RAPGEF6

Summary

Gene Symbol: RAPGEF6
Description: Rap guanine nucleotide exchange factor 6
Alias: KIA001LB, PDZ-GEF2, PDZGEF2, RA-GEF-2, RAGEF2, rap guanine nucleotide exchange factor 6, PDZ domain containing guanine nucleotide exchange factor (GEF) 2, PDZ domain-containing guanine nucleotide exchange factor 2, PDZ domain-containing guanine nucleotide exchange factor I, Rap guanine nucleotide exchange factor (GEF) 6
Species: human

Top Publications

  1. ncbi Characterisation of PDZ-GEFs, a family of guanine nucleotide exchange factors specific for Rap1 and Rap2
    H Bea Kuiperij
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
    Biochim Biophys Acta 1593:141-9. 2003
  2. pmc Junctional adhesion molecule A interacts with Afadin and PDZ-GEF2 to activate Rap1A, regulate beta1 integrin levels, and enhance cell migration
    Eric A Severson
    Epithelial Pathobiology Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
    Mol Biol Cell 20:1916-25. 2009
  3. doi Rap2A links intestinal cell polarity to brush border formation
    Martijn Gloerich
    Molecular Cancer Research, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht 3584 CG, The Netherlands
    Nat Cell Biol 14:793-801. 2012
  4. pmc Crucial Role of Rapgef2 and Rapgef6, a Family of Guanine Nucleotide Exchange Factors for Rap1 Small GTPase, in Formation of Apical Surface Adherens Junctions and Neural Progenitor Development in the Mouse Cerebral Cortex
    Kazuhiro Maeta
    Department of Biochemistry and Molecular and Biology, Division of Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650 0017, Japan
    Eneuro 3:. 2016
  5. pmc Deletion of Rapgef6, a candidate schizophrenia susceptibility gene, disrupts amygdala function in mice
    R J Levy
    Department of Neuroscience, Columbia University, New York, NY, USA
    Transl Psychiatry 5:e577. 2015
  6. pmc The PDZ domain of the guanine nucleotide exchange factor PDZGEF directs binding to phosphatidic acid during brush border formation
    Sarah V Consonni
    Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
    PLoS ONE 9:e98253. 2014
  7. doi Critical function of RA-GEF-2/Rapgef6, a guanine nucleotide exchange factor for Rap1, in mouse spermatogenesis
    Keisuke Okada
    Division of Urology, Department of Organs Therapeutics, Kobe University Graduate School of Medicine, 7 5 1 Kusunoki cho, Chuo Ku, Kobe 650 0017, Japan
    Biochem Biophys Res Commun 445:89-94. 2014
  8. pmc JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function
    Ana C Monteiro
    Department of Pathology, Emory University School of Medicine, Atlanta, GA 30306 Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30306 Emory Rollins School of Public Health, Atlanta, GA 30306 Interfaculty Institute of Biochemistry, University of Tubingen, D 72076 Tubingen, Germany Department of Pediatrics and Pathology, Vanderbilt University School of Medicine, Nashville, TN 37230 Departments of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37230 Elizabeth B Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN 37230
    Mol Biol Cell 24:2849-60. 2013
  9. ncbi Energetics of peptide recognition by the second PDZ domain of human protein tyrosine phosphatase 1E
    Stoyan Milev
    Biochemisches Institut der Universitat Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Biochemistry 46:1064-78. 2007
  10. pmc Interaction between interleukin 3 and dystrobrevin-binding protein 1 in schizophrenia
    Todd L Edwards
    Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Schizophr Res 106:208-17. 2008

