Gene Symbol: Gnai1
Description: G protein subunit alpha i1
Alias: BPGTPB, guanine nucleotide-binding protein G(i) subunit alpha-1, adenylate cyclase-inhibiting G alpha protein, guanine nucleotide binding protein (G protein), alpha inhibiting 1, guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1, guanine nucleotide binding protein, alpha inhibiting 1, guanine nucleotide-binding protein G(i), alpha-1 subunit
Species: rat
Products:     Gnai1

Top Publications

  1. Shu F, Ramineni S, Amyot W, Hepler J. Selective interactions between Gi alpha1 and Gi alpha3 and the GoLoco/GPR domain of RGS14 influence its dynamic subcellular localization. Cell Signal. 2007;19:163-76 pubmed
    ..These findings highlight the importance of the GoLoco/GPR domain and its interactions with Gi alpha1/3 in determining RGS14 subcellular localization and linked functions. ..
  2. Thomas C, Tall G, Adhikari A, Sprang S. Ric-8A catalyzes guanine nucleotide exchange on G alphai1 bound to the GPR/GoLoco exchange inhibitor AGS3. J Biol Chem. 2008;283:23150-60 pubmed publisher
    ..Galpha(i1) complex, even when present at very high concentrations. The action of Ric-8A on AGS3:Galpha(i1).GDP ensures unidirectional activation of Galpha subunits that cannot be reversed by AGS3. ..
  3. Tall G, Krumins A, Gilman A. Mammalian Ric-8A (synembryn) is a heterotrimeric Galpha protein guanine nucleotide exchange factor. J Biol Chem. 2003;278:8356-62 pubmed
    ..Ric-8A interacts with GDP-bound Galpha proteins, stimulates release of GDP, and forms a stable nucleotide-free transition state complex with the Galpha protein; this complex dissociates upon binding of GTP to Galpha. ..
  4. Kapoor N, Menon S, Chauhan R, Sachdev P, Sakmar T. Structural evidence for a sequential release mechanism for activation of heterotrimeric G proteins. J Mol Biol. 2009;393:882-97 pubmed publisher
    ..Interestingly, this mechanistic model for heterotrimeric G protein activation is similar to that suggested for the activation of the plant small G protein Rop4 by RopGEF8. ..
  5. Coleman D, Berghuis A, Lee E, Linder M, Gilman A, Sprang S. Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis. Science. 1994;265:1405-12 pubmed
    ..The amino-terminal 33 residues are disordered in GTP gamma S-Gi alpha 1, suggesting a mechanism that may promote release of the beta gamma subunit complex when the alpha subunit is activated by GTP. ..
  6. Vellano C, Shu F, Ramineni S, Yates C, Tall G, Hepler J. Activation of the regulator of G protein signaling 14-G?i1-GDP signaling complex is regulated by resistance to inhibitors of cholinesterase-8A. Biochemistry. 2011;50:752-62 pubmed publisher
    ..These findings demonstrate that RGS14 is a newly appreciated integrator of unconventional Ric-8A and G?i1 signaling. ..
  7. Kiyomitsu T, Cheeseman I. Chromosome- and spindle-pole-derived signals generate an intrinsic code for spindle position and orientation. Nat Cell Biol. 2012;14:311-7 pubmed publisher
    ..We propose that these chromosome- and spindle-pole-derived gradients generate an intrinsic code to control spindle position and orientation. ..
  8. Watson C, Jeng Y, Hu G, Wozniak A, Bulayeva N, Guptarak J. Estrogen- and xenoestrogen-induced ERK signaling in pituitary tumor cells involves estrogen receptor-? interactions with G protein-?i and caveolin I. Steroids. 2012;77:424-32 pubmed publisher
    ..Xenoestrogens, like physiologic estrogens, can evoke downstream kinase signaling involving selective interactions of ER? with G(?i) and caveolin I, but with some different characteristics, which could explain their disruptive actions. ..
  9. Kimple R, de Vries L, Tronchere H, Behe C, Morris R, Gist Farquhar M, et al. RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor Activity. J Biol Chem. 2001;276:29275-81 pubmed
    ..The presence of two, independent G alpha interaction sites suggests that RGS12 and RGS14 participate in a complex coordination of G-protein signaling beyond simple G alpha GAP activity. ..

