{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:12:17Z","timestamp":1791227537973,"version":"4.1.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2005,3,7]],"date-time":"2005-03-07T00:00:00Z","timestamp":1110153600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2005,3,7]],"date-time":"2005-03-07T00:00:00Z","timestamp":1110153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Genomics"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Background<\/jats:title>\n                        <jats:p>Malaria caused by protozoan parasites of the genus <jats:italic>Plasmodium spp<\/jats:italic>. is a major health burden in tropical countries. The development of new control tools, including vaccines and drugs, is urgently needed. The availability of genome sequences from several malaria parasite species provides a basis on which to identify new potential intervention targets. Database mining for orthologs to the <jats:italic>Plasmodium falciparum<\/jats:italic> trophozoite protein R45, a vaccine candidate, led us identify a new gene family.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Orthologs to the <jats:italic>P. falciparum<\/jats:italic> trophozoite protein R45 were detected exclusively in protozoan parasites of the phylum <jats:italic>Apicomplexa<\/jats:italic>, including several <jats:italic>Plasmodium spp<\/jats:italic>., <jats:italic>Toxoplasma gondii and Cryptosporidium parvum<\/jats:italic>. All family members are hybrid genes with a conserved C-terminal protein kinase domain of a novel type, recently called FIKK kinase, associated with a non conserved N-terminal region without any known functional signature. While a single copy gene was detected in most species, considerable gene expansion was observed in <jats:italic>P. falciparum<\/jats:italic> and its closest phylogenic relative <jats:italic>P. reichenowi<\/jats:italic>, with 20 and six copies, respectively, each with a distinct N-terminal domain. Based on full length protein sequence, pairs of orthologs were observed in closely related species, such as <jats:italic>P. berghei<\/jats:italic> and <jats:italic>P.y. yoelii<\/jats:italic>, <jats:italic>P. vivax<\/jats:italic> and <jats:italic>P. knowlesi<\/jats:italic>, or <jats:italic>P. reichenowi<\/jats:italic> and <jats:italic>P. falciparum<\/jats:italic>. All 20 <jats:italic>P. falciparum<\/jats:italic> paralogs possess a canonical <jats:italic>Plasmodium<\/jats:italic> export element downstream of a signal \/ anchor sequence required for exportation outside the parasitophorous vacuole. This is consistent with the reported association of the trophozoite protein R45, the only paralog characterised to date, with the infected red blood cell membrane. Interestingly, most genes are located in the subtelomeric region of chromosomes, in association with other multigene families contributing to the remodelling of the infected red blood cell membrane, in particular the ring erythrocyte surface antigen multigene family.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>This Apicomplexan-specific gene family was called R45-FIKK kinase. The family hallmark is a kinase domain with unusual characteristics, raising the possibility of designing drug or vaccine strategies targeting this domain. The characteristics of the <jats:italic>P. falciparum<\/jats:italic> family suggest a role in remodelling the infected cell and as such possibly contribute to the particular virulence of this species.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/1471-2164-6-30","type":"journal-article","created":{"date-parts":[[2005,3,8]],"date-time":"2005-03-08T12:49:09Z","timestamp":1110286149000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["A new Apicomplexa-specific protein kinase family : multiple members in Plasmodium falciparum, all with an export signature"],"prefix":"10.1186","volume":"6","author":[{"given":"Achim G","family":"Schneider","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Mercereau-Puijalon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2005,3,7]]},"reference":[{"key":"231_CR1","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/nature01097","volume":"419","author":"MJ Gardner","year":"2002","unstructured":"Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, Carlton JM, Pain A, Nelson KE, Bowman S, Paulsen IT, James K, Eisen JA, Rutherford K, Salzberg SL, Craig A, Kyes S, Chan M-S, Nene V, Shalom SJ, Suh B, Peterson J, Angiuoli S, Pertea M, Allen J, Selengut J, Haft D, Mather MW, Vaidya AB, Martin DMA, Fairlamb AH, Fraunholz MJ, Roos DS, Ralph SA, McFadden GI, Cummings LM, Subramanian GM, Mungall C, Venter JC, Carucci DJ, Hoffman SL, Newbold C, Davis RW, Fraser CM, Barell B: Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 2002, 419: 498-511. 