GNA13

Last updated
GNA13
Protein GNA13 PDB 1zcb.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases GNA13 , G13, G protein subunit alpha 13, HG1N
External IDs OMIM: 604406 MGI: 95768 HomoloGene: 55976 GeneCards: GNA13
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001282425
NM_006572

NM_010303
NM_001359034

RefSeq (protein)

NP_001269354
NP_006563

NP_034433
NP_001345963

Location (UCSC) Chr 17: 65.01 – 65.06 Mb Chr 11: 109.25 – 109.29 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Guanine nucleotide-binding protein subunit alpha-13 is a protein that in humans is encoded by the GNA13 gene. [5] [6]

Contents

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. [7] 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. [8] [9]

Active GTP-bound G12 alpha subunit interacts with and activates ARHGEF1, [10] [11] [12] ARHGEF11, [13] [14] and ARHGEF12. [15] [16] These ARHGEF proteins function as guanine nucleotide exchange factors for the Rho small GTPases to regulate the actin cytoskeleton. [17]

GNA13 has been shown to interact with AKAP3, [18] RIC8A, [19] [20] and Radixin. [21]

Clinical significance

Recurrent mutations in this gene have been associated to cases of diffuse large B-cell lymphoma. [22] [23]

See also

Related Research Articles

GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a protein domain common to many GTPases.

Heterotrimeric G protein Class of enzymes

Heterotrimeric G protein, also sometimes referred to as the "large" G proteins are membrane-associated G proteins that form a heterotrimeric complex. The biggest non-structural difference between heterotrimeric and monomeric G protein is that heterotrimeric proteins bind to their cell-surface receptors, called G protein-coupled receptors, directly. These G proteins are made up of alpha (α), beta (β) and gamma (γ) subunits. The alpha subunit is attached to either a GTP or GDP, which serves as an on-off switch for the activation of G-protein.

G12/G13 alpha subunits are alpha subunits of heterotrimeric G proteins that link cell surface G protein-coupled receptors primarily to guanine nucleotide exchange factors for the Rho small GTPases to regulate the actin cytoskeleton. Together, these two proteins comprise one of the four classes of G protein alpha subunits. 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. G12/G13 are not targets of pertussis toxin or cholera toxin, as are other classes of G protein alpha subunits.

GNAQ Protein-coding gene in the species Homo sapiens

Guanine nucleotide-binding protein G(q) subunit alpha is a protein that in humans is encoded by the GNAQ gene. Together with GNA11, it functions as a Gq alpha subunit.

GNAI2

Guanine nucleotide-binding protein G(i), alpha-2 subunit is a protein that in humans is encoded by the GNAI2 gene.

GNAI1 Protein-coding gene in the species Homo sapiens

Guanine nucleotide-binding protein G(i), alpha-1 subunit is a protein that in humans is encoded by the GNAI1 gene.

GNB1

Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 is a protein that in humans is encoded by the GNB1 gene.

GNAO1

Guanine nucleotide-binding protein G(o) subunit alpha is a protein that in humans is encoded by the GNAO1 gene.

AKAP13

A-kinase anchor protein 13 is an protein that in humans is encoded by the AKAP13 gene. This protein is also called AKAP-Lbc because it encodes the lymphocyte blast crisis (Lbc) oncogene, and ARHGEF13/RhoGEF13 because it contains a guanine nucleotide exchange factor (GEF) domain for the RhoA small GTP-binding protein.

GNG2

Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 is a protein that in humans is encoded by the GNG2 gene.

RGS16

Regulator of G-protein signaling 16 is a protein that in humans is encoded by the RGS16 gene.

ARHGEF1

Rho guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the ARHGEF1 gene. This protein is also called RhoGEF1 or p115-RhoGEF.

ARHGEF11

Rho guanine nucleotide exchange factor 11 is a protein that in humans is encoded by the ARHGEF11 gene. This protein is also called RhoGEF11 or PDZ-RhoGEF.

ARHGEF12 Protein-coding gene in the species Homo sapiens

Rho guanine nucleotide exchange factor 12 is a protein that in humans is encoded by the ARHGEF12 gene. This protein is also called RhoGEF12 or Leukemia-associated Rho guanine nucleotide exchange factor (LARG).

GNB4

Guanine nucleotide-binding protein subunit beta-4 is a protein that in humans is encoded by the GNB4 gene.

