ID DCPS_HUMAN Reviewed; 337 AA. AC Q96C86; Q8NHL8; Q9Y2S5; DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 185. DE RecName: Full=m7GpppX diphosphatase; DE EC=3.6.1.59 {ECO:0000269|PubMed:15273322, ECO:0000269|PubMed:15383679, ECO:0000269|PubMed:18839960, ECO:0000269|PubMed:22985415}; DE AltName: Full=DCS-1; DE AltName: Full=Decapping scavenger enzyme; DE AltName: Full=Hint-related 7meGMP-directed hydrolase; DE AltName: Full=Histidine triad nucleotide-binding protein 5; DE AltName: Full=Histidine triad protein member 5; DE Short=HINT-5; DE AltName: Full=Scavenger mRNA-decapping enzyme DcpS; GN Name=DCPS; Synonyms=DCS1, HINT5; ORFNames=HSPC015; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RA Huang C.-H., Peng J., Chen H., Chen Y.; RT "Cloning and characterization of a novel member of the histidine triad RT protein family (HINT-5) in different vertebrate species."; RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, RP MUTAGENESIS OF HIS-277, AND SUBUNIT. RX PubMed=12198172; DOI=10.1093/emboj/cdf448; RA Liu H., Rodgers N.D., Jiao X., Kiledjian M.; RT "The scavenger mRNA decapping enzyme DcpS is a member of the HIT family of RT pyrophosphatases."; RL EMBO J. 21:4699-4708(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Placenta; RX PubMed=12871939; DOI=10.1074/jbc.m306355200; RA Kwasnicka D.A., Krakowiak A., Thacker C., Brenner C., Vincent S.R.; RT "Coordinate expression of NADPH-dependent flavin reductase, Fre-1, and RT Hint-related 7meGMP-directed hydrolase, DCS-1."; RL J. Biol. Chem. 278:39051-39058(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-73. RC TISSUE=Bone marrow; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 2-11; 129-138 AND 243-255, CLEAVAGE OF INITIATOR RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Ovarian carcinoma; RA Bienvenut W.V.; RL Submitted (JAN-2010) to UniProtKB. RN [7] RP FUNCTION, AND INTERACTION WITH EXOSOME PROTEINS. RX PubMed=11747811; DOI=10.1016/s0092-8674(01)00592-x; RA Wang Z., Kiledjian M.; RT "Functional link between the mammalian exosome and mRNA decapping."; RL Cell 107:751-762(2001). RN [8] RP FUNCTION. RX PubMed=14523240; DOI=10.1073/pnas.1635192100; RA van Dijk E., Le Hir H., Seraphin B.; RT "DcpS can act in the 5'-3' mRNA decay pathway in addition to the 3'-5' RT pathway."; RL Proc. Natl. Acad. Sci. U.S.A. 100:12081-12086(2003). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, DOMAIN, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF HIS-277. RX PubMed=15273322; DOI=10.1261/rna.7660804; RA Liu S.-W., Jiao X., Liu H., Gu M., Lima C.D., Kiledjian M.; RT "Functional analysis of mRNA scavenger decapping enzymes."; RL RNA 10:1412-1422(2004). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY. RX PubMed=15383679; DOI=10.1261/rna.7690504; RA Cohen L.S., Mikhli C., Friedman C., Jankowska-Anyszka M., Stepinski J., RA Darzynkiewicz E., Davis R.E.; RT "Nematode m7GpppG and m3(2,2,7)GpppG decapping: activities in Ascaris RT embryos and characterization of C. elegans scavenger DcpS."; RL RNA 10:1609-1624(2004). RN [11] RP FUNCTION IN CYTOTOXICITY INHIBITION, INDUCTION, AND INTERACTION WITH NDOR1. RX PubMed=16140270; DOI=10.1016/j.bbrc.2005.08.129; RA Kwasnicka-Crawford D.A., Vincent S.R.; RT "Role of a novel dual flavin reductase (NR1) and an associated histidine RT triad protein (DCS-1) in menadione-induced cytotoxicity."; RL Biochem. Biophys. Res. Commun. 