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Gene Review

GUK1  -  guanylate kinase 1

Homo sapiens

Synonyms: GMK, GMP kinase, Guanylate kinase
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Disease relevance of GUK1

  • HGS and GUK1 mRNA expression were chosen to be validated by quantitative RT-qPCR, however, only GUK1 had the differential expression confirmed between the adenomas and the metastasis of a pituitary carcinoma [1].
  • CONCLUSION: This trial demonstrated a significant treatment benefit of HDI versus GMK in terms of RFS and OS in melanoma patients at high risk of recurrence [2].
  • The E2696 trial was undertaken to evaluate the toxicity and other effects of the established adjuvant high-dose IFNalpha2b regimen in relation to immune responses to GMK and to evaluate the potential clinical and immunologic effects of the combined therapies [3].
  • Calorimetric and crystallographic analysis of the oligomeric structure of Escherichia coli GMP kinase [4].
  • A recessive mutation leading to vertebral ankylosis in zebrafish is associated with amino acid alterations in the homologue of the human membrane-associated guanylate kinase DLG3 [5].

High impact information on GUK1

  • Members of the MAGUK (membrane-associated guanylate kinase) protein family, like PSD-95, use multiple domains to cluster ion channels, receptors, adhesion molecules and cytosolic signaling proteins at synapses, cellular junctions, and polarized membrane domains [6].
  • The minute amount of residual activity in erythrocytes could represent a small amount of the AK2 isozyme, which has not been thought to be present in erythrocytes, or the activity of erythrocyte guanylate kinase with AMP substituting as substrate for GMP [7].
  • In hippocampal neurons, altered accumulation of PIP3 by overexpression of GAKIN constructs led to the loss of the axonally differentiated neurites [8].
  • Transport of PIP3 by GAKIN, a kinesin-3 family protein, regulates neuronal cell polarity [8].
  • Recombinant GAKIN and PIP3BP form a complex on synthetic liposomes containing PIP3 and support the motility of the liposomes along microtubules in vitro [8].

Chemical compound and disease context of GUK1


Biological context of GUK1

  • Evidence for the assignment of GUK 1 gene locus to 1q32 leads to q43 segment from gene dosage effect [11].
  • Specifically, the association of the Src homology 3 (SH3) domain and sequences situated between the SH3 and GUK domains with the GUK domain was found to interfere with GKAP binding [12].
  • Screening of a mouse thymus cDNA library yielded CARD11, a membrane-associated guanylate kinase (MAGUK) family member containing CARD, PDZ, SH3 and GUK domains [13].
  • Point mutations in either the putative beta2a SH3 or GK domains severely blunted modulation of recombinant L-type channels, showing the importance of both motifs for a functional alpha1-beta interaction [14].
  • Phosphorylation of the antiviral precursor 9-(1,3-dihydroxy-2-propoxymethyl)guanine monophosphate by guanylate kinase isozymes [15].

Anatomical context of GUK1

  • After 3 days starvation hepatic GMP kinase activity decreased slightly faster than total cytosol protein, while GMP synthetase activity was preferentially maintained [16].
  • The MAGUKs (membrane-associated guanylate kinase homologs) are a family of proteins that act as molecular scaffolds for signaling pathway components at the plasma membrane of animal cells [17].
  • Taken together, these results indicate that Lin-7 functions in tight junction formation by stabilizing its membrane-associated guanylate kinase binding partner PALS1 [18].
  • MAGUKs (membrane-associated guanylate kinase homologs) are proteins involved in cell junction organization, tumor suppression, and signalling [19].
  • Analysis of truncated forms of the PSD-95 indicated that the N-terminal PDZ-containing region localizes to caveolae, but the C-terminal region, containing the SH3 and the guanylate kinase domains does not [20].

Associations of GUK1 with chemical compounds

  • 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 [21].
  • Genetic studies in non-vertebrates assigned two families of basolateral proteins, MAGUK (membrane-associated and guanylate kinase) and LAP (leucine-rich repeats and PDZ) proteins, to a common pathway crucial for the epithelial architecture and acting as a gatekeeper to malignancy [22].
  • The extreme C termini of alternatively spliced "b"-type Ca2+ pump isoforms resemble those of K+ channels and N-methyl-D-aspartate receptor subunits that interact with channel-clustering proteins of the membrane-associated guanylate kinase (MAGUK) family via PDZ domains [23].
  • Mg(2+) binding was considerably enhanced in functional high affinity complexes, such as observed between guanylate kinase and its bisubstrate inhibitor P(1)-(5'-guanosyl)-P(5)-(5'-adenosyl) pentaphosphate or with the tight nucleotide-binding protein p21(ras) and GDP [24].
  • For guanylate kinase (EC 2.7.4. 8), the transfer of HPO(3) between nucleotides was observed whenever a ternary complex with adenylate or guanylate nucleotides was formed [24].