10.1038\/nature01097.","journal-title":"Nature"},{"key":"231_CR2","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1038\/nature01099","volume":"419","author":"JM Carlton","year":"2002","unstructured":"Carlton JM, Angiuoli SV, Suh BB, Kooij TW, Pertea M, Silva JC, Ermolaeva MD, Allen JE, Selengut JD, Koo HL, Peterson JD, Pop M, Kosack DS, Shumway MF, Bidwell SL, Shallom SJ, Van Aken SE, Riedmuller SB, Feldblyum TV, Cho JK, Quackenbush J, Sedegah M, Shoaibi A, Cummings LM, Florens L, Yates JR, Raine JD, Sinden RE, Harris MA, Cunningham DA, Preiser PR, Bergman LW, Vaidya AB, Van Lin LH, Janse CJ, Waters AP, Smith HO, White OR, Salzberg SL, Venter JC, Fraser CM, Hoffman SL, Gardner MJ, Carucci DJ: Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii. Nature. 2002, 419: 512-519. 10.1038\/nature01099.","journal-title":"Nature"},{"key":"231_CR3","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1126\/science.1094786","volume":"304","author":"MS Abrahamsen","year":"2004","unstructured":"Abrahamsen MS, Templeton TJ, Enomoto S, Abrahante JE, Zhu G, Lancto CA, Deng M, Liu C, Widmer G, Tzipori S, Buck GA, Xu P, Bankier AT, Dear PH, Konfortov BA, Spriggs HF, Iyer L, Anantharaman V, Aravind L, Kapur V: Complete genome sequence of the apicomplexan, Cryptosporidium parvum. Science. 2004, 304: 441-445. 10.1126\/science.1094786.","journal-title":"Science"},{"key":"231_CR4","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/0014-4894(92)90206-P","volume":"74","author":"S Bonnefoy","year":"1992","unstructured":"Bonnefoy S, Guillotte M, Langsley G, Mercereau-Puijalon O: Plasmodium falciparum: characterization of gene R45 encoding a trophozoite antigen containing a central block of six amino acid repeats. Exp Parasitol. 1992, 74: 441-451. 10.1016\/0014-4894(92)90206-P.","journal-title":"Exp Parasitol"},{"key":"231_CR5","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/0022-1759(93)90159-5","volume":"159","author":"J Gysin","year":"1993","unstructured":"Gysin J, Gavoille S, Mattei D, Scherf A, Bonnefoy S, Mercereau-Puijalon O, Feldmann T, M\u00fcller-Hill B, Pereira da Silva L: In vitro phagocytosis inhibition assay for thre screening of potential candidates antigens for subunit vaccines against asexual blood atage of Plasmodium falciparum. Journal of Immunological Methods. 1993, 159: 209-219. 10.1016\/0022-1759(93)90159-5.","journal-title":"Journal of Immunological Methods"},{"key":"231_CR6","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1128\/iai.63.2.554-562.1995","volume":"63","author":"R Perraut","year":"1995","unstructured":"Perraut R, Mercereau-Puijalon O, Mattei D, Bourreau E, Garraud O, Bonnemains B, Pereira da Silva L, Michel JC: Induction of opsonizing antibodies after injection of recombinant Plasmodium falciparum vaccine candidate antigens in preimmune Saimiri sciureus monkeys. Infection & Immunity. 1995, 63: 554-562.","journal-title":"Infection & Immunity"},{"key":"231_CR7","doi-asserted-by":"crossref","first-page":"343","DOI":"10.4269\/ajtmh.1997.56.343","volume":"56","author":"R Perraut","year":"1997","unstructured":"Perraut R, Mercereau-Puijalon O, Mattei D, Bourreau E, Bonnefoy S, Bonnemains B, Gysin J, Michel JC, Pereira da Silva L: Immunogenicity and efficacy trials with Plasmodium falciparum recombinant antigens identified as targets of opsonizing antibodies in the naive squirrel monkey Saimiri sciureus. Am J Trop Med Hyg. 1997, 56: 343-350.","journal-title":"Am J Trop Med Hyg"},{"key":"231_CR8","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/S0264-410X(00)00158-4","volume":"19","author":"R Perraut","year":"2001","unstructured":"Perraut R, Morales-Betoulle S, Le Scanf C, Bourreau E, Guillotte M, Michel JC, Mercereau-Puijalon : Evaluation of immunogenicity and protective efficacy of carrier-free Plasmodium falciparum R23 antigen in pre-exposed saimiri sciureus monkeys. Vaccine. 