InterPro: IPR020590 Guanylate kinase, conserved site

Guanylate kinase (EC:2.7.4.8) (GK) [1] catalyzes the ATP-dependent phosphorylation of GMP into GDP. It is essential for recycling GMP and indirectly, cGMP. In prokaryotes (such as Escherichia coli), lower eukaryotes (such as yeast) and in vertebrates, GK is a highly conserved monomeric protein of about 200 amino acids. GK has been shown [2, 3, 4] to be structurally similar to protein A57R (or SalG2R) from various strains of Vaccinia virus.

Proteins containing one or more copies of the DHR domain, an SH3 domain as well as a C-terminal GK-like domain, are collectively termed MAGUKs (membrane-associated guanylate kinase homologs) [5], and include Drosophila lethal(1)discs large-1 tumor suppressor protein (gene dlg1); mammalian tight junction protein Zo-1; a family of mammalian synaptic proteins that seem to interact with the cytoplasmic tail of NMDA receptor subunits (SAP90/PSD-95, CHAPSYN-110/PSD-93, SAP97/DLG1 and SAP102); vertebrate 55kDa erythrocyte membrane protein (p55); Caenorhabditis elegans protein lin-2; rat protein CASK; and human proteins DLG2 and DLG3. There is an ATP-binding site (P-loop) in the N-terminal section of GK, which is not conserved in the GK-like domain of the above proteins. However these proteins retain the residues known, in GK, to be involved in the binding of GMP.

This signature pattern covers a highly conserved region that contains two arginine and a tyrosine which are involved in GMP-binding.