PRPS-Associated Disorders and the Drosophila Model of Arts Syndrome
Abstract
:1. Introduction
2. Phosphoribosyl Pyrophosphate Synthetase (PRPS) Is a Rate-Limiting Enzyme in Nucleotide Metabolism
3. PRPS Is Highly Conserved
4. PRPS Mutations in Neurological Disorder
5. PRPS in Cancer
6. Post-Translational Modification of PRPS
7. Model Systems of PRPS-Associated Disorder
7.1. Mouse Models of PRPS-Associated Disorders
7.2. Zebrafish Models of PRPS-Associated Disorders
7.3. Drosophila Models of PRPS-Associated Disorders
8. Investigating Inborn Error in Metabolism Using Drosophila CRISPR/Cas9
9. Concluding Remarks
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
- Nyhan, W.L. Disorders of purine and pyrimidine metabolism. Mol. Genet. Metab. 2005, 86, 25–33. [Google Scholar] [CrossRef]
- Simmonds, H.A.; Van Gennip, A.H. Purine and pyrimidine disorders. In Physician’s Guide to the Laboratory Diagnosis of Metabolic Diseases; Springer: Berlin/Heidelberg, Germany, 2003; pp. 445–466. [Google Scholar]
- Balasubramaniam, S.; Duley, J.A.; Christodoulou, J. Inborn errors of purine metabolism: Clinical update and therapies. J. Inherit. Metab. Dis. 2014, 37, 669–686. [Google Scholar] [CrossRef] [PubMed]
- Jurecka, A. Inborn errors of purine and pyrimidine metabolism. J. Inherit. Metab. Dis. 2009, 32, 247–263. [Google Scholar] [CrossRef] [PubMed]
- Lu, B.; Vogel, H. Drosophila models of neurodegenerative diseases. Annu. Rev. Pathol. Mech. Dis. 2009, 4, 315–342. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Williams, D.W.; Tyrer, M.; Shepherd, D. Tau and tau reporters disrupt central projections of sensory neurons in Drosophila. J. Comp. Neurol. 2000, 428, 630–640. [Google Scholar] [CrossRef]
- Julienne, H.; Buhl, E.; Leslie, D.S.; Hodge, J.J.L. Drosophila PINK1 and parkin loss-of-function mutants display a range of non-motor Parkinson’s disease phenotypes. Neurobiol. Dis. 2017, 104, 15–23. [Google Scholar] [CrossRef]
- Xiong, Y.; Yu, J. Modeling Parkinson’s disease in Drosophila: What have we learned for dominant traits? Front. Neurol. 2018, 9, 228. [Google Scholar] [CrossRef] [Green Version]
- Mizuno, H.; Fujikake, N.; Wada, K.; Nagai, Y. α-Synuclein transgenic Drosophila as a model of Parkinson’s disease and related synucleinopathies. Parkinsons Dis. 2011. [Google Scholar] [CrossRef] [Green Version]
- Santos, K.D.; Kim, M.; Yergeau, C.; Jean, S.; Moon, N.-S. Pleiotropic role of Drosophila phosphoribosyl pyrophosphate synthetase in autophagy and lysosome homeostasis. PLoS Genet. 2019, 15, e1008376. [Google Scholar] [CrossRef]
- Hove-Jensen, B.; Andersen, K.R.; Kilstrup, M.; Martinussen, J.; Switzer, R.L.; Willemoës, M. Phosphoribosyl Diphosphate (PRPP): Biosynthesis, Enzymology, Utilization, and Metabolic Significance. Microbiol. Mol. Biol. Rev. 2016, 81, e00040-16. [Google Scholar] [CrossRef] [Green Version]