More Information


  1. Kleuss C, Raw A, Lee E, Sprang S, Gilman A. Mechanism of GTP hydrolysis by G-protein alpha subunits. Proc Natl Acad Sci U S A. 1994;91:9828-31 pubmed
  2. Saha S, Li Y, Lappas G, Anand Srivastava M. Activation of natriuretic peptide receptor-C attenuates the enhanced oxidative stress in vascular smooth muscle cells from spontaneously hypertensive rats: implication of Gialpha protein. J Mol Cell Cardiol. 2008;44:336-44 pubmed
    ..These results suggest that C-ANP(4-23) decreases the enhanced oxidative stress in SHR by attenuating the enhanced expression of Gialpha proteins and also the enhanced levels of NADPH oxidase. ..
  3. Berg K, Zardeneta G, Hargreaves K, Clarke W, Milam S. Integrins regulate opioid receptor signaling in trigeminal ganglion neurons. Neuroscience. 2007;144:889-97 pubmed
    ..g. Galphai vs. Galphas). Collectively, these data provide the first evidence that specific integrins regulate opioid receptor signaling in sensory neurons. ..
  4. Kotak S, Busso C, G nczy P. Cortical dynein is critical for proper spindle positioning in human cells. J Cell Biol. 2012;199:97-110 pubmed publisher
    ..Overall, we propose a model in which the ternary complex serves to anchor dynein at the plasma membrane to ensure correct spindle positioning...
  5. Vellano C, Brown N, Blumer J, Hepler J. Assembly and function of the regulator of G protein signaling 14 (RGS14)·H-Ras signaling complex in live cells are regulated by G?i1 and G?i-linked G protein-coupled receptors. J Biol Chem. 2013;288:3620-31 pubmed publisher
    ..Together, these findings indicate that inactive G?(i1)-GDP enhances the affinity of RGS14 for H-Ras-GTP in live cells, resulting in a ternary signaling complex that is further regulated by GPCRs. ..
  6. Simon K, Hennen S, Merten N, Blättermann S, Gillard M, Kostenis E, et al. The Orphan G Protein-coupled Receptor GPR17 Negatively Regulates Oligodendrocyte Differentiation via Gαi/o and Its Downstream Effector Molecules. J Biol Chem. 2016;291:705-18 pubmed publisher
    ..We envisage that treatments augmenting PKA and/or EPAC activity represent a beneficial approach for therapeutic enhancement of remyelination in those demyelinating diseases where GPR17 is highly expressed, such as multiple sclerosis. ..
  7. Berghuis A, Lee E, Raw A, Gilman A, Sprang S. Structure of the GDP-Pi complex of Gly203-->Ala gialpha1: a mimic of the ternary product complex of galpha-catalyzed GTP hydrolysis. Structure. 1996;4:1277-90 pubmed
    ..Thus, a conformational rearrangement of the Switch II helix may be required in Galpha-catalyzed GTP hydrolysis. ..
  8. Zhu Y, Miwa Y, Yamanaka A, Yada T, Shibahara M, Abe Y, et al. Orexin receptor type-1 couples exclusively to pertussis toxin-insensitive G-proteins, while orexin receptor type-2 couples to both pertussis toxin-sensitive and -insensitive G-proteins. J Pharmacol Sci. 2003;92:259-66 pubmed
    ..This suggests that although OX2R couples to multiple G-proteins, activation of neurons by orexins through OX2R is mediated via a PTX-insensitive, PLC dependent pathway. ..
  9. Chiu C, Monat C, Robitaille M, Lacomme M, Daulat A, Macleod G, et al. SAPCD2 Controls Spindle Orientation and Asymmetric Divisions by Negatively Regulating the Gαi-LGN-NuMA Ternary Complex. Dev Cell. 2016;36:50-62 pubmed publisher
    ..These results uncover SAPCD2 as a key regulator of the ternary complex controlling spindle orientation during morphogenesis and asymmetric cell divisions. ..
  10. Kiyomitsu T, Cheeseman I. Cortical dynein and asymmetric membrane elongation coordinately position the spindle in anaphase. Cell. 2013;154:391-402 pubmed publisher
    ..Our results reveal the anaphase-specific spindle centering systems that achieve equal-sized cell division. ..
  11. Thaker T, Sarwar M, Preininger A, Hamm H, Iverson T. A transient interaction between the phosphate binding loop and switch I contributes to the allosteric network between receptor and nucleotide in G?i1. J Biol Chem. 2014;289:11331-41 pubmed publisher
    ..Further site-directed mutagenesis suggests that this interaction between Switch I and the phosphate binding loop is important for receptor-mediated nucleotide exchange in the wild-type G?i1 subunit. ..
