Available structures
PDBOrtholog search: PDBe RCSB
AliasesGNA12, NNX3, RMP, gep, G protein subunit alpha 12, HG1M1
External IDsOMIM: 604394 MGI: 95767 HomoloGene: 22398 GeneCards: GNA12
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 7: 2.73 – 2.84 MbChr 5: 140.74 – 140.82 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Guanine nucleotide-binding protein subunit alpha-12 is a protein that in humans is encoded by the GNA12 gene.[5][6][7]

Interactions and functions

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.[8] 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.[9][10]

Active GTP-bound G12 alpha subunit interacts with and activates ARHGEF1,[11] ARHGEF11,[12][13] and ARHGEF12.[14][15] These ARHGEF proteins function as guanine nucleotide exchange factors for the Rho small GTPases to regulate the actin cytoskeleton.[16]

GNA12 also interacts with PPP5C,[17] HSP90,[18] Resistance to inhibitors of cholinesterase-8A (Ric-8A)[19] and TEC.[15]

See also


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000146535 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000149 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ 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.
  7. ^ "Entrez Gene: GNA12 guanine nucleotide binding protein (G protein) alpha 12".
  8. ^ 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.
  9. ^ Gilman, AG (1987). "G proteins: transducers of receptor-generated signals". Annual Review of Biochemistry. 56: 615–649. doi:10.1146/ PMID 3113327.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.