Abstract
The GHMP genes family, a unique class of ATP-dependent enzymes, consists of galactokinases, homoserine kinases, mevalonate kinases and phosphomevalonate kinase etc. It was implicated in the biosynthesis of isoprenes and amino acids as well as in carbohydrate metabolism. Previous studies mainly focused on the structure, catalytic mechanism or function in abiotic stress signaling. In this study, we integrated the research progress on GHMP genes and identified 12 members (five previously discovered and seven newly identified here) of this family in Arabidopsis thaliana. The gene ontology, phylogenetic relationship, motifs, cis-acting element, expression profiles, structures and protein–protein interaction network of GHMP family were analyzed. The neighbor-joining tree and cluster of gene structures indicated that the 12 members were divided into two classes. The three motifs in the GHMP family were highly conserved among the GHMP family by Multiple EM for Motif Elicitation, providing further proof on their phylogenetic relationship. Additionally, prediction on cis-acting elements indicated that these genes were likely to be involved in multiple responses stimulated by various hormones and abiotic stress. It is roughly consistent with the data of microarray. The identification and bioinformatic analysis of GHMP family in Arabidopsis thaliana could provide reference data for further study on their biological functions, especially in the responsiveness to hormones and stress signaling.
Similar content being viewed by others
References
Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucl Acids Res 25:3389–33402
Andreassi JL 2nd, Vetting MW, Bilder PW, Roderick SL, Leyh TS (2009) Structure of the ternary complex of phosphomevalonate kinase: the enzyme and its family. Biochemistry 48:6461–6468
Bader GD, Betel D, Hogue CW (2003) BIND: the Biomolecular Interaction Network Database. Nucl Acids Res 31:248–250
Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, Ren J, Li WW, Noble WS (2009) MEME SUITE: tools for motif discovery and searching. Nucl Acids Res 37:W202–W208
Baker D, Sali A (2001) Protein structure prediction and structural genomics. Science 294:93–96
Baloglu MC, Eldem V, Hajyzadeh M, Unver T (2014) Genome-wide analysis of the bZIP transcription factors in cucumber. PLoS ONE 9:e96014
Benkert P, Biasini M, Schwede T (2011) Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics 27:343–350
Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T, Kiefer F, Cassarino TG, Bertoni M, Bordoli L, Schwede T (2014) SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucl Acids Res 42:W252–W258
Bork P, Sander C, Valencia A (1993) Convergent evolution of similar enzymatic function on different protein folds: the hexokinase, ribokinase, and galactokinase families of sugar kinases. Protein Sci 2:31–40
Cao M, Pietras CM, Feng X, Doroschak KJ, Schaffner T, Park J, Zhang H, Cowen LJ, Hescott BJ (2014) New directions for diffusion-based network prediction of protein function: incorporating pathways with confidence. Bioinformatics 30:i219–i227
Daugherty M, Vonstein V, Overbeek R, Osterman A (2001) Archaeal shikimate kinase, a new member of the GHMP-kinase family. J Bacteriol 183:292–300
Diep CQ, Tao X, Pilauri V, Losiewicz M, Blank TE, Hopper JE (2008) Genetic evidence for sites of interaction between the Gal3 and Gal80 proteins of the saccharomyces cerevisiae GAL Gene switch. Genetics 178:725–736
Du Z, Zhou X, Ling Y, Zhang Z, Su Z (2010) agriGO: a GO analysis toolkit for the agricultural community. Nucl Acids Res 38:W64–W70
Egert A, Peters S, Guyot C, Stieger B, Keller F (2012) An Arabidopsis T-DNA insertion mutant for galactokinase (AtGALK, At3g06580) hyperaccumulates free galactose and is insensitive to exogenous galactose. Pl Cell Physiol 53:921–929
Fan C, Bobik TA (2008) The PduX enzyme of Salmonella enterica is an l-threonine kinase used for coenzyme B12 synthesis. J Biol Chem 283:11322–11329
Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, Sonnhammer EL, Tate J, Punta M (2014) Pfam: the protein families database. Nucl Acids Res 42:D222–D230
Foglietti MJ, Percheron F (1976) Purification and mechanism of action of a plant galactokinase. Biochimie 58:499–504
Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, Lin J, Minguez P, Bork P, von Mering C, Jensen LJ (2013) STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucl Acids Res 41:D808–D815
Gangl R, Behmüller R, Tenhaken R (2014) Molecular cloning of a novel glucuronokinase/putative pyrophosphorylase from zebrafish acting in an UDP-glucuronic acid salvage pathway. PLoS ONE 9:e89690
Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins MR, Appel RD, Bairoch A (2005) In: Walker JM (ed) The proteomics protocols handbook. Humana Press, New Jersey
Gopal S, Schroeder M, Pieper U, Sczyrba A, Aytekin-Kurban G, Bekiranov S, Fajardo JE, Eswar N, Sanchez R, Sali A, Gaasterland T (2001) Homology-based annotation yields 1,042 new candidate genes in the Drosophila melanogaster genome. Nat Genet 27:337–340
Grierson I, Lee WR, Albert DM (1999) The fine structure of an iridectomy specimen from a patient with latanoprost-induced eye color change. Arch Ophthalmol 117:394–396
Guex N, Peitsch MC (1997) SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18:2714–2723
Guex N, Peitsch MC, Schwede T (2009) Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: a historical perspective. Electrophoresis 30(Suppl 1):S162–S173
Holden HM, Thoden JB, Timson DJ, Reece RJ (2004) Galactokinase: structure, function and role in type II galactosemia. Cell Molec Life Sci 61:2471–2484
Houten SM, Schneiders MS, Wanders RJ, Waterham HR (2003) Regulation of isoprenoid/cholesterol biosynthesis in cells from mevalonate kinase-deficient patients. J Biol Chem 278:5736–5743
Kanehisa M, Goto S (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucl Acids Res 28:27–30
Kaplan CP, Tugal HB, Baker A (1997) Isolation of a cDNA encoding an Arabidopsis galactokinase by functional expression in yeast. Pl Molec Biol 34:497–506
Kim HJ, Ryu H, Hong SH, Woo HR, Lim PO, Lee IC, Sheen J, Nam HG, Hwang I (2006) Cytokinin-mediated control of leaf longevity by AHK3 through phosphorylation of ARR2 in Arabidopsis. Proc Natl Acad Sci USA 103:814–819
Kyte J, Doolittle RF (1982) A simple method for displaying the hydropathic character of a protein. J Molec Biol 157:105–132
Lavy T, Kumar PR, He H, Joshua-Tor L (2012) The Gal3p transducer of the GAL regulon interacts with the Gal80p repressor in its ligand-induced closed conformation. Genes Developm 26:294–303
Lee M, Leustek T (1999) Identification of the gene encoding homoserine kinase from Arabidopsis thaliana and characterization of the recombinant enzyme derived from the gene. Arch Biochem Biophys 372:135–142
Lee M, Martin MN, Hudson AO, Lee J, Muhitch MJ, Leustek T (2005) Methionine and threonine synthesis are limited by homoserine availability and not the activity of homoserine kinase in Arabidopsis thaliana. Pl J 41:685–696
Lehane AM, Marchetti RV, Spry C, van Schalkwyk DA, Teng R, Kirk K, Saliba KJ (2007) Feedback inhibition of pantothenate kinase regulates pantothenol uptake by the malaria parasite. J Biol Chem 282:25395–25405
Lescot M, Déhais P, Thijs G, Marchal K, Moreau Y, Van de Peer Y, Rouzé P, Rombauts S (2002) PlantCARE, a database of plant cis-acting regulatory elements and a portal to tools for in silico analysis of promoter sequences. Nucl Acids Res 30:325–327
Letunic I, Bork P (2007) Interactive tree of life (iTOL): an online tool for phylogenetic tree display and annotation. Bioinformatics 23:127–128
Li SQ, Xu LL, Chen WH, Xie JH, Ling YZ, Yang ZM (2005) Fusion expression of cell wall-associated kinase 1 and its polyclonal anti-body preparation of Arabidopsis thaliana. Pl Physiol Commun 41:652–654 (in Chinese)