  12. Posner B, Mixon M, Wall M, Sprang S, Gilman A. The A326S mutant of Gialpha1 as an approximation of the receptor-bound state. J Biol Chem. 1998;273:21752-8 pubmed
  13. Hilal Dandan R, He H, Martin J, Brunton L, Dillmann W. Endothelin downregulates SERCA2 gene and protein expression in adult rat ventricular myocytes: regulation by pertussis toxin-sensitive Gi protein and cAMP. Am J Physiol Heart Circ Physiol. 2009;296:H728-34 pubmed publisher
    ..The data indicate that, in adult myocytes, ET downregulates SERCA2 mRNA and protein levels, and the effect requires cross-talk between G(q) and PTX-sensitive G(i) pathways. ..
  14. Kaya A, Lokits A, Gilbert J, Iverson T, Meiler J, Hamm H. A conserved phenylalanine as a relay between the ?5 helix and the GDP binding region of heterotrimeric Gi protein ? subunit. J Biol Chem. 2014;289:24475-87 pubmed publisher
    ..Rather, destabilization of the backdoor region of the G? subunit is sufficient for triggering the activation process. ..
  15. Thomas C, Briknarová K, Hilmer J, Movahed N, Bothner B, Sumida J, et al. The nucleotide exchange factor Ric-8A is a chaperone for the conformationally dynamic nucleotide-free state of G?i1. PLoS ONE. 2011;6:e23197 pubmed publisher
  16. Black L, Thomas C, Nix G, Terwilliger M, Sprang S, Ross J. Nanosecond Dynamics of G?i1 Bound to Nucleotides or Ric-8A, a G? Chaperone with GEF Activity. Biophys J. 2016;111:722-731 pubmed publisher
    ..Induction of G?i1 structural heterogeneity by Ric-8A provides a mechanism for nucleotide release. ..
  17. De Souza C, Pereira da Silva M, Araujo E, Morari J, Alvarez Rojas F, Bordin S, et al. Distinct subsets of hypothalamic genes are modulated by two different thermogenesis-inducing stimuli. Obesity (Silver Spring). 2008;16:1239-47 pubmed publisher
  18. Mannoury La Cour C, El Mestikawy S, Hanoun N, Hamon M, Lanfumey L. Regional differences in the coupling of 5-hydroxytryptamine-1A receptors to G proteins in the rat brain. Mol Pharmacol. 2006;70:1013-21 pubmed
    ..Such a disparity in G-protein coupling might explain regional differences in adaptive regulations of brain 5-HT1A receptors. ..
  19. Clement N, Glorian M, Raymondjean M, Andreani M, Limon I. PGE2 amplifies the effects of IL-1beta on vascular smooth muscle cell de-differentiation: a consequence of the versatility of PGE2 receptors 3 due to the emerging expression of adenylyl cyclase 8. J Cell Physiol. 2006;208:495-505 pubmed
    ..Using real time PCR, pharmacological tools and small interfering RNA (siRNA), we demonstrated that the different integration of PGE2 signals depends on the upregulation of calcium/calmodulin stimulable adenylyl cyclase 8. ..
  20. Arejian M, Li Y, Anand Srivastava M. Nitric oxide attenuates the expression of natriuretic peptide receptor C and associated adenylyl cyclase signaling in aortic vascular smooth muscle cells: role of MAPK. Am J Physiol Heart Circ Physiol. 2009;296:H1859-67 pubmed publisher
  21. de Vries L, Fischer T, Tronchere H, Brothers G, Strockbine B, Siderovski D, et al. Activator of G protein signaling 3 is a guanine dissociation inhibitor for Galpha i subunits. Proc Natl Acad Sci U S A. 2000;97:14364-9 pubmed
    ..Inhibition of the Galpha subunit and stimulation of heterotrimeric G protein signaling, presumably by stimulating Gbetagamma, extend the possibilities for modulating signal transduction through heterotrimeric G proteins. ..
  22. van Keulen S, Rothlisberger U. Effect of N-Terminal Myristoylation on the Active Conformation of G?i1-GTP. Biochemistry. 2017;56:271-280 pubmed publisher
  23. Jones D, Reed R. Molecular cloning of five GTP-binding protein cDNA species from rat olfactory neuroepithelium. J Biol Chem. 1987;262:14241-9 pubmed
    ..In olfactory tissue, G alpha s was the most abundant of these messages and in combination with the biochemical studies suggests that G alpha s is the G-protein component of the olfactory signal transduction cascade. ..
