G2Cdb::Gene report

Gene id
Gene symbol
Homo sapiens
adenylate kinase 1
G00000443 (Mus musculus)

Databases (8)

Curated Gene
OTTHUMG00000020722 (Vega human gene)
ENSG00000106992 (Ensembl human gene)
203 (Entrez Gene)
805 (G2Cdb plasticity & disease)
AK1 (GeneCards)
103000 (OMIM)
Marker Symbol
Protein Sequence
P00568 (UniProt)

Literature (24)

Pubmed - other

  • Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.

    Martins-de-Souza D, Gattaz WF, Schmitt A, Rewerts C, Maccarrone G, Dias-Neto E and Turck CW

    Laboratório de Neurociências, Instituto de Psiquiatria, Universidade de São Paulo, Rua. Dr. Ovidio Pires de Campos, no 785, Consolação, São Paulo, SP 05403-010, Brazil.

    Schizophrenia is a complex disease, likely to be caused by a combination of serial alterations in a number of genes and environmental factors. The dorsolateral prefrontal cortex (Brodmann's Area 46) is involved in schizophrenia and executes high-level functions such as working memory, differentiation of conflicting thoughts, determination of right and wrong concepts and attitudes, correct social behavior and personality expression. Global proteomic analysis of post-mortem dorsolateral prefrontal cortex samples from schizophrenia patients and non-schizophrenic individuals was performed using stable isotope labeling and shotgun proteomics. The analysis resulted in the identification of 1,261 proteins, 84 of which showed statistically significant differential expression, reinforcing previous data supporting the involvement of the immune system, calcium homeostasis, cytoskeleton assembly, and energy metabolism in schizophrenia. In addition a number of new potential markers were found that may contribute to the understanding of the pathogenesis of this complex disease.

    European archives of psychiatry and clinical neuroscience 2009;259;3;151-63

  • Smoking and human reproduction: the effect of adenylate kinase genetic polymorphism.

    Gloria-Bottini F, Magrini A, Pietropolli A, Bergamaschi A and Bottini E

    Department of Biopathology and Imaging Diagnostics, University of Rome Tor Vergata, School of Medicine, Rome, Italy. gloria@med.uniroma2.it

    We investigated the possible influence of adenylate kinase genetic variability on the effect of maternal smoking on intrauterine selection and development. Adenylate kinase locus 1 belongs to a family of monophosphate kinases that plays an important role in the synthesis of nucleotides involved in several metabolic functions. Three hundred forty-five newborn consecutive infants from the Caucasian population of Rome and 360 consecutive infants from the Caucasian population of Penne were studied. The proportion of newborns carrying AK1*2 allele was analyzed in relation to smoking and maternal age. The effect of smoking on birth weight was also analyzed in relation to AK1 phenotype and maternal age. Statistical analyses have been performed according to SPSS programs. In offspring of women aged 28 years or less, the proportion of newborns carrying the AK1*2 allele is much higher in smoking than in nonsmoking mothers (13.2% versus 2.6%). Such association is lacking in mothers aged more than 28 years (6.5% versus 9.2%). The negative effects of smoke on birth weight is more marked in AK11 mothers than in AK1*2 carriers. The data suggest that zygotes carrying AK1*2 allele are relatively protected from the damaging effects of smoking, resulting in a relatively higher proportion of newborns carrying this allele among smoking mothers.

    American journal of perinatology 2009;26;2;117-21

  • Acyclic phosphonate nucleotides and human adenylate kinases: impact of a borano group on alpha-P position.

    Topalis D, Alvarez K, Barral K, Munier-Lehmann H, Schneider B, Véron M, Guerreiro C, Mulard L, El-Amri C, Canard B and Deville-Bonne D

    Laboratoire d'Enzymologie, Université Paris, Paris, France.