Li LY, Jin MJ, Liu Q, Liu GZ (2008) Function and substrate identification of plant receptor-like kinases. Chin J Biochem Molec Biol 24:113–119 (in Chinese)
Licata L, Briganti L, Peluso D, Perfetto L, Iannuccelli M, Galeota E, Sacco F, Palma A, Nardozza AP, Santonico E, Castagnoli L, Cesareni G (2012) MINT, the molecular interaction database: 2012 update. Nucl Acids Res 40:D857–D861
Liu HY, Toyn JH, Chiang YC, Draper MP, Johnston LH, Denis CL (1997) DBF2, a cell cycle-regulated protein kinase, is physically and functionally associated with the CCR4 transcriptional regulatory complex. EMBO J 16:5289–5298
Liu Z, Lv Y, Zhang M, Liu Y, Kong L, Zou M, Lu G, Cao J, Yu X (2013) Identification, expression, and comparative genomic analysis of the IPT and CKX gene families in Chinese cabbage (Brassica rapa ssp. pekinensis). BMC Genom 14:594
Luz JG, Hassig CA, Pickle C, Godzik A, Meyer BJ, Wilson IA (2003) XOL-1, primary determinant of sexual fate in C. elegans, is a GHMP kinase family member and a structural prototype for a class of developmental regulators. Genes Developm 17:977–990
Mannhaupt G, Pohlenz HD, Seefluth AK, Pilz U, Feldmann H (1990) Yeast homoserine kinase. Characteristics of the corresponding gene, THR1, and the purified enzyme, and evolutionary relationships with other enzymes of threonine metabolism. Eur J Biochem 191:115–122
Nakabayashi K, Okamoto M, Koshiba T, Kamiya Y, Nambara E (2005) Genome-wide profiling of stored mRNA in Arabidopsis thaliana seed germination: epigenetic and genetic regulation of transcription in seed. Pl J 41:697–709
Pieslinger AM, Hoepflinger MC, Tenhaken R (2009) Cloning of Glucuronokinase from Arabidopsis thaliana, the last missing enzyme of the myo-inositol oxygenase pathway to nucleotide sugars. J Biol Chem 285:2902–2910
Platt A, Ross HC, Hankin S, Reece RJ (2000) The insertion of two amino acids into a transcriptional inducer converts it into a galactokinase. Proc Natl Acad Sci USA 97:3154–3159
Remmert M, Biegert A, Hauser A, Söding J (2011) HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment. Nat Methods 9:173–175
Riou C, Tourte Y, Lacroute F, Karst F (1994) Isolation and characterization of a cDNA encoding Arabidopsis thaliana mevalonate kinase by genetic complementation in yeast. Gene 148:293–297
Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Molec Biol Evol 4:406–425
Sali A, Blundell TL (1993) Comparative protein modelling by satisfaction of spatial restraints. J Molec Biol 234:779–815
Sherson S, Gy I, Medd J, Schmidt R, Dean C, Kreis M, Lecharny A, Cobbett C (1999) The arabinose kinase, ARA1, gene of Arabidopsis is a novel member of the galactose kinase gene family. Pl Molec Biol 39:1003–1012
Stark C, Breitkreutz BJ, Reguly T, Boucher L, Breitkreutz A, Tyers M (2006) BioGRID: a general repository for interaction datasets. Nuleic Acids Res 34:D535–D539
Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Molec Biol Evol 28:2731–2739
Thoden JB, Timson DJ, Reece RJ, Holden HM (2005) Molecular structure of human galactokinase: implications for type II galactosemia. J Biol Chem 280:9662–9670
Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucl Acids Res 25:4876–4882
Timson DJ (2007) GHMP Kinases-Structures, Mechanisms and Potential for Therapeutically Relevant Inhibition. Curr Enzyme Inhibition 3:77–94
Tomita H, Yokooji Y, Ishibashi T, Imanaka T, Atomi H (2012) Biochemical characterization of pantoate kinase, a novel enzyme necessary for coenzyme a biosynthesis in the Archaea. J Bacteriol 194:5434–5443
Toufighi K, Brady SM, Austin R, Ly E, Provart NJ (2005) The Botany array resource: e-northerns, expression angling, and promoter analyses. Pl J 43:153–163
Tsay YH, Robinson GW (1991) Cloning and characterization of ERG8, an essential gene of Saccharomyces cerevisiae that encodes phosphomevalonate kinase. Molec Cell Biol 11:620–631
