This superfamily comprises nucleotide cyclase structural domains, specifically a catalytic domain found in adenylate and guanylate cyclases. It has a ferredoxin-like fold with additional secondary structures, and is often known as the GGDEF domain, named after the conserved central sequence pattern GG[DE][DE]F. Though the fold of the GGDEF domain is similar to adenylate cyclase, the nucleotide-binding mode is substantially different PMID:15569936. It is typically present in multidomain proteins containing regulatory domains of signalling pathways or protein-protein or protein-ligand interaction modules, such as the response regulatory domain, the PAS/PAC domain, the HAMP domain, the GAF domain, the FHA domain or the TPR repeat. However a few single-domain proteins are also known. The GGDEF domain is involved in signal transduction and is likely to catalyse synthesis or hydrolysis of cyclic diguanylate (c-diGMP, bis(3',5')-cyclic diguanylic acid), an effector molecule that consists of two cGMP moieties bound head-to-tail.

PFAM:PF00211, INTERPRO:IPR029787, INTERPRO:IPR000160,PMID:11557134,PMID:11682196,PMID:11682196