Genomes and Genes
nucleoside phosphate kinase
Summary: An enzyme that catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside monophosphate, e.g., UMP, to form ADP and UDP. Many nucleoside monophosphates can act as acceptor while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 22.214.171.124.
- Van Rompay A, Johansson M, Karlsson A. Phosphorylation of nucleosides and nucleoside analogs by mammalian nucleoside monophosphate kinases. Pharmacol Ther. 2000;87:189-98 pubmed..This overview is focused on the substrate specificity, tissue distribution, and subcellular location of the mammalian monophosphate kinases and their role in the activation of nucleoside and nucleotide analogs. ..
- Dimitratos S, Woods D, Stathakis D, Bryant P. Signaling pathways are focused at specialized regions of the plasma membrane by scaffolding proteins of the MAGUK family. Bioessays. 1999;21:912-21 pubmed..BioEssays 1999;21:912-921. ..
- Woods D, Bryant P. The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions. Cell. 1991;66:451-64 pubmed..The results suggest that a signal transduction process involving guanine nucleotides occurs at the septate junction and is necessary for cell proliferation control in Drosophila epithelia. ..
- Ponting C, Phillips C, Davies K, Blake D. PDZ domains: targeting signalling molecules to sub-membranous sites. Bioessays. 1997;19:469-79 pubmed..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 E, Naisbitt S, Hsueh Y, Rao A, Rothschild A, Craig A, 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 pubmed
- Kim E, Cho K, Rothschild A, Sheng M. Heteromultimerization and NMDA receptor-clustering activity of Chapsyn-110, a member of the PSD-95 family of proteins. Neuron. 1996;17:103-13 pubmed..Thus, chapsyn-110 and PSD-95 may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signalling proteins. ..
- Newton K, Dixit V. Mice lacking the CARD of CARMA1 exhibit defective B lymphocyte development and impaired proliferation of their B and T lymphocytes. Curr Biol. 2003;13:1247-51 pubmed..Thus, CARMA1 has an essential role in mediating B and T lymphocyte proliferation and requires its CARD to engage downstream signaling components. ..
- Niethammer M, Kim E, Sheng M. Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases. J Neurosci. 1996;16:2157-63 pubmed..Members of the PSD-95 family might serve to anchor NMDA receptors to the submembrane cytoskeleton and aid in the assembly of signal transduction complexes at postsynaptic sites. ..
- Tseng T, Marfatia S, Bryant P, Pack S, Zhuang Z, O Brien J, et al. VAM-1: a new member of the MAGUK family binds to human Veli-1 through a conserved domain. Biochim Biophys Acta. 2001;1518:249-59 pubmed..Our results therefore suggest that VAM-1 may function by promoting the assembly of a Veli-1 containing protein complex in neuronal as well as epithelial cells. ..
- Marfatia S, Leu R, Branton D, Chishti A. Identification of the protein 4.1 binding interface on glycophorin C and p55, a homologue of the Drosophila discs-large tumor suppressor protein. J Biol Chem. 1995;270:715-9 pubmed..Our data provide new insights into how protein 4.1, glycophorin C, p55, and their non-erythroid homologues, interact with the cytoskeleton to exert their physiological effects. ..
- Huang S, Tang A, Drisco B, Zhang S, Seeger R, Li C, et al. Human dTMP kinase: gene expression and enzymatic activity coinciding with cell cycle progression and cell growth. DNA Cell Biol. 1994;13:461-71 pubmed..The identification of the human dTMP kinase gene and expression of its product in the baculovirus expression system should facilitate study of the mechanism of gene regulation and its role in pyrimidine metabolism. ..
- Liou J, Dutschman G, Lam W, Jiang Z, Cheng Y. Characterization of human UMP/CMP kinase and its phosphorylation of D- and L-form deoxycytidine analogue monophosphates. Cancer Res. 2002;62:1624-31 pubmed..UMP/CMPK localized predominantly to the cytoplasm. In addition, 196-amino acid UMP/CMPK was the actual form of UMP/CMPK, rather than the 228-amino acid form as suggested before. ..
