Human herpesvirus 1 (HHV-1) (Human herpes simplex virus 1) glycoprotein K (gK) plays an essential role in viral replication and cell fusion. gK is a very hydrophobic membrane protein that contains a signal sequence and several hydrophobic regions. gK contains three transmembrane domains (amino acids 125-139, 226-239, and 311-325) and another hydrophobic domain (amino acids 241-265), which is relatively less hydrophobic and much longer compared with the transmembrane sequences located in the extracellular loop. The domains may interact with each other to form a complex tertiary structure that is critical for the biological function of gK [].
This entry corresponds to a group of metazoan glycerol kinases (GKs), coded by X chromosome-linked GK genes, and glycerol kinase (GK)-like proteins, coded by autosomal testis-specific GK-like genes GK2, GK3 and Gykl1 (in mouse). These are thought to have arise by the transposition of Gk located on the Xchromosome []. Sequence comparison shows that metazoan GKs and GK-like proteins in this family are closely related to the bacterial GKs, which catalyze the Mg-ATP dependent phosphorylation of glycerol to yield glycerol 3-phosphate (G3P). The metazoan GKs do have GK enzymatic activity. However, the GK-like metazoan proteins do not exhibit GK activity and their biological functions are not yet clear []. Some of them lack important functional residues involved in the binding of ADP and Mg2+, which may result in the loss of GK catalytic function. Others that have conserved catalytic residues have lost their GK activity as well; the reason remains unclear. It has been suggested the conserved catalytic residues might facilitate them performing a distinct function. GK2 seem to be necessary for the formation of the mitochondrial sheath during spermatogenesis [, ].GKs belong to the FGGY family of carbohydrate kinases, the monomers of which contain two large domains, which are separated by a deep cleft that forms the active site [].
Glutamate 5-kinase () (gamma-glutamyl kinase) (GK) is the enzyme that catalyzes the first step in the biosynthesis of proline from glutamate, the ATP-dependent phosphorylation of L-glutamate into L-glutamate 5-phosphate.In eubacteria (gene proB) and yeast [](gene PRO1), GK is a monofunctionalprotein, while in plants and mammals, it is a bifunctional enzyme (P5CS) []that consists of two domains: a N-terminal GK domain and a C-terminal gamma-glutamyl phosphate reductase domain ().This entry represents a highly conserved glycine-and alanine-rich region located in the central section of these enzymes.
The zona occuldens proteins (ZO-1, ZO-2 and ZO-3) are a family of TJ- associated proteins that function as cross-linkers, anchoring the TJ strand proteins to the actin-based cytoskeleton []. Each protein contains three PDZ (postsynaptic density, disc-large, ZO-1) domains, a single SH3 (Src Homology-3) domain and a GK (guanylate kinase) domain, the presence of whichidentifies them as members of the membrane-associated guanylate kinase (MAGUK) protein family. They also share an acidic domain at the C-terminal region of the molecules not found in other MAGUK proteins. It has been demonstrated that the first PDZ domain is involved in binding the C-terminal-Y-V motif of claudins []. By contrast, the occludin-binding domain ofZO-1 has been shown to lie in the GK and acidic domains []. Although the precise location of the actin-binding motif has not been elucidated, it appears to be within the C-terminal half of the molecules, since transfection of this region into fibroblasts induces co-localisation of ZO-1 and ZO-2 with actin fibres.
This entry represents a domain found in guanylate kinase () and in L-type calcium channel.Guanylate kinase () (GK) []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 [, , ]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.
This entry includes a group of metazoan putative glycerol kinases (GK), which may be coded by the GK-like gene, GK5. Sequence comparison shows members of this group are homologues of bacterial GKs, and they retain all functionally important residues. However, GK-like proteins in this family do not have detectable GK activity. The reason remains unclear. It has been suggested that the conserved catalytic residues might facilitate them performing a distinct function. GKs belong to the FGGY family of carbohydrate kinases, the monomers of which contain two large domains, which are separated by a deep cleft that forms the active site [, , , , ].
