Trifunctional purine biosynthetic protein adenosine-3

Phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase
PDB rendering based on 1rbm.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1MEJ​, 1MEN​, 1MEO​, 1NJS​, 1RBM​, 1RBQ​, 1RBY​, 1RBZ​, 1RC0​, 1RC1​, 1ZLX​, 1ZLY​, 2QK4​, 2V9Y​, 4EW1​, 4EW2​, 4EW3​
Identifiers
Symbols	GART ; AIRS; GARS; GARTF; PAIS; PGFT; PRGS
External IDs	OMIM: 138440 MGI: 95654 HomoloGene: 637 IUPHAR: 2612 ChEMBL: 3972 GeneCards: GART Gene
EC number	2.1.2.2, 6.3.3.1, 6.3.4.13
Gene ontology Molecular function • phosphoribosylamine-glycine ligase activity • phosphoribosylformylglycinamidine cyclo-ligase activity • phosphoribosylglycinamide formyltransferase activity • ATP binding • methyltransferase activity • metal ion binding Cellular component • cytosol • extracellular exosome Biological process • brainstem development • purine nucleobase metabolic process • 'de novo' IMP biosynthetic process • glycine metabolic process • purine nucleobase biosynthetic process • purine ribonucleoside monophosphate biosynthetic process • response to organic substance • response to inorganic substance • cerebellum development • cerebral cortex development • methylation • small molecule metabolic process • tetrahydrofolate biosynthetic process • nucleobase-containing small molecule metabolic process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2618	14450
Ensembl	ENSG00000159131	ENSMUSG00000022962
UniProt	P22102	Q64737
RefSeq (mRNA)	NM_000819	NM_010256
RefSeq (protein)	NP_000810	NP_034386
Location (UCSC)	Chr 21: 33.5 – 33.54 Mb	Chr 16: 91.62 – 91.65 Mb
PubMed search

Trifunctional purine biosynthetic protein adenosine-3 is an enzyme that in humans is encoded by the GART gene.^[1]

This protein is a trifunctional polypeptide. It has Phosphoribosylamine—glycine ligase (EC 6.3.4.13), Phosphoribosylglycinamide formyltransferase (EC 2.1.2.2), AIR synthetase (FGAM cyclase) (EC 6.3.3.1) activity which is required for de novo purine biosynthesis.

References

1. Gnirke A, Barnes TS, Patterson D, Schild D, Featherstone T, Olson MV (July 1991). "Cloning and in vivo expression of the human GART gene using yeast artificial chromosomes". EMBO J. 10 (7): 1629–34. PMC 452831. PMID 2050105.

Further reading

• Hattori M, Fujiyama A, Taylor TD, et al. (2000). "The DNA sequence of human chromosome 21.". Nature 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953.
• Banerjee D, Nandagopal K (2007). "Potential interaction between the GARS-AIRS-GART Gene and CP2/LBP-1c/LSF transcription factor in Down syndrome-related Alzheimer disease.". Cell. Mol. Neurobiol. 27 (8): 1117–26. doi:10.1007/s10571-007-9217-2. PMID 17902044.
• Dahms TE, Sainz G, Giroux EL, et al. (2005). "The apo and ternary complex structures of a chemotherapeutic target: human glycinamide ribonucleotide transformylase.". Biochemistry 44 (29): 9841–50. doi:10.1021/bi050307g. PMID 16026156.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Dagle JM, Lepp NT, Cooper ME, et al. (2009). "Determination of genetic predisposition to patent ductus arteriosus in preterm infants.". Pediatrics 123 (4): 1116–23. doi:10.1542/peds.2008-0313. PMC 2734952. PMID 19336370.
• Franke B, Vermeulen SH, Steegers-Theunissen RP, et al. (2009). "An association study of 45 folate-related genes in spina bifida: Involvement of cubilin (CUBN) and tRNA aspartic acid methyltransferase 1 (TRDMT1).". Birth Defects Res. Part A Clin. Mol. Teratol. 85 (3): 216–26. doi:10.1002/bdra.20556. PMID 19161160.
• Barbe L, Lundberg E, Oksvold P, et al. (2008). "Toward a confocal subcellular atlas of the human proteome.". Mol. Cell Proteomics 7 (3): 499–508. doi:10.1074/mcp.M700325-MCP200. PMID 18029348.
• Zhang Y, Desharnais J, Marsilje TH, et al. (2003). "Rational design, synthesis, evaluation, and crystal structure of a potent inhibitor of human GAR Tfase: 10-(trifluoroacetyl)-5,10-dideazaacyclic-5,6,7,8-tetrahydrofolic acid.". Biochemistry 42 (20): 6043–56. doi:10.1021/bi034219c. PMID 12755606.
• Brodsky G, Barnes T, Bleskan J, et al. (1997). "The human GARS-AIRS-GART gene encodes two proteins which are differentially expressed during human brain development and temporally overexpressed in cerebellum of individuals with Down syndrome.". Hum. Mol. Genet. 6 (12): 2043–50. doi:10.1093/hmg/6.12.2043. PMID 9328467.
• Kan JL, Moran RG (1997). "Intronic polyadenylation in the human glycinamide ribonucleotide formyltransferase gene.". Nucleic Acids Res. 25 (15): 3118–23. doi:10.1093/nar/25.15.3118. PMC 146841. PMID 9224613.
• Gomez HL, Santillana SL, Vallejos CS, et al. (2006). "A phase II trial of pemetrexed in advanced breast cancer: clinical response and association with molecular target expression.". Clin. Cancer Res. 12 (3 Pt 1): 832–8. doi:10.1158/1078-0432.CCR-05-0295. PMID 16467096.
• Zhang Y, Desharnais J, Greasley SE, et al. (2002). "Crystal structures of human GAR Tfase at low and high pH and with substrate beta-GAR.". Biochemistry 41 (48): 14206–15. doi:10.1021/bi020522m. PMID 12450384.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Manieri W, Moore ME, Soellner MB, et al. (2007). "Human glycinamide ribonucleotide transformylase: active site mutants as mechanistic probes.". Biochemistry 46 (1): 156–63. doi:10.1021/bi0619270. PMC 2518408. PMID 17198385.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Rush J, Moritz A, Lee KA, et al. (2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.". Nat. Biotechnol. 23 (1): 94–101. doi:10.1038/nbt1046. PMID 15592455.
• Zalkin H, Dixon JE (1992). "De novo purine nucleotide biosynthesis.". Prog. Nucleic Acid Res. Mol. Biol. 42: 259–87. doi:10.1016/s0079-6603(08)60578-4. PMID 1574589.
• Vieira AR, McHenry TG, Daack-Hirsch S, et al. (2008). "Candidate gene/loci studies in cleft lip/palate and dental anomalies finds novel susceptibility genes for clefts.". Genet. Med. 10 (9): 668–74. doi:10.1097/GIM.0b013e3181833793. PMC 2734954. PMID 18978678.
• Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry.". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
• Banerjee D, Nandagopal K (2009). "Phylogenetic analysis and in silico characterization of the GARS-AIRS-GART gene which codes for a tri-functional enzyme protein involved in de novo purine biosynthesis.". Mol. Biotechnol. 42 (3): 306–19. doi:10.1007/s12033-009-9160-1. PMID 19301155.

External links

• Phosphoribosylglycinamide formyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)