- Ostermann N, Segura Peña D, Meier C, Veit T, Monnerjahn C, Konrad M, et al. Structures of human thymidylate kinase in complex with prodrugs: implications for the structure-based design of novel compounds. Biochemistry. 2003;42:2568-77 pubmed..Our results show the drastic effects that slight modifications of the substrates exert on the enzyme's conformation and, hence, activity and suggest the type of substitutions that are compatible with efficient phosphorylation by TMPK. ..
- Ruefli Brasse A, French D, Dixit V. Regulation of NF-kappaB-dependent lymphocyte activation and development by paracaspase. Science. 2003;302:1581-4 pubmed..Paracaspase acts downstream of Bcl10 to induce NF-kappaB activation and is required for the normal development of B cells, indicating that paracaspase provides the missing link between Bcl10 and activation of the IkappaB kinase complex. ..
- Berger S, Bulgakova N, Grawe F, Johnson K, Knust E. Unraveling the genetic complexity of Drosophila stardust during photoreceptor morphogenesis and prevention of light-induced degeneration. Genetics. 2007;176:2189-200 pubmed..These results suggest that Stardust-based protein scaffolds are dynamic, which is not only mediated by multiple interaction partners, but in addition by various forms of the Stardust protein itself. ..
- Jun J, Wilson L, Vinuesa C, Lesage S, Blery M, Miosge L, et al. Identifying the MAGUK protein Carma-1 as a central regulator of humoral immune responses and atopy by genome-wide mouse mutagenesis. Immunity. 2003;18:751-62 pubmed..These results define Carma-1 as a key regulator of the plasticity in antigen receptor signaling that underpins opposing mechanisms of immunity and tolerance. ..
- Daniels D, Cohen A, Anderson J, Brunger A. Crystal structure of the hCASK PDZ domain reveals the structural basis of class II PDZ domain target recognition. Nat Struct Biol. 1998;5:317-25 pubmed..The C-terminal carboxylate binding loop of the PDZ domain is structurally conserved in both classes suggesting a generalized carboxylate binding motif (h-Gly-h) where h is a hydrophobic residue. ..
- Cohen A, Woods D, Marfatia S, Walther Z, Chishti A, Anderson J, et al. Human CASK/LIN-2 binds syndecan-2 and protein 4.1 and localizes to the basolateral membrane of epithelial cells. J Cell Biol. 1998;142:129-38 pubmed..1. Like other membrane-associated guanylate kinases, its multidomain structure enables it to act as a scaffold at the membrane, potentially recruiting multiple proteins and coordinating signal transduction. ..
- Dobrosotskaya I, Guy R, James G. MAGI-1, a membrane-associated guanylate kinase with a unique arrangement of protein-protein interaction domains. J Biol Chem. 1997;272:31589-97 pubmed..This distribution, which is reminiscent of that seen for the tight junction protein ZO-1, suggests that MAGI-1 may participate in the transmission of regulatory signals from the cell surface to the nucleus. ..
- Kim S. Tight junctions, membrane-associated guanylate kinases and cell signaling. Curr Opin Cell Biol. 1995;7:641-9 pubmed
- Satoh K, Yanai H, Senda T, Kohu K, Nakamura T, Okumura N, et al. DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95. Genes Cells. 1997;2:415-24 pubmed..Our findings suggest that DAP-1 may play several roles in the molecular organization of synapses and neuronal cell signalling by interacting with hDLG and PSD-95, which in turn are associated with receptors, ion channels and APC. ..
- Dobrosotskaya I, James G. MAGI-1 interacts with beta-catenin and is associated with cell-cell adhesion structures. Biochem Biophys Res Commun. 2000;270:903-9 pubmed..In agreement with this observation, a significant portion of a GFP fusion of MAGI-1b localizes to the basolateral membrane of polarized MDCK cells. ..
- Dimitratos S, Woods D, Bryant P. Camguk, Lin-2, and CASK: novel membrane-associated guanylate kinase homologs that also contain CaM kinase domains. Mech Dev. 1997;63:127-30 pubmed..These new MAGUKs may regulate transmembrane molecules that bind calcium, calmodulin, or nucleotides, camguk (cmg) is a Drosophila member of this novel MAGUK subfamily; we report its sequence and domain structure. ..
- Roh M, Makarova O, Liu C, Shin K, Lee S, Laurinec S, et al. The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost. J Cell Biol. 2002;157:161-72 pubmed..Thus, our data identifies a new multiprotein complex that appears to be evolutionarily conserved and likely plays an important role in protein targeting and cell polarity. ..