Scientific Experts

  • Xiangning Chen
  • G Kempermann
  • Johannes L Bos
  • Kazuhiro Maeta
  • Tohru Kataoka
  • Shymaa E Bilasy
  • Hironori Edamatsu
  • Kenneth S Kendler
  • Qi Chen
  • R J Levy
  • Keisuke Okada
  • Sarah V Consonni
  • Chih Wei Tong
  • Ana C Monteiro
  • Martijn Gloerich
  • Charles A Parkos
  • Asma Nusrat
  • Jingchun Chen
  • Marjolein J Vliem
  • Masahiro Iwasaki
  • Eric A Severson
  • Nadia Dubé
  • Dermot Walsh
  • Xu Wang
  • T Kataoka
  • Todd L Edwards
  • Yoko Yoshikawa
  • Stoyan Milev
  • Holger Rehmann
  • Karl Hackmann
  • Ernesto J Fuentes
  • Junji Ikutomo
  • H Bea Kuiperij
  • Robert Papp
  • Kaori Nishihara
  • Y Yoshikawa
  • V Y Bolshakov
  • W Dong
  • Irena Ekiel
  • J A Gogos
  • M Karayiorgou
  • M Kvajo
  • Y Li
  • E Tsvetkov
  • Patricia M Brouwer
  • Masato Fujisawa
  • Eleonora S van Slobbe
  • Kohei Yamaguchi
  • Koji Chiba
  • Guennadi Kozlov
  • Hideaki Miyake
  • Thilo Stehle
  • Stacy A Schaefer
  • Randy A Hall
  • Terence S Dermody
  • Dirk M Reiter
  • Chia Hao Hsu
  • Wen Teng Chang
  • Carl R Rankin
  • A Min Huang
  • Giovanna Leoni
  • Michael J Mina
  • Ronen Sumagin
  • Jen Ling Wang
  • Mei Sian Jiang
  • X Gao
  • Hans Clevers
  • Thijs Koorman
  • Jean Paul ten Klooster
  • Fried J Zwartkruis
  • Po Hsiu Kuo
  • Kia Jackson
  • Bradley T Webb
  • Darlene H Brunzell
  • Douglas F Levinson
  • Richard Sherva
  • Thomas J Payne
  • Joel Gelernter
  • Andrew van der Vaart
  • Ming D Li
  • Jennie Z Ma
  • Steven H Aggen
  • Henry R Kranzler
  • Lindsay A Farrer
  • Raymond Anton
  • Pablo Gejman
  • Imad Damaj
  • Peter Holmans
  • Sachiko Homma
  • Ryoichi Tanaka