Guanylate kinase () (GK) []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 [, , ]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 homologues) [], andinclude 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.
The zona occuldens proteins (ZO-1, ZO-2 and ZO-3) are a family of tight junction associated proteins that function as cross-linkers, anchoring the TJ strand proteins to the actin-based cytoskeleton []. Each protein contains three PDZ (postsynaptic density, disc-large, ZO-1) domains, a single SH3 (Src Homology-3) domain and a GK (guanylate kinase) domain, the presence of which identifies them as members of the membrane-associated guanylate kinase (MAGUK) protein family. They also share an acidic domain at the C-terminal region of the molecules not found in other MAGUK proteins. It has been demonstrated that the first PDZ domain is involved in binding the C-terminal -Y-V motif of claudins []. By contrast, the occludin-binding domain of ZO-1 has been shown to lie in the GK and acidic domains []. Although the precise location of the actin-binding motif has not been elucidated, it appears to be within the C-terminal half of the molecules, since transfection of this region into fibroblasts induces co-localisation of ZO-1 and ZO-2 with actin fibres.This entry represents ZO-2, which was first identified as a 160kDa protein that co-immunoprecipitates with ZO-1 []. It shares ~65% overall similarity with ZO-1 and ZO-3 proteins, with highest levels of similarity in the MAGUK and acid domains. In vitro binding studies indicate that ZO-2 may interact directly with ZO-1 through its second PDZ domain, although it does not appear to bind directly to ZO-3.
The zona occuldens proteins (ZO-1, ZO-2 and ZO-3) are a family of tight junction associated proteins that function as cross-linkers, anchoring the TJ strand proteins to the actin-based cytoskeleton []. Each protein contains three PDZ (postsynaptic density, disc-large, ZO-1) domains, a single SH3 (Src Homology-3) domain and a GK (guanylate kinase) domain, the presence of which identifies them as members of the membrane-associated guanylate kinase (MAGUK) protein family. They also share an acidic domain at the C-terminal region of the molecules not found in other MAGUK proteins. It has been demonstrated that the first PDZ domain is involved in binding the C-terminal -Y-V motif of claudins []. By contrast, the occludin-binding domain of ZO-1 has been shown to lie in the GK and acidic domains []. Although the precise location of the actin-binding motif has not been elucidated, it appears to be within the C-terminal half of the molecules, since transfection of this region into fibroblasts induces co-localisation of ZO-1 and ZO-2 with actin fibres.This entry represents ZO-3, which was first identified as a 130kDa protein that co-immunoprecipitates with ZO-1 []. It shares ~65% overall similarity with ZO-1 and ZO-2 proteins, with highest levels of similarity in the MAGUK and acid domains. In vitro binding studies indicate that ZO-3 may interact directly with ZO-1 through its second PDZ domain, although it does not appear to bind directly to ZO-2 [].
This entry represents the SH3 domain of ZO-1.The zona occuldens proteins (ZO-1, ZO-2 and ZO-3) are a family of tight junction associated proteins that function as cross-linkers, anchoring the TJ strand proteins to the actin-based cytoskeleton []. Each protein contains three PDZ (postsynaptic density, disc-large, ZO-1) domains, a single SH3 (Src Homology-3) domain and a catalytically inactive GK (guanylate kinase) domain, the presence of which identifies them as members of the membrane-associated guanylate kinase (MAGUK) protein family. The signature PDZ-SH3-GuK tandem of MAGUKs may form a structural supramodule with three domains interacting with each other to assemble into an integral structural unit [, ]. They also share an acidic domain at the C-terminal region of the molecules not found in other MAGUK proteins. It has been demonstrated that the first PDZ domain is involved in binding the C-terminal -Y-V motif of claudins []. By contrast, the occludin-binding domain of ZO-1 has been shown to lie in the GK and acidic domains []. Although the precise location of the actin-binding motif has not been elucidated, it appears to be within the C-terminal half of the molecules, since transfection of this region into fibroblasts induces co-localisation of ZO-1 and ZO-2 with actin fibres.