- E Jones, M. Pyrimidine Nucleotide Biosynthesis in Animals: Genes, Enzymes, and Regulation of UMP Biosynthesis. Annu. Rev. Biochem. 1980, 49, 253–279. [Google Scholar] [CrossRef] [PubMed]
- Taira, M.; Iizasa, T.; Yamada, K.; Shimada, H.; Tatibana, M. Tissue-differential expression of two distinct genes for phosphoribosyl pyrophosphate synthetase and existence of the testis-specific transcript. Biochim. Biophys. Acta (BBA) Gene Struct. Expr. 1989, 1007, 203–208. [Google Scholar] [CrossRef]
- Li, S.; Lu, Y.; Peng, B.; Ding, J. Crystal structure of human phosphoribosylpyrophosphate synthetase 1 reveals a novel allosteric site. Biochem. J. 2006, 401, 39–47. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Begovich, K.; Yelon, D.; Wilhelm, J.E. PRPS polymerization influences lens fiber organization in zebrafish. Dev. Dyn. 2020. [Google Scholar] [CrossRef] [PubMed]
- Noree, C.; Begovich, K.; Samilo, D.; Broyer, R.; Monfort, E.; Wilhelm, J.E. A quantitative screen for metabolic enzyme structures reveals patterns of assembly across the yeast metabolic network. Mol. Biol. Cell 2019, 30, 2721–2736. [Google Scholar] [CrossRef]
- Lynch, E.; Hicks, D.R.; Shepherd, M.; Endrizzi, J.A.; Maker, A.; Hansen, J.M.; Barry, R.M.; Gitai, Z.; Baldwin, E.; Kollman, J.M. Human CTP synthase filament structure reveals the active enzyme conformation. Nat. Struct. Mol. Biol. 2017, 24, 507–514. [Google Scholar] [CrossRef]
- Kita, K.; Otsuki, T.; Ishizuka, T.; Tatibana, M. Rat Liver Phosphoribosyl Pyrophosphate Synthetase: Existence of the Purified Enzyme as Heterogeneous Aggregates and Identification of the Catalytic Subunit1. J. Biochem. 1989, 105, 736–741. [Google Scholar] [CrossRef]
- Moran, R.; Kuilenburg, A.B.; Duley, J.; Nabuurs, S.B.; Retno-Fitri, A.; Christodoulou, J.; Roelofsen, J.; Yntema, H.G.; Friedman, N.; Van Bokhoven, H.; et al. Phosphoribosylpyrophosphate synthetase superactivity and recurrent infections is caused by a p.Val142Leu mutation in PRS-I. Am. J. Med. Genet. Part A 2012, 158, 455–460. [Google Scholar] [CrossRef]
- Mittal, R.; Patel, K.; Mittal, J.; Chan, B.; Yan, D.; Grati, M.; Liu, X.Z. Association of PRPS1 Mutations with Disease Phenotypes. Dis. Mark. 2015, 2015, 1–7. [Google Scholar] [CrossRef] [Green Version]
- Chen, P.; Liu, Z.; Wang, X.; Peng, J.; Sun, Q.; Li, J.; Wang, M.; Niu, L.; Zhang, Z.; Cai, G.; et al. Crystal and EM Structures of Human Phosphoribosyl Pyrophosphate Synthase I (PRS1) Provide Novel Insights into the Disease-Associated Mutations. PLoS ONE 2015, 10, e0120304. [Google Scholar] [CrossRef] [Green Version]
- Al-Maawali, A.; Dupuis, L.; Blaser, S.; Heon, E.; Tarnopolsky, M.; Al-Murshedi, F.; Marshall, C.R.; Paton, T.; Scherer, S.W.; Roelofsen, J.; et al. Prenatal growth restriction, retinal dystrophy, diabetes insipidus and white matter disease: Expanding the spectrum of PRPS1-related disorders. Eur. J. Hum. Genet. 2014, 23, 310–316. [Google Scholar] [CrossRef] [Green Version]
