m7GpppX diphosphatase

Details

Name
m7GpppX diphosphatase
Synonyms
  • 3.6.1.59
  • DCS-1
  • DCS1
  • Decapping scavenger enzyme
  • HINT-5
  • Hint-related 7meGMP-directed hydrolase
  • HINT5
  • Histidine triad nucleotide-binding protein 5
  • Histidine triad protein member 5
  • Scavenger mRNA-decapping enzyme DcpS
Gene Name
DCPS
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010846|m7GpppX diphosphatase
MADAAPQLGKRKRELDVEEAHAASTEEKEAGVGNGTCAPVRLPFSGFRLQKVLRESARDK
IIFLHGKVNEASGDGDGEDAVVILEKTPFQVEQVAQLLTGSPELQLQFSNDIYSTYHLFP
PRQLNDVKTTVVYPATEKHLQKYLRQDLRLIRETGDDYRNITLPHLESQSLSIQWVYNIL
DKKAEADRIVFENPDPSDGFVLIPDLKWNQQQLDDLYLIAICHRRGIRSLRDLTPEHLPL
LRNILHQGQEAILQRYRMKGDHLRVYLHYLPSYYHLHVHFTALGFEAPGSGVERAHLLAE
VIENLECDPRHYQQRTLTFALRADDPLLKLLQEAQQS
Number of residues
337
Molecular Weight
38608.45
Theoretical pI
6.35
GO Classification
Functions
m7G(5')pppN diphosphatase activity / RNA 7-methylguanosine cap binding
Processes
cellular response to menadione / deadenylation-dependent decapping of nuclear-transcribed mRNA / exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay / gene expression / mRNA cis splicing, via spliceosome / negative regulation of programmed cell death / nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
Components
cytoplasm / cytosol / mitochondrion / nucleoplasm / nucleus
General Function
Rna 7-methylguanosine cap binding
Specific Function
Decapping scavenger enzyme that catalyzes the cleavage of a residual cap structure following the degradation of mRNAs by the 3'->5' exosome-mediated mRNA decay pathway. Hydrolyzes cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG) with up to 10 nucleotide substrates (small capped oligoribonucleotides) and specifically releases 5'-phosphorylated RNA fragments and 7-methylguanosine monophosphate (m7GMP). Cleaves cap analog structures like tri-methyl guanosine nucleoside triphosphate (m3(2,2,7)GpppG) with very poor efficiency. Does not hydrolyze unmethylated cap analog (GpppG) and shows no decapping activity on intact m7GpppG-capped mRNA molecules longer than 25 nucleotides. Does not hydrolyze 7-methylguanosine diphosphate (m7GDP) to m7GMP (PubMed:22985415). May also play a role in the 5'->3 mRNA decay pathway; m7GDP, the downstream product released by the 5'->3' mRNA mediated decapping activity, may be also converted by DCPS to m7GMP (PubMed:14523240). Binds to m7GpppG and strongly to m7GDP. Plays a role in first intron splicing of pre-mRNAs. Inhibits activation-induced cell death.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0010847|m7GpppX diphosphatase (DCPS)
ATGGCGGACGCAGCTCCTCAACTAGGCAAGAGGAAGCGCGAATTGGACGTGGAGGAGGCC
CACGCCGCCAGCACAGAGGAAAAGGAGGCAGGAGTTGGAAATGGTACCTGTGCTCCTGTC
CGCTTACCGTTCTCCGGCTTCAGACTGCAGAAGGTGCTGAGGGAGTCTGCGCGGGACAAA
ATCATTTTCCTACACGGGAAGGTGAATGAGGCCTCTGGGGATGGGGATGGAGAGGATGCC
GTTGTGATCCTGGAGAAGACGCCATTTCAGGTGGAACAGGTGGCTCAGCTCCTGACGGGC
AGCCCTGAGCTCCAGTTGCAGTTCTCCAATGATATCTACAGCACCTATCACTTGTTCCCT
CCAAGACAACTGAATGATGTAAAGACGACCGTGGTTTACCCTGCCACAGAGAAACACCTG
CAGAAGTACCTGCGCCAGGACCTCCGCCTGATCCGAGAGACGGGAGATGACTACAGGAAT