2001, 19: 59-67. 10.1016\/S0264-410X(00)00158-4.","journal-title":"Vaccine"},{"key":"231_CR9","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.1086\/379838","volume":"188","author":"R Perraut","year":"2003","unstructured":"Perraut R, Marrama L, Diouf B, Fontenille D, Tall A, Sokhna C, Trape JF, Garraud O, Mercereau-Puijalon O: Distinct surrogate markers for protection against Plasmodium falciparum infection and clinical malaria identified in a Senegalese community after radical drug cure. J Infect Dis. 2003, 188: 1940-1950. 10.1086\/379838.","journal-title":"J Infect Dis"},{"key":"231_CR10","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.jmb.2004.05.028","volume":"340","author":"JD Bendtsen","year":"2004","unstructured":"Bendtsen JD, Nielsen H, von Heijne G, Brunak S: Improved prediction of signal peptides: SignalP 3.0. J Mol Biol. 2004, 340: 783-795. 10.1016\/j.jmb.2004.05.028.","journal-title":"J Mol Biol"},{"key":"231_CR11","doi-asserted-by":"publisher","first-page":"4673","DOI":"10.1093\/nar\/22.22.4673","volume":"22","author":"JD Thompson","year":"1994","unstructured":"Thompson JD, Higgins DG, Gibson TJ: CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994, 22: 4673-4680.","journal-title":"Nucleic Acids Res"},{"key":"231_CR12","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1096\/fasebj.9.8.7768349","volume":"9","author":"SK Hanks","year":"1995","unstructured":"Hanks SK, Hunter T: Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J. 1995, 9: 576-596.","journal-title":"FASEB J"},{"key":"231_CR13","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1016\/j.str.2003.09.020","volume":"11","author":"S Holton","year":"2003","unstructured":"Holton S, Merckx A, Burgess D, Doerig C, Noble M, Endicott J: Structures of P. falciparum PfPK5 test the CDK regulation paradigm and suggest mechanisms of small molecule inhibition. Structure (Camb). 2003, 11: 1329-1337. 10.1016\/j.str.2003.09.020.","journal-title":"Structure (Camb)"},{"key":"231_CR14","first-page":"406","volume":"4","author":"N Saitou","year":"1987","unstructured":"Saitou N, Nei M: The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987, 4: 406-425.","journal-title":"Mol Biol Evol"},{"key":"231_CR15","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1146\/annurev.ge.22.120188.002513","volume":"22","author":"J Felsenstein","year":"1988","unstructured":"Felsenstein J: Phylogenies from molecular sequences: inference and reliability. Annu Rev Genet. 1988, 22: 521-565. 10.1146\/annurev.ge.22.120188.002513. Review","journal-title":"Annu Rev Genet"},{"key":"231_CR16","doi-asserted-by":"publisher","first-page":"E5","DOI":"10.1371\/journal.pbio.0000005","volume":"1","author":"Z Bozdech","year":"2003","unstructured":"Bozdech Z, Llinas M, Pulliam BL, Wong ED, Zhu J, Derisi JL: The Transcriptome of the Intraerythrocytic Developmental Cycle of Plasmodium falciparum. PLoS Biol. 2003, 1: E5-10.1371\/journal.pbio.0000005.","journal-title":"PLoS Biol"},{"key":"231_CR17","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1126\/science.1087025","volume":"301","author":"KG Le Roch","year":"2003","unstructured":"Le Roch KG, Zhou Y, Blair PL, Grainger M, Moch JK, Haynes JD, De La Vega P, Holder AA, Batalov S, Carucci DJ, Winzeler EA: Discovery of gene function by expression profiling of the malaria parasite life cycle. Science. 2003, 301: 1503-1508. 10.1126\/science.1087025.","journal-title":"Science"},{"key":"231_CR18","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1046\/j.1365-2958.2000.01788.x","volume":"35","author":"E Bischoff","year":"2000","unstructured":"Bischoff E, Guillotte M, Mercereau-Puijalon O, Bonnefoy S: A member of the of a Pf60 gene from the Pf60\/var Plasmodium falciparum multigene family codes for a nuclear protein expressed by readthrough of internal stop codon. Mol Microbiol. 2000, 35: 1005-1016. 