SMART: GuKc domain annotation

GuKc Guanylate kinase homologues.

SMART accession number:	SM00072
Description:	Active enzymes catalyze ATP-dependent phosphorylation of GMP to GDP. Structure resembles that of adenylate kinase. So-called membrane-associated guanylate kinase homologues (MAGUKs) do not possess guanylate kinase activities; instead at least some possess protein-binding functions.
Interpro abstract (IPR008145):	This entry represents a domain found in guanylate kinase ( EC 2.7.4.8 ) and in L-type calcium channel. Guanylate kinase ( EC 2.7.4.8 ) (GK) [ (PUBMED:1314905) ] 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 [ (PUBMED:1310897) (PUBMED:8097461) (PUBMED:1329277) ] to be structurally similar to protein A57R (or SalG2R) from various strains of Vaccinia virus. L-type calcium channnels are formed from different alpha-1 subunit isoforms that determine the pharmacological properties of the channel, since they form the drug binding domain. Other properties, such as gating voltage-dependence, G protein modulation and kinase susceptibility, are influenced by alpha-2, delta and beta subunits.
Family alignment:	View or

There are 42084 GuKc domains in 42042 proteins in SMART's nrdb database.

Click on the following links for more information.

Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing GuKc domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with GuKc domain is also avaliable.