- De Brouwer, A.P.; Williams, K.L.; Duley, J.A.; Van Kuilenburg, A.B.P.; Nabuurs, S.B.; Egmont-Petersen, M.; Lugtenberg, D.; Zoetekouw, L.; Banning, M.J.G.; Roeffen, M.; et al. Arts Syndrome Is Caused by Loss-of-Function Mutations in PRPS1. Am. J. Hum. Genet. 2007, 81, 507–518. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Meng, L.; Wang, K.; Lv, H.; Wang, Z.; Zhang, W.; Yuan, Y. A novel mutation in PRPS1 causes X-linked Charcot-Marie-Tooth disease-5. Neuropathology 2019, 39, 342–347. [Google Scholar] [CrossRef]
- De Brouwer, A.P.; Van Bokhoven, H.; Nabuurs, S.B.; Arts, W.F.; Christodoulou, J.; Duley, J. PRPS1 Mutations: Four Distinct Syndromes and Potential Treatment. Am. J. Hum. Genet. 2010, 86, 506–518. [Google Scholar] [CrossRef] [Green Version]
- Zoref, E.; De Vries, A.; Sperling, O. Mutant feedback-resistant phosphoribosylpyrophosphate synthetase associated with purine overproduction and gout. Phosphoribosylpyrophosphate and purine metabolism in cultured fibroblasts. J. Clin. Investig. 1975, 56, 1093–1099. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, B.-Y.; Yu, H.-X.; Min, J.; Song, X.-X. A novel mutation in gene of PRPS1 in a young Chinese woman with X-linked gout: A case report and review of the literature. Clin. Rheumatol. 2019, 39, 949–956. [Google Scholar] [CrossRef] [PubMed]
- Fiorentino, A.; Fujinami, K.; Arno, G.; Robson, A.; Pontikos, N.; Armengol, M.A.; Plagnol, V.; Hayashi, T.; Iwata, T.; Parker, M.O.; et al. Missense variants in the X-linked gene PRPS1 cause retinal degeneration in females. Hum. Mutat. 2017, 39, 80–91. [Google Scholar] [CrossRef] [PubMed]
- Mateos, J.; Labora, J.F.; López, M.M.; Rodriguez, I.L.; Monserrat, L.; Ódena, M.A.; de Oliveira, E.; de Toro, J.; Arufe, M.C. Next-Generation Sequencing and Quantitative Proteomics of Hutchinson-Gilford progeria syndrome-derived cells point to a role of nucleotide metabolism in premature aging. PLoS ONE 2018, 13, e0205878. [Google Scholar] [CrossRef] [Green Version]
- Li, B.; Li, H.; Bai, Y.; Schwabe, R.K.; Yang, J.J.; Chen, Y.; Lu, G.; Tzoneva, G.; Ma, X.; Wu, T.; et al. Negative feedback–defective PRPS1 mutants drive thiopurine resistance in relapsed childhood ALL. Nat. Med. 2015, 21, 563–571. [Google Scholar] [CrossRef] [Green Version]
- Li, B.; Brady, S.W.; Ma, X.; Shen, S.; Zhang, Y.; Li, Y.; Szlachta, K.; Dong, L.; Liu, Y.; Yang, F.; et al. Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia. Blood 2020, 135, 41–55. [Google Scholar] [CrossRef]
- Wang, D.; Chen, Y.; Fang, H.; Zheng, L.; Li, Y.; Yang, F.; Xu, Y.; Du, L.; Zhou, B.-B.S.; Li, H. Increase of PRPP enhances chemosensitivity of PRPS1 mutant acute lymphoblastic leukemia cells to 5-Fluorouracil. J. Cell. Mol. Med. 2018, 22, 6202–6212. [Google Scholar] [CrossRef] [PubMed]
