GNA12

GNA12
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1ZCA
Identifiers
Aliases	GNA12 , NNX3, RMP, gep, G protein subunit alpha 12, HG1M1
External IDs	OMIM: 604394; MGI: 95767; HomoloGene: 22398; GeneCards: GNA12; OMA:GNA12 - orthologs
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7p22.3-p22.2 Start 2,728,105 bp [1] End 2,844,308 bp [1]
Gene location (Mouse) Chr. Chromosome 5 (mouse) [2] Band 5 G2|5 79.3 cM Start 140,744,163 bp [2] End 140,816,186 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte stromal cell of endometrium internal globus pallidus C1 segment Amygdala nucleus accumbens putamen caudate nucleus substantia nigra right coronary artery Top expressed in right kidney myocardium of ventricle ventricular zone interventricular septum zygote stroma of bone marrow cardiac muscle tissue of left ventricle molar right ventricle proximal tubule More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding GTP binding metal ion binding protein binding guanyl nucleotide binding G protein-coupled receptor binding D5 dopamine receptor binding signal transducer activity G-protein beta/gamma-subunit complex binding GTPase activity Cellular component membrane focal adhesion heterotrimeric G-protein complex brush border membrane cytoplasm plasma membrane lateral plasma membrane Biological process cell differentiation intracellular signal transduction regulation of TOR signaling adenylate cyclase-modulating G protein-coupled receptor signaling pathway small GTPase mediated signal transduction embryonic digit morphogenesis blood coagulation in utero embryonic development platelet activation regulation of cell shape regulation of proteasomal ubiquitin-dependent protein catabolic process signal transduction G protein-coupled receptor signaling pathway regulation of fibroblast migration Rho protein signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2768 14673 Ensembl ENSG00000146535 ENSMUSG00000000149 UniProt Q03113 P27600 RefSeq (mRNA) NM_001282440 NM_001282441 NM_001293092 NM_007353 NM_010302 RefSeq (protein) NP_001269369 NP_001269370 NP_001280021 NP_031379 NP_034432 Location (UCSC) Chr 7: 2.73 – 2.84 Mb Chr 5: 140.74 – 140.82 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/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

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

References

1. GRCh38: Ensembl release 89: ENSG00000146535 – Ensembl, May 2017
2. 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): 762–768. 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 (Jul 1991). "G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits". Proceedings of the National Academy of Sciences of the United States of America. 88 (13): 5582–5586. 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/annurev.bi.56.070187.003151. 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, et al. (December 2003). "RGS16 inhibits signalling through the G alpha 13-Rho axis". Nature Cell Biology. 5 (12): 1095–1103. 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". The Journal of Biological Chemistry. 274 (9): 5868–5879. doi: 10.1074/jbc.274.9.5868 . PMID   10026210.
13. Rumenapp U, Blomquist A, Schworer 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): 183–188. doi: 10.1016/S0014-5793(00)02224-9 . PMID   11094164. S2CID   7300556.
15. 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): 733–738. Bibcode:2003PNAS..100..733S. doi: 10.1073/pnas.0234057100 . PMC   141065 . PMID   12515866.
16. Dhanasekaran N, Dermott JM (Jun 1996). "Signaling by the G12 class of G proteins". Cellular Signalling. 8 (4): 235–245. 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): 1353–1358. 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): 46088–46093. doi: 10.1074/jbc.M108711200 . PMID   11598136.
19. Wang L, Guo D, Xing B, Zhang JJ, Shu HB, Guo L, et al. (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): 31055–31061. doi: 10.1074/jbc.M111.253427 . PMC   3162464 . PMID   21771786.

External links

• GNA12+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt : P27600 (Mouse Guanine nucleotide-binding protein subunit alpha-12 (GNA12)) at the PDBe-KB .