FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
CV Term Report
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General Information
Term guanyl-nucleotide exchange factor activity ID (Ontology) GO:0005085 (Gene Ontology)
Definition Stimulates the exchange of GDP to GTP on a signaling GTPase, changing its conformation to its active form. Guanine nucleotide exchange factors (GEFs) act by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP), which is more abundant in the cell under normal cellular physiological conditions.[ PubMed:23303910 PubMed:27218782 ]
Also Known As "GDP-dissociation stimulator activity" ; "GDS" ; "GEF" (for all, see Synonyms field below)
Comment
Links to External Ontologies
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Annotations
Records annotated with this term OR any of its CHILD TERMS
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Records annotated with this exact term (annotations to child terms are NOT included)
Data Class Field Records
Genes (FBgn)  GO_BIOLOGICAL_PROCESS       4
Genes (FBgn)  GO_MOLECULAR_FUNCTION      88
show Full annotation statements including this term (annotations to child terms are NOT included), and relevant FlyBase records
 Full annotation statements 
Relevant FlyBase reports
 Gene Groups Genes
 guanyl-nucleotide exchange factor activity (all annotations which use CV term, excluding "NOT" statements)      15     88
     contributes_to | guanyl-nucleotide exchange factor activity       --      17
     enables | guanyl-nucleotide exchange factor activity       --      72
Spanning Tree (Parents/Children)
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  nucleoside-triphosphatase regulator activity
   |__GTPase regulator activity
       |__guanyl-nucleotide exchange factor activity  103 rec.
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Is a GTPase regulator activity
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Synonyms
  • "ARF guanyl-nucleotide exchange factor activity" NARROW
    "cAMP-dependent guanyl-nucleotide exchange factor activity" NARROW
    "GDP-dissociation stimulator activity" EXACT
    "GDS" EXACT
    "GEF" EXACT
    "GNRP" NARROW
    "guanyl-nucleotide release factor activity" EXACT
    "guanyl-nucleotide releasing factor" EXACT
    "Rab guanyl-nucleotide exchange factor activity" NARROW
    "Rac guanyl-nucleotide exchange factor activity" NARROW
    "Ral guanyl-nucleotide exchange factor activity" NARROW
    "Ran guanyl-nucleotide exchange factor activity" NARROW
    "Rap guanyl-nucleotide exchange factor activity" NARROW
    "Ras guanyl-nucleotide exchange factor activity" NARROW
    "Rho guanine nucleotide exchange factor" EXACT
    "Rho guanyl-nucleotide exchange factor activity" NARROW
    "RhoGEF" EXACT
    "Sar guanyl-nucleotide exchange factor activity" NARROW
Secondary IDs
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Reactome:R-HSA-109807 "GRB2:SOS:p-Y427-SHC1 mediated nucleotide exchange of RAS"
Reactome:R-HSA-109817 "GRB2:SOS1:p-Y-IRS1,p-Y-IRS2 mediated nucleotide exchange of RAS"
Reactome:R-HSA-114544 "p115-RhoGEF activation of RHOA"