- Ma, Y.; An, X.; Guan, X.; Kong, Q.; Wang, Y.; Li, P.; Meng, Y.; Cui, Y.; Wen, X.; Guo, Y.; et al. High expression of PRPS1 induces an anti-apoptotic effect in B-ALL cell lines and predicts an adverse prognosis in Chinese children with B-ALL. Oncol. Lett. 2018, 15, 4314–4322. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sjöblom, T.; Jones, S.; Wood, L.D.; Parsons, D.W.; Lin, J.; Barber, T.D.; Mandelker, D.; Leary, R.J.; Ptak, J.; Silliman, N.; et al. The Consensus Coding Sequences of Human Breast and Colorectal Cancers. Science 2006, 314, 268–274. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Qian, X.; Peng, L.-X.; Jiang, Y.; Hawke, D.H.; Zheng, Y.; Xia, Y.; Lee, J.-H.; Cote, G.; Wang, H.; et al. A splicing switch from ketohexokinase-C to ketohexokinase-A drives hepatocellular carcinoma formation. Nat. Cell Biol. 2016, 18, 561–571. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jing, X.; Wang, X.-J.; Zhang, T.; Zhu, W.; Fang, Y.; Wu, H.; Liu, X.; Ma, D.; Ji, X.; Jiang, Y.; et al. Cell-Cycle-Dependent Phosphorylation of PRPS1 Fuels Nucleotide Synthesis and Promotes Tumorigenesis. Cancer Res. 2019, 79, 4650–4664. [Google Scholar] [CrossRef] [PubMed]
- Qian, X.; Li, X.; Tan, L.; Lee, J.-H.; Xia, Y.; Cai, Q.; Zheng, Y.; Wang, H.; Lorenzi, P.L.; Lu, Z. Conversion of PRPS Hexamer to Monomer by AMPK-Mediated Phosphorylation Inhibits Nucleotide Synthesis in Response to Energy Stress. Cancer Discov. 2017, 8, 94–107. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, F.; Patel, D.M.; Colavita, K.; Rodionova, I.; Buckley, B.; Scott, D.A.; Kumar, A.; Shabalina, S.A.; Saha, S.; Chernov, M.; et al. Arginylation regulates purine nucleotide biosynthesis by enhancing the activity of phosphoribosyl pyrophosphate synthase. Nat. Commun. 2015, 6, 7517. [Google Scholar] [CrossRef] [Green Version]
- Brommage, R.; Liu, J.; Hansen, G.M.; Kirkpatrick, L.L.; Potter, D.G.; Sands, A.T.; Zambrowicz, B.; Powell, D.R.; Vogel, P. High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes. Bone Res. 2014, 2, 14034. [Google Scholar] [CrossRef] [Green Version]
- Cunningham, J.T.; Moreno, M.V.; Lodi, A.; Ronen, S.M.; Ruggero, D. Protein and nucleotide biosynthesis are coupled by a single rate-limiting enzyme, PRPS2, to drive cancer. Cell 2014, 157, 1088–1103. [Google Scholar] [CrossRef] [Green Version]
- Pei, W.; Xu, L.; Varshney, G.K.; Carrington, B.; Bishop, K.; Jones, M.; Huang, S.C.; Idol, J.; Pretorius, P.R.; Beirl, A.; et al. Additive reductions in zebrafish PRPS1 activity result in a spectrum of deficiencies modeling several human PRPS1-associated diseases. Sci. Rep. 2016, 6, 29946. [Google Scholar] [CrossRef] [Green Version]
- DeSmidt, A.A.; Zou, B.; Grati, M.; Yan, D.; Mittal, R.; Yao, Q.; Richmond, M.T.; Denyer, S.; Liu, X.Z.; Lu, Z. Zebrafish Model for Nonsyndromic X-Linked Sensorineural Deafness, DFNX1. Anat. Rec. Adv. Integr. Anat. Evol. Biol. 2019, 303, 544–555. [Google Scholar] [CrossRef] [PubMed]