  24. Frank M, Thümer L, Lohse M, Bünemann M. G Protein activation without subunit dissociation depends on a G{alpha}(i)-specific region. J Biol Chem. 2005;280:24584-90 pubmed
    ..The discovery of subtype-selective mechanisms of G protein activation illustrates that G protein subfamilies have specific mechanisms of activation that may provide a previously unknown basis for G protein signaling specificity. ..
  25. Coleman D, Sprang S. Crystal structures of the G protein Gi alpha 1 complexed with GDP and Mg2+: a crystallographic titration experiment. Biochemistry. 1998;37:14376-85 pubmed
    ..Mg2+ binding also induces binding of an SO42- molecule to the active site in a manner which may mimic a Gi alpha 1.GDP.PO42-.Mg2+ product complex. Implications of these findings are discussed. ..
  26. Cho H, Kehrl J. Localization of Gi alpha proteins in the centrosomes and at the midbody: implication for their role in cell division. J Cell Biol. 2007;178:245-55 pubmed
    ..These results suggest that G(ialpha) proteins and their regulators at these sites may play essential roles during mammalian cell division. ..
  27. Bassil M, Anand Srivastava M. Cyclic GMP modulates the expression of Gi protein and adenylyl cyclase signaling in vascular smooth muscle cells. Cell Biochem Biophys. 2007;47:99-108 pubmed
    ..From these studies, it can be suggested that 8Br-cGMP-induced decreased levels of Gi proteins and resultant increased levels of cAMP may be an additional mechanism through which cGMP regulates vascular tone and thereby blood pressure. ..
  28. Haga T. Molecular properties of muscarinic acetylcholine receptors. Proc Jpn Acad Ser B Phys Biol Sci. 2013;89:226-56 pubmed
    ..This paper summarizes the molecular properties of muscarinic receptors with reference to the historical background and bias to studies performed in our laboratories...
  29. Wall M, Coleman D, Lee E, Iñiguez Lluhí J, Posner B, Gilman A, et al. The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2. Cell. 1995;83:1047-58 pubmed
    ..Repeated WD motifs in beta form a circularized sevenfold beta propeller. The conserved cores of these motifs are a scaffold for display of their more variable linkers on the exterior face of each propeller blade. ..
  30. Tesmer J, Berman D, Gilman A, Sprang S. Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis. Cell. 1997;89:251-61 pubmed
    ..The binding site for RGS4 on G(i alpha1) is also consistent with the activity of RGS proteins as antagonists of G(alpha) effectors. ..
  31. Álvarez R, López D, Casas J, Lladó V, Higuera M, Nagy T, et al. G protein-membrane interactions I: Gαi1 myristoyl and palmitoyl modifications in protein-lipid interactions and its implications in membrane microdomain localization. Biochim Biophys Acta. 2015;1851:1511-20 pubmed publisher
    ..These results also serve as an example of how membrane lipid alterations can change membrane signaling or how membrane lipid therapy can regulate the cell's physiology. ..
  32. Straiker A, Borden C, Sullivan J. G-protein alpha subunit isoforms couple differentially to receptors that mediate presynaptic inhibition at rat hippocampal synapses. J Neurosci. 2002;22:2460-8 pubmed
    ..Differential coupling of G-protein alpha subunits may be a means of achieving specificity between different GPCRs and their molecular targets for mediating presynaptic inhibition. ..
  33. Kapoor N, Gupta R, Menon S, Folta Stogniew E, Raleigh D, Sakmar T. Nucleobindin 1 is a calcium-regulated guanine nucleotide dissociation inhibitor of G{alpha}i1. J Biol Chem. 2010;285:31647-60 pubmed publisher
    ..We propose that cytoplasmic NUCB1 might function to regulate heterotrimeric G protein trafficking and G protein-coupled receptor-mediated signal transduction pathways. ..
  34. Andhirka S, Vignesh R, Aradhyam G. The nucleotide-free state of heterotrimeric G proteins α-subunit adopts a highly stable conformation. FEBS J. 2017;284:2464-2481 pubmed publisher
  35. Martin N, Whalen E, Zamah M, Pierce K, Lefkowitz R. PKA-mediated phosphorylation of the beta1-adrenergic receptor promotes Gs/Gi switching. Cell Signal. 2004;16:1397-403 pubmed
    ..These results strongly support the hypothesis that the beta(1)-AR, like the beta(2)-AR, can undergo PKA-dependent "G(s)/G(i) switching". ..