Reactome:R-HSA-1168636 "p-RasGRP1,3:DAG cause RAS to exchange GDP for GTP"
Reactome:R-HSA-1225951 "SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with ligand-responsive p-6Y-EGFR mutants)"
Reactome:R-HSA-1225957 "SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with phosphorylated SHC1 and ligand-responsive p-6Y-EGFR mutants)"
Reactome:R-HSA-1250383 "RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-Y349,350-SHC1:p-ERBB4"
Reactome:R-HSA-1250463 "RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-SHC1:Phosphorylated ERBB2 heterodimers"
Reactome:R-HSA-1250498 "RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and phosphorylated EGFR:ERBB2 heterodimers"
Reactome:R-HSA-1306972 "RAS guanyl nucleotide exchange mediated by SOS1 bound to GRB2 in complex with phosphorylated ERBB4:ERBB2 heterodimers"
Reactome:R-HSA-1433415 "Activation of RAC1"
Reactome:R-HSA-1433471 "Activation of RAS by p-KIT bound SOS1"
Reactome:R-HSA-156913 "Regeneration of eEF1A:GTP by eEF1B activity"
Reactome:R-HSA-169904 "C3G stimulates nucleotide exchange on Rap1"
Reactome:R-HSA-170979 "(Frs2)C3G stimulates nucleotide exchange on Rap1"
Reactome:R-HSA-171026 "Guanine nucleotide exchange on RAL"
Reactome:R-HSA-177938 "SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:GRB2:SOS1)"
Reactome:R-HSA-177945 "SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:SHC1:GRB2:SOS1)"
Reactome:R-HSA-180687 "Conversion of Ran-GDP to Ran-GTP"
Reactome:R-HSA-186834 "SOS-mediated nucleotide exchange on RAS (PDGF receptor:GRB2:SOS)"
Reactome:R-HSA-187746 "RIT/RIN are activated"
Reactome:R-HSA-194518 "RhoA is activated by nucleotide exchange and inhibits axonal growth"
Reactome:R-HSA-2029445 "An unknown GEF exchanges GTP for GDP on CDC42:GDP"
Reactome:R-HSA-2029451 "Activation of RAC1 by VAV"
Reactome:R-HSA-2029467 "Activation of RAC1 by CRKII:DOCK180:ELMO"
Reactome:R-HSA-203977 "SAR1 Activation And Membrane Binding"
Reactome:R-HSA-205039 "p75NTR indirectly activates RAC and Cdc42 via a guanyl-nucleotide exchange factor"
Reactome:R-HSA-210977 "Sos-mediated nucleotide exchange of Ras (Tie2 receptor:Grb2:Sos)"
Reactome:R-HSA-2179407 "SOS1-mediated nucleotide exchange of RAS (HB-EFG-initiated)"
Reactome:R-HSA-2424476 "Activation of RAC1 by VAV2/3"
Reactome:R-HSA-2424477 "SOS mediated nucleotide exchange of RAS (SHC)"
Reactome:R-HSA-2485180 "MII catalyses GDP/GTP exchange on Gt"
Reactome:R-HSA-2730840 "Activation of RAC1 by VAV"
Reactome:R-HSA-350769 "trans-Golgi Network Coat Activation"
Reactome:R-HSA-354173 "Activation of Rap1 by cytosolic GEFs"
Reactome:R-HSA-379044 "Liganded Gs-activating GPCR acts as a GEF for Gs"
Reactome:R-HSA-379048 "Liganded Gq/11-activating GPCRs act as GEFs for Gq/11"
Reactome:R-HSA-380073 "Liganded Gi-activating GPCR acts as a GEF for Gi"
Reactome:R-HSA-389348 "Activation of Rac1 by pVav1"
Reactome:R-HSA-389350 "Activation of Cdc42 by pVav1"
Reactome:R-HSA-392054 "NCAM1:pFAK:Grb2:Sos-mediated nucleotide exchange of Ras"
Reactome:R-HSA-392195 "Gi activation by P2Y purinoceptor 12"
Reactome:R-HSA-3928592 "p190RhoGEF exchanges GTP for GDP on RHOA, activating it"
Reactome:R-HSA-3928612 "KALRN exchanges GTP for GDP on RAC1, activating it"