- Gratz, S.J.; Cummings, A.M.; Nguyen, J.N.; Hamm, D.C.; Donohue, L.K.; Harrison, M.M.; Wildonger, J.; O’Connor-Giles, K. Genome engineering of Drosophila with the CRISPR RNA-guided Cas9 nuclease. Genetics 2013, 194, 1029–1035. [Google Scholar] [CrossRef] [Green Version]
- Meltzer, H.; Marom, E.; Alyagor, I.; Mayseless, O.; Berkun, V.; Segal-Gilboa, N.; Unger, T.; Luginbuhl, D.; Schuldiner, O. Tissue-specific (ts)CRISPR as an efficient strategy for in vivo screening in Drosophila. Nat. Commun. 2019, 10, 2113. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Port, F.; Strein, C.; Stricker, M.; Rauscher, B.; Heigwer, F.; Zhou, J.; Beyersdörffer, C.; Frei, J.; Hess, A.; Kern, K.; et al. A large-scale resource for tissue-specific CRISPR mutagenesis in Drosophila. Elife 2020, 9, 53865. [Google Scholar] [CrossRef]
- Zirin, J.; Hu, Y.; Liu, L.; Yang-Zhou, D.; Colbeth, R.; Yan, D.; Ewen-Campen, B.; Tao, R.; Vogt, E.; Vannest, S.; et al. Large-Scale Transgenic Drosophila Resource Collections for Loss- and Gain-of-Function Studies. Genetics 2020, 214, 755–767. [Google Scholar] [CrossRef] [PubMed]
- Madabattula, S.T.; Strautman, J.C.; Bysice, A.M.; O’Sullivan, J.A.; Androschuk, A.; Rosenfelt, C.; Doucet, K.; Rouleau, G.; Bolduc, F.V. Quantitative Analysis of Climbing Defects in a Drosophila Model of Neurodegenerative Disorders. J. Vis. Exp. 2015, 100, e52741. [Google Scholar] [CrossRef] [PubMed]
- Pedley, A.M.; Benkovic, S.J. A New View into the Regulation of Purine Metabolism: The Purinosome. Trends Biochem. Sci. 2016, 42, 141–154. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hales, K.G.; Korey, C.A.; Larracuente, A.M.; Roberts, D.M. Genetics on the Fly: A Primer on theDrosophilaModel System. Genetics 2015, 201, 815–842. [Google Scholar] [CrossRef] [Green Version]
- Anzalone, A.V.; Randolph, P.B.; Davis, J.R.; Sousa, A.A.; Koblan, L.W.; Levy, J.M.; Chen, P.J.; Wilson, C.; Newby, G.A.; Raguram, A.; et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 2019, 576, 149–157. [Google Scholar] [CrossRef] [PubMed]
- A Becker, M.; Smith, P.R.; Taylor, W.; Mustafi, R.; Switzer, R.L. The genetic and functional basis of purine nucleotide feedback-resistant phosphoribosylpyrophosphate synthetase superactivity. J. Clin. Investig. 1995, 96, 2133–2141. [Google Scholar] [CrossRef] [PubMed]
- Roessler, B.J.; Golovoy, N.; Palella, T.D.; Heidler, S.; Becker, M.A. Identification of Distinct PRS1 Mutations in Two Patients with X-Linked Phosphoribosylpyrophosphate Synthetase Superactivity. In Plant Promoters and Transcription Factors; Springer: Berlin/Heidelberg, Germany, 1991; Volume 309, pp. 125–128. [Google Scholar]
- Becker, M.A.; Taylor, W.; Smith, P.R.; Ahmed, M. Overexpression of the Normal Phosphoribosylpyrophosphate Synthetase 1 Isoform Underlies Catalytic Superactivity of Human Phosphoribosylpyrophosphate Synthetase. J. Biol. Chem. 1996, 271, 19894–19899. [Google Scholar] [CrossRef] [Green Version]