    Adenylate kinases are involved in the activation of antiviral drugs such as the acyclic phosphonates analogs PMEA and (R)PMPA. We examine the in vitro phosphorylation of PMEA and PMPA bearing a borano- or a H- group on the phosphorus atom. The alpha-borano or alpha-H on PMEA and PMPA were detrimental to the activity of recombinant human AMP kinases 1 and 2. Docking PMEA to the active site of AMP kinase 1 indicated that the borano group may prevent two conserved critical Arg interactions with the alpha-phosphate, resulting in substrate bad positioning.

    Nucleosides, nucleotides & nucleic acids 2008;27;4;319-31

  • Toward a confocal subcellular atlas of the human proteome.

    Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, Asplund A, Pontén F, Brismar H, Uhlén M and Andersson-Svahn H

    Department of Biotechnology, AlbaNova University Center, Royal Institute of Technology, SE-106 91 Stockholm, Sweden.

    Information on protein localization on the subcellular level is important to map and characterize the proteome and to better understand cellular functions of proteins. Here we report on a pilot study of 466 proteins in three human cell lines aimed to allow large scale confocal microscopy analysis using protein-specific antibodies. Approximately 3000 high resolution images were generated, and more than 80% of the analyzed proteins could be classified in one or multiple subcellular compartment(s). The localizations of the proteins showed, in many cases, good agreement with the Gene Ontology localization prediction model. This is the first large scale antibody-based study to localize proteins into subcellular compartments using antibodies and confocal microscopy. The results suggest that this approach might be a valuable tool in conjunction with predictive models for protein localization.

    Molecular & cellular proteomics : MCP 2008;7;3;499-508

  • Large-scale mapping of human protein-protein interactions by mass spectrometry.

    Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T and Figeys D

    Protana, Toronto, Ontario, Canada.

    Mapping protein-protein interactions is an invaluable tool for understanding protein function. Here, we report the first large-scale study of protein-protein interactions in human cells using a mass spectrometry-based approach. The study maps protein interactions for 338 bait proteins that were selected based on known or suspected disease and functional associations. Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24,540 potential protein interactions. False positives and redundant hits were filtered out using empirical criteria and a calculated interaction confidence score, producing a data set of 6463 interactions between 2235 distinct proteins. This data set was further cross-validated using previously published and predicted human protein interactions. In-depth mining of the data set shows that it represents a valuable source of novel protein-protein interactions with relevance to human diseases. In addition, via our preliminary analysis, we report many novel protein interactions and pathway associations.

    Molecular systems biology 2007;3;89

  • Ectoadenylate kinase and plasma membrane ATP synthase activities of human vascular endothelial cells.

    Quillen EE, Haslam GC, Samra HS, Amani-Taleshi D, Knight JA, Wyatt DE, Bishop SC, Colvert KK, Richter ML and Kitos PA

    Department of Molecular Biosciences, Kansas University, Lawrence, 66045-7534, USA.

    Formation of ATP from ADP on the external surface of vascular endothelial cells has been attributed to plasma membrane ATP synthase, ectoadenylate kinase (ecto-AK), and/or ectonucleoside diphosphokinase. These enzymes or their catalytic products have been causatively linked to the elaboration of vascular networks and the regulation of capillary function. The amount of ATP generated extracellularly is small, requiring sensitive analytical methods for quantification. Human umbilical vein endothelial cells were used to revisit extracellular ATP synthesis using a reliable tetrazolium reduction assay and multiwell plate cultures. Test conditions compatible with AK stability were established. Extracellular AK activity was found to be <1% of the total (intracellular and extracellular), raising the possibility that the external enzyme could have leaked from living cells and/or a few dying cells. To determine whether AK inadvertently leaked from the cells, the activity of another cytoplasmic enzyme, glucose-6-phosphate dehydrogenase (G6PD), was also measured. G6PD is present in the cytoplasm in similar abundance to AK. The activity ratio of G6PD (extracellular/total) was found to be similar to that of AK. Because G6PD in the medium was probably due to leakage, other cytoplasmic macromolecules, including AK, should be released proportionately from the cells. The role of plasma membrane ATP synthase in extracellular ATP formation was examined using Hanks' balanced salt solution with and without selective inhibitors of AK and ATP synthase activities. With P(1),P(5)-di(adenosine 5')-pentaphosphate (inhibitor of AK activity), no extracellular ATP synthesis was detected, whereas with oligomycin, piceatannol, and aurovertin (inhibitors of F(1)F(0)-ATP synthase and F(1)-ATPase activities), no inhibition of extracellular ATP synthesis was observed. AK activity alone could account for the observed extracellular ATP synthesis. The possible impact of ADP impurity in the assays is discussed.