Reactome:R-HSA-3928628 "VAV exchanges GTP for GDP on RAC1, activating it"
Reactome:R-HSA-3928632 "ITSN1 exchanges GTP for GDP on CDC42, activating it"
Reactome:R-HSA-3928633 "bPIX exchanges GTP for GDP on RAC, activating it"
Reactome:R-HSA-3928642 "TIAM1 exchanges GTP for GDP on RAC1, activating it"
Reactome:R-HSA-3928651 "NGEF exchanges GTP for GDP on RHOA"
Reactome:R-HSA-392870 "Gs activation by prostacyclin receptor"
Reactome:R-HSA-3965444 "WNT:FZD complex promotes G-protein nucleotide exchange"
Reactome:R-HSA-399938 "Activation of Rac1 by FARP2"
Reactome:R-HSA-399995 "Muscarinic Acetylcholine Receptor M3 activates Gq"
Reactome:R-HSA-400092 "Alpha-2A,alpha-2C Adrenergic Receptors activate Gi.Go heterotrimeric G proteins"
Reactome:R-HSA-4093336 "p-TIAM1 exchanges GTP for GDP on RAC1, activating it"
Reactome:R-HSA-416530 "FFAR1:FFAR1 ligands activate Gq"
Reactome:R-HSA-416588 "Activation of Rho by LARG and PDZ-RhoGEF"
Reactome:R-HSA-418579 "Gq activation by P2Y purinoceptor 1"
Reactome:R-HSA-418850 "Activation of Cdc42"
Reactome:R-HSA-418856 "Activation of Rac1"
Reactome:R-HSA-419166 "GEFs activate RhoA,B,C"
Reactome:R-HSA-420883 "Opsins act as GEFs for G alpha-t"
Reactome:R-HSA-428535 "Activation of RAC1 by SOS"
Reactome:R-HSA-428750 "Gq activation by TP receptor"
Reactome:R-HSA-428917 "G13 activation by TP receptor"
Reactome:R-HSA-442273 "VAV1 is a GEF for Rho/Rac family GTPases"
Reactome:R-HSA-442291 "VAV2 is a GEF for Rho/Rac family kinases"
Reactome:R-HSA-442314 "VAV3 is a GEF for Rho/Rac family kinases"
Reactome:R-HSA-442732 "NMDA-activated RASGRF1 activates RAS"
Reactome:R-HSA-445064 "Activation of Rac1 by VAV2"
Reactome:R-HSA-5218829 "VEGF induces CDC42 activation by unknown mechanism"
Reactome:R-HSA-5218839 "DOCK180:ELMO exchanges GTP for GDP, activating RAC1"
Reactome:R-HSA-5218850 "VAV exchanges GTP for GDP on RAC1, activating it"
Reactome:R-HSA-5617816 "RAB3IP stimulates nucleotide exchange on RAB8A"
Reactome:R-HSA-5623508 "GBF1 stimulates nucleotide exchange on ARF4"
Reactome:R-HSA-5623521 "RAB3IP stimulates nucleotide exchange on RAB8A"
Reactome:R-HSA-5637806 "SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with p-EGFRvIII)"
Reactome:R-HSA-5637808 "SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with phosphorylated SHC1 and p-EGFRvIII)"
Reactome:R-HSA-5654392 "Activated FGFR1:p-FRS:GRB2:SOS1 activates RAS nucleotide exchange"
Reactome:R-HSA-5654402 "Activated FGFR2:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange"
Reactome:R-HSA-5654413 "Activated FGFR3:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange"
Reactome:R-HSA-5654426 "Activated FGFR4:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange"
Reactome:R-HSA-5654600 "Activated FGFR1:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange"
Reactome:R-HSA-5654618 "Activated FGFR2:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange"
Reactome:R-HSA-5654647 "Activated FGFR3:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange"
Reactome:R-HSA-5654663 "Activated FGFR4:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange"
Reactome:R-HSA-5655241 "Activated FGFR2 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange"