Physical interactions of GUK1


Other interactions of GUK1

  • GUK1 and PEPC, known to be syntenic in man, were found to be asyntenic in MIM and could not be assigned [27].
  • We report the sequence of this human GK (GUK1) and a further refinement of its localization to 1q32-41, placing it in the same interval as USH2A [28].
  • Human discs large (hDlg) protein binds to protein 4.1R via a motif encoded by an alternatively spliced exon located between the SH3 and the C-terminal guanylate kinase-like domains [29].
  • CARMA proteins are scaffold molecules that contain a caspase recruitment domain and a membrane-associated guanylate kinase-like domain [30].
  • MAGI-2 is a multidomain scaffolding protein that contains nine potential protein-protein interaction modules, including 6 PDZ domains, 2 WW domains, and a guanylate kinase-like domain [31].

Analytical, diagnostic and therapeutic context of GUK1


  1. Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) and guanylate kinase 1 (GUK1) are differentially expressed in GH-secreting adenomas. da Rocha, A.A., Giorgi, R.R., de Sa, S.V., Correa-Giannella, M.L., Fortes, M.A., Cavaleiro, A.M., Machado, M.C., Cescato, V.A., Bronstein, M.D., Giannella-Neto, D. Pituitary (2006) [Pubmed]
  2. High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. Kirkwood, J.M., Ibrahim, J.G., Sosman, J.A., Sondak, V.K., Agarwala, S.S., Ernstoff, M.S., Rao, U. J. Clin. Oncol. (2001) [Pubmed]
  3. High-dose interferon alfa-2b does not diminish antibody response to GM2 vaccination in patients with resected melanoma: results of the Multicenter Eastern Cooperative Oncology Group Phase II Trial E2696. Kirkwood, J.M., Ibrahim, J., Lawson, D.H., Atkins, M.B., Agarwala, S.S., Collins, K., Mascari, R., Morrissey, D.M., Chapman, P.B. J. Clin. Oncol. (2001) [Pubmed]
  4. Calorimetric and crystallographic analysis of the oligomeric structure of Escherichia coli GMP kinase. Hible, G., Renault, L., Schaeffer, F., Christova, P., Zoe Radulescu, A., Evrin, C., Gilles, A.M., Cherfils, J. J. Mol. Biol. (2005) [Pubmed]
  5. A recessive mutation leading to vertebral ankylosis in zebrafish is associated with amino acid alterations in the homologue of the human membrane-associated guanylate kinase DLG3. König, C., Yan, Y.L., Postlethwait, J., Wendler, S., Campos-Ortega, J.A. Mech. Dev. (1999) [Pubmed]
  6. Protein modules as organizers of membrane structure. Fanning, A.S., Anderson, J.M. Curr. Opin. Cell Biol. (1999) [Pubmed]
  7. Metabolic compensation for profound erythrocyte adenylate kinase deficiency. A hereditary enzyme defect without hemolytic anemia. Beutler, E., Carson, D., Dannawi, H., Forman, L., Kuhl, W., West, C., Westwood, B. J. Clin. Invest. (1983) [Pubmed]
  8. Transport of PIP3 by GAKIN, a kinesin-3 family protein, regulates neuronal cell polarity. Horiguchi, K., Hanada, T., Fukui, Y., Chishti, A.H. J. Cell Biol. (2006) [Pubmed]
  9. Liposomes for microcompartmentation of enzymes and their influence on catalytic activity. Wichmann, C., Naumann, P.T., Spangenberg, O., Konrad, M., Mayer, F., Hoppert, M. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  10. Phosphorylation of ganciclovir phosphonate by cellular GMP kinase determines the stereoselectivity of anti-human cytomegalovirus activity. Miller, W.H., Beauchamp, L.M., Meade, E., Reardon, J.E., Biron, K.K., Smith, A.A., Goss, C.A., Miller, R.L. Nucleosides Nucleotides Nucleic Acids (2000) [Pubmed]
  11. Evidence for the assignment of GUK 1 gene locus to 1q32 leads to q43 segment from gene dosage effect. Dallapiccola, B., Lungarotti, M.S., Falorni, A., Magnani, M., Dacha, M. Ann. Genet. (1980) [Pubmed]
  12. Intramolecular interactions regulate SAP97 binding to GKAP. Wu, H., Reissner, C., Kuhlendahl, S., Coblentz, B., Reuver, S., Kindler, S., Gundelfinger, E.D., Garner, C.C. EMBO J. (2000) [Pubmed]
  13. CARD11 mediates factor-specific activation of NF-kappaB by the T cell receptor complex. Pomerantz, J.L., Denny, E.M., Baltimore, D. EMBO J. (2002) [Pubmed]