336:565-571(2005). RN [12] RP FUNCTION IN SPLICING, MUTAGENESIS OF 10-LYS--ARG-13; LEU-148 AND LEU-150, RP AND SUBCELLULAR LOCATION. RX PubMed=18426921; DOI=10.1261/rna.1008208; RA Shen V., Liu H., Liu S.W., Jiao X., Kiledjian M.; RT "DcpS scavenger decapping enzyme can modulate pre-mRNA splicing."; RL RNA 14:1132-1142(2008). RN [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [14] RP INDUCTION, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=18725266; DOI=10.1016/j.biochi.2008.07.009; RA Mariller C., Hardiville S., Hoedt E., Benaissa M., Mazurier J., Pierce A.; RT "Proteomic approach to the identification of novel delta-lactoferrin target RT genes: Characterization of DcpS, an mRNA scavenger decapping enzyme."; RL Biochimie 91:109-122(2009). RN [15] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-138 AND LYS-142, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [17] RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND ACTIVITY RP REGULATION. RX PubMed=22985415; DOI=10.1021/bi300781g; RA Wypijewska A., Bojarska E., Lukaszewicz M., Stepinski J., Jemielity J., RA Davis R.E., Darzynkiewicz E.; RT "7-Methylguanosine diphosphate (m(7)GDP) is not hydrolyzed but strongly RT bound by decapping scavenger (dcpS) enzymes and potently inhibits their RT activity."; RL Biochemistry 51:8003-8013(2012). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [22] RP INVOLVEMENT IN ARS. RX PubMed=25712129; DOI=10.1093/hmg/ddv067; RA Ng C.K., Shboul M., Taverniti V., Bonnard C., Lee H., Eskin A., RA Nelson S.F., Al-Raqad M., Altawalbeh S., Seraphin B., Reversade B.; RT "Loss of the scavenger mRNA decapping enzyme DCPS causes syndromic RT intellectual disability with neuromuscular defects."; RL Hum. Mol. Genet. 24:3163-3171(2015). RN [23] RP INVOLVEMENT IN ARS, VARIANT ARS MET-316, AND CHARACTERIZATION OF VARIANT RP ARS MET-316. RX PubMed=25701870; DOI=10.1093/hmg/ddv069; RA Ahmed I., Buchert R., Zhou M., Jiao X., Mittal K., Sheikh T.I., RA Scheller U., Vasli N., Rafiq M.A., Brohi M.Q., Mikhailov A., Ayaz M., RA Bhatti A., Sticht H., Nasr T., Carter M.T., Uebe S., Reis A., Ayub M., RA John P., Kiledjian M., Vincent J.B., Jamra R.A.; RT "Mutations in DCPS and EDC3 in autosomal recessive intellectual disability RT indicate a crucial role for mRNA decapping in neurodevelopment."; RL Hum. Mol. Genet. 24:3172-3180(2015). RN [24] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF MUTANT ASN-277 IN COMPLEX WITH RP SUBSTRATE, SUBUNIT, AND MUTAGENESIS OF ARG-58; ILE-61; PHE-63; ILE-83; RP GLU-85; PHE-108; ASN-110; TYR-113; LYS-128; LYS-138; ARG-145; GLN-146; RP TRP-175; GLU-185; PRO-204; ASP-205; LEU-206; LYS-207; TYR-217; HIS-268; RP SER-272; HIS-277; HIS-279; ARG-294 AND ARG-322. RX PubMed=15068804; DOI=10.1016/s1097-2765(04)00180-7; RA Gu M., Fabrega C., Liu S.-W., Liu H., Kiledjian M., Lima C.D.; RT "Insights into the structure, mechanism, and regulation of scavenger mRNA RT decapping activity."; RL Mol. Cell 14:67-80(2004). RN [25] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH SUBSTRATE, FUNCTION, RP SUBUNIT, AND MUTAGENESIS OF TYR-273. RX PubMed=15769464; DOI=10.1016/j.jmb.2005.01.062; RA Chen N., Walsh M.A., Liu Y., Parker R., Song H.; RT "Crystal structures of human DcpS in ligand-free and m7GDP-bound forms RT suggest a dynamic mechanism for scavenger mRNA decapping."; RL J. Mol. Biol. 347:707-718(2005). RN [26] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 38-337 IN COMPLEX WITH SUBSTRATE RP ANALOGS, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=18839960; DOI=10.1021/cb800120t; RA Singh J., Salcius M., Liu S.W., Staker B.L., Mishra R., Thurmond J., RA Michaud G., Mattoon D.R., Printen J., Christensen J., Bjornsson J.M., RA Pollok B.A., Kiledjian M., Stewart L., Jarecki J., Gurney M.E.; RT "DcpS as a therapeutic target for spinal muscular atrophy."; RL ACS Chem. Biol. 3:711-722(2008). CC -!