GNAI3

Guanine nucleotide-binding protein G(k) subunit alpha is a protein that in humans is encoded by the GNAI3 gene.

GNA11

Guanine nucleotide-binding protein subunit alpha-11 is a protein that in humans is encoded by the GNA11 gene. Together with GNAQ, it functions as a Gq alpha subunit.

GNA12

Guanine nucleotide-binding protein subunit alpha-12 is a protein that in humans is encoded by the GNA12 gene.

GoLoco motif

GoLoco motif is a protein structural motif.

PLEKHG2 Protein-coding gene in the species Homo sapiens

Pleckstrin homology domain containing, family G member 2 (PLEKHG2) is a protein that in humans is encoded by the PLEKHG2 gene. It is sometimes written as ARHGEF42, FLJ00018.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000120063 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020611 - 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. Kabouridis PS, Waters ST, Escobar S, Stanners J, Tsoukas CD (Mar 1995). "Expression of GTP-binding protein alpha subunits in human thymocytes". Molecular and Cellular Biochemistry. 144 (1): 45–51. doi:10.1007/BF00926739. PMID   7791744. S2CID   8911988.
  6. "Entrez Gene: GNA13 guanine nucleotide binding protein (G protein), alpha 13".
  7. 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.
  8. 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.
  9. Rodbell, M (1995). "Nobel Lecture: Signal transduction: Evolution of an idea". Bioscience Reports. 15 (3): 117–133. doi:10.1007/bf01207453. PMID   7579038. S2CID   11025853.
  10. Johnson EN, Seasholtz TM, Waheed AA, Kreutz B, Suzuki N, Kozasa T, Jones TL, Brown JH, Druey KM (Dec 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.
  11. Bhattacharyya R, Wedegaertner PB (Apr 2003). "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. doi:10.1016/s0014-5793(03)00267-9. PMID   12681510. S2CID   84132104.
  12. Hart MJ, Jiang X, Kozasa T, Roscoe W, Singer WD, Gilman AG, Sternweis PC, Bollag G (Jun 1998). "Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13". Science. 280 (5372): 2112–4. doi:10.1126/science.280.5372.2112. PMID   9641916.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. Niu J, Vaiskunaite R, Suzuki N, Kozasa T, Carr DW, Dulin N, Voyno-Yasenetskaya TA (Oct 2001). "Interaction of heterotrimeric G13 protein with an A-kinase-anchoring protein 110 (AKAP110) mediates cAMP-independent PKA activation". Current Biology. 11 (21): 1686–90. doi: 10.1016/s0960-9822(01)00530-9 . PMID   11696326. S2CID   19027128.
  19. Tall GG, Krumins AM, Gilman AG (Mar 2003). "Mammalian Ric-8A (synembryn) is a heterotrimeric Galpha protein guanine nucleotide exchange factor". The Journal of Biological Chemistry. 278 (10): 8356–62. doi: 10.1074/jbc.M211862200 . PMID   12509430.
  20. 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.
  21. Vaiskunaite R, Adarichev V, Furthmayr H, Kozasa T, Gudkov A, Voyno-Yasenetskaya TA (Aug 2000). "Conformational activation of radixin by G13 protein alpha subunit". The Journal of Biological Chemistry. 275 (34): 26206–12. doi: 10.1074/jbc.M001863200 . PMID   10816569.
  22. Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA (Aug 2011). "Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma". Nature. 476 (7360): 298–303. Bibcode:2011Natur.476..298M. doi:10.1038/nature10351. PMC   3210554 . PMID   21796119.
  23. Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C, Cruz-Gordillo P, Knoechel B, Asmann YW, Slager SL, Novak AJ, Dogan A, Ansell SM, Link BK, Zou L, Gould J, Saksena G, Stransky N, Rangel-Escareño C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Hernández-Lemus E, Schwarz-Cruz y Celis A, Imaz-Rosshandler I, Ojesina AI, Jung J, Pedamallu CS, Lander ES, Habermann TM, Cerhan JR, Shipp MA, Getz G, Golub TR (Mar 2012). "Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing". Proceedings of the National Academy of Sciences of the United States of America. 109 (10): 3879–84. Bibcode:2012PNAS..109.3879L. doi: 10.1073/pnas.1121343109 . PMC   3309757 . PMID   22343534.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.