- García-Pavía, P.; Torres, R.J.; Rivero, M.; Ahmed, M.; García-Puig, J.; Becker, M.A. Phosphoribosylpyrophosphate synthetase overactivity as a cause of uric acid overproduction in a young woman. Arthritis Rheum. 2003, 48, 2036–2041. [Google Scholar] [CrossRef] [PubMed]
- Liu, X.; Han, D.; Li, J.; Han, B.; Ouyang, X.; Cheng, J.; Li, X.; Jin, Z.; Wang, Y.; Bitner-Glindzicz, M.; et al. Loss-of-Function Mutations in the PRPS1 Gene Cause a Type of Nonsyndromic X-linked Sensorineural Deafness, DFN2. Am. J. Hum. Genet. 2010, 86, 65–71. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, H.-J.; Sohn, K.-M.; Shy, M.E.; Krajewski, K.M.; Hwang, M.; Park, J.-H.; Jang, S.-Y.; Won, H.-H.; Choi, B.-O.; Hong, S.H.; et al. Mutations in PRPS1, Which Encodes the Phosphoribosyl Pyrophosphate Synthetase Enzyme Critical for Nucleotide Biosynthesis, Cause Hereditary Peripheral Neuropathy with Hearing Loss and Optic Neuropathy (CMTX5). Am. J. Hum. Genet. 2007, 81, 552–558. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Synofzik, M.; Hagen, J.M.V.; Haack, T.B.; Wilhelm, C.; Lindig, T.; Beck-Wödl, S.; Nabuurs, S.B.; Van Kuilenburg, A.B.P.; De Brouwer, A.P.M.; Schöls, L. X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: Evidence from a family with a novel PRPS1 mutation. Orphanet J. Rare Dis. 2014, 9, 24. [Google Scholar] [CrossRef] [Green Version]
- Robusto, M.; Fang, M.; Asselta, R.; Castorina, P.; Previtali, S.; Caccia, S.; Benzoni, E.; De Cristofaro, R.; Yu, C.; Cesarani, A.; et al. The expanding spectrum of PRPS1-associated phenotypes: Three novel mutations segregating with X-linked hearing loss and mild peripheral neuropathy. Eur. J. Hum. Genet. 2014, 23, 766–773. [Google Scholar] [CrossRef] [Green Version]
- Park, J.-M.; Hyun, Y.S.; Kim, Y.J.; Nam, S.H.; Kim, S.-H.; Bin Hong, Y.; Chung, K.W.; Choi, B.-O. Exome Sequencing Reveals a Novel PRPS1 Mutation in a Family with CMTX5 without Optic Atrophy. J. Clin. Neurol. 2013, 9, 283–288. [Google Scholar] [CrossRef] [Green Version]
- Almoguera, B.; He, S.; Corton, M.; Jose, P.F.-S.; Blanco-Kelly, F.; Lopez-Molina, M.I.; Garcia-Sandoval, B.; Del Val, J.; Guo, Y.; Tian, L.; et al. Expanding the phenotype of PRPS1 syndromes in females: Neuropathy, hearing loss and retinopathy. Orphanet J. Rare Dis. 2014, 9, 190. [Google Scholar] [CrossRef] [Green Version]
Disorder | Effect on PRPS1 Function | Mutation | Amino Acid Change |
---|---|---|---|
PRPS-1 Superactivity | Gain of Function | 154G > C [51] | D52H |
341A > G [52] | N114S | ||
385C > A [51] | L129I | ||
521G > T [27] | G174V | ||
547G > C [52] | D183H 1 | ||
569C > T [53] | A190V 1 | ||
578A > T [54] | H192L | ||
579C > G [51] | H193Q 1 | ||
Nonsyndromic X-linked sensorineural deafness (DFN2) | Loss of Function | 193G > A [55] | D65N |
259G > A [55] | A87T | ||
869T > C [55] | I290T | ||
916G > A [55] | G306R | ||
Charcot-Marie-Tooth neuropathy type 5 (CMTX5) | Loss of Function | 129A > C [56] | E43D |
