Exchange proteins activated by cyclic AMP (EPACs) | Enzymes | IUPHAR/BPS Guide to IMMUNOPHARMACOLOGY

Home
Targets
Enzymes
Cyclic nucleotide turnover/signalling
Exchange proteins activated by cyclic AMP (EPACs)

Exchange proteins activated by cyclic AMP (EPACs) C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

Show »« Hide

Epacs are members of a family of guanine nucleotide exchange factors (ENSFM00250000000899), which also includes RapGEF5 (GFR, KIAA0277, MR-GEF, Q92565) and RapGEFL1 (Link-GEFII, Q9UHV5). They are activated endogenously by cyclic AMP and with some pharmacological selectivity by 8-pCPT-2'-O-Me-cAMP [4]. Once activated, Epacs induce an enhanced activity of the monomeric G proteins, Rap1 and Rap2 by facilitating binding of guanosine-5'-triphosphate in place of guanosine 5'-diphosphate, leading to activation of phospholipase C [6].

Enzymes

1292

Targets of relevance to immunopharmacology are highlighted in blue

Epac1 (Rap guanine nucleotide exchange factor 3) C Show summary »« Hide summary

Target Id

1292

Nomenclature

Rap guanine nucleotide exchange factor 3

Common abbreviation

Epac1

Previous and unofficial names

Genes

RAPGEF3 (Hs), Rapgef3 (Mm), Rapgef3 (Rn)

Ensembl ID

ENSG00000079337 (Hs), ENSMUSG00000022469 (Mm), ENSRNOG00000059961 (Rn)

UniProtKB AC

O95398 (Hs), Q8VCC8 (Mm), Q9Z1C8 (Rn)

Inhibitors

ESI-09 pIC₅₀ 5.5 [1]

CE3F4

Comment

EPAC1 enhances growth of brown adipose tissue, and is suggested as a molecular target to combat metabolic diseases [5].

Epac2 (Rap guanine nucleotide exchange factor 4) C Show summary »« Hide summary

Target Id

1293

Nomenclature

Rap guanine nucleotide exchange factor 4

Common abbreviation

Epac2

Previous and unofficial names

Genes

RAPGEF4 (Hs), Rapgef4 (Mm), Rapgef4 (Rn)

Ensembl ID

ENSG00000091428 (Hs), ENSMUSG00000049044 (Mm), ENSRNOG00000001516 (Rn)

UniProtKB AC

Q8WZA2 (Hs), Q9EQZ6 (Mm), Q9Z1C7 (Rn)

Inhibitors

HJC 0350 pIC₅₀ 6.5 [2]

ESI-09 pIC₅₀ 4.4 – 5.2 [1,3]

References

Show »« Hide

1. Almahariq M, Tsalkova T, Mei FC, Chen H, Zhou J, Sastry SK, Schwede F, Cheng X. (2013) A novel EPAC-specific inhibitor suppresses pancreatic cancer cell migration and invasion. Mol Pharmacol, 83 (1): 122-8. [PMID:23066090]

2. Chen H, Tsalkova T, Chepurny OG, Mei FC, Holz GG, Cheng X, Zhou J. (2013) Identification and characterization of small molecules as potent and specific EPAC2 antagonists. J Med Chem, 56 (3): 952-62. [PMID:23286832]

3. Chen H, Wild C, Zhou X, Ye N, Cheng X, Zhou J. (2014) Recent advances in the discovery of small molecules targeting exchange proteins directly activated by cAMP (EPAC). J Med Chem, 57 (9): 3651-65. [PMID:24256330]

4. Enserink JM, Christensen AE, de Rooij J, van Triest M, Schwede F, Genieser HG, Døskeland SO, Blank JL, Bos JL. (2002) A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK. Nat Cell Biol, 4 (11): 901-6. [PMID:12402047]

5. Reverte-Salisa L, Siddig S, Hildebrand S, Yao X, Zurkovic J, Jaeckstein MY, Heeren J, Lezoualc'h F, Krahmer N, Pfeifer A. (2024) EPAC1 enhances brown fat growth and beige adipogenesis. Nat Cell Biol, 26 (1): 113-123. [PMID:38195707]

6. Schmidt M, Evellin S, Weernink PA, von Dorp F, Rehmann H, Lomasney JW, Jakobs KH. (2001) A new phospholipase-C-calcium signalling pathway mediated by cyclic AMP and a Rap GTPase. Nat Cell Biol, 3 (11): 1020-4. [PMID:11715024]

How to cite this family page

Database page citation:

Exchange proteins activated by cyclic AMP (EPACs). Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=259.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.