GNA12

The GNA12 gene encodes the G₁₂ G protein alpha subunit. Together with GNA13, these two proteins comprise one of the four classes of heterotrimeric G protein alpha subunits.{{cite journal | vauthors = Strathmann MP, Simon MI | title = G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 13 | pages = 5582–5586 | date = Jul 1991 | pmid = 1905812 | pmc = 51921 | doi = 10.1073/pnas.88.13.5582 | bibcode = 1991PNAS...88.5582S | doi-access = free }} Heterotrimeric G proteins function in transducing hormone and neurotransmitter signals detected by cell surface G protein-coupled receptors to intracellular signaling pathways to modulate cell functions. G protein alpha subunits bind to guanine nucleotides and function in a regulatory cycle, and are active when bound to GTP but inactive and associated with the G beta-gamma complex when bound to GDP.{{cite journal | vauthors = Gilman AG | title = G proteins: transducers of receptor-generated signals | journal = Annual Review of Biochemistry | volume = 56 | pages = 615–649 | date = 1987 | pmid = 3113327 | doi = 10.1146/annurev.bi.56.070187.003151 }}{{cite journal | vauthors = Rodbell M | title = Nobel Lecture: Signal transduction: Evolution of an idea | journal = Bioscience Reports | volume = 15 | issue = 3 | pages = 117–133 | date = 1995 | pmid = 7579038 | pmc = 1519115 | doi = 10.1007/bf01207453 | s2cid = 11025853 }}

Active GTP-bound G₁₂ alpha subunit interacts with and activates ARHGEF1,{{cite journal | vauthors = Johnson EN, Seasholtz TM, Waheed AA, Kreutz B, Suzuki N, Kozasa T, Jones TL, Brown JH, Druey KM | title = RGS16 inhibits signalling through the G alpha 13-Rho axis | journal = Nature Cell Biology | volume = 5 | issue = 12 | pages = 1095–1103 | date = December 2003 | pmid = 14634662 | doi = 10.1038/ncb1065 | s2cid = 6798899 | url = https://zenodo.org/record/1233351 }} ARHGEF11,{{cite journal | vauthors = Fukuhara S, Murga C, Zohar M, Igishi T, Gutkind JS | title = A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho | journal = The Journal of Biological Chemistry | volume = 274 | issue = 9 | pages = 5868–5879 | date = 1999-02-26 | pmid = 10026210 | doi = 10.1074/jbc.274.9.5868 | doi-access = free }}{{cite journal | vauthors = Rumenapp U, Blomquist A, Schworer G, Schablowski H, Psoma A, Jakobs KH | title = Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member | journal = FEBS Letters | volume = 459 | issue = 3 | pages = 313–318 | date = 1999-10-15 | pmid = 10526156 | doi = 10.1016/s0014-5793(99)01270-3 | s2cid = 8529412 }} and ARHGEF12.{{cite journal | vauthors = Fukuhara S, Chikumi H, Gutkind JS | title = Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G(12) family to Rho | journal = FEBS Letters | volume = 485 | issue = 2–3 | pages = 183–188 | date = November 2000 | pmid = 11094164 | doi = 10.1016/S0014-5793(00)02224-9 | s2cid = 7300556 | doi-access = free }}{{cite journal | vauthors = Suzuki N, Nakamura S, Mano H, Kozasa T | title = Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 2 | pages = 733–738 | date = January 2003 | pmid = 12515866 | pmc = 141065 | doi = 10.1073/pnas.0234057100 | bibcode = 2003PNAS..100..733S | doi-access = free }} These ARHGEF proteins function as guanine nucleotide exchange factors for the Rho small GTPases to regulate the actin cytoskeleton.{{cite journal | vauthors = Dhanasekaran N, Dermott JM | title = Signaling by the G12 class of G proteins | journal = Cellular Signalling | volume = 8 | issue = 4 | pages = 235–245 | date = Jun 1996 | pmid = 8842523 | doi = 10.1016/0898-6568(96)00048-4 }}

GNA12 also interacts with PPP5C,{{cite journal | vauthors = Yamaguchi Y, Katoh H, Mori K, Negishi M | title = Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity | journal = Current Biology | volume = 12 | issue = 15 | pages = 1353–1358 | date = August 2002 | pmid = 12176367 | doi = 10.1016/S0960-9822(02)01034-5 | s2cid = 11485795 | doi-access = free }} HSP90,{{cite journal | vauthors = Vaiskunaite R, Kozasa T, Voyno-Yasenetskaya TA | title = Interaction between the G alpha subunit of heterotrimeric G(12) protein and Hsp90 is required for G alpha(12) signaling | journal = The Journal of Biological Chemistry | volume = 276 | issue = 49 | pages = 46088–46093 | date = December 2001 | pmid = 11598136 | doi = 10.1074/jbc.M108711200 | doi-access = free }} Resistance to inhibitors of cholinesterase-8A (Ric-8A){{cite journal | vauthors = Wang L, Guo D, Xing B, Zhang JJ, Shu HB, Guo L, Huang XY | title = Resistance to inhibitors of cholinesterase-8A (Ric-8A) is critical for growth factor receptor-induced actin cytoskeletal reorganization | journal = The Journal of Biological Chemistry | volume = 286 | issue = 35 | pages = 31055–31061 | date = September 2011 | pmid = 21771786 | pmc = 3162464 | doi = 10.1074/jbc.M111.253427 | doi-access = free }} and TEC.

• G12/G13 alpha subunits
• G protein-coupled receptor
• Heterotrimeric G protein
• Rho family of GTPases

{{Reflist}}

• {{MeshName|GNA12+protein,+human}}
• {{PDBe-KB2|P27600|Mouse Guanine nucleotide-binding protein subunit alpha-12 (GNA12)}}

{{PDB Gallery|geneid=2768}}

{{Intracellular signaling peptides and proteins}}

{{GTPases}}

{{gene-7-stub}}