- FUNCTION: Decapping scavenger enzyme that catalyzes the cleavage of a CC residual cap structure following the degradation of mRNAs by the 3'->5' CC exosome-mediated mRNA decay pathway. Hydrolyzes cap analog structures CC like 7-methylguanosine nucleoside triphosphate (m7GpppG) with up to 10 CC nucleotide substrates (small capped oligoribonucleotides) and CC specifically releases 5'-phosphorylated RNA fragments and 7- CC methylguanosine monophosphate (m7GMP). Cleaves cap analog structures CC like tri-methyl guanosine nucleoside triphosphate (m3(2,2,7)GpppG) with CC very poor efficiency. Does not hydrolyze unmethylated cap analog CC (GpppG) and shows no decapping activity on intact m7GpppG-capped mRNA CC molecules longer than 25 nucleotides. Does not hydrolyze 7- CC methylguanosine diphosphate (m7GDP) to m7GMP (PubMed:22985415). May CC also play a role in the 5'->3 mRNA decay pathway; m7GDP, the downstream CC product released by the 5'->3' mRNA mediated decapping activity, may be CC also converted by DCPS to m7GMP (PubMed:14523240). Binds to m7GpppG and CC strongly to m7GDP. Plays a role in first intron splicing of pre-mRNAs. CC Inhibits activation-induced cell death. {ECO:0000269|PubMed:11747811, CC ECO:0000269|PubMed:12198172, ECO:0000269|PubMed:12871939, CC ECO:0000269|PubMed:14523240, ECO:0000269|PubMed:15273322, CC ECO:0000269|PubMed:15383679, ECO:0000269|PubMed:15769464, CC ECO:0000269|PubMed:16140270, ECO:0000269|PubMed:18426921, CC ECO:0000269|PubMed:22985415}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside CC in mRNA + H2O = a 5'-end diphospho-ribonucleoside in mRNA + 2 H(+) + CC N(7)-methyl-GMP; Xref=Rhea:RHEA:65388, Rhea:RHEA-COMP:17165, CC Rhea:RHEA-COMP:17167, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:58285, ChEBI:CHEBI:156461, ChEBI:CHEBI:167616; CC EC=3.6.1.59; Evidence={ECO:0000269|PubMed:15273322, CC ECO:0000269|PubMed:15383679, ECO:0000269|PubMed:18839960, CC ECO:0000269|PubMed:22985415}; CC -!- ACTIVITY REGULATION: The hydrolytic product 7-methylguanosine CC diphosphate (m7GDP) efficiently inhibits the decapping scavenger CC activity and acts as a competitive inhibitor in vitro. Inhibited by CC 2,4-diaminoquinazoline. {ECO:0000269|PubMed:18839960, CC ECO:0000269|PubMed:22985415}. CC -!- SUBUNIT: Homodimer. Associates with components of the exosome CC multienzyme ribonuclease complex, such as EXOSC3 and EXOSC4. Interacts CC with NDOR1. {ECO:0000269|PubMed:11747811, ECO:0000269|PubMed:12198172, CC ECO:0000269|PubMed:15068804, ECO:0000269|PubMed:15769464, CC ECO:0000269|PubMed:16140270, ECO:0000269|PubMed:18839960}. CC -!- INTERACTION: CC Q96C86; Q96C86: DCPS; NbExp=3; IntAct=EBI-3917181, EBI-3917181; CC Q96C86; P52292: KPNA2; NbExp=3; IntAct=EBI-3917181, EBI-349938; CC Q96C86; O15131: KPNA5; NbExp=3; IntAct=EBI-3917181, EBI-540602; CC Q96C86; O60684: KPNA6; NbExp=5; IntAct=EBI-3917181, EBI-359923; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Predominantly localized CC in the nucleus. Nucleocytoplasmic shuttling protein that can CC transiently enter the cytoplasm in mammalian cells in a XPO1/CRM1- CC dependent manner. CC -!