHFTFKDLHFKMFDVGGQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEMNRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAAAYIQCQFEDLNKRKDTKEIYTHFTCATDTKNVQFVFDAVTDVIIKNNLKDCGLF
InterPro domains: - IPR011025: G protein alpha subunit, helical insertion (homologous_superfamily) [61-181]
- IPR001019: Guanine nucleotide binding protein (G-protein), alpha subunit (family) [7-354]
- IPR001408: G-protein alpha subunit, group I (family) [79-354]
- IPR027417: P-loop containing nucleoside triphosphate hydrolase (homologous_superfamily) [32-349]
Interaction partners: - Guanine nucleotide-binding protein G
- D
- Guanine nucleotide-binding protein G
- Lysophosphatidic acid receptor 1
- Regulator of G-protein signaling 14
- Cannabinoid receptor 1
- Prostaglandin E2 receptor EP3 subtype
- Sphingosine 1-phosphate receptor 1
- Mu-type opioid receptor
- Gamma-aminobutyric acid type B receptor subunit 2
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0097367 (carbohydrate derivative binding), GO:0036094 (small molecule binding), GO:1901363 (heterocyclic compound binding), GO:0016787 (hydrolase activity), GO:0043167 (ion binding), GO:0097159 (organic cyclic compound binding), GO:0005515 (protein binding), GO:0016817 (hydrolase activity, acting on acid anhydrides), GO:1901265 (nucleoside phosphate binding), GO:0043168 (anion binding), GO:0000166 (nucleotide binding), GO:0032553 (ribonucleotide binding), GO:0019003 (GDP binding), GO:0032555 (purine ribonucleotide binding), GO:0016818 (hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides), GO:0017076 (purine nucleotide binding), GO:0016462 (pyrophosphatase activity), GO:0019001 (guanyl nucleotide binding), GO:0032561 (guanyl ribonucleotide binding), GO:0017111 (ribonucleoside triphosphate phosphatase activity), GO:0003924 (GTPase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0051301 (cell division), GO:0071704 (organic substance metabolic process), GO:0044237 (cellular metabolic process), GO:0044281 (small molecule metabolic process), GO:0009719 (response to endogenous stimulus), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0065009 (regulation of molecular function), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0050790 (regulation of catalytic activity), GO:1901564 (organonitrogen compound metabolic process), GO:0046483 (heterocycle metabolic process), GO:0044092 (negative regulation of molecular function), GO:0019637 (organophosphate metabolic process), GO:0071495 (cellular response to endogenous stimulus), GO:1901700 (response to oxygen-containing compound), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0010033 (response to organic substance), GO:1901135 (carbohydrate derivative metabolic process), GO:0006793 (phosphorus metabolic process), GO:0009894 (regulation of catabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:1901698 (response to nitrogen compound), GO:0031325 (positive regulation of cellular metabolic process), GO:0070887 (cellular response to chemical stimulus), GO:0055086 (nucleobase-containing small molecule metabolic process), GO:0007186 (G protein-coupled receptor signaling pathway), GO:0031323 (regulation of cellular metabolic process), GO:0007212 (dopamine receptor signaling pathway), GO:0009896 (positive regulation of catabolic process), GO:0071417 (cellular response to organonitrogen compound), GO:0043086 (negative regulation of catalytic activity), GO:0006753 (nucleoside phosphate metabolic process), GO:0071310 (cellular response to organic substance), GO:0031279 (regulation of cyclase activity), GO:0010506 (regulation of autophagy), GO:1901699 (cellular response to nitrogen compound), GO:0006796 (phosphate-containing compound metabolic process), GO:0072521 (purine-containing compound metabolic process), GO:0071869 (response to catecholamine), GO:0010243 (response to organonitrogen compound), GO:0010508 (positive regulation of autophagy), GO:0051339 (regulation of lyase activity), GO:0019693 (ribose phosphate metabolic process), GO:0031331 (positive regulation of cellular catabolic process), GO:0014070 (response to organic cyclic compound), GO:0007188 (adenylate cyclase-modulating G protein-coupled receptor signaling pathway), GO:0031329 (regulation of cellular catabolic process), GO:1901701 (cellular response to oxygen-containing compound), GO:0071870 (cellular response to catecholamine stimulus), GO:0045761 (regulation of adenylate cyclase activity), GO:0009141 (nucleoside triphosphate metabolic process), GO:0007193 (adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway), GO:1903350 (response to dopamine), GO:0031280 (negative regulation of cyclase activity), GO:0051350 (negative regulation of lyase activity), GO:0009117 (nucleotide metabolic process), GO:0016241 (regulation of macroautophagy), GO:0071868 (cellular response to monoamine stimulus), GO:0071407 (cellular response to organic cyclic compound), GO:0071867 (response to monoamine), GO:0009259 (ribonucleotide metabolic process), GO:0006163 (purine nucleotide metabolic process), GO:0016239 (positive regulation of macroautophagy), GO:0009144 (purine nucleoside triphosphate metabolic process), GO:0009150 (purine ribonucleotide metabolic process), GO:0009199 (ribonucleoside triphosphate metabolic process), GO:0007194 (negative regulation of adenylate cyclase activity), GO:1903351 (cellular response to dopamine), GO:0046039 (GTP metabolic process), GO:0009205 (purine ribonucleoside triphosphate metabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005815 (microtubule organizing center), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0071944 (cell periphery), GO:0031984 (organelle subcompartment), GO:0030496 (midbody), GO:0005615 (extracellular space), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005576 (extracellular region), GO:0031090 (organelle membrane), GO:0005886 (plasma membrane), GO:0043229 (intracellular organelle), GO:0043230 (extracellular organelle), GO:0043228 (non-membrane-bounded organelle), GO:0005813 (centrosome), GO:0098827 (endoplasmic reticulum subcompartment), GO:0042175 (nuclear outer membrane-endoplasmic reticulum membrane network), GO:0005794 (Golgi apparatus), GO:0005773 (vacuole), GO:0005783 (endoplasmic reticulum), GO:0070062 (extracellular exosome), GO:0043227 (membrane-bounded organelle), GO:0000323 (lytic vacuole), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0065010 (extracellular membrane-bounded organelle), GO:0005789 (endoplasmic reticulum membrane), GO:0005774 (vacuolar membrane), GO:0031982 (vesicle), GO:0000139 (Golgi membrane), GO:0005764 (lysosome), GO:1903561 (extracellular vesicle), GO:0005856 (cytoskeleton), GO:0098852 (lytic vacuole membrane), GO:0005765 (lysosomal membrane), GO:0015630 (microtubule cytoskeleton)