Reactome:R-HSA-5655277 "Activated FGFR3 point, translocation and fusion mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange"
Reactome:R-HSA-5655326 "Activated FGFR1 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange"
Reactome:R-HSA-5655347 "Activated FGFR4 mutants:p-FRS2:GRB2:SOS1 activates RAS nucleotide exchange"
Reactome:R-HSA-5672965 "RAS GEFs promote RAS nucleotide exchange"
Reactome:R-HSA-5686071 "GRB2-1:SOS1:p-Y-SHC mediated nucleotide exchange of RAS"
Reactome:R-HSA-5686318 "GRB2-1:SOS1:p-3Y-SHC1 mediated nucleotide exchange of RAS"
Reactome:R-HSA-5694409 "Nucleotide exchange on RAB1"
Reactome:R-HSA-6807868 "GBF1 stimulates ARF nucleotide exchange"
Reactome:R-HSA-6811414 "GBF1 stimulates nucleotide exchange on ARF"
Reactome:R-HSA-6811418 "ARFGAPs stimulate ARF GTPase activity at the Golgi membrane"
Reactome:R-HSA-6811429 "RIC1:RGP1 stimulates nucleotide RAB6 nucleotide exchange"
Reactome:R-HSA-749453 "Liganded Gz-activating GPCR acts as a GEF for Gz"
Reactome:R-HSA-751029 "Liganded G12/13-activating GPCR acts as a GEF for G12/13"
Reactome:R-HSA-825631 "Glucagon:GCGR mediates GTP-GDP exchange"
Reactome:R-HSA-8848618 "Activation of RAC1 by the PXN:CRK complex"
Reactome:R-HSA-8850041 "RAB3GAP1:RAB3GAP2 promotes nucleotide exchange on RAB18"
Reactome:R-HSA-8851827 "RAS guanyl nucleotide exchange by MET-bound GRB2:SOS1"
Reactome:R-HSA-8851877 "RAS guanyl nucleotide exchange by SOS1 associated with RANBP9 and MET"
Reactome:R-HSA-8851899 "RAS guanyl nucleotide exchange by SOS1 bound to GRB2, SCH1-2 and MET"
Reactome:R-HSA-8875318 "RAB3 GEFs exchange GTP for GDP on RAB3A"
Reactome:R-HSA-8875320 "RAB5 GEFs exchange GTP for GDP on RAB5"
Reactome:R-HSA-8875568 "RAPGEF1 activates RAP1"
Reactome:R-HSA-8875591 "DOCK7 activates RAC1"
Reactome:R-HSA-8876188 "DENND4s exchange GTP for GDP on RAB10"
Reactome:R-HSA-8876190 "RAB8 GEFs exchange GTP for GDP on RAB8"
Reactome:R-HSA-8876191 "RAB9 GEFs exchange GTP for GDP on RAB9"
Reactome:R-HSA-8876193 "RIC1-RGP1 exchanges GTP for GDP on RAB6"
Reactome:R-HSA-8876454 "DENND3 exchanges GTP for GDP on RAB12"
Reactome:R-HSA-8876615 "RAB13 GEFs exchange GTP for GDP on RAB13"
Reactome:R-HSA-8876616 "DENND6A,B exchange GTP for GDP on RAB14"
Reactome:R-HSA-8876837 "RAB21 GEFs exchange GTP for GDP on RAB21"
Reactome:R-HSA-8877308 "MADD exchanges GTP for GDP on RAB27"
Reactome:R-HSA-8877311 "RAB31 GEFs exchange GTP for GDP on RAB31"
Reactome:R-HSA-8877451 "MON1:CCZ1 exchanges GTP for GDP on RAB7"
Reactome:R-HSA-8877475 "TRAPPC complexes exchange GTP for GDP on RAB1"
Reactome:R-HSA-8877612 "DENND1s exchange GTP for GDP on RAB35"
Reactome:R-HSA-8877760 "HPS1:HPS4 exchange GTP for GDP on RAB32 and RAB38"
Reactome:R-HSA-8877813 "DENND5A,B exchange GTP for GDP on RAB39"
Reactome:R-HSA-8877998 "RAB3GAP1:RAB3GAP2 exchanges GTP for GDP on RAB18"
Reactome:R-HSA-8964604 "CDC42 in GNB/GNG:PAK1:ARHGEF6:CDC42 is activated"
Reactome:R-HSA-8980691 "RHOA GEFs activate RHOA"
Reactome:R-HSA-8982637 "Opsins binds G alpha-t"
Reactome:R-HSA-8982640 "G-alpha(t):G-beta-gamma:Opsins complex dissociates to active G-alpha(t)"