    The Journal of biological chemistry 2006;281;30;20728-37

  • Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.

    Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T and Sugano S

    Life Science Research Laboratory, Central Research Laboratory, Hitachi, Ltd., Kokubunji, Tokyo, 185-8601, Japan.

    By analyzing 1,780,295 5'-end sequences of human full-length cDNAs derived from 164 kinds of oligo-cap cDNA libraries, we identified 269,774 independent positions of transcriptional start sites (TSSs) for 14,628 human RefSeq genes. These TSSs were clustered into 30,964 clusters that were separated from each other by more than 500 bp and thus are very likely to constitute mutually distinct alternative promoters. To our surprise, at least 7674 (52%) human RefSeq genes were subject to regulation by putative alternative promoters (PAPs). On average, there were 3.1 PAPs per gene, with the composition of one CpG-island-containing promoter per 2.6 CpG-less promoters. In 17% of the PAP-containing loci, tissue-specific use of the PAPs was observed. The richest tissue sources of the tissue-specific PAPs were testis and brain. It was also intriguing that the PAP-containing promoters were enriched in the genes encoding signal transduction-related proteins and were rarer in the genes encoding extracellular proteins, possibly reflecting the varied functional requirement for and the restricted expression of those categories of genes, respectively. The patterns of the first exons were highly diverse as well. On average, there were 7.7 different splicing types of first exons per locus partly produced by the PAPs, suggesting that a wide variety of transcripts can be achieved by this mechanism. Our findings suggest that use of alternate promoters and consequent alternative use of first exons should play a pivotal role in generating the complexity required for the highly elaborated molecular systems in humans.

    Genome research 2006;16;1;55-65

  • The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

    Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Morrin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J and MGC Project Team

    The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

    Funded by: PHS HHS: N01-C0-12400

    Genome research 2004;14;10B;2121-7

  • Red cell adenylate kinase deficiency: molecular study of 3 new mutations (118G>A, 190G>A, and GAC deletion) associated with hereditary nonspherocytic hemolytic anemia.

    Corrons JL, Garcia E, Tusell JJ, Varughese KI, West C and Beutler E

    Red Cell Patholology Unit, ICMHO-IDIBAPS, Hospital Clinic i Provincial, Villarroel 170, 08036-Barcelona, Spain. jlvives@medicina.ub.es

    We report here 2 patients with chronic nonspherocytic hemolytic anemia (CNSHA) and severe red blood cell (RBC) adenylate kinase (AK) deficiency. One of these patients, a boy of Spanish origin, exhibited a neonatal icterus and splenomegaly and required blood transfusions until the age of 2 years. The other patient was a white, American infant born to parents who were first cousins; he also presented with neonatal icterus and anemia. In neither case was psychomotor impairment observed. The first patient was found to be a compound heterozygote for 2 different missense mutations, 118G>A(Gly40Arg) and 190G>A(Gly64Arg) (cDNA sequence first described by Matsuura et al, 1989). The second patient was homozygous for an in-frame deletion (GAC) from nucleotide (nt) 498 to 500 or nt 501 to 503 of the cDNA sequence, predicting deletion of either aspartic acid (Asp) 140 or 141. The crystal structure of porcine cytosolic AK was used as a molecular model to investigate how these mutations may affect enzyme structure and function.

    Funded by: NCRR NIH HHS: RR 00833; NHLBI NIH HHS: HL 0555375, HL 25552, HL 55375

    Blood 2003;102;1;353-6

  • Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2.

    Lange S, Auerbach D, McLoughlin P, Perriard E, Schäfer BW, Perriard JC and Ehler E

    Institute of Cell Biology, ETH Hönggerberg, 8093 Zurich, Switzerland.