ATTACTTTACCCCACCTGGAGTCCCAGAGCCTCAGCATCCAGTGGGTGTATAACATTCTC
GACAAGAAGGCTGAAGCGGACCGGATTGTTTTCGAGAACCCAGATCCCTCTGATGGTTTT
GTCCTCATCCCTGACCTCAAGTGGAACCAACAGCAGCTCGATGACTTGTACTTGATCGCC
ATCTGCCATCGCCGGGGCATCAGATCCCTACGCGACCTTACTCCGGAGCACTTGCCGCTG
CTCAGGAACATCCTCCACCAGGGGCAGGAGGCCATCCTGCAGCGCTACCGGATGAAGGGA
GACCATCTGCGAGTATACCTGCACTACCTGCCCTCCTACTACCACCTGCATGTGCACTTC
ACCGCCCTGGGCTTCGAGGCCCCCGGCTCAGGCGTGGAGCGGGCCCACCTGCTGGCTGAG
GTGATCGAGAACTTGGAGTGTGACCCTAGGCACTACCAGCAGCGCACGCTCACCTTCGCC
CTCAGGGCTGACGACCCCCTGCTCAAGCTCTTGCAGGAGGCTCAGCAAAGCTGA
Chromosome Location
11
Locus
11q24.2
External Identifiers
ResourceLink
UniProtKB IDQ96C86
UniProtKB Entry NameDCPS_HUMAN
GenBank Protein ID21654920
GenBank Gene IDAY040773
GenAtlas IDDCPS
HGNC IDHGNC:29812
General References
  1. Liu H, Rodgers ND, Jiao X, Kiledjian M: The scavenger mRNA decapping enzyme DcpS is a member of the HIT family of pyrophosphatases. EMBO J. 2002 Sep 2;21(17):4699-708. [Article]
  2. Kwasnicka DA, Krakowiak A, Thacker C, Brenner C, Vincent SR: Coordinate expression of NADPH-dependent flavin reductase, Fre-1, and Hint-related 7meGMP-directed hydrolase, DCS-1. J Biol Chem. 2003 Oct 3;278(40):39051-8. Epub 2003 Jul 18. [Article]
  3. Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z: Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. Genome Res. 2000 Oct;10(10):1546-60. [Article]
  4. 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, 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: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Wang Z, Kiledjian M: Functional link between the mammalian exosome and mRNA decapping. Cell. 2001 Dec 14;107(6):751-62. [Article]
  6. van Dijk E, Le Hir H, Seraphin B: DcpS can act in the 5'-3' mRNA decay pathway in addition to the 3'-5' pathway. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12081-6. Epub 2003 Oct 1. [Article]
  7. Liu SW, Jiao X, Liu H, Gu M, Lima CD, Kiledjian M: Functional analysis of mRNA scavenger decapping enzymes. RNA. 2004 Sep;10(9):1412-22. Epub 2004 Jul 23. [Article]
  8. Cohen LS, Mikhli C, Friedman C, Jankowska-Anyszka M, Stepinski J, Darzynkiewicz E, Davis RE: Nematode m7GpppG and m3(2,2,7)GpppG decapping: activities in Ascaris embryos and characterization of C. elegans scavenger DcpS. RNA. 2004 Oct;10(10):1609-24. [Article]
  9. Kwasnicka-Crawford DA, Vincent SR: Role of a novel dual flavin reductase (NR1) and an associated histidine triad protein (DCS-1) in menadione-induced cytotoxicity. Biochem Biophys Res Commun. 2005 Oct 21;336(2):565-71. [Article]
  10. Shen V, Liu H, Liu SW, Jiao X, Kiledjian M: DcpS scavenger decapping enzyme can modulate pre-mRNA splicing. RNA. 2008 Jun;14(6):1132-42. doi: 10.1261/rna.1008208. Epub 2008 Apr 21. [Article]
  11. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
  12. Mariller C, Hardiville S, Hoedt E, Benaissa M, Mazurier J, Pierce A: Proteomic approach to the identification of novel delta-lactoferrin target genes: Characterization of DcpS, an mRNA scavenger decapping enzyme. Biochimie. 2009 Jan;91(1):109-22. doi: 10.1016/j.biochi.2008.07.009. Epub 2008 Aug 7. [Article]