Detail Information

Publications24

  1. ncbi Characterisation of PDZ-GEFs, a family of guanine nucleotide exchange factors specific for Rap1 and Rap2
    H Bea Kuiperij
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
    Biochim Biophys Acta 1593:141-9. 2003
    ..We conclude that both PDZ-GEF1 and 2 are specific for Rap1 and Rap2 and unresponsive to cAMP and various other nucleotides...
  2. pmc Junctional adhesion molecule A interacts with Afadin and PDZ-GEF2 to activate Rap1A, regulate beta1 integrin levels, and enhance cell migration
    Eric A Severson
    Epithelial Pathobiology Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
    Mol Biol Cell 20:1916-25. 2009
    ..These findings suggest that JAM-A dimerization facilitates formation of a complex with Afadin and PDZ-GEF2 that activates Rap1A, which regulates beta1 integrin levels and cell migration...
  3. doi Rap2A links intestinal cell polarity to brush border formation
    Martijn Gloerich
    Molecular Cancer Research, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht 3584 CG, The Netherlands
    Nat Cell Biol 14:793-801. 2012
    ..Thus, epithelial cell polarization is translated directly into the acquisition of brush borders through a small G protein signalling module whose action is positioned by a cortical lipid cue...
  4. pmc Crucial Role of Rapgef2 and Rapgef6, a Family of Guanine Nucleotide Exchange Factors for Rap1 Small GTPase, in Formation of Apical Surface Adherens Junctions and Neural Progenitor Development in the Mouse Cerebral Cortex
    Kazuhiro Maeta
    Department of Biochemistry and Molecular and Biology, Division of Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650 0017, Japan
    Eneuro 3:. 2016
    ..Rapgef2 and Rapgef6 constitute a unique family of guanine nucleotide exchange factors for Rap1 small GTPase, which is known to play ..
  5. pmc Deletion of Rapgef6, a candidate schizophrenia susceptibility gene, disrupts amygdala function in mice
    R J Levy
    Department of Neuroscience, Columbia University, New York, NY, USA
    Transl Psychiatry 5:e577. 2015
    In human genetic studies of schizophrenia, we uncovered copy-number variants in RAPGEF6 and RAPGEF2 genes. To discern the effects of RAPGEF6 deletion in humans, we investigated the behavior and neural functions of a mouse lacking Rapgef6...
  6. pmc The PDZ domain of the guanine nucleotide exchange factor PDZGEF directs binding to phosphatidic acid during brush border formation
    Sarah V Consonni
    Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
    PLoS ONE 9:e98253. 2014
    ....
  7. doi Critical function of RA-GEF-2/Rapgef6, a guanine nucleotide exchange factor for Rap1, in mouse spermatogenesis
    Keisuke Okada
    Division of Urology, Department of Organs Therapeutics, Kobe University Graduate School of Medicine, 7 5 1 Kusunoki cho, Chuo Ku, Kobe 650 0017, Japan
    Biochem Biophys Res Commun 445:89-94. 2014
    ..In the present study, we investigated the functional significance of RA-GEF-2/Rapgef6, a guanine nucleotide exchange factor for Rap1, in testicular differentiation using mice lacking RA-GEF-2...
  8. pmc JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function
    Ana C Monteiro
    Department of Pathology, Emory University School of Medicine, Atlanta, GA 30306 Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30306 Emory Rollins School of Public Health, Atlanta, GA 30306 Interfaculty Institute of Biochemistry, University of Tubingen, D 72076 Tubingen, Germany Department of Pediatrics and Pathology, Vanderbilt University School of Medicine, Nashville, TN 37230 Departments of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37230 Elizabeth B Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN 37230
    Mol Biol Cell 24:2849-60. 2013
    ..These results suggest that JAM-A regulates epithelial permeability via association with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and control contraction of the apical cytoskeleton. ..
  9. ncbi Energetics of peptide recognition by the second PDZ domain of human protein tyrosine phosphatase 1E
    Stoyan Milev
    Biochemisches Institut der Universitat Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Biochemistry 46:1064-78. 2007
    ..In our hands, the C-terminal segment of the tumor suppressor APC binds much less tightly to PDZ2 than what has been proposed earlier from surface plasmon resonance experiments...
  10. pmc Interaction between interleukin 3 and dystrobrevin-binding protein 1 in schizophrenia
    Todd L Edwards
    Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Schizophr Res 106:208-17. 2008
    ..We also observed a significant main effect in DTNBP1, which survived correction for multiple comparisons, and numerous nominally significant effects in several genes...
  11. ncbi Ligand-dependent dynamics and intramolecular signaling in a PDZ domain
    Ernesto J Fuentes
    Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    J Mol Biol 335:1105-15. 2004
    ....
  12. doi Novel genes that mediate nuclear respiratory factor 1-regualted neurite outgrowth in neuroblastoma IMR-32 cells