    During sarcomere contraction skeletal and cardiac muscle cells consume large amounts of energy. To satisfy this demand, metabolic enzymes are associated with distinct regions of the sarcomeres in the I-band and in the M-band, where they help to maintain high local concentrations of ATP. To date, the mechanism by which metabolic enzymes are coupled to the sarcomere has not been elucidated. Here, we show that the four and a half LIM-only protein DRAL/FHL-2 mediates targeting of the metabolic enzymes creatine kinase, adenylate kinase and phosphofructokinase by interaction with the elastic filament protein titin in cardiomyocytes. Using yeast two-hybrid assays, colocalisation experiments, co-immunoprecipitation and protein pull-down assays, we show that DRAL/FHL-2 is bound to two distinct sites on titin. One binding site is situated in the N2B region, a cardiac-specific insertion in the I-band part of titin, and the other is located in the is2 region of M-band titin. We also show that DRAL/FHL-2 binds to the metabolic enzymes creatine kinase, adenylate kinase and phosphofructokinase and might target these enzymes to the N2B and is2 regions in titin. We propose that DRAL/FHL-2 acts as a specific adaptor protein to couple metabolic enzymes to sites of high energy consumption in the cardiac sarcomere.

    Journal of cell science 2002;115;Pt 24;4925-36

  • Adenylate kinase AK1 knockout heart: energetics and functional performance under ischemia-reperfusion.

    Pucar D, Bast P, Gumina RJ, Lim L, Drahl C, Juranic N, Macura S, Janssen E, Wieringa B, Terzic A and Dzeja PP

    Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic and Foundation, Rochester, MN 55905, USA.

    Deletion of the major adenylate kinase AK1 isoform, which catalyzes adenine nucleotide exchange, disrupts cellular energetic economy and compromises metabolic signal transduction. However, the consequences of deleting the AK1 gene on cardiac energetic dynamics and performance in the setting of ischemia-reperfusion have not been determined. Here, at the onset of ischemia, AK1 knockout mice hearts displayed accelerated loss of contractile force compared with wild-type controls, indicating reduced tolerance to ischemic stress. On reperfusion, AK1 knockout hearts demonstrated reduced nucleotide salvage, resulting in lower ATP, GTP, ADP, and GDP levels and an altered metabolic steady state associated with diminished ATP-to-P(i) and creatine phosphate-to-P(i) ratios. Postischemic AK1 knockout hearts maintained approximately 40% of beta-phosphoryl turnover, suggesting increased phosphotransfer flux through remaining adenylate kinase isoforms. This was associated with sustained creatine kinase flux and elevated cellular glucose-6-phosphate levels as the cellular energetic system adapted to deletion of AK1. Such metabolic rearrangements, along with sustained ATP-to-ADP ratio and total ATP turnover rate, maintained postischemic contractile recovery of AK1 knockout hearts at wild-type levels. Thus deletion of the AK1 gene reveals that adenylate kinase phosphotransfer supports myocardial function on initiation of ischemic stress and safeguards intracellular nucleotide pools in postischemic recovery.

    Funded by: NHLBI NIH HHS: HL 64822

    American journal of physiology. Heart and circulatory physiology 2002;283;2;H776-82

  • wt p53 dependent expression of a membrane-associated isoform of adenylate kinase.

    Collavin L, Lazarevic D, Utrera R, Marzinotto S, Monte M and Schneider C

    Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, AREA Science Park, Padriciano 99, 34012 Trieste, Italy.