This entry represents the SH3 domain of ZO-2.The zona occuldens proteins (ZO-1, ZO-2 and ZO-3) are a family of tight junction associated proteins that function as cross-linkers, anchoring the TJ strand proteins to the actin-based cytoskeleton []. Each protein contains three PDZ (postsynaptic density, disc-large, ZO-1) domains, a single SH3 (Src Homology-3) domain and a catalytically inactive GK (guanylate kinase) domain, the presence of which identifies them as members of the membrane-associated guanylate kinase (MAGUK) protein family. Thesignature PDZ-SH3-GuK tandem of MAGUKs may form a structural supramodule with three domains interacting with each other to assemble into an integral structural unit [, ]. They also share an acidic domain at the C-terminal region of the molecules not found in other MAGUK proteins. It has been demonstrated that the first PDZ domain is involved in binding the C-terminal -Y-V motif of claudins []. By contrast, the occludin-binding domain of ZO-1 has been shown to lie in the GK and acidic domains []. Although the precise location of the actin-binding motif has not been elucidated, it appears to be within the C-terminal half of the molecules, since transfection of this region into fibroblasts induces co-localisation of ZO-1 and ZO-2 with actin fibres.
Guanylate kinase () (GK) []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 [, , ]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 homologues) [], andinclude 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.
Gamma-glutamyl phosphate reductase () (GPR) is the enzyme that catalyses the second step in the biosynthesis of proline from glutamate, the NADP-dependent reduction of L-glutamate 5-phosphate into L-glutamate 5-semialdehyde and phosphate. In bacteria (gene proA) and yeast [](gene PRO2), GPR is a monofunctional protein, while in plants and mammals, it is a bifunctional enzyme (P5CS) []that consists of two domains, an N-terminal glutamate 5-kinase domain () and a C-terminal GPR domain. In humans, the P5CS (ALDH18A1), an inner mitochondrial membrane enzyme, is essential to the de novo synthesis of the amino acids proline and arginine []. Tomato (Lycopersicon esculentum) has both the prokaryotic-like polycistronic operons encoding GK and GPR (PRO1, ALDH19) and the full-length, bifunctional P5CS (PRO2, ALDH18B1) [].This entry represents the C-terminal GPR domain of the gamma-glutamyl phosphate reductase.
The zona occuldens proteins (ZO-1, ZO-2 and ZO-3) are a family of tight junction associated proteins that function as cross-linkers, anchoring the TJ strand proteins to the actin-based cytoskeleton []. Each protein contains three PDZ (postsynaptic density, disc-large, ZO-1) domains, a single SH3 (Src Homology-3) domain and a catalytically inactive GK (guanylate kinase) domain, the presence of which identifies them as members of the membrane-associated guanylate kinase (MAGUK) protein family. The signature PDZ-SH3-GuK tandem of MAGUKs may form a structural supramodule with three domains interacting with each other to assemble into an integral structural unit [, ]. They also share an acidic domain at the C-terminal region of the molecules not found in other MAGUK proteins. It has been demonstrated that the first PDZ domain is involved in binding the C-terminal -Y-V motif of claudins []. By contrast, the occludin-binding domain of ZO-1 has been shown to lie in the GK and acidic domains []. Although the precise location of the actin-binding motif has not been elucidated, it appears to be within the C-terminal half of the molecules, since transfection of this region into fibroblasts induces co-localisation of ZO-1 and ZO-2 with actin fibres.This entry represents ZO-1, which was first identified as a 220kDa antigen for a monoclonal antibody raised to junction-enriched cell fractions []. The protein shares ~65% overall similarity with ZO-2 and ZO-3 proteins, with highest levels of similarity in the MAGUK and acid domains. The structure of ZO-1 is distinct from the other ZO protein family members in that it contains a ZU5 domain at the C-terminal end of the molecule, although the function of this domain is unknown. Binding and tranfection studies indicate that ZO-1 is capable of associating with ZO-2 and ZO-3 through binding of the second PDZ domains [].
