Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTOS63B)

• DTT Name: Rap guanine nucleotide exchange factor 4 (EPAC2)
• Synonyms: cAMP-regulated guanine nucleotide exchange factor II; cAMP-GEFII; Exchange protein directly activated by cAMP 2; Exchange factor directly activated by cAMP 2; EPAC2; EPAC 2; CGEF2
• Gene Name: RAPGEF4
• DTT Type: Literature-reported target; [1]
• UniProt ID: RPGF4_HUMAN
• TTD ID: T74607
• Sequence:
  MVAAHAAHSSSSAEWIACLDKRPLERSSEDVDIIFTRLKEVKAFEKFHPNLLHQICLCGY
  YENLEKGITLFRQGDIGTNWYAVLAGSLDVKVSETSSHQDAVTICTLGIGTAFGESILDN
  TPRHATIVTRESSELLRIEQKDFKALWEKYRQYMAGLLAPPYGVMETGSNNDRIPDKENT
  PLIEPHVPLRPANTITKVPSEKILRAGKILRNAILSRAPHMIRDRKYHLKTYRQCCVGTE
  LVDWMMQQTPCVHSRTQAVGMWQVLLEDGVLNHVDQEHHFQDKYLFYRFLDDEHEDAPLP
  TEEEKKECDEELQDTMLLLSQMGPDAHMRMILRKPPGQRTVDDLEIIYEELLHIKALSHL
  STTVKRELAGVLIFESHAKGGTVLFNQGEEGTSWYIILKGSVNVVIYGKGVVCTLHEGDD
  FGKLALVNDAPRAASIVLREDNCHFLRVDKEDFNRILRDVEANTVRLKEHDQDVLVLEKV
  PAGNRASNQGNSQPQQKYTVMSGTPEKILEHFLETIRLEATLNEATDSVLNDFIMMHCVF
  MPNTQLCPALVAHYHAQPSQGTEQEKMDYALNNKRRVIRLVLQWAAMYGDLLQEDDVSMA
  FLEEFYVSVSDDARMIAALKEQLPELEKIVKQISEDAKAPQKKHKVLLQQFNTGDERAQK
  RQPIRGSDEVLFKVYCMDHTYTTIRVPVATSVKEVISAVADKLGSGEGLIIVKMSSGGEK
  VVLKPNDVSVFTTLTINGRLFACPREQFDSLTPLPEQEGPTVGTVGTFELMSSKDLAYQM
  TIYDWELFNCVHELELIYHTFGRHNFKKTTANLDLFLRRFNEIQFWVVTEICLCSQLSKR
  VQLLKKFIKIAAHCKEYKNLNSFFAIVMGLSNVAVSRLALTWEKLPSKFKKFYAEFESLM
  DPSRNHRAYRLTVAKLEPPLIPFMPLLIKDMTFTHEGNKTFIDNLVNFEKMRMIANTART
  VRYYRSQPFNPDAAQANKNHQDVRSYVRQLNVIDNQRTLSQMSHRLEPRRP
• Function: Guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and RAP2A small GTPases that is activated by binding cAMP. Seems not to activate RAB3A. Involved in cAMP-dependent, PKA-independent exocytosis through interaction with RIMS2 (By similarity).
• KEGG Pathway:
  Rap1 signaling pathway (hsa04015)
  cAMP signaling pathway (hsa04024)
  Phospholipase D signaling pathway (hsa04072)
  Adrenergic signaling in cardiomyocytes (hsa04261)
  Leukocyte transendothelial migration (hsa04670)
  Insulin secretion (hsa04911)
• 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

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ESI-09	DMTJDXY	Discovery agent	N.A.	Investigative	[2]
HJC 0350	DMNI5FW	Discovery agent	N.A.	Investigative	[1]

References

• [1] Identification and characterization of small molecules as potent and specific EPAC2 antagonists. J Med Chem. 2013 Feb 14;56(3):952-62.
• [2] A novel EPAC-specific inhibitor suppresses pancreatic cancer cell migration and invasion. Mol Pharmacol. 2013 Jan;83(1):122-8.