Reactome:R-HSA-9013023 "RHOB GEFs activate RHOB"
Reactome:R-HSA-9013109 "RHOC GEFs activate RHOC"
Reactome:R-HSA-9013143 "RAC1 GEFs activate RAC1"
Reactome:R-HSA-9013159 "CDC42 GEFs activate CDC42"
Reactome:R-HSA-9013435 "RHOD auto-activates"
Reactome:R-HSA-9014296 "RAC2 GEFs activate RAC2"
Reactome:R-HSA-9014433 "RHOG GEFs activate RHOG"
Reactome:R-HSA-9017491 "RHOJ GEFs activate RHOJ"
Reactome:R-HSA-9018747 "RHOQ GEFs activate RHOQ"
Reactome:R-HSA-9018768 "RHOU auto-activates"
Reactome:R-HSA-9018804 "RAC3 GEFs activate RAC3"
Reactome:R-HSA-9018817 "RHOT1 GEFs activate RHOT1"
Reactome:R-HSA-9018825 "RHOT2 GEFs activate RHOT2"
Reactome:R-HSA-9026891 "NTRK2 activates RAS signaling through SHC1"
Reactome:R-HSA-9029158 "EPO:phospho-EPOR:phospho-JAK2:LYN:IRS2:phospho-CRKL:RAPGEF1:GRB2-1:SOS1,phospho-VAV1 mediates exchange of GTP for GDP bound to RAS"
Reactome:R-HSA-9032067 "NTRK2 activates RAS signaling through FRS2"
Reactome:R-HSA-9032798 "DOCK3 activates RAC1"
Reactome:R-HSA-9033292 "NTRK2 and CDK5 promote activation of RAC1 by TIAM1"
Reactome:R-HSA-9036301 "ESTG stimulates GTP exchange on GPER:heterotrimeric G-protein s"
Reactome:R-HSA-939265 "Activation of Rap1 by membrane-associated GEFs"
Reactome:R-HSA-9607304 "SOS1-mediated nucleotide exchange of RAS downstream of FLT3"
Reactome:R-HSA-9619803 "p-S516-ARHGEF7 activates RAC1"
Reactome:R-HSA-9624845 "RCC1 stimulates GDP to GTP exchange on RAN"
Reactome:R-HSA-9634418 "RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and ERBB2 homodimer:p-SHC1"
Reactome:R-HSA-9639286 "RRAGC,D exchanges GTP for GDP"
Reactome:R-HSA-9640167 "RRAGA,B exchanges GDP for GTP"
Reactome:R-HSA-9660824 "ADORA2B (in Ade-Rib:ADORA2B:Heterotrimeric G-protein Gs) exchanges GDP for GTP on Gs"
Reactome:R-HSA-9664991 "RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants"
Reactome:R-HSA-9665009 "RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants and EGFR"
Reactome:R-HSA-9665404 "RAS guanyl nucleotide exchange mediated by the p-6Y- ERBB2 ECD mutants:EGF:p-6Y-EGFR:p-SHC1:GRB2:SOS1"
Reactome:R-HSA-9665408 "RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 ECD mutants and EGFR through GRB2"
Reactome:R-HSA-9665700 "RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants"
Reactome:R-HSA-9665707 "RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants and EGFR"
Reactome:R-HSA-9666428 "DOCK180 exchanges GTP for GDP on RAC1:GDP"
Reactome:R-HSA-9666430 "p-VAV1,2,3 exchanges GTP for GDP on RAC1:GDP"
Reactome:R-HSA-9670436 "p-KIT mutants:GRB2:SOS catalyzes nucleotide exchange on RAS"
Reactome:R-HSA-9672163 "SOS-mediated nucleotide exchange on RAS downstream of PDGFRA extracellular domain dimers"
Reactome:R-HSA-9672170 "SOS-mediated nucleotide exchange of RAS downstream of mutant PDGFR receptors"
Reactome:R-HSA-9680385 "CSF1R-associated SOS1 mediates exchange of GTP for GDP bound to RAS"
Reactome:R-HSA-9693111 "RHOF auto-activates"
Reactome:R-HSA-9695853 "FLT3 mutants:GRB2:SOS1-mediated nucleotide exchange on RAS"
Reactome:R-HSA-9703441 "SOS1-mediated nucleotide exchange of RAS downstream of FLT3 fusion mutants"
Reactome:R-HSA-9751201 "p-VAV1,2,3 exchange 6TGTP for GDP on RAC1"