  13. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  14. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  15. Wypijewska A, Bojarska E, Lukaszewicz M, Stepinski J, Jemielity J, Davis RE, Darzynkiewicz E: 7-methylguanosine diphosphate (m(7)GDP) is not hydrolyzed but strongly bound by decapping scavenger (DcpS) enzymes and potently inhibits their activity. Biochemistry. 2012 Oct 9;51(40):8003-13. doi: 10.1021/bi300781g. Epub 2012 Sep 25. [Article]
  16. Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C: Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-alpha-acetylation features. Mol Cell Proteomics. 2012 Jun;11(6):M111.015131. doi: 10.1074/mcp.M111.015131. Epub 2012 Jan 5. [Article]
  17. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]
  18. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  19. Ng CK, Shboul M, Taverniti V, Bonnard C, Lee H, Eskin A, Nelson SF, Al-Raqad M, Altawalbeh S, Seraphin B, Reversade B: Loss of the scavenger mRNA decapping enzyme DCPS causes syndromic intellectual disability with neuromuscular defects. Hum Mol Genet. 2015 Jun 1;24(11):3163-71. doi: 10.1093/hmg/ddv067. Epub 2015 Feb 24. [Article]
  20. Ahmed I, Buchert R, Zhou M, Jiao X, Mittal K, Sheikh TI, Scheller U, Vasli N, Rafiq MA, Brohi MQ, Mikhailov A, Ayaz M, Bhatti A, Sticht H, Nasr T, Carter MT, Uebe S, Reis A, Ayub M, John P, Kiledjian M, Vincent JB, Jamra RA: Mutations in DCPS and EDC3 in autosomal recessive intellectual disability indicate a crucial role for mRNA decapping in neurodevelopment. Hum Mol Genet. 2015 Jun 1;24(11):3172-80. doi: 10.1093/hmg/ddv069. Epub 2015 Feb 20. [Article]
  21. Gu M, Fabrega C, Liu SW, Liu H, Kiledjian M, Lima CD: Insights into the structure, mechanism, and regulation of scavenger mRNA decapping activity. Mol Cell. 2004 Apr 9;14(1):67-80. [Article]
  22. Chen N, Walsh MA, Liu Y, Parker R, Song H: Crystal structures of human DcpS in ligand-free and m7GDP-bound forms suggest a dynamic mechanism for scavenger mRNA decapping. J Mol Biol. 2005 Apr 8;347(4):707-18. [Article]
  23. Singh J, Salcius M, Liu SW, Staker BL, Mishra R, Thurmond J, Michaud G, Mattoon DR, Printen J, Christensen J, Bjornsson JM, Pollok BA, Kiledjian M, Stewart L, Jarecki J, Gurney ME: DcpS as a therapeutic target for spinal muscular atrophy. ACS Chem Biol. 2008 Nov 21;3(11):711-22. doi: 10.1021/cb800120t. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB016497-methyl-GpppAexperimentalunknownDetails
DB019607-methyl-7,8-dihydroguanosine-5'-diphosphateexperimentalunknownDetails
DB035937-methyl-5'-guanylic acidexperimentalunknownDetails
DB039587-methyl-guanosine-5'-triphosphate-5'-guanosineexperimentalunknownDetails
DB076425-{[1-(2-fluorobenzyl)piperidin-4-yl]methoxy}quinazoline-2,4-diamineexperimentalunknownDetails
DB076435-{[1-(2,3-dichlorobenzyl)piperidin-4-yl]methoxy}quinazoline-2,4-diamineexperimentalunknownDetails
DB076445-[(1S)-1-(3-chlorophenyl)ethoxy]quinazoline-2,4-diamineexperimentalunknownDetails