Guanine nucleotide-binding protein subunit alpha-12

Function

Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF12/LARG). GNA12-dependent Rho signaling subsequently regulates transcription factor AP-1 (activating protein-1) (By similarity). GNA12-dependent Rho signaling also regulates protein phosphatese 2A activation causing dephosphorylation of its target proteins. Promotes tumor cell invasion and metastasis by activating RhoA/ROCK signaling pathway and up-regulating pro-inflammatory cytokine production. Inhibits CDH1-mediated cell adhesion in process independent from Rho activation. Together with NAPA promotes CDH5 localization to plasma membrane. May play a role in the control of cell migration through the TOR signaling cascade.

Classification

Family (Pfam)

PF00503 G-alpha

InterPro

Gprotein_alpha_12/13, Gprotein_alpha_su, GproteinA_insert, P-loop_NTPase

Functional cluster

Ribosome-Biogenesis GTPases (Obg/Era/Der)

Experimental structures · PDB · 1

• 7YDJ EM 3.03A

A predicted model is available from AlphaFold.

Gene Ontology · 27

• GO:0031526 brush border membrane
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005925 focal adhesion
• GO:0005834 heterotrimeric G-protein complex
• GO:0016328 lateral plasma membrane
• GO:0043005 neuron projection
• GO:0043025 neuronal cell body
• GO:0005886 plasma membrane
• GO:0031752 D5 dopamine receptor binding
• GO:0003925 G protein activity
• GO:0031683 G-protein beta/gamma-subunit complex binding
• GO:0005525 GTP binding
• GO:0003924 GTPase activity
• GO:0046872 metal ion binding
• GO:0051721 protein phosphatase 2A binding
• GO:0072542 protein phosphatase activator activity
• GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway
• GO:0007596 blood coagulation
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0008217 regulation of blood pressure
• GO:0010762 regulation of fibroblast migration
• GO:0032434 regulation of proteasomal ubiquitin-dependent protein catabolic process
• GO:0032006 regulation of TOR signaling
• GO:0009410 response to xenobiotic stimulus
• GO:0007266 Rho protein signal transduction
• GO:0160221 Rho-activating G protein-coupled receptor signaling pathway

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Guanine nucleotide-binding protein subunit alpha-12 0.99
• Guanine nucleotide-binding protein subunit alpha-12 0.99
• Guanine nucleotide-binding protein subunit alpha-13 0.89
• Guanine nucleotide-binding protein subunit alpha-13 0.89
• Guanine nucleotide-binding protein subunit alpha-13 0.88
• Guanine nucleotide-binding protein alpha-12 subunit 0.84
• Guanine nucleotide-binding protein alpha-12 subunit 0.83
• Guanine nucleotide binding protein alpha subunit B 0.82
• Guanine nucleotide-binding protein alpha-2 subunit 0.81
• Guanine nucleotide binding protein alpha subunit C 0.80
• Guanine nucleotide-binding protein G(i) subunit alpha 0.80
• Guanine nucleotide-binding protein G(o) subunit alpha 0.80

Co-cited proteins · studied together in the literature

• Guanine nucleotide-binding protein subunit alpha-13 10 shared papers
• UBX domain-containing protein 11 1 shared papers
• Alpha-soluble NSF attachment protein 1 shared papers
• Rho guanine nucleotide exchange factor 12 1 shared papers
• Rho guanine nucleotide exchange factor 11 1 shared papers
• Regulator of G protein signaling 22 1 shared papers
• Regulator of G protein signaling 22 1 shared papers
• Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform 1 shared papers
• E3 ubiquitin-protein ligase rififylin 1 shared papers
• Proline-rich protein 5-like 1 shared papers
• Cadherin-5 1 shared papers
• Guanine nucleotide-binding protein subunit alpha-12 2 shared papers

Literature · 20 cited papers

• Galpha12/13 signaling promotes cervical cancer invasion through the RhoA/ROCK-JNK signaling axis. Biochem. Biophys. Res. Commun. · 2016
• Galpha(1)(2) drives invasion of oral squamous cell carcinoma through up-regulation of proinflammatory cytokines. PLoS ONE · 2013
• PRR5L degradation promotes mTORC2-mediated PKC-delta phosphorylation and cell migration downstream of Galpha12. Nat. Cell Biol. · 2012
• RGS22, a novel testis-specific regulator of G-protein signaling involved in human and mouse spermiogenesis along with GNA12/13 subunits. Biol. Reprod. · 2008
• Galpha12 stimulates apoptosis in epithelial cells through JNK1-mediated Bcl-2 degradation and up-regulation of IkappaBalpha. J. Biol. Chem. · 2007
• A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion. J. Biol. Chem. · 2006
• The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis. Proc. Natl. Acad. Sci. U.S.A. · 2006
• Socius, a novel binding partner of Galpha12/13, promotes the Galpha12-induced RhoA activation. Biochem. Biophys. Res. Commun. · 2005
• G alpha12 interaction with alphaSNAP induces VE-cadherin localization at endothelial junctions and regulates barrier function. J. Biol. Chem. · 2005
• Galpha12 directly interacts with PP2A: evidence for Galpha12-stimulated PP2A phosphatase activity and dephosphorylation of microtubule-associated protein, tau. J. Biol. Chem. · 2004
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• A role for Galpha12/Galpha13 in p120ctn regulation. Proc. Natl. Acad. Sci. U.S.A. · 2004
• … and 8 more in the literature graph