GNA13 explained

Guanine nucleotide-binding protein subunit alpha-13 is a protein that in humans is encoded by the GNA13 gene.^{[1] [2]}

Interactions and functions

The GNA13 gene encodes the G₁₃ G protein alpha subunit. Together with GNA12, these two proteins comprise one of the four classes of heterotrimeric G protein alpha subunits.^[3] 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.^{[4] [5]}

Active GTP-bound G₁₂ alpha subunit interacts with and activates ARHGEF1,^{[6] [7] [8]} ARHGEF11,^{[9] [10]} and ARHGEF12.^{[11] [12]} These ARHGEF proteins function as guanine nucleotide exchange factors for the Rho small GTPases to regulate the actin cytoskeleton.^[13]

GNA13 has been shown to interact with AKAP3,^[14] RIC8A,^{[15] [16]} and Radixin.^[17]

Clinical significance

Recurrent mutations in this gene have been associated to cases of diffuse large B-cell lymphoma.^{[18] [19]}

See also

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

Further reading

• Ruppel KM, Willison D, Kataoka H, Wang A, Zheng YW, Cornelissen I, Yin L, Xu SM, Coughlin SR . Essential role for Galpha13 in endothelial cells during embryonic development . Proceedings of the National Academy of Sciences of the United States of America . 102 . 23 . 8281–8286 . Jun 2005 . 15919816 . 1149452 . 10.1073/pnas.0503326102 . 2005PNAS..102.8281R . free .
• Downes GB, Gautam N . The G protein subunit gene families . Genomics . 62 . 3 . 544–52 . Dec 1999 . 10644457 . 10.1006/geno.1999.5992 .
• Offermanns S, Laugwitz KL, Spicher K, Schultz G . G proteins of the G12 family are activated via thromboxane A2 and thrombin receptors in human platelets . Proceedings of the National Academy of Sciences of the United States of America . 91 . 2 . 504–8 . Jan 1994 . 8290554 . 42977 . 10.1073/pnas.91.2.504 . 1994PNAS...91..504O . free .
• Laugwitz KL, Allgeier A, Offermanns S, Spicher K, Van Sande J, Dumont JE, Schultz G . The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families . Proceedings of the National Academy of Sciences of the United States of America . 93 . 1 . 116–20 . Jan 1996 . 8552586 . 40189 . 10.1073/pnas.93.1.116 . 1996PNAS...93..116L . free .
• Offermanns S, Hu YH, Simon MI . Galpha12 and galpha13 are phosphorylated during platelet activation . The Journal of Biological Chemistry . 271 . 42 . 26044–8 . Oct 1996 . 8824244 . 10.1074/jbc.271.42.26044 . free .
• Offermanns S, Mancino V, Revel JP, Simon MI . Vascular system defects and impaired cell chemokinesis as a result of Galpha13 deficiency . Science . 275 . 5299 . 533–6 . Jan 1997 . 8999798 . 10.1126/science.275.5299.533 . 32210248 .
• Macrez-Leprêtre N, Kalkbrenner F, Morel JL, Schultz G, Mironneau J . G protein heterotrimer Galpha13beta1gamma3 couples the angiotensin AT1A receptor to increases in cytoplasmic Ca2+ in rat portal vein myocytes . The Journal of Biological Chemistry . 272 . 15 . 10095–102 . Apr 1997 . 9092554 . 10.1074/jbc.272.15.10095 . free .
• Hart MJ, Jiang X, Kozasa T, Roscoe W, Singer WD, Gilman AG, Sternweis PC, Bollag G . Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13 . Science . 280 . 5372 . 2112–4 . Jun 1998 . 9641916 . 10.1126/science.280.5372.2112 .
• Becker KP, Garnovskaya M, Gettys T, Halushka PV . Coupling of thromboxane A2 receptor isoforms to Galpha13: effects on ligand binding and signalling . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1450 . 3 . 288–96 . Jul 1999 . 10395940 . 10.1016/S0167-4889(99)00068-3 . free .
• Windh RT, Lee MJ, Hla T, An S, Barr AJ, Manning DR . Differential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and H218/Edg-5 to the G(i), G(q), and G(12) families of heterotrimeric G proteins . The Journal of Biological Chemistry . 274 . 39 . 27351–8 . Sep 1999 . 10488065 . 10.1074/jbc.274.39.27351 . free .
• Brydon L, Roka F, Petit L, de Coppet P, Tissot M, Barrett P, Morgan PJ, Nanoff C, Strosberg AD, Jockers R . Dual signaling of human Mel1a melatonin receptors via G(i2), G(i3), and G(q/11) proteins . Molecular Endocrinology . 13 . 12 . 2025–38 . Dec 1999 . 10598579 . 10.1210/me.13.12.2025 . free .
• Bhattacharyya R, Wedegaertner PB . Galpha 13 requires palmitoylation for plasma membrane localization, Rho-dependent signaling, and promotion of p115-RhoGEF membrane binding . The Journal of Biological Chemistry . 275 . 20 . 14992–9 . May 2000 . 10747909 . 10.1074/jbc.M000415200 . free .
• Vaiskunaite R, Adarichev V, Furthmayr H, Kozasa T, Gudkov A, Voyno-Yasenetskaya TA . Conformational activation of radixin by G13 protein alpha subunit . The Journal of Biological Chemistry . 275 . 34 . 26206–12 . Aug 2000 . 10816569 . 10.1074/jbc.M001863200 . free .
• Shi CS, Sinnarajah S, Cho H, Kozasa T, Kehrl JH . G13alpha-mediated PYK2 activation. PYK2 is a mediator of G13alpha -induced serum response element-dependent transcription . The Journal of Biological Chemistry . 275 . 32 . 24470–6 . Aug 2000 . 10821841 . 10.1074/jbc.M908449199 . free .
• Ponimaskin E, Behn H, Adarichev V, Voyno-Yasenetskaya TA, Offermanns S, Schmidt MF . Acylation of Galpha(13) is important for its interaction with thrombin receptor, transforming activity and actin stress fiber formation . FEBS Letters . 478 . 1–2 . 173–7 . Jul 2000 . 10922491 . 10.1016/S0014-5793(00)01845-7 . 31417083 . free .
• Jin S, Exton JH . Activation of RhoA by association of Galpha(13) with Dbl . Biochemical and Biophysical Research Communications . 277 . 3 . 718–21 . Nov 2000 . 11062019 . 10.1006/bbrc.2000.3744 .
• Fukuhara S, Chikumi H, Gutkind JS . 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 . Nov 2000 . 11094164 . 10.1016/S0014-5793(00)02224-9 . 7300556 . free .
• Meigs TE, Fields TA, McKee DD, Casey PJ . Interaction of Galpha 12 and Galpha 13 with the cytoplasmic domain of cadherin provides a mechanism for beta -catenin release . Proceedings of the National Academy of Sciences of the United States of America . 98 . 2 . 519–24 . Jan 2001 . 11136230 . 14619 . 10.1073/pnas.021350998 . free .