- TISSUE SPECIFICITY: Detected in liver, brain, kidney, testis and CC prostate. {ECO:0000269|PubMed:12871939}. CC -!- INDUCTION: Up-regulated by menadione. Up-regulated by the transcription CC factor LTF isoform delta-lactoferrin (at protein level). CC {ECO:0000269|PubMed:16140270, ECO:0000269|PubMed:18725266}. CC -!- DOMAIN: The C-terminal histidine triad (HIT) motif and the N-terminal CC domain are required for the decapping activity. The N-terminus is CC necessary but not sufficient for binding cap structures. CC {ECO:0000269|PubMed:15273322}. CC -!- DISEASE: Al-Raqad syndrome (ARS) [MIM:616459]: A syndrome characterized CC by delayed psychomotor development, moderate to severe intellectual CC disability, poor or absent speech, microcephaly, congenital hypotonia, CC and severe growth delay. {ECO:0000269|PubMed:25701870, CC ECO:0000269|PubMed:25712129}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the HIT family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AH010984; AAK91763.1; -; Genomic_DNA. DR EMBL; AY040771; AAK91765.1; -; mRNA. DR EMBL; AF532613; AAM90310.1; -; mRNA. DR EMBL; AY077684; AAL77216.1; -; mRNA. DR EMBL; AF077201; AAD26996.1; -; mRNA. DR EMBL; BC014532; AAH14532.1; -; mRNA. DR CCDS; CCDS8473.1; -. DR RefSeq; NP_054745.1; NM_014026.4. DR PDB; 1ST0; X-ray; 1.90 A; A/B=1-337. DR PDB; 1ST4; X-ray; 2.02 A; A/B=1-337. DR PDB; 1XML; X-ray; 2.00 A; A/B=1-337. DR PDB; 1XMM; X-ray; 2.50 A; A/B/C/D=1-337. DR PDB; 3BL7; X-ray; 2.31 A; A/B=38-337. DR PDB; 3BL9; X-ray; 1.80 A; A/B=38-337. DR PDB; 3BLA; X-ray; 2.60 A; A/B=38-337. DR PDB; 4QDE; X-ray; 2.90 A; A/B/C/D=2-337. DR PDB; 4QDV; X-ray; 2.80 A; A/B/C/D=2-337. DR PDB; 4QEB; X-ray; 3.21 A; A/B/C/D=2-337. DR PDB; 5OSY; X-ray; 2.06 A; A/B=37-337. DR PDBsum; 1ST0; -. DR PDBsum; 1ST4; -. DR PDBsum; 1XML; -. DR PDBsum; 1XMM; -. DR PDBsum; 3BL7; -. DR PDBsum; 3BL9; -. DR PDBsum; 3BLA; -. DR PDBsum; 4QDE; -. DR PDBsum; 4QDV; -. DR PDBsum; 4QEB; -. DR PDBsum; 5OSY; -. DR AlphaFoldDB; Q96C86; -. DR SMR; Q96C86; -. DR BioGRID; 118787; 395. DR IntAct; Q96C86; 8. DR STRING; 9606.ENSP00000263579; -. DR BindingDB; Q96C86; -. DR ChEMBL; CHEMBL1949488; -. DR DrugBank; DB07644; 5-[(1S)-1-(3-chlorophenyl)ethoxy]quinazoline-2,4-diamine. DR DrugBank; DB07643; 5-{[1-(2,3-dichlorobenzyl)piperidin-4-yl]methoxy}quinazoline-2,4-diamine. DR DrugBank; DB07642; 5-{[1-(2-fluorobenzyl)piperidin-4-yl]methoxy}quinazoline-2,4-diamine. DR DrugBank; DB03593; 7-methyl-5'-guanylic acid. DR DrugBank; DB01960; 7-methyl-7,8-dihydroguanosine-5'-diphosphate. DR DrugBank; DB01649; 7-methyl-GpppA. DR DrugBank; DB03958; 7-methyl-guanosine-5'-triphosphate-5'-guanosine. DR GlyGen; Q96C86; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96C86; -. DR PhosphoSitePlus; Q96C86; -. DR SwissPalm; Q96C86; -. DR BioMuta; DCPS; -. DR DMDM; 116241325; -. DR REPRODUCTION-2DPAGE; IPI00335385; -. DR EPD; Q96C86; -. DR jPOST; Q96C86; -. DR MassIVE; Q96C86; -. DR MaxQB; Q96C86; -. DR PaxDb; 9606-ENSP00000263579; -. DR PeptideAtlas; Q96C86; -. DR ProteomicsDB; 76164; -. DR Pumba; Q96C86; -. DR Antibodypedia; 32998; 259 antibodies from 24 providers. DR DNASU; 28960; -. DR Ensembl; ENST00000263579.5; ENSP00000263579.4; ENSG00000110063.10. DR GeneID; 28960; -. DR KEGG; hsa:28960; -. DR MANE-Select; ENST00000263579.5; ENSP00000263579.4; NM_014026.6; NP_054745.1. DR UCSC; uc001qdp.3; human. DR AGR; HGNC:29812; -. DR CTD; 28960; -. DR DisGeNET; 28960; -. DR GeneCards; DCPS; -. DR HGNC; HGNC:29812; DCPS. DR HPA; ENSG00000110063; Tissue enhanced (liver). DR MalaCards; DCPS; -. DR