Protein-coding gene in the species Homo sapiens
Guanine nucleotide-binding protein subunit alpha-12 is aprotein that in humans is encoded by theGNA12 gene .[ 5] [ 6] [ 7]
Interactions and functions [ edit ] The GNA12 gene encodes the G12 G protein alpha subunit . Together withGNA13 , these two proteins comprise one of the four classes ofheterotrimeric G protein alpha subunits.[ 8] hormone andneurotransmitter signals detected by cell surfaceG protein-coupled receptors tointracellular 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 toGTP but inactive and associated with theG beta-gamma complex when bound toGDP .[ 9] [ 10]
Active GTP-bound G12 alpha subunitinteracts with and activatesARHGEF1 ,[ 11] ARHGEF11 ,[ 12] [ 13] ARHGEF12 .[ 14] [ 15] guanine nucleotide exchange factors for theRho small GTPases to regulate theactin cytoskeleton .[ 16]
GNA12 also interacts withPPP5C ,[ 17] HSP90 ,[ 18] Resistance to inhibitors of cholinesterase-8A (Ric-8A) [ 19] TEC .[ 15]
^a b c GRCh38: Ensembl release 89: ENSG00000146535 –Ensembl , May 2017^a b c GRCm38: Ensembl release 89: ENSMUSG00000000149 –Ensembl , May 2017^ "Human PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ Chan AM, Fleming TP, McGovern ES, Chedid M, Miki T, Aaronson SA (February 1993)."Expression cDNA cloning of a transforming gene encoding the wild-type G alpha 12 gene product" .Molecular and Cellular Biology .13 (2):762– 8.doi :10.1128/mcb.13.2.762 .PMC 358958 PMID 8423800 . ^ Kumar RN, Shore SK, Dhanasekaran N (February 2006)."Neoplastic transformation by the gep oncogene, Galpha12, involves signaling by STAT3" .Oncogene .25 (6):899– 906.doi :10.1038/sj.onc.1209132 PMID 16247467 . ^ "Entrez Gene: GNA12 guanine nucleotide binding protein (G protein) alpha 12" .^ Strathmann MP, Simon MI (1991)."G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits" .Proc. Natl. Acad. Sci. U.S.A .88 (13):5582– 6.Bibcode :1991PNAS...88.5582S .doi :10.1073/pnas.88.13.5582 PMC 51921 PMID 1905812 . ^ Gilman, AG (1987). "G proteins: transducers of receptor-generated signals".Annual Review of Biochemistry .56 :615– 649.doi :10.1146/annurev.bi.56.070187.003151 .PMID 3113327 . ^ Rodbell, M (1995)."Nobel Lecture: Signal transduction: Evolution of an idea" .Bioscience Reports .15 (3):117– 133.doi :10.1007/bf01207453 .PMC 1519115 PMID 7579038 .S2CID 11025853 . ^ Johnson EN, Seasholtz TM, Waheed AA, Kreutz B, Suzuki N, Kozasa T, Jones TL, Brown JH, Druey KM (December 2003)."RGS16 inhibits signalling through the G alpha 13-Rho axis" .Nature Cell Biology .5 (12):1095– 103.doi :10.1038/ncb1065 .PMID 14634662 .S2CID 6798899 . ^ Fukuhara, S; Murga, C; Zohar, M; Igishi, T; Gutkind, JS (1999-02-26)."A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho" .Journal of Biological Chemistry .274 (9):5868– 5879.doi :10.1074/jbc.274.9.5868 PMID 10026210 . ^ Rümenapp, U; Blomquist, A; Schwörer, G; Schablowski, H; Psoma, A; Jakobs, KH (1999-10-15). "Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member".FEBS Letters .459 (3):313– 318.doi :10.1016/s0014-5793(99)01270-3 .PMID 10526156 .S2CID 8529412 . ^ Fukuhara S, Chikumi H, Gutkind JS (November 2000)."Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G(12) family to Rho" .FEBS Letters .485 (2– 3):183– 8.doi :10.1016/S0014-5793(00)02224-9 PMID 11094164 .S2CID 7300556 . ^a b Suzuki N, Nakamura S, Mano H, Kozasa T (January 2003)."Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF" .Proceedings of the National Academy of Sciences of the United States of America .100 (2):733– 8.Bibcode :2003PNAS..100..733S .doi :10.1073/pnas.0234057100 PMC 141065 PMID 12515866 . ^ Dhanasekaran N, Dermott JM (1996). "Signaling by the G12 class of G proteins".Cell. Signal .8 (4):235– 45.doi :10.1016/0898-6568(96)00048-4 .PMID 8842523 . ^ Yamaguchi Y, Katoh H, Mori K, Negishi M (August 2002)."Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity" .Current Biology .12 (15):1353– 8.doi :10.1016/S0960-9822(02)01034-5 PMID 12176367 .S2CID 11485795 . ^ Vaiskunaite R, Kozasa T, Voyno-Yasenetskaya TA (December 2001)."Interaction between the G alpha subunit of heterotrimeric G(12) protein and Hsp90 is required for G alpha(12) signaling" .The Journal of Biological Chemistry .276 (49):46088– 93.doi :10.1074/jbc.M108711200 PMID 11598136 . ^ Wang L, Guo D, Xing B, Zhang JJ, Shu HB, Guo L, Huang XY (September 2011)."Resistance to inhibitors of cholinesterase-8A (Ric-8A) is critical for growth factor receptor-induced actin cytoskeletal reorganization" .The Journal of Biological Chemistry .286 (35):31055– 61.doi :10.1074/jbc.M111.253427 PMC 3162464 PMID 21771786 .