Notes and References

1. Kabouridis PS, Waters ST, Escobar S, Stanners J, Tsoukas CD . Expression of GTP-binding protein alpha subunits in human thymocytes . Molecular and Cellular Biochemistry . 144 . 1 . 45–51 . Mar 1995 . 7791744 . 10.1007/BF00926739 . 8911988 .
2. Web site: Entrez Gene: GNA13 guanine nucleotide binding protein (G protein), alpha 13.
3. Strathmann MP, Simon MI . 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 . 1991 . 1905812 . 10.1073/pnas.88.13.5582 . 51921 . 1991PNAS...88.5582S . free .
4. Gilman . AG . 1987 . G proteins: transducers of receptor-generated signals . Annual Review of Biochemistry . 56 . 615–649 . 10.1146/annurev.bi.56.070187.003151 . 3113327 .
5. Rodbell . M . 1995 . Nobel Lecture: Signal transduction: Evolution of an idea . Bioscience Reports . 15 . 3 . 117–133 . 10.1007/bf01207453 . 7579038 . 11025853 . 1519115 .
6. Johnson EN, Seasholtz TM, Waheed AA, Kreutz B, Suzuki N, Kozasa T, Jones TL, Brown JH, Druey KM . RGS16 inhibits signalling through the G alpha 13-Rho axis . Nature Cell Biology . 5 . 12 . 1095–103 . Dec 2003 . 14634662 . 10.1038/ncb1065 . 6798899 .
7. Bhattacharyya R, Wedegaertner PB . Mutation of an N-terminal acidic-rich region of p115-RhoGEF dissociates alpha13 binding and alpha13-promoted plasma membrane recruitment . FEBS Letters . 540 . 1–3 . 211–6 . Apr 2003 . 12681510 . 10.1016/s0014-5793(03)00267-9. 84132104 .
8. Hart MJ, Jiang X, Kozasa T, Roscoe W, Singer WD, Gilman AG, Sternweis PC, Bollag G . Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13 . Science . 280 . 5372 . 2112–4 . Jun 1998 . 9641916 . 10.1126/science.280.5372.2112.
9. 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 . 10.1074/jbc.274.9.5868 . 10026210 . free .
10. 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 . 10.1016/s0014-5793(99)01270-3 . 10526156 . 8529412 .
11. Fukuhara S, Chikumi H, Gutkind JS . 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 . November 2000 . 11094164 . 10.1016/S0014-5793(00)02224-9 . 7300556 . free .
12. Suzuki N, Nakamura S, Mano H, Kozasa T . 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 . January 2003 . 12515866 . 141065 . 10.1073/pnas.0234057100 . 2003PNAS..100..733S . free .
13. Dhanasekaran N, Dermott JM . Signaling by the G12 class of G proteins . Cell. Signal. . 8 . 4 . 235–45 . 1996 . 8842523 . 10.1016/0898-6568(96)00048-4 .
14. Niu J, Vaiskunaite R, Suzuki N, Kozasa T, Carr DW, Dulin N, Voyno-Yasenetskaya TA . Interaction of heterotrimeric G13 protein with an A-kinase-anchoring protein 110 (AKAP110) mediates cAMP-independent PKA activation . Current Biology . 11 . 21 . 1686–90 . Oct 2001 . 11696326 . 10.1016/s0960-9822(01)00530-9. 19027128 . free . 2001CBio...11.1686N .
15. Tall GG, Krumins AM, Gilman AG . Mammalian Ric-8A (synembryn) is a heterotrimeric Galpha protein guanine nucleotide exchange factor . The Journal of Biological Chemistry . 278 . 10 . 8356–62 . Mar 2003 . 12509430 . 10.1074/jbc.M211862200 . free .
16. Wang L, Guo D, Xing B, Zhang JJ, Shu HB, Guo L, Huang XY . 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 . September 2011 . 21771786 . 10.1074/jbc.M111.253427 . 3162464. free .
17. Vaiskunaite R, Adarichev V, Furthmayr H, Kozasa T, Gudkov A, Voyno-Yasenetskaya TA . Conformational activation of radixin by G13 protein alpha subunit . The Journal of Biological Chemistry . 275 . 34 . 26206–12 . Aug 2000 . 10816569 . 10.1074/jbc.M001863200 . free .
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