MIM; 610534; gene. DR MIM; 616459; phenotype. DR neXtProt; NX_Q96C86; -. DR OpenTargets; ENSG00000110063; -. DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability. DR PharmGKB; PA134863866; -. DR VEuPathDB; HostDB:ENSG00000110063; -. DR eggNOG; KOG3969; Eukaryota. DR GeneTree; ENSGT00390000003924; -. DR HOGENOM; CLU_041045_2_0_1; -. DR InParanoid; Q96C86; -. DR OMA; HVHINPI; -. DR OrthoDB; 5490768at2759; -. DR PhylomeDB; Q96C86; -. DR TreeFam; TF105622; -. DR BRENDA; 3.6.1.59; 2681. DR PathwayCommons; Q96C86; -. DR Reactome; R-HSA-429958; mRNA decay by 3' to 5' exoribonuclease. DR SignaLink; Q96C86; -. DR BioGRID-ORCS; 28960; 258 hits in 1184 CRISPR screens. DR ChiTaRS; DCPS; human. DR EvolutionaryTrace; Q96C86; -. DR GeneWiki; DCPS_(gene); -. DR GenomeRNAi; 28960; -. DR Pharos; Q96C86; Tchem. DR PRO; PR:Q96C86; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q96C86; Protein. DR Bgee; ENSG00000110063; Expressed in right lobe of liver and 156 other cell types or tissues. DR ExpressionAtlas; Q96C86; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0000932; C:P-body; IBA:GO_Central. DR GO; GO:0140932; F:5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA] diphosphatase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0000340; F:RNA 7-methylguanosine cap binding; IDA:UniProtKB. DR GO; GO:0004532; F:RNA exonuclease activity; TAS:Reactome. DR GO; GO:0000290; P:deadenylation-dependent decapping of nuclear-transcribed mRNA; IBA:GO_Central. DR GO; GO:0043928; P:exonucleolytic catabolism of deadenylated mRNA; TAS:Reactome. DR GO; GO:0110156; P:methylguanosine-cap decapping; IDA:WormBase. DR GO; GO:0045292; P:mRNA cis splicing, via spliceosome; IDA:UniProtKB. DR GO; GO:0000288; P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; TAS:UniProtKB. DR Gene3D; 3.30.428.10; HIT-like; 1. DR Gene3D; 3.30.200.40; Scavenger mRNA decapping enzyme, N-terminal domain; 1. DR InterPro; IPR008594; DcpS/DCS2. DR InterPro; IPR019808; Histidine_triad_CS. DR InterPro; IPR036265; HIT-like_sf. DR InterPro; IPR011145; Scavenger_mRNA_decap_enz_N. DR PANTHER; PTHR12978; HISTIDINE TRIAD HIT PROTEIN MEMBER; 1. DR PANTHER; PTHR12978:SF0; M7GPPPX DIPHOSPHATASE; 1. DR Pfam; PF05652; DcpS; 1. DR Pfam; PF11969; DcpS_C; 1. DR PIRSF; PIRSF028973; Scavenger_mRNA_decap_enz; 1. DR SUPFAM; SSF54197; HIT-like; 1. DR SUPFAM; SSF102860; mRNA decapping enzyme DcpS N-terminal domain; 1. DR PROSITE; PS00892; HIT_1; 1. DR Genevisible; Q96C86; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; KW Disease variant; Hydrolase; Intellectual disability; mRNA processing; KW mRNA splicing; Nucleus; Phosphoprotein; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT CHAIN 2..337 FT /note="m7GpppX diphosphatase" FT /id="PRO_0000109794" FT REGION 1..35 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 10..13 FT /note="nuclear localization signal (NLS)" FT MOTIF 142..154 FT /note="nuclear export sequence (NES)" FT MOTIF 275..279 FT /note="Histidine triad motif" FT COMPBIAS 1..26 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 277 FT /note="Nucleophile" FT BINDING 175 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:15068804, FT ECO:0000269|PubMed:15769464" FT BINDING 185 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:15068804, FT ECO:0000269|PubMed:15769464" FT BINDING 205 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:15068804, FT ECO:0000269|PubMed:15769464" FT BINDING 207 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:15068804, FT