    Chih Wei Tong
    Department of Physiology, National Cheng Kung University, College of Medicine, Tainan, Taiwan
    Gene 515:62-70. 2013
    ..Fifteen genes, MAPRE3, NPDC1, RAB3IP, TRAPPC3, SMAD5, PIP5K1A, USP10, SPRY4, GTF2F2, NR1D1, SUV39H2, SKA3, RHOA, RAPGEF6, and SMAP1 were selected for biological confirmation...
  13. pmc Is the histidine triad nucleotide-binding protein 1 (HINT1) gene a candidate for schizophrenia?
    Qi Chen
    Department of Psychiatry and Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, United States
    Schizophr Res 106:200-7. 2008
    ..It was also found to be associated with the dysregulation of postsynaptic dopamine transmission, thus suggesting a potential role in several neuropsychiatric diseases...
  14. pmc ACSL6 is associated with the number of cigarettes smoked and its expression is altered by chronic nicotine exposure
    Jingchun Chen
    Department of Psychiatry and Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America
    PLoS ONE 6:e28790. 2011
    ..The independent associations of this locus with schizophrenia and with numCIG in non-schizophrenic subjects suggest that this locus may be a common liability to both conditions...
  15. pmc BAG3 directly associates with guanine nucleotide exchange factor of Rap1, PDZGEF2, and regulates cell adhesion
    Masahiro Iwasaki
    Medical College of Georgia, 1210 Laney Walker Street, Augusta, GA 92023, USA
    Biochem Biophys Res Commun 400:413-8. 2010
    ..The PDZ domain containing guanine nucleotide exchange factor 2 (PDZGEF2) was cloned as a BAG3-interacting protein...
  16. ncbi Identification and characterization of RA-GEF-2, a Rap guanine nucleotide exchange factor that serves as a downstream target of M-Ras
    X Gao
    Division of Molecular Biology, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, 7 5 1 Kusunoki cho, Chuo Ku, Japan
    J Biol Chem 276:42219-25. 2001
    ..Thus, RA-GEF-2 acts as a GEF for Rap1 and Rap2 downstream of M-Ras in the plasma membrane, whereas RA-GEF-1 exerts Rap GEF function in perinuclear compartments including the Golgi apparatus...
  17. doi The RapGEF PDZ-GEF2 is required for maturation of cell-cell junctions
    Nadia Dubé
    Department of Physiological Chemistry, Centre for Biomedical Genetics and Cancer Genomics Centre, Utrecht, The Netherlands
    Cell Signal 20:1608-15. 2008
    ..Our results present the first direct evidence that PDZ-GEF2 plays a critical role in the maturation of adherens junctions...
  18. pmc The M-Ras-RA-GEF-2-Rap1 pathway mediates tumor necrosis factor-alpha dependent regulation of integrin activation in splenocytes
    Yoko Yoshikawa
    Division of Molecular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650 0017, Japan
    Mol Biol Cell 18:2949-59. 2007
    ..These findings proved a crucial role of the cross-talk between two Ras-family GTPases M-Ras and Rap1, mediated by RA-GEF-2, in adhesion signaling...
  19. ncbi Haplotypes spanning SPEC2, PDZ-GEF2 and ACSL6 genes are associated with schizophrenia
    Xiangning Chen
    Department of Psychiatry and Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richimond, VA 23298, USA
    Hum Mol Genet 15:3329-42. 2006
    ..However, due to the extended high LD in this region, we were unable to distinguish whether the association signals came from one or more of these genes...
  20. pmc Natural variation and genetic covariance in adult hippocampal neurogenesis
    Gerd Kempermann
    Max Delbröck Center for Molecular Medicine, Berlin Buch, 13125 Berlin, Germany
    Proc Natl Acad Sci U S A 103:780-5. 2006
    ..Only one cis-acting candidate was linked to both neurogenesis and gliogenesis, Rapgef6, a downstream target of ras signaling...
  21. ncbi A splice form of polycystin-2, lacking exon 7, does not interact with polycystin-1
    Karl Hackmann
    Institut fur Humangenetik, Universitatsklinikum Munster, Germany
    Hum Mol Genet 14:3249-62. 2005
    ..The predominant expression in brain indicates a function in this organ. The inability to interact with polycystin-1 expands further the PKD1-independent functions of polycystin-2 forms...
  22. ncbi ESI-MS and FTIR studies of the interaction between the second PDZ domain of hPTP1E and target peptides
    Robert Papp
    Department of Chemistry and Biochemistry, Concordia University, 1455 de Maisonneuve Boulevard West, Montreal, Quebec, Canada H3G 1M8
    Biochem Cell Biol 81:71-80. 2003
    ..Our results demonstrate that even a single atom (O --> S) substitution from Ser to Cys in the -2 position disrupts C-terminal peptide binding to PDZ2...
  23. ncbi Solution structure of the PDZ2 domain from cytosolic human phosphatase hPTP1E complexed with a peptide reveals contribution of the beta2-beta3 loop to PDZ domain-ligand interactions
    Guennadi Kozlov
    Department of Biochemistry, McIntyre Medical Science Building, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6
    J Mol Biol 320:813-20. 2002
    ..This work underlines the importance of the beta2/beta3 loop for ligand selection by PDZ domains...