Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

SYX/PLEKHG5, A Rhoa Guanine Exchange Factor Involved in Cell Migration and Angiogenesis

  • Arie HorowitzEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_567


 Plekhg5;  Syx;  Tech

Historical Background

Plekhg5 first emerged as a partial cDNA clone KIAA0720 in the HUGE (Human Unidentified Gene-Encoded) database of large proteins analyzed by the Kazusa Human cDNA Project in Japan (http://www.kazusa.or.jp/huge). It was initially characterized as a RhoA-specific GEF and a potential oncogen named GEF720 (de Toledo et al. 2003). Independently, the rat cDNA of the same protein (named Tech) was characterized also as a RhoA-specific GEF that was highly expressed in cortical and hippocampal neurons (Marx et al. 2005). Two full-length cDNA clones of the mouse ortholog were identified as splice variants (named Syx1 and Syx2) and characterized as participants in cell motility (Liu and Horowitz 2006).

Splice Variants and Domain Structure

The majority of the known splice-variants of Plekhg5 are produced by the initiation of transcription at alternate 5′ start codons (http://www.uniprot.org/uniprot/O94827). These five transcripts code for...

This is a preview of subscription content, log in to check access.


  1. de Toledo M, Senic-Matuglia F, Salamero J, Uze G, Comunale F, Fort P, Blangy A. The GTP/GDP cycling of rho GTPase TCL is an essential regulator of the early endocytic pathway. Mol Biol Cell. 2003;14(12):4846–56. PMID 12960428.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Ernkvist M, Luna Persson N, Audebert S, Lecine P, Sinha I, Liu M, Schlueter M, Horowitz A, Aase K, Weide T, Borg JP, Majumdar A, Holmgren L. The Amot/Patj/Syx signaling complex spatially controls RhoA GTPase activity in migrating endothelial cells. Blood. 2009;113(1):244–53. PMID 18824598.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Estevez MA, Henderson JA, Ahn D, Zhu XR, Poschmann G, Lubbert H, Marx R, Baraban JM. The neuronal RhoA GEF, Tech, interacts with the synaptic multi-PDZ-domain-containing protein, MUPP1. J Neurochem. 2008;106(3):1287–97. PMID 18537874.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Garcia-Mata R, Burridge K. Catching a GEF by its tail. Trends Cell Biol. 2007;17(1):36–43. PMID 17126549.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Garnaas MK, Moodie KL, Liu ML, Samant GV, Li K, Marx R, Baraban JM, Horowitz A, Ramchandran R. Syx, a RhoA guanine exchange factor, is essential for angiogenesis in vivo. Circ Res. 2008;103(7):710–6. PMID 18757825.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Goh LL, Manser E. The RhoA GEF Syx is a target of Rnd3 and regulated via a Raf1-like ubiquitin-related domain. PLoS One. 2010;5(8):e12409. PMID 20811643.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Liu M, Horowitz A. A PDZ-binding motif as a critical determinant of Rho guanine exchange factor function and cell phenotype. Mol Biol Cell. 2006;17(4):1880–7. PMID 16467373.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Marx R, Henderson J, Wang J, Baraban JM. Tech: a RhoA GEF selectively expressed in hippocampal and cortical neurons. J Neurochem. 2005;92(4):850–8. PMID 15686487.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, Doi T, Shimotohno K, Harada T, Nishida E, Hayashi H, Sugano S. Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. Oncogene. 2003;22(21):3307–18. PMID 12761501.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Maystadt I, Zarhrate M, Leclair-Richard D, Estournet B, Barois A, Renault F, Routon MC, Durand MC, Lefebvre S, Munnich A, Verellen-Dumoulin C, Viollet L. A gene for an autosomal recessive lower motor neuron disease with childhood onset maps to 1p36. Neurology. 2006;67(1):120–4. PMID 16728649.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Maystadt I, Rezsohazy R, Barkats M, Duque S, Vannuffel P, Remacle S, Lambert B, Najimi M, Sokal E, Munnich A, Viollet L, Verellen-Dumoulin C. The nuclear factor kappaB-activator gene PLEKHG5 is mutated in a form of autosomal recessive lower motor neuron disease with childhood onset. Am J Hum Genet. 2007;81(1):67–76. PMID 17564964.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Ross CA, Poirier MA. Opinion: what is the role of protein aggregation in neurodegeneration? Nat Rev Mol Cell Biol. 2005;6(11):891–8. PMID 16167052.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Wells CD, Fawcett JP, Traweger A, Yamanaka Y, Goudreault M, Elder K, Kulkarni S, Gish G, Virag C, Lim C, Colwill K, Starostine A, Metalnikov P, Pawson T. A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell. 2006;125(3):535–48. PMID 16678097.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Wennerberg K, Forget MA, Ellerbroek SM, Arthur WT, Burridge K, Settleman J, Der CJ, Hansen SH. Rnd proteins function as RhoA antagonists by activating p190 RhoGAP. Curr Biol. 2003;13(13):1106–15. PMID 12842009.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Wu C, Agrawal SA, Vasanji A, Sarkaria S, Xie J, Liu M, Anand-Apte B, Horowitz A. Rab13-dependent trafficking of RhoA is required for directional migration and angiogenesis. J Biol Chem. 2011;286(26):23511–20. PMID 21543326.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Yanai I, Benjamin H, Shmoish M, Chalifa-Caspi V, Shklar M, Ophir R, Bar-Even A, Horn-Saban S, Safran M, Domany E, Lancet D, Shmueli O. Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification. Bioinformatics. 2005;21(5):650–9. PMID 15388519.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation and Department of Physiology and BiophysicsCase Western Reserve UniversityClevelandUSA