    Six novel p53-inducible transcripts were recently cloned from Val5, a murine cell line stably expressing a temperature-sensitive p53 allele. One of the isolated clones represented a novel isoform of cytosolic adenylate kinase (AK1), a highly conserved monomeric enzyme involved in cellular homeostasis of adenine nucleotides. The corresponding protein, which we named AK1beta, was specifically induced upon activation of wt p53 in Val5 cells. The AK1beta protein differs from cytoplasmic AK1 by having 18 extra amino acids at the N-terminus. The extra residues in AK1beta provide a consensus signal for N-terminal myristoylation; as expected, AK1beta was shown to localize to the plasma membrane. The human AK1 gene contains several consensus p53 binding sites and we report that p53-dependent induction of the alternative AK1beta transcript also occurs in human cells. By using antisense ablation experiments in Val5 fibroblasts we show that AK1beta plays a relevant role in the establishment of reversible cell-cycle arrest as induced by p53 in these cells. These findings suggest that within a p53-dependent genetic program, a specific isoform of adenylate kinase has a previously undescribed growth-regulatory function, which might not necessarily require its best characterized biochemical activity.

    Oncogene 1999;18;43;5879-88

  • A case of complete adenylate kinase deficiency due to a nonsense mutation in AK-1 gene (Arg 107 --> Stop, CGA --> TGA) associated with chronic haemolytic anaemia.

    Bianchi P, Zappa M, Bredi E, Vercellati C, Pelissero G, Barraco F and Zanella A

    Divisione di Ematologia, IRCCS Ospedale Maggiore, Milano, Italy.

    Two siblings of Italian origin with mild chronic haemolytic anaemia, psychomotor impairment and undetectable adenylate kinase (AK) activity are reported. The other red cell enzyme activities were normal except for a slight decrease of PFK. 2,3-DPG levels were increased in both siblings, and AMP decreased in one only. The parents were not consanguineous and displayed intermediate AK activity. The sequence of complete erythrocyte AK-1 cDNA showed the presence of a nonsense homozygous mutation at codon 107 (CGA --> TGA, Arg --> Stop) in the siblings. The mutation results in a truncated protein of 107 amino acids in comparison with the 194 of the normal one. Moreover a 37 bp deletion in the first part of exon 6 (from nt 326 to nt 362 of the cDNA sequence) was detected in one allele; this deletion is not likely to further affect the enzyme structure, being localized after the stop codon. The new variant was named AK Fidenza, from the origin of the patients.

    British journal of haematology 1999;105;1;75-9

  • Cloning and expression of human adenylate kinase 2 isozymes: differential expression of adenylate kinase 1 and 2 in human muscle tissues.

    Lee Y, Kim JW, Lee SM, Kim HJ, Lee KS, Park C and Choe IS

    Molecular and Cellular Biology Research Division, Korea Research Institute of Bioscience and Biotechnology, Taejon.

    A cDNA clone coding for adenylate kinase 2B was isolated from fetal liver, and the expression of AK2 was investigated in human tissues. The ORF in the cDNA clone for human AK2B predicted a protein comprising 232 amino acids (25.6 kDa). The features of AK2A and AK2B sequences in human were the same as those in the bovine system. Each of the recombinant proteins, AK2A and AK2B, was expressed in Escherichia coli cells, and the purified recombinant proteins were enzymatically active. The distribution of AK2 transcripts in various human tissues was examined by Northern analysis. Unlike in the bovine system, it was found that the AK2A transcript was the major form of AK2 mRNA species in all human tissues. The transcripts of AK2 isozymes were relatively abundant in heart, liver, and also in skeletal muscle, where the expression level of AK2 was known to be low. Western blot analysis of AK isozymes in human heart and skeletal muscle revealed that AK2 protein was found only in heart, whereas AK1 was detected in both tissues. These tissue-specific expressions of the AK isozymes in human might suggest the presence of organ-specific regulation of the AK2 gene including a post-transcriptional control in skeletal muscle.

    Journal of biochemistry 1998;123;1;47-54

  • Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.

    Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A and Sugano S

    International and Interdisciplinary Studies, The University of Tokyo, Japan.