- Lee S, Fan S, Makarova O, Straight S, Margolis B. A novel and conserved protein-protein interaction domain of mammalian Lin-2/CASK binds and recruits SAP97 to the lateral surface of epithelia. Mol Cell Biol. 2002;22:1778-91 pubmed..Our data identify evolutionarily conserved protein-protein interaction domains that link mLin-2/CASK to SAP97 and account for their common phenotype when mutated in mice. ..
- Bertin J, Wang L, Guo Y, Jacobson M, Poyet J, Srinivasula S, et al. CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B. J Biol Chem. 2001;276:11877-82 pubmed..These findings suggest that CARD11 and CARD14 are novel MAGUK family members that function as upstream activators of BCL10 and NF-kappaB signaling. ..
- Caruana G. Genetic studies define MAGUK proteins as regulators of epithelial cell polarity. Int J Dev Biol. 2002;46:511-8 pubmed..In addition, our recent genetic analysis of mouse Dlg, in combination with genetic and biochemical studies of Lin-2/CASK by others suggests a model placing Dlg and Lin-2/CASK within the same developmental pathway. ..
- Borg J, Lopez Figueroa M, de Taddèo Borg M, Kroon D, Turner R, Watson S, et al. Molecular analysis of the X11-mLin-2/CASK complex in brain. J Neurosci. 1999;19:1307-16 pubmed..Together, our data demonstrate that the X11alpha-mLin-2 complex contacts many partners, creating a macrocomplex suitable for receptor targeting at the neuronal plasma membrane. ..
- Pochet S, Dugue L, Labesse G, Delepierre M, Munier Lehmann H. Comparative study of purine and pyrimidine nucleoside analogues acting on the thymidylate kinases of Mycobacterium tuberculosis and of humans. Chembiochem. 2003;4:742-7 pubmed..5-Halogenated 2'-deoxyuridines are the best inhibitors of TMPKmt found and present the highest selectivity indexes in favor of TMPKmt. ..
- Kim E, Niethammer M, Rothschild A, Jan Y, Sheng M. Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases. Nature. 1995;378:85-8 pubmed..3) and syntrophin), suggest that PDZ-domain-containing polypeptides may be widely involved in the organization of proteins at sites of membrane specialization. ..
- Bilder D, Schober M, Perrimon N. Integrated activity of PDZ protein complexes regulates epithelial polarity. Nat Cell Biol. 2003;5:53-8 pubmed..Our data suggest a model in which the maturation of epithelial cell polarity is driven by integration of the sequential activities of PDZ-based protein complexes. ..
- Egawa T, Albrecht B, Favier B, Sunshine M, Mirchandani K, O BRIEN W, et al. Requirement for CARMA1 in antigen receptor-induced NF-kappa B activation and lymphocyte proliferation. Curr Biol. 2003;13:1252-8 pubmed..Together, these results show that CARMA1 has a central role in antigen receptor signaling that results in activation and proliferation of both B and T lymphocytes. ..
- Bachmann A, Schneider M, Theilenberg E, Grawe F, Knust E. Drosophila Stardust is a partner of Crumbs in the control of epithelial cell polarity. Nature. 2001;414:638-43 pubmed..The Stardust proteins represent versatile candidates as structural and possibly regulatory constituents of the SAC, a crucial element in the control of epithelial cell polarity. ..
- Colledge M, Dean R, Scott G, Langeberg L, Huganir R, Scott J. Targeting of PKA to glutamate receptors through a MAGUK-AKAP complex. Neuron. 2000;27:107-19 pubmed..As AMPA receptor phosphorylation is implicated in regulating synaptic plasticity, these data suggest that a MAGUK-AKAP complex may be centrally involved. ..