Click on the protein counts, or double click on taxonomic names to display all proteins containing GuKc domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Kawabe H, Hata Y, Takeuchi M, Ide N, Mizoguchi A, Takai Y
- nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP).
- J Biol Chem. 1999; 274: 30914-8
- Display abstract
- Postsynaptic density (PSD)-95/synapse-associated protein (SAP) 90 and synaptic scaffolding molecule (S-SCAM) are synaptic membrane-associated guanylate kinases. Both the proteins interact with SAP90/PSD-95-associated protein (SAPAP) (also called guanylate kinase-associated protein/Dlg-associated protein). SAPAP is a protein highly enriched in the PSD fraction and may link PSD-95/SAP90 and S-SCAM to Triton X-100-insoluble structures. We found here a novel SAPAP-interacting protein, which was specifically expressed in neural tissue and was present in the postsynaptic density fraction in brain. This protein had a sorbin homology domain in the N terminus, a zinc finger motif in the middle region, and three src homology (SH) 3 domains in the C terminus and was homologous to the ponsin/ArgBP2/vinexin family proteins. We named this protein nArgBP2 because it was the most homologous to ArgBP2. nArgBP2 is a neural member of a growing family of SH3-containing proteins. nArgBP2 bound to the proline-rich region of SAPAP via its third SH3 domain and was coimmunoprecipitated with SAPAP from the extract of rat brain. Furthermore, nArgBP2 was colocalized with SAPAP at synapses in cerebellum. nArgBP2 bound to not only SAPAP but also vinculin and l-afadin, known to bind to ponsin and vinexin. nArgBP2 may be implicated in the protein network around SAPAP in the PSD.
- Kuhlendahl S, Spangenberg O, Konrad M, Kim E, Garner CC
- Functional analysis of the guanylate kinase-like domain in the synapse-associated protein SAP97.
- Eur J Biochem. 1998; 252: 305-13
- Display abstract
- SAP97 is a membrane cytoskeletal protein localized at the presynaptic nerve terminals of type 1 asymmetric synapses. It has been implicated in the assembly of synapses and in particular in the localization and clustering of ion channels. The C-terminal GK domain of SAP97 shares a high degree of sequence similarity with low-molecular-mass guanylate kinases. These enzymes are involved in the guanine nucleotide metabolic cycle and in the maintenance of GTP/GDP pools required for example in Ras-mediated cell signaling. It has therefore been hypothesized that SAP97 plays an essential role in cellular signaling by regulating the guanine nucleotide pools at synaptic junctions. Here, we test this hypothesis by assessing whether the GK domain in SAP97 encodes an authentic guanylate kinase. We show that the GK domain in and of itself does not encode an active guanylate kinase, that it cannot be activated by its binding partner GKAP and that flanking regions are not acting as inhibitory regulators for enzymatic activity. Thus, it would appear that the GK domain of SAP97 is not involved in the metabolism of guanine nucleotides required for signaling events.
- Rizo J, Sudhof TC
- C2-domains, structure and function of a universal Ca2+-binding domain.
- J Biol Chem. 1998; 273: 15879-82
- Kim E et al.
- GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules.
- J Cell Biol. 1997; 136: 669-78
- Display abstract
- The molecular mechanisms underlying the organization of ion channels and signaling molecules at the synaptic junction are largely unknown. Recently, members of the PSD-95/SAP90 family of synaptic MAGUK (membrane-associated guanylate kinase) proteins have been shown to interact, via their NH2-terminal PDZ domains, with certain ion channels (NMDA receptors and K+ channels), thereby promoting the clustering of these proteins. Although the function of the NH2-terminal PDZ domains is relatively well characterized, the function of the Src homology 3 (SH3) domain and the guanylate kinase-like (GK) domain in the COOH-terminal half of PSD-95 has remained obscure. We now report the isolation of a novel synaptic protein, termed GKAP for guanylate kinase-associated protein, that binds directly to the GK domain of the four known members of the mammalian PSD-95 family. GKAP shows a unique domain structure and appears to be a major constituent of the postsynaptic density. GKAP colocalizes and coimmunoprecipitates with PSD-95 in vivo, and coclusters with PSD-95 and K+ channels/NMDA receptors in heterologous cells. Given their apparent lack of guanylate kinase enzymatic activity, the fact that the GK domain can act as a site for protein-protein interaction has implications for the function of diverse GK-containing proteins (such as p55, ZO-1, and LIN-2/CASK).
- Ponting CP, Phillips C, Davies KE, Blake DJ
- PDZ domains: targeting signalling molecules to sub-membranous sites.
- Bioessays. 1997; 19: 469-79
- Display abstract
- PDZ (also called DHR or GLGF) domains are found in diverse membrane-associated proteins including members of the MAGUK family of guanylate kinase homologues, several protein phosphatases and kinases, neuronal nitric oxide synthase, and several dystrophin-associated proteins, collectively known as syntrophins. Many PDZ domain-containing proteins appear to be localised to highly specialised submembranous sites, suggesting their participation in cellular junction formation, receptor or channel clustering, and intracellular signalling events. PDZ domains of several MAGUKs interact with the C-terminal polypeptides of a subset of NMDA receptor subunits and/or with Shaker-type K+ channels. Other PDZ domains have been shown to bind similar ligands of other transmembrane receptors. Recently, the crystal structures of PDZ domains, with and without ligand, have been determined. These demonstrate the mode of ligand-binding and the structural bases for sequence conservation among diverse PDZ domains.
- Kim SK
- Tight junctions, membrane-associated guanylate kinases and cell signaling.
- Curr Opin Cell Biol. 1995; 7: 641-9
- Display abstract
- Proteins that define a new family, termed membrane-associated guanylate kinases, have recently been identified as structural components of epithelial tight junctions and neuronal synapses, and as cell signaling proteins in Drosophila and Caenorhabditis elegans. In particular, the lin-2 gene has been shown to encode a membrane-associated guanylate kinase and to act in the let-23 receptor tyrosine kinase/let-60 ras signaling pathway that controls vulval induction in C. elegans. The combined data from recent biochemical and genetic analyses of membrane-associated guanylate kinases suggest that certain tight junction proteins can play an important role in cell signaling pathways. One possibility is that asymmetric segregation of signaling receptors to the basolateral membrane domain of polarized epithelial cells is crucial for proper cell signaling, and that membrane-associated guanylate kinases may be required for this localization.
- Stehle T, Schulz GE
- Three-dimensional structure of the complex of guanylate kinase from yeast with its substrate GMP.
- J Mol Biol. 1990; 211: 249-54
- Display abstract
- The enzyme guanylate kinase was isolated from baker's yeast and crystallized as a complex with its substrate GMP. The crystal structure was solved by multiple isomorphous replacement, solvent-flattening, restrained least-squares refinement, and simulated annealing. The current R-factor is 28.9% at a resolution of 2.0 A. The model is given as a backbone tracing, the GMP binding site is shown in atomic detail. In its major domain (residues 1 to 32 and 82 to 186), the chain fold is closely similar to the adenylate kinases, while the minor domain (residues 33 to 81) differs grossly from the 3-helix fold of the adenylate kinases. Structural homology and mechanistical similarity allow us to assign the AMP site of the adenylate kinases on the basis of the GMP site.
Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