10.1046\/j.1365-2958.2000.01788.x.","journal-title":"Mol Microbiol"},{"key":"231_CR19","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/1471-2164-5-79","volume":"5","author":"P Ward","year":"2004","unstructured":"Ward P, Equinet L, Packer J, Doerig C: Protein kinases of the human malaria parasite Plasmodium falciparum: the kinome of a divergent eukaryote. BMC Genomics. 2004, 5: 79-10.1186\/1471-2164-5-79.","journal-title":"BMC Genomics"},{"key":"231_CR20","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1126\/science.1102737","volume":"306","author":"NL Hiller","year":"2004","unstructured":"Hiller NL, Bhattacharjee S, van Ooij C, Liolios K, Harrison T, Lopez-Estrano , Haldar K: A host-targeting signal in virulence proteins reveals a secretome in malarial infection. Science. 2004, 306: 1934-1937. 10.1126\/science.1102737.","journal-title":"Science"},{"key":"231_CR21","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1126\/science.1102452","volume":"306","author":"M Marti","year":"2004","unstructured":"Marti M, Good RT, Rug M, Knuepfer E, Cowman A: Targeting malaria virulence and remodelling proteins to the host erythrocyte. Science. 2004, 306: 1930-1933. 10.1126\/science.1102452.","journal-title":"Science"},{"key":"231_CR22","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.bbapap.2003.11.021","volume":"1697","author":"C Doerig","year":"2004","unstructured":"Doerig C: Protein kinases as targets for anti-parasitic chemotherapy. Biochim Biophys Acta. 2004, 1697: 155-168.","journal-title":"Biochim Biophys Acta"},{"key":"231_CR23","doi-asserted-by":"publisher","first-page":"11373","DOI":"10.1073\/pnas.91.24.11373","volume":"91","author":"AA Escalante","year":"1994","unstructured":"Escalante AA, Ayala FJ: Phylogeny of the malarial genus Plasmodium, derived from rRNA gene sequences. Proceedings of the National Academy of Sciences of the United States of America. 1994, 91: 11373-11377.","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"231_CR24","first-page":"616","volume":"12","author":"AA Escalante","year":"1995","unstructured":"Escalante AA, Barrio E, Ayala FJ: Evolutionary origin of human and primate malarias: evidence from the circumsporozoite protein gene. Mol Biol Evol. 1995, 12: 616-626.","journal-title":"Mol Biol Evol"},{"key":"231_CR25","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1038\/nature01107","volume":"419","author":"L Florens","year":"2002","unstructured":"Florens L, Washburn MP, Raine JD, Anthony RM, Grainger M, Haynes JD, Moch JK, Muster N, Sacci JB, Tabb DL, Whitney AA, Wolters D, Wu Y, Gardner MJ, Holder AA, Sinden RE, Yates JR, Carucci DJ: A proteomic view of the Plasmodium falciparum life cycle. Nature. 2002, 419: 520-526. 10.1038\/nature01107.","journal-title":"Nature"},{"key":"231_CR26","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/35071118","volume":"410","author":"HA del Portillo","year":"2001","unstructured":"del Portillo HA, Fernandez-Beccera C, Bowman S, Oliver K, Preuss M, Sanchez CP, Schneider NK, Villalobos JM, Rajandream MA, Pereira da Silva LH, Barrell B, Lanzer M: A superfamily of variant genes encoded in the subtelomeric region of Plasmodium vivax. Nature. 2001, 410: 839-842. 10.1038\/35071118.","journal-title":"Nature"}],"container-title":["BMC Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2164-6-30.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/1471-2164-6-30\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2164-6-30.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T12:54:36Z","timestamp":1728305676000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcgenomics.biomedcentral.com\/articles\/10.1186\/1471-2164-6-30"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3,7]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2005,12]]}},"alternative-id":["231"],"URL":"https:\/\/doi.org\/10.1186\/1471-2164-6-30","relation":{},"ISSN":["1471-2164"],"issn-type":[{"value":"1471-2164","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,3,7]]},"assertion":[{"value":"22 September 2004","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2005","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2005","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"30"}}