van Damme M, Zeilmaker T, Elberse J, Andel A, de Sain-van der Velden M, van den Ackerveken G (2009) Downy mildew resistance in Arabidopsis by mutation of homoserine kinase. Pl Cell 21:2179–2189
Van Montagu M, Verbruggen N (1999) A highly conserved kinase is an essential component for stress tolerance in yeast and plant cells. Proc Natl Acad Sci USA 96:5873–5877
Vinebrooke RD, Cottingham KL, Norberg J, Scheffer M, Dodson SI, Maberly SC, Sommer U (2004) Impacts of multiple stressors on biodiversity and ecosystem functioning: the role of species co-tolerance. Oikos 104:451–457
von Mering C, Jensen LJ, Snel B, Hooper SD, Krupp M, Foglierini M, Jouffre N, Huynen MA, Bork P (2005) STRING: known and predicted protein-protein associations, integrated and transferred across organisms. Nucl Acids Res 33(Database issue):D433–D437
Voynova NE, Fu Z, Battaile KP, Herdendorf TJ, Kim JJ, Miziorko HM (2008) Human mevalonate diphosphate decarboxylase: characterization, investigation of the mevalonate diphosphate binding site, and crystal structure. Arch Biochem Biophys 480:58–67
Wada T, Kuzuyama T, Satoh S, Kuramitsu S, Yokoyama S, Unzai S, Tame JR, Park SY (2003) Crystal structure of 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase, an enzyme in the non-mevalonate pathway of isoprenoid synthesis. J Biol Chem 278:30022–30027
Xenarios I, Salwínski L, Duan XJ, Higney P, Kim SM, Eisenberg D (2002) DIP, the Database of Interacting Proteins: a research tool for studying cellular networks of protein interactions. Nucl Acids Res 30:303–305
Yang D, Shipman LW, Roessner CA, Scott AI, Sacchettini JC (2002) Structure of the Methanococcus jannaschii mevalonate kinase, a member of the GHMP kinase superfamily. J Biol Chem 277:9462–9467
Yang T, Bar-Peled L, Gebhart L, Lee SG, Bar-Peled M (2009) Identification of galacturonic acid-1-phosphate kinase, a new member of the GHMP kinase superfamily in plants, and comparison with galactose-1-phosphate kinase. J Biol Chem 284:21526–21535
Zhao Q, Yu D, Chang H, Guo X, Yuan C, Hu S, Zhang C, Wang P, Wang Y (2013) Regulation and function of Arabidopsis AtGALK2 gene in abscisic acid response signaling. Molec Bio Rep 40:6605–6612
Zhuang N, Seo KH, Chen C, Zhou J, Kim SW, Lee KH (2012) Crystallization and preliminary X-ray diffraction analysis of mevalonate kinase from Methanosarcina mazei. Acta Crystallogr Sect F Struct Biol Cryst Commun 68:1560–1563
Acknowledgments
This research was supported by Grants from the National Natural Science Foundation of China (31071076, 61472127, 30871325 and 61272395), the Program for New Century Excellent Talents in University (NCET-10-0363 to X. Guo), the Excellent Youth Foundation of Hunan Province (11JJ1005), the Ph.D. Programs Foundation of Ministry of Education of China (20130161110005), Changsha Science and Technology Funds (K1406036-21 to X. Guo), International S&T Cooperation Program of Hunan Province (2014WK3012 to J. Ye, 2015WK to X. Guo), the interdisciplinary research project of Hunan University (2015 to X. Guo), the National Key Technology R&D Program (2012BAH09B02), and the SIT Project of Hunan University, 2013 and 2014.
Author information
Authors and Affiliations
Corresponding authors
Additional information
Handling editor: Martin Lysak.
W. Xiao and H. Chang contributed equally to this work.
Electronic supplementary material
Below is the link to the electronic supplementary material.
606_2015_1219_MOESM1_ESM.jpg
Supplementary material 1 (JPEG 4394 kb) Supplemental Fig. S1 Protein-coding sequences alignment of 12 GHMP genes in Arabidopsis thaliana. The conservative amino acids were highlighted in blue, while the more conservative in red
Rights and permissions
About this article
Cite this article
Xiao, W., Chang, H., Zhou, P. et al. Genome-wide identification, classification and expression analysis of GHMP genes family in Arabidopsis thaliana . Plant Syst Evol 301, 2125–2140 (2015). https://doi.org/10.1007/s00606-015-1219-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00606-015-1219-9