    Using 'oligo-capped' mRNA [Maruyama, K., Sugano, S., 1994. Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 138, 171-174], whose cap structure was replaced by a synthetic oligonucleotide, we constructed two types of cDNA library. One is a 'full length-enriched cDNA library' which has a high content of full-length cDNA clones and the other is a '5'-end-enriched cDNA library', which has a high content of cDNA clones with their mRNA start sites. The 5'-end-enriched library was constructed especially for isolating the mRNA start sites of long mRNAs. In order to characterize these libraries, we performed one-pass sequencing of randomly selected cDNA clones from both libraries (84 clones for the full length-enriched cDNA library and 159 clones for the 5'-end-enriched cDNA library). The cDNA clones of the polypeptide chain elongation factor 1 alpha were most frequently (nine clones) isolated, and more than 80% of them (eight clones) contained the mRNA start site of the gene. Furthermore, about 80% of the cDNA clones of both libraries whose sequence matched with known genes had the known 5' ends or sequences upstream of the known 5' ends (28 out of 35 for the full length-enriched library and 51 out of 62 for the 5'-end-enriched library). The longest full-length clone of the full length-enriched cDNA library was about 3300 bp (among 28 clones). In contrast, seven clones (out of the 51 clones with the mRNA start sites) from the 5'-end-enriched cDNA library came from mRNAs whose length is more than 3500 bp. These cDNA libraries may be useful for generating 5' ESTs with the information of the mRNA start sites that are now scarce in the EST database.

    Gene 1997;200;1-2;149-56

  • Congenital haemolytic anaemia associated with adenylate kinase deficiency.

    Toren A, Brok-Simoni F, Ben-Bassat I, Holtzman F, Mandel M, Neumann Y, Ramot B, Rechavi G and Kende G

    Institute of Haematology, Chaim Sheba Medical Centre, Tel-Aviv University, Israel.

    Chronic haemolytic anaemia associated with adenylate kinase (AK) deficiency is very rare and only seven cases in five families have been described. We present six children of one family who are deficient of this enzyme and in three of them a combined G6PD deficiency was found. AK deficiency was transmitted by an autosomal recessive gene and heterozygous state was not accompanied by disease, whereas homozygously affected individuals present a congenital chronic non-spherocytic haemolytic anaemia with haemoglobin levels of 8-9 g/dl. Patients also deficient in G6PD suffer from a more severe haemolytic anaemia with haemoglobin levels around 6 g/dl. The AK-deficient children are also mentally retarded. Splenectomy performed in five of the six patients resulted in complete remission of the haemolytic process.

    British journal of haematology 1994;87;2;376-80

  • Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.

    Maruyama K and Sugano S

    Institute of Medical Science, University of Tokyo, Japan.

    We have devised a method to replace the cap structure of a mRNA with an oligoribonucleotide (r-oligo) to label the 5' end of eukaryotic mRNAs. The method consists of removing the cap with tobacco acid pyrophosphatase (TAP) and ligating r-oligos to decapped mRNAs with T4 RNA ligase. This reaction was made cap-specific by removing 5'-phosphates of non-capped RNAs with alkaline phosphatase prior to TAP treatment. Unlike the conventional methods that label the 5' end of cDNAs, this method specifically labels the capped end of the mRNAs with a synthetic r-oligo prior to first-strand cDNA synthesis. The 5' end of the mRNA was identified quite simply by reverse transcription-polymerase chain reaction (RT-PCR).

    Gene 1994;138;1-2;171-4

  • Human adenylate kinase deficiency associated with hemolytic anemia. A single base substitution affecting solubility and catalytic activity of the cytosolic adenylate kinase.

    Matsuura S, Igarashi M, Tanizawa Y, Yamada M, Kishi F, Kajii T, Fujii H, Miwa S, Sakurai M and Nakazawa A

    Department of Biochemistry, Yamaguchi University School of Medicine, Ube, Japan.

