Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTOE7I0)

• DTT Name: Rap guanine nucleotide exchange factor 3 (RAPGEF3)
• Synonyms: Exchange factor directly activated by cAMP 1; Exchange protein directly activated by cAMP 1; EPAC 1; Rap1 guanine-nucleotide-exchange factor directly activated by cAMP; cAMP-regulated guanine nucleotide exchange factor I; cAMP-GEFI
• Gene Name: RAPGEF3
• DTT Type: Clinical trial target; [1]
• UniProt ID: RPGF3_HUMAN
• TTD ID: T52489
• Sequence:
  MKVGWPGESCWQVGLAVEDSPALGAPRVGALPDVVPEGTLLNMVLRRMHRPRSCSYQLLL
  EHQRPSCIQGLRWTPLTNSEESLDFSESLEQASTERVLRAGRQLHRHLLATCPNLIRDRK
  YHLRLYRQCCSGRELVDGILALGLGVHSRSQVVGICQVLLDEGALCHVKHDWAFQDRDAQ
  FYRFPGPEPEPVRTHEMEEELAEAVALLSQRGPDALLTVALRKPPGQRTDEELDLIFEEL
  LHIKAVAHLSNSVKRELAAVLLFEPHSKAGTVLFSQGDKGTSWYIIWKGSVNVVTHGKGL
  VTTLHEGDDFGQLALVNDAPRAATIILREDNCHFLRVDKQDFNRIIKDVEAKTMRLEEHG
  KVVLVLERASQGAGPSRPPTPGRNRYTVMSGTPEKILELLLEAMGPDSSAHDPTETFLSD
  FLLTHRVFMPSAQLCAALLHHFHVEPAGGSEQERSTYVCNKRQQILRLVSQWVALYGSML
  HTDPVATSFLQKLSDLVGRDTRLSNLLREQWPERRRCHRLENGCGNASPQMKARNLPVWL
  PNQDEPLPGSSCAIQVGDKVPYDICRPDHSVLTLQLPVTASVREVMAALAQEDGWTKGQV
  LVKVNSAGDAIGLQPDARGVATSLGLNERLFVVNPQEVHELIPHPDQLGPTVGSAEGLDL
  VSAKDLAGQLTDHDWSLFNSIHQVELIHYVLGPQHLRDVTTANLERFMRRFNELQYWVAT
  ELCLCPVPGPRAQLLRKFIKLAAHLKEQKNLNSFFAVMFGLSNSAISRLAHTWERLPHKV
  RKLYSALERLLDPSWNHRVYRLALAKLSPPVIPFMPLLLKDMTFIHEGNHTLVENLINFE
  KMRMMARAARMLHHCRSHNPVPLSPLRSRVSHLHEDSQVARISTCSEQSLSTRSPASTWA
  YVQQLKVIDNQRELSRLSRELEP
• Function: Guanine nucleotide exchange factor (GEF) for RAP1A and RAP2A small GTPases that is activated by binding cAMP. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which it activates the PI3K gamma complex and which is involved in angiogenesis. Plays a role in the modulation of the cAMP-induced dynamic control of endothelial barrier function through a pathway that is independent on Rho-mediated signaling. Required for the actin rearrangement at cell-cell junctions, such as stress fibers and junctional actin.
• KEGG Pathway:
  Rap1 signaling pathway (hsa04015)
  cAMP signaling pathway (hsa04024)
  Phospholipase D signaling pathway (hsa04072)
  Adrenergic signaling in cardiomyocytes (hsa04261)
  Leukocyte transendothelial migration (hsa04670)
  Long-term potentiation (hsa04720)
  Serotonergic synapse (hsa04726)
• Reactome Pathway:
  Glucagon-like Peptide-1 (GLP1) regulates insulin secretion (R-HSA-381676)
  Rap1 signalling (R-HSA-392517)
  Regulation of insulin secretion (R-HSA-422356)
  Integrin signaling (R-HSA-354192)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AM001	DM9UMSJ	Actinic keratosis	EK90.0	Phase 2	[1]

References

• [1] Identification of a pharmacological inhibitor of Epac1 that protects the heart against acute and chronic models of cardiac stress. Cardiovasc Res. 2019 Oct 1;115(12):1766-1777.