334G > C [24] | V112L | ||
344T > C [56] | M115T | ||
Arts syndrome | Loss of Function | 398A > C [23] | Q133P |
455T > C [23] | L152P | ||
856C > T [22] | R196W | ||
PRPS-1 Superactivity and Arts syndrome | Loss of Function | 424G > C [19] | V142L |
CMTX5 and Arts syndrome | Loss of Function | 830A > C [57] | Q277P |
DFN2 and CMTX5 | Loss of Function | 337G > T [58] | All3S |
DFN2 and CMTX6 | Loss of Function | 343A > G [58] | M115V |
DFN2 and CMTX7 | Loss of Function | 925G > T [58] | V309F |
DFN2 and CMTX8 | Loss of Function | 62C > G [59] | A121G |
Retinal Dystrophy | Loss of Function | 46T > C [60] | S16P |
47C > T [28] | S16F | ||
586C > T [28] | R196W | ||
640C > T [28] | R214W | ||
641G > C [28] | R214P |
Cancer Type | Gene | Amino Acid Change |
---|---|---|
Relapse-specific ALL | PRPS1 | V53A [30] |
I72V [30] | ||
C77S [30] | ||
S103I [30] | ||
S103N [30] | ||
S103T [30] | ||
S103R [31] | ||
N114D [30] | ||
D139G [30] | ||
N144S [30] | ||
G174E [30] | ||
K176N [30] | ||
R177S [31] | ||
D183E [30] | ||
A190V [30] | ||
A190T [30] | ||
L191F [30] | ||
T303S [30] | ||
Y311C [30] | ||
V316L [31] | ||
PRPS2 | V48M [31] | |
S120S [31] | ||
A134T [31] | ||
P173Y [31] | ||
A175T [31] | ||
Breast Cancer | PRPS1 | D203H [34] |
V219G [34] | ||
Colorectal Cancer | PRPS1 | H231D [34] |
Gene | ensID | Gene Name | Drosophila Homologues | FB ID | Homology between Human and Fruit Fly Orthologs |
---|---|---|---|---|---|
ADSL | ENSG00000239900 | adenylosuccinate lyase (de Novo) | AdSL | FBgn0038467 | Identity: 65.6% |
Similarity: 78.7% | |||||
ATIC | ENSG00000138363 | 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (de Novo) | CG11089 | FBgn0039241 | Identity: 70.6% |
Similarity: 83.3% | |||||
PNP | ENSG00000198805 | purine nucleoside phosphorylase (Catabolism) | CG16758 | FBgn0035348 | Identity: 44.6% |
Similarity: 59.8% | |||||
ADA | ENSG00000196839 | adenosine deaminase (Catabolism) | ADA (?) | FBgn0037661 | Identity: 23.7% |
Similarity: 38.8% | |||||
APRT | ENSG00000198931 | adenine phosphoribosyltransferase (Salvage) | APRT | FBgn0000109 | Identity: 44.3% |
Similarity: 62.7% | |||||
HPRT1 | ENSG00000165704 | hypoxanthine phosphoribosyltransferase 1 (Salvage) | Unknown | - | - |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Delos Santos, K.; Kwon, E.; Moon, N.-S. PRPS-Associated Disorders and the Drosophila Model of Arts Syndrome. Int. J. Mol. Sci. 2020, 21, 4824. https://doi.org/10.3390/ijms21144824
Delos Santos K, Kwon E, Moon N-S. PRPS-Associated Disorders and the Drosophila Model of Arts Syndrome. International Journal of Molecular Sciences. 2020; 21(14):4824. https://doi.org/10.3390/ijms21144824
Chicago/Turabian StyleDelos Santos, Keemo, Eunjeong Kwon, and Nam-Sung Moon. 2020. "PRPS-Associated Disorders and the Drosophila Model of Arts Syndrome" International Journal of Molecular Sciences 21, no. 14: 4824. https://doi.org/10.3390/ijms21144824