    Adenylate kinase deficiency in the erythrocyte is a rare genetic disorder associated with hemolytic anemia. To determine the molecular basis of this disorder, we first cloned the normal gene encoding human cytosolic adenylate kinase (AK1) and determined the structure. The gene was 12 kilobase pairs long and was split into 7 exons. The structures of 5'- and 3'-flanking regions were determined by primer extension and RNA blot analysis. The results showed that two species of mRNA with 0.9 and 2.5 kilobases, which differed at the 3'-end portion, were generated by the AK1 gene. Alu sequences were found in the largest intron (intron 5) and in the noncoding region of exon 7. Next, both alleles of the AK1 gene were cloned from DNA of a patient bearing the adenylate kinase deficiency and their nucleotide sequences determined. A transition (C----T) was found in exon 6 on an allele, which resulted in an Arg to Trp (CGG----TGG) substitution at the 128th residue of AK1. Since chicken AK1 is highly homologous to human AK1 with respect to the amino acid sequence, we introduced an Arg to Trp substitution to chicken AK1 at the same position by oligodeoxynucleotide-directed mutagenesis. The mutant chicken AK1 expressed in Escherichia coli showed a reduced catalytic activity as well as a decreased solubility and a change in affinity to phosphocellulose. Thus it was considered that the observed C----T transition was a cause of the decreased AK1 activity of the patient's erythrocyte. Analysis on phosphocellulose chromatography of erythrocyte AK1 of the patient and parents revealed that the patient's mutant allele was derived from the mother.

    The Journal of biological chemistry 1989;264;17;10148-55

  • Regional assignment of the loci for adenylate kinase to 9q32 and for alpha 1-acid glycoprotein to 9q31-q32. A locus for Goltz syndrome in region 9q32-qter?

    Zuffardi O, Caiulo A, Maraschio P, Tupler R, Bianchi E, Amisano P, Beluffi G, Moratti R and Liguri G

    Dipartimento di Scienze Biochimiche, Università di Firenze, Italy.

    Normal levels of adenylate kinase (AK-1) and of alpha 1-acid glycoprotein (ORM1) were found in a girl with a deletion 9q32-qter secondary to a maternal translocation (4q35; 9q32), thus excluding these loci from the deleted region. These results, and comparison with other informative data, map the locus for AK-1 to 9q32 and that for ORM1 to region 9q31-q32. The girl has several signs of the Goltz syndrome (Focal dermal hypoplasia), which is listed in the McKusick catalog (no. 30560) as an X-linked dominant condition. Our finding indicates that the locus for Golz syndrome is autosomal and in region 9q32-qter or that there are two such conditions, one autosomal and one X-linked.

    Human genetics 1989;82;1;17-9

  • Segregation of marker loci in families with an inherited paracentric insertion of chromosome 9.

    Allderdice PW, Kaita H, Lewis M, McAlpine PJ, Wong P, Anderson J and Giblett ER

    Cytogenetic, enzyme dosage, serological, and electrophoretic analyses of blood samples from members of three Newfoundland kindreds in which one specific paracentric insertion chromosome inv ins(9)(q22.1q34.3q34.1) is segregating provide data indicating that ABO lies in 9q22.1-q34.3, AK1 in 9q34.1-q34.3, and ORM in 9q34.3-qter.

    Funded by: NHLBI NIH HHS: HL17265

    American journal of human genetics 1986;39;5;612-7

  • Red cell adenylate kinase deficiency associated with hereditary nonspherocytic hemolytic anemia: clinical and biochemical studies.

    Miwa S, Fujii H, Tani K, Takahashi K, Takizawa T and Igarashi T

    We report here a case of red cell adenylate kinase (AK) deficiency associated with hereditary hemolytic anemia. The proband is a 10-year-old Japanese girl. Her physical and mental development was normal. She has shown moderate to mild hemolytic anemia since the neonatal period and hepatosplenomegaly. The red cell AK activity was 44% of normal. Contents of red cell glycolytic intermediates and adenine nucleotides were normal when compared with a comparable reticulocyte-rich control. Glucose consumption and lactate formation were normal. Hexose monophosphate shunt activity was somewhat lower than that of a comparable reticulocyte-rich control. There were no significant differences in the contents of adenine nucleotides between the younger and older red cells of the patient. Enzymatic characterization by hemolysate revealed that the patient's AK had an increased Michaelis constant for adenosine diphosphate and slight thermal instability. The patient's enzyme migrated approximately half-way between the AK 1 and AK 2 position on starch-gel electrophoresis. The mode of inheritance of this case is obscure. The mechanism of hemolysis might be a structural gene mutation that caused altered electrophoretic and kinetic properties.

