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
- Functionsm7G(5')pppN diphosphatase activity / RNA 7-methylguanosine cap bindingProcessescellular 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 decayComponentscytoplasm / 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
- DcpS (PF05652)
- 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
Resource Link UniProtKB ID Q96C86 UniProtKB Entry Name DCPS_HUMAN GenBank Protein ID 21654920 GenBank Gene ID AY040773 GenAtlas ID DCPS HGNC ID HGNC:29812 - General References
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- 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]
- 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]
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- Wang Z, Kiledjian M: Functional link between the mammalian exosome and mRNA decapping. Cell. 2001 Dec 14;107(6):751-62. [Article]
- 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]
- 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]
- 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]
- 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]
- 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]
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- 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]
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- 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]
- 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]
- 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]
- 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]
- 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]
- 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 ID Name Drug group Pharmacological action? Actions Details DB01649 7-methyl-GpppA experimental unknown Details DB01960 7-methyl-7,8-dihydroguanosine-5'-diphosphate experimental unknown Details DB03593 7-methyl-5'-guanylic acid experimental unknown Details DB03958 7-methyl-guanosine-5'-triphosphate-5'-guanosine experimental unknown Details DB07642 5-{[1-(2-fluorobenzyl)piperidin-4-yl]methoxy}quinazoline-2,4-diamine experimental unknown Details DB07643 5-{[1-(2,3-dichlorobenzyl)piperidin-4-yl]methoxy}quinazoline-2,4-diamine experimental unknown Details DB07644 5-[(1S)-1-(3-chlorophenyl)ethoxy]quinazoline-2,4-diamine experimental unknown Details