CPLM-019109

Genbank Nucleotide ID

m7GpppX diphosphatase

Protein Synonyms/Alias

DCS-1; Decapping scavenger enzyme; Hint-related 7meGMP-directed hydrolase; Histidine triad nucleotide-binding protein 5; Histidine triad protein member 5; HINT-5; Scavenger mRNA-decapping enzyme DcpS

DCS1; HINT5; HSPC015

Homo sapiens (Human)

Position	Peptide	Type	References
10	DAAPQLGKRKRELDV	acetylation	[1, 2, 3]
10	DAAPQLGKRKRELDV	ubiquitination	[4]
128	PRQLNDVKTTVVYPA	acetylation	[2]
128	PRQLNDVKTTVVYPA	ubiquitination	[3, 4, 5, 6, 7, 8, 9, 10]
138	VVYPATEKHLQKYLR	acetylation	[3, 11]
138	VVYPATEKHLQKYLR	ubiquitination	[3, 4, 5, 10]
142	ATEKHLQKYLRQDLR	acetylation	[1, 3, 11]
142	ATEKHLQKYLRQDLR	ubiquitination	[4]
329	RADDPLLKLLQEAQQ	ubiquitination	[4, 6]

[1] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
[2] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
PLoS One. 2012;7(12):e50545. [PMID: 23236377]
[3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
[4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[6] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[7] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
[8] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
[9] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[10] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[11] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]

Functional Description

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.

REGION 268 279 Substrate binding.
MOTIF 10 13 nuclear localization signal (NLS).
MOTIF 142 154 nuclear export sequence (NES).
MOTIF 275 279 Histidine triad motif.
ACT_SITE 277 277 Nucleophile.
BINDING 175 175 Substrate.
BINDING 185 185 Substrate.
BINDING 205 205 Substrate.
BINDING 207 207 Substrate.
MOD_RES 2 2 N-acetylalanine.
MOD_RES 138 138 N6-acetyllysine.
MOD_RES 142 142 N6-acetyllysine.

3D-structure; Acetylation; Complete proteome; Cytoplasm; Direct protein sequencing; Hydrolase; mRNA processing; mRNA splicing; Nucleus; Polymorphism; Reference proteome.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; TAS:Reactome.
GO:0005739; C:mitochondrion; IDA:HPA.
GO:0005634; C:nucleus; IDA:UniProtKB.
GO:0050072; F:m7G(5')pppN diphosphatase activity; IDA:UniProtKB.
GO:0000340; F:RNA 7-methylguanosine cap binding; IDA:UniProtKB.
GO:0036245; P:cellular response to menadione; IDA:UniProtKB.
GO:0000290; P:deadenylation-dependent decapping of nuclear-transcribed mRNA; IEA:InterPro.
GO:0043928; P:exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay; TAS:Reactome.
GO:0045292; P:mRNA cis splicing, via spliceosome; IDA:UniProtKB.
GO:0043069; P:negative regulation of programmed cell death; IDA:UniProtKB.

IPR008594; DcpS/DCS2.
IPR019808; Histidine_triad_CS.
IPR011146; HIT-like.
IPR011145; Scavenger_mRNA_decap_enz_N.