    American journal of hematology 1983;14;4;325-33

  • AMP (dAMP) kinase from human erythrocytes.

    Tsuboi KK

    Methods in enzymology 1978;51;467-73

  • Primary and tertiary structure of the principal human adenylate kinase.

    Von Zabern I, Wittmann-Liebold B, Untucht-Grau R, Schirmer RH and Pai EF

    1. Human adenylate kinase (isoenzyme AK-1-1) from skeletal muscle is a single polypeptide chain of 194 amino-acid residues with an acetylmethionine at the N-terminus and a lysine at the C-terminus. 2. The primary structure of the enzyme was determined: Ac-Met-Glu-Glu-Lys-Leu-Lys-Lys-Thr-Lys-Ile-Ile-Phe-Val-Val-Gly-Gly-Pro-Gly-Ser-Gly-Lys-Gly-Thr-Gln-Cys-Glu-Lys-Ile-Val-Gln-Lys-Tyr-Gly-Tyr-Thr-His-Leu-Ser-Thr-Gly-Asp-Leu-Leu-Arg-Ser-Glu-Val-Ser-Ser-Gly-Ser-Ala-Arg-Gly-Lys-Lys-Leu-Ser-Glu-Ile-Met-Glu-Lys-Gly-Gln-Leu-Val-Pro-Leu-Glu-Thr-Val-Leu-Asp-Met-Leu-Arg-Asp-Ala-Met-Val-Ala-Lys-Val-Asn-Thr-Ser-Lys-Gly-Phe-Leu-Ile-Asp-Gly-Tyr-Pro-Arg-Glu-Val-Gln-Gln-Gly-Glu-Glu-Phe-Glu-Arg-Arg-Ile-Gly-Gln-Pro-Thr-Leu-Leu-Leu-Tyr-Val-Asp-Ala-Gly-Pro-Glu-Thr-Met-Thr-Arg-Arg-Leu-Leu-Lys-Arg-Gly-Glu-Thr-Ser-Gly-Arg-Val-Asp-Asn-Glu-Glu-Thr-Ile-Lys-Lys-Arg-Leu-Glu-Thr-Tyr-Tyr-Lys-Ala-Thr-Glu-Pro-Val-Ile-Ala-Phe-Tyr-Glu-Lys-Arg-Gly-Ile-Val-Arg-Lys-Val-Asn-Ala-Glu-Gly-Ser-Val-Asp-Glu-Val-Phe-Ser-Gln-Val-Cys-Thr-His-Leu-Asp-Ala-Leu-Lys. 3. When the primary structure of the human enzyme was fitted to the electron density map of porcine adenylate kinase, all nine amino acids which are different in the homologous enzymes from pig and man were located on the surface of the molecule. 4. Precession photographs of crystalline human and of crystalline porcine adenylate kinase corroborated the result that the polypeptide chains of the two enzymes are folded in a closely related manner. 5. The structure of human adenylate kinase incorporates the so-called nucleotide-binding domain which is present in a wide variety of proteins in nature. Some implications of this phenomenom for the molecular biology and the molecular pharmacology of man are discussed.

    European journal of biochemistry 1976;68;1;281-90

Gene lists (7)

Gene List Source Species Name Description Gene count
L00000009 G2C Homo sapiens Human PSD Human orthologues of mouse PSD adapted from Collins et al (2006) 1080
L00000010 G2C Homo sapiens Human mitochondria Human orthologues of mouse mitochondria adapted from Collins et al (2006) 91
L00000011 G2C Homo sapiens Human clathrin Human orthologues of mouse clathrin coated vesicle genes adapted from Collins et al (2006) 150
L00000012 G2C Homo sapiens Human Synaptosome Human orthologues of mouse synaptosome adapted from Collins et al (2006) 152
L00000016 G2C Homo sapiens Human PSP Human orthologues of mouse PSP adapted from Collins et al (2006) 1121
L00000059 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-CONSENSUS Human cortex PSD consensus 748
L00000069 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-FULL Human cortex biopsy PSD full list 1461
© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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