  14. Membrane-associated guanylate kinase-like properties of beta-subunits required for modulation of voltage-dependent Ca2+ channels. Takahashi, S.X., Miriyala, J., Colecraft, H.M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  15. Phosphorylation of the antiviral precursor 9-(1,3-dihydroxy-2-propoxymethyl)guanine monophosphate by guanylate kinase isozymes. Boehme, R.E. J. Biol. Chem. (1984) [Pubmed]
  16. Guanosine-5'-phosphate synthetase and guanosine-5'-phosphate kinase in rat hepatomas and kidney tumors. Boritzki, T.J., Jackson, R.C., Morris, H.P., Weber, G. Biochim. Biophys. Acta (1981) [Pubmed]
  17. Signaling pathways are focused at specialized regions of the plasma membrane by scaffolding proteins of the MAGUK family. Dimitratos, S.D., Woods, D.F., Stathakis, D.G., Bryant, P.J. Bioessays (1999) [Pubmed]
  18. Mammalian lin-7 stabilizes polarity protein complexes. Straight, S.W., Pieczynski, J.N., Whiteman, E.L., Liu, C.J., Margolis, B. J. Biol. Chem. (2006) [Pubmed]
  19. Camguk, Lin-2, and CASK: novel membrane-associated guanylate kinase homologs that also contain CaM kinase domains. Dimitratos, S.D., Woods, D.F., Bryant, P.J. Mech. Dev. (1997) [Pubmed]
  20. The N-terminal PDZ-containing region of postsynaptic density-95 mediates association with caveolar-like lipid domains. Perez, A.S., Bredt, D.S. Neurosci. Lett. (1998) [Pubmed]
  21. GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules. Kim, E., Naisbitt, S., Hsueh, Y.P., Rao, A., Rothschild, A., Craig, A.M., Sheng, M. J. Cell Biol. (1997) [Pubmed]
  22. Lano, a novel LAP protein directly connected to MAGUK proteins in epithelial cells. Saito, H., Santoni, M.J., Arsanto, J.P., Jaulin-Bastard, F., Le Bivic, A., Marchetto, S., Audebert, S., Isnardon, D., Adélaïde, J., Birnbaum, D., Borg, J.P. J. Biol. Chem. (2001) [Pubmed]
  23. Plasma membrane Ca2+ ATPase isoform 4b binds to membrane-associated guanylate kinase (MAGUK) proteins via their PDZ (PSD-95/Dlg/ZO-1) domains. Kim, E., DeMarco, S.J., Marfatia, S.M., Chishti, A.H., Sheng, M., Strehler, E.E. J. Biol. Chem. (1998) [Pubmed]
  24. Binding of nucleotides to guanylate kinase, p21(ras), and nucleoside-diphosphate kinase studied by nano-electrospray mass spectrometry. Prinz, H., Lavie, A., Scheidig, A.J., Spangenberg, O., Konrad, M. J. Biol. Chem. (1999) [Pubmed]
  25. Direct interaction with a kinesin-related motor mediates transport of mammalian discs large tumor suppressor homologue in epithelial cells. Asaba, N., Hanada, T., Takeuchi, A., Chishti, A.H. J. Biol. Chem. (2003) [Pubmed]
  26. Complete genomic organization of the human erythroid p55 gene (MPP1), a membrane-associated guanylate kinase homologue. Kim, A.C., Metzenberg, A.B., Sahr, K.E., Marfatia, S.M., Chishti, A.H. Genomics (1996) [Pubmed]
  27. Gene mapping of Microcebus murinus (Lemuridae): a comparison with man and Cebus capucinus (Cebidae). Cochet, C., Créau-Goldberg, N., Turleau, C., De Grouchy, J. Cytogenet. Cell Genet. (1982) [Pubmed]
  28. Human guanylate kinase (GUK1): cDNA sequence, expression and chromosomal localisation. Fitzgibbon, J., Katsanis, N., Wells, D., Delhanty, J., Vallins, W., Hunt, D.M. FEBS Lett. (1996) [Pubmed]
  29. Protein 4.1-mediated membrane targeting of human discs large in epithelial cells. Hanada, T., Takeuchi, A., Sondarva, G., Chishti, A.H. J. Biol. Chem. (2003) [Pubmed]
  30. Physical and functional interaction of CARMA1 and CARMA3 with Ikappa kinase gamma-NFkappaB essential modulator. Stilo, R., Liguoro, D., Di Jeso, B., Formisano, S., Consiglio, E., Leonardi, A., Vito, P. J. Biol. Chem. (2004) [Pubmed]
  31. beta 1-adrenergic receptor association with the synaptic scaffolding protein membrane-associated guanylate kinase inverted-2 (MAGI-2). Differential regulation of receptor internalization by MAGI-2 and PSD-95. Xu, J., Paquet, M., Lau, A.G., Wood, J.D., Ross, C.A., Hall, R.A. J. Biol. Chem. (2001) [Pubmed]
  32. Potential involvement of galectin-3 and SNAP23 in Aeromonas hydrophila cytotoxic enterotoxin-induced host cell apoptosis. Galindo, C.L., Gutierrez, C., Chopra, A.K. Microb. Pathog. (2006) [Pubmed]
  33. Glycosphingolipids of a green monkey kidney cell line (GMK AH-1). Evidence for a novel pentaglycosylceramide based on globotetraosylceramide. Blomberg, J., Breimer, M.E., Karlsson, K.A. Biochim. Biophys. Acta (1982) [Pubmed]
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