- Vonrhein C, Schlauderer G, Schulz G. Movie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases. Structure. 1995;3:483-90 pubmed
- Scheffzek K, Kliche W, Wiesmuller L, Reinstein J. Crystal structure of the complex of UMP/CMP kinase from Dictyostelium discoideum and the bisubstrate inhibitor P1-(5'-adenosyl) P5-(5'-uridyl) pentaphosphate (UP5A) and Mg2+ at 2.2 A: implications for water-mediated specificity. Biochemistry. 1996;35:9716-27 pubmed..ADP.ADP complex [Müller-Dieckmann & Schulz (1994) J. Mol. Biol. 236, 361-367] suggests that UP5A in our structure mimics an ADP.Mg.UDP biproduct inhibitor rather than an ATP. MG.UMP bisubstrate inhibitor. ..
- Hsueh Y, Kim E, Sheng M. Disulfide-linked head-to-head multimerization in the mechanism of ion channel clustering by PSD-95. Neuron. 1997;18:803-14 pubmed..PSD-95 and its relative chapsyn-110 exist as disulfide-linked complexes in rat brain, consistent with head-to-head multimerization of these proteins in vivo. ..
- Takeuchi M, Hata Y, Hirao K, Toyoda A, Irie M, Takai Y. SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density. J Biol Chem. 1997;272:11943-51 pubmed..SAPAPs induce the enrichment of PSD-95/SAP90 to the plasma membrane in transfected cells. Thus, SAPAPs may have a potential activity to maintain the structure of PSD by concentrating its components to the membrane area. ..
- Munier Lehmann H, Chaffotte A, Pochet S, Labesse G. Thymidylate kinase of Mycobacterium tuberculosis: a chimera sharing properties common to eukaryotic and bacterial enzymes. Protein Sci. 2001;10:1195-205 pubmed
- Segura Peña D, Sekulic N, Ort S, Konrad M, Lavie A. Substrate-induced conformational changes in human UMP/CMP kinase. J Biol Chem. 2004;279:33882-9 pubmed..In addition, a homology model of the human enzyme in the closed state based on the structure of D. discoideum UMP/CMP kinase aids to rationalize the substrate specificity of the human enzyme. ..
- Topalis D, Collinet B, Gasse C, Dugue L, Balzarini J, Pochet S, et al. Substrate specificity of vaccinia virus thymidylate kinase. FEBS J. 2005;272:6254-65 pubmed..Several thymidine and dTMP derivatives were found to bind the enzyme with micromolar affinities. The present study provides the basis for the design of specific inhibitors or substrates for poxvirus TMP kinase. ..
- Kim E, Sheng M. Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases. Neuropharmacology. 1996;35:993-1000 pubmed..4 clustering occurs in > 60% of cotransfected cells, whereas Kv1.1 and Kv1.2 form convincing clusters with PSD-95 only in approximately 10% of cells. ..
- Pasti C, Gallois Montbrun S, Munier Lehmann H, Veron M, Gilles A, Deville Bonne D. Reaction of human UMP-CMP kinase with natural and analog substrates. Eur J Biochem. 2003;270:1784-90 pubmed..Human UMP-CMP kinase has a relaxed enantiospecificity for the nucleoside monophosphate acceptor site, but it is restricted to d-nucleotides at the donor site. ..
- Butz S, Okamoto M, Sudhof T. A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Cell. 1998;94:773-82 pubmed..We propose that the tripartite complex acts as a nucleation site for the assembly of proteins involved in synaptic vesicle exocytosis and synaptic junctions. ..
- Gentry D, Bengra C, Ikehara K, Cashel M. Guanylate kinase of Escherichia coli K-12. J Biol Chem. 1993;268:14316-21 pubmed..These results indicate that, despite extensive sequence similarity to its eukaryotic counterparts, E. coli guanylate kinase is structurally and enzymatically different. ..
- Pochet S, Dugue L, Douguet D, Labesse G, Munier Lehmann H. Nucleoside analogues as inhibitors of thymidylate kinases: possible therapeutic applications. Chembiochem. 2002;3:108-10 pubmed
- Schobert B. Enzymatic synthesis of ATP analogs and their purification by reverse-phase high-performance liquid chromatography. Anal Biochem. 1995;226:288-92 pubmed..After freeze-drying of the pooled fractions, the yield of the synthesized nucleoside triphosphate was approximately 70%. The described procedures are applicable either for analytical investigations or for semi-preparative purposes. ..