3D Structures of GuKc domains in PDB

PDB code	Main view	Title
1ex6		CRYSTAL STRUCTURE OF UNLIGANDED FORM OF GUANYLATE KINASE FROM YEAST
1ex7		CRYSTAL STRUCTURE OF YEAST GUANYLATE KINASE IN COMPLEX WITH GUANOSINE-5'-MONOPHOSPHATE
1gky		REFINED STRUCTURE OF THE COMPLEX BETWEEN GUANYLATE KINASE AND ITS SUBSTRATE GMP AT 2.0 ANGSTROMS RESOLUTION
1jxm		CRYSTAL STRUCTURE OF THE GMP BOUND SH3-HOOK-GK FRAGMENT OF PSD-95
1jxo		Crystal Structure of the SH3-HOOK-GK Fragment of PSD-95
1kgd		Crystal Structure of the Guanylate Kinase-like Domain of Human CASK
1kjw		SH3-Guanylate Kinase Module from PSD-95
1lvg		Crystal structure of mouse guanylate kinase in complex with GMP and ADP
1s4q		Crystal Structure of Guanylate Kinase from Mycobacterium tuberculosis (Rv1389)
1s96		The 2.0 A X-ray structure of Guanylate Kinase from E.coli
1t0h		Crystal structure of the Rattus norvegicus voltage gated calcium channel beta subunit isoform 2a
1t0j		Crystal structure of a complex between voltage-gated calcium channel beta2a subunit and a peptide of the alpha1c subunit
1t3l		Structural Analysis of the Voltage-Dependent Calcium Channel Beta Subunit Functional Core in Complex with Alpha1 Interaction Domain
1t3s		Structural Analysis of the Voltage-Dependent Calcium Channel Beta Subunit Functional Core
1vyt		beta3 subunit complexed with aid
1vyu		Beta3 subunit of Voltage-gated Ca2+-channel
1vyv		beta4 subunit of Ca2+ channel
1z6g		Crystal structure of guanylate kinase from Plasmodium falciparum
1z8f		Guanylate Kinase Double Mutant A58C, T157C from Mycobacterium tuberculosis (Rv1389)
1znw		Crystal Structure Of Unliganded Form Of Mycobacterium tuberculosis Guanylate Kinase
1znx		Crystal Structure Of Mycobacterium tuberculosis Guanylate Kinase In Complex With GMP
1zny		Crystal Structure Of Mycobacterium tuberculosis Guanylate Kinase In Complex With GDP
1znz		Crystal Structure Of The Reduced Form Of Mycobacterium tuberculosis Guanylate Kinase In Complex With GDP
2an9		Crystal Structure Of Oligomeric E.coli Guanylate Kinase In Complex With GDP
2anb		Crystal Structure Of Oligomeric E.coli Guanylate Kinase In Complex With GMP
2anc		Crystal Structure Of Unliganded Form Of Oligomeric E.coli Guanylate Kinase
2f3r		Crystal Structure Of E.coli Guanylate Kinase In Complex With Ap5G
2f3t		Crystal Structure Of E.coli Guanylate Kinase In Complex With Ganciclovir monophosphate
2j41		Crystal structure of Staphylococcus aureus guanylate monophosphate kinase
2qor		Crystal structure of Plasmodium vivax guanylate kinase
2xkx		Single particle analysis of PSD-95 in negative stain
3jbr		3JBR
3kfv		Crystal structure of the SH3-kinase fragment of tight junction protein 3 (TJP3) in apo-form
3lh5		Crystal Structure of the SH3-Guanylate kinase core domain of ZO-1
3lnc		Crystal structure of guanylate kinase from Anaplasma phagocytophilum
3ney		Crystal structure of the kinase domain of MPP1/p55
3shw		Crystal structure of ZO-1 PDZ3-SH3-Guk supramodule complex with Connexin-45 peptide
3tau		Crystal Structure of a Putative Guanylate Monophosphaste Kinase from Listeria monocytogenes EGD-e
3tr0		Structure of guanylate kinase (gmk) from Coxiella burnetii
3tsw		crystal structure of the PDZ3-SH3-GUK core module of Human ZO-1
3tsz		crystal structure of PDZ3-SH3-GUK core module from human ZO-1 in complex with 12mer peptide from human JAM-A cytoplasmic tail
3tvt		Structural basis for Discs Large interaction with Pins
3uat		Guanylate Kinase Domains of the MAGUK Family Scaffold Proteins as Specific Phospho-Protein Binding Modules
3w9y		Crystal structure of the human DLG1 guanylate kinase domain
3wp0		Crystal structure of Dlg GK in complex with a phosphor-Lgl2 peptide
3wp1		Phosphorylation-dependent interaction between tumor suppressors Dlg and Lgl
4dex		Crystal structure of the Voltage Dependent Calcium Channel beta-2 Subunit in Complex With The CaV2.2 I-II Linker.
4dey		Crystal structure of the Voltage Dependent Calcium Channel beta-2 Subunit in Complex With The CaV1.2 I-II Linker.
4f4j		Conversion of the enzyme guanylate kinase into a mitotic spindle orienting protein by a single mutation that inhibits gmp- induced closing
4qrh		4QRH
4wsi		4WSI
4zw2		4ZW2
5b64		5B64
5gjv		5GJV
5gjw		5GJW

Links (links to other resources describing this domain)
PROSITE GuKc_DOMAIN
INTERPRO IPR008145

PROSITE	GuKc_DOMAIN
INTERPRO	IPR008145

GuKc

Taxonomic distribution of proteins containing GuKc domain.

3D Structures of GuKc domains in PDB