- Skinner M, Moore J, Binns M, Smith G, Boursnell M. Deletion of fowlpox virus homologues of vaccinia virus genes between the 3 beta-hydroxysteroid dehydrogenase (A44L) and DNA ligase (A50R) genes. J Gen Virol. 1994;75 ( Pt 9):2495-8 pubmed..Increased 3 beta-HSD activity has been demonstrated in cells infected with either of two different strains of FPV or with canarypox virus...
- McGee A, Nunziato D, Maltez J, Prehoda K, Pitt G, Bredt D. Calcium channel function regulated by the SH3-GK module in beta subunits. Neuron. 2004;42:89-99 pubmed..In MAGUKs, the SH3-GK module controls protein scaffolding. In beta subunits, this module regulates the inactivation of VGCCs and provides an additional mechanism for tuning calcium responsiveness. ..
- Hu C, Chang Z. Synthetic lethality by lentiviral short hairpin RNA silencing of thymidylate kinase and doxorubicin in colon cancer cells regardless of the p53 status. Cancer Res. 2008;68:2831-40 pubmed publisher..Our results suggest the lentiviral delivery of small hairpin RNA targeting TMPK in combination with a low dose of doxorubicin as a new approach to kill colon cancer cells regardless of p53 status. ..
- Gao L, Macara I. Isoforms of the polarity protein par6 have distinct functions. J Biol Chem. 2004;279:41557-62 pubmed..Unexpectedly, the localization of Par6A to cell-cell contacts is Cdc42-independent. ..
- Mayer B. SH3 domains: complexity in moderation. J Cell Sci. 2001;114:1253-63 pubmed..Processes regulated by SH3 domains also raise important questions about the nature of specificity and the overall logic governing networks of protein interactions. ..
- Vanheusden V, Munier Lehmann H, Froeyen M, Dugue L, Heyerick A, De Keukeleire D, et al. 3'-C-branched-chain-substituted nucleosides and nucleotides as potent inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase. J Med Chem. 2003;46:3811-21 pubmed..This series of inhibitors holds promise for the development of a new class of antituberculosis agents. ..
- Yap C, Liang F, Yamazaki Y, Muto Y, Kishida H, Hayashida T, et al. CIP98, a novel PDZ domain protein, is expressed in the central nervous system and interacts with calmodulin-dependent serine kinase. J Neurochem. 2003;85:123-34 pubmed..In view of its direct association with CASK, CIP98 may be involved in the formation of CASK scaffolding proteins complex to facilitate synaptic transmission in the CNS. ..
- Epps D, Sarver R, Rogers J, Herberg J, Tomich P. The ligand affinity of proteins measured by isothermal denaturation kinetics. Anal Biochem. 2001;292:40-50 pubmed
- Larsson M, Hjälm G, Sakwe A, Engström Å, Höglund A, Larsson E, et al. Selective interaction of megalin with postsynaptic density-95 (PSD-95)-like membrane-associated guanylate kinase (MAGUK) proteins. Biochem J. 2003;373:381-91 pubmed..Surface plasmon resonance experiments revealed that mutation of SAP97 Thr(389) to alanine, as with the other PSD-95-like membrane-associated guanylate kinases, induced binding to megalin. ..
- Wollacott A, Desjarlais J. Virtual interaction profiles of proteins. J Mol Biol. 2001;313:317-42 pubmed..Overall, this method can significantly enhance the information contained within a protein- peptide crystal structure, and enrich the data obtained by experimental selection methods such as phage display. ..
- Gasse C, Huteau V, Douguet D, Munier Lehmann H, Pochet S. A new family of inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase. Nucleosides Nucleotides Nucleic Acids. 2007;26:1057-61 pubmed
- Byun Y, Vogel S, Phipps A, Carnrot C, Eriksson S, Tiwari R, et al. Synthesis and biological evaluation of inhibitors of thymidine monophosphate kinase from Bacillus anthracis. Nucleosides Nucleotides Nucleic Acids. 2008;27:244-60 pubmed publisher..Additional studies will be necessary to elucidate the potential of this type of B. anthracis thymidine monophosphate inhibitors as novel antibiotics in the treatment of anthrax. ..
- Shimma Y, Nishikawa A, bin Kassim B, Eto A, Jigami Y. A defect in GTP synthesis affects mannose outer chain elongation in Saccharomyces cerevisiae. Mol Gen Genet. 1997;256:469-80 pubmed