ECO:0000269|PubMed:15769464" FT BINDING 268..279 FT /ligand="substrate" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT MOD_RES 24 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 101 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9DAR7" FT MOD_RES 138 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 142 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VARIANT 73 FT /note="G -> E (in dbSNP:rs11557735)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_027958" FT VARIANT 316 FT /note="T -> M (in ARS; results in a severe decrease of FT decapase activity; dbSNP:rs137941190)" FT /evidence="ECO:0000269|PubMed:25701870" FT /id="VAR_073956" FT MUTAGEN 10..13 FT /note="Missing: Increases cytoplasmic localization." FT /evidence="ECO:0000269|PubMed:18426921" FT MUTAGEN 58 FT /note="R->A: Increases decapping activity to 125% of FT wild-type." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 61 FT /note="I->A: No effect." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 63 FT /note="F->A: No effect." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 83 FT /note="I->A: Strongly reduces decapping activity." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 85 FT /note="E->A: Reduces decapping activity." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 108 FT /note="F->A: Reduces decapping activity." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 110 FT /note="N->A: Loss of decapping activity." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 113 FT /note="Y->A: Loss of decapping activity." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 128 FT /note="K->A: No effect." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 138 FT /note="K->D: Increases decapping activity to 250% of FT wild-type." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 145 FT /note="R->A: Increases decapping activity to 180% of FT wild-type." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 146 FT /note="Q->P: Increases decapping activity to 140% of FT wild-type." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 148 FT /note="L->A: Inhibits nuclear export to the cytoplasm." FT /evidence="ECO:0000269|PubMed:18426921" FT MUTAGEN 150 FT /note="L->A: Inhibits nuclear export to the cytoplasm." FT /evidence="ECO:0000269|PubMed:18426921" FT MUTAGEN 175 FT /note="W->A: Loss of decapping activity." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 185 FT /note="E->A: Loss of decapping activity." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 204 FT /note="P->A: Reduces decapping activity." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 205 FT /note="D->A: Reduces decapping activity." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 206 FT /note="L->A: No effect." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 207 FT /note="K->A: Reduces decapping activity." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 207 FT /note="K->R: No effect." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 217 FT /note="Y->A: No effect." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 217 FT /note="Y->F: Reduces decapping activity." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 268 FT /note="H->N: Loss of decapping activity." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 272 FT /note="S->A: No effect." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 273 FT /note="Y->A: Reduces decapping activity." FT /evidence="ECO:0000269|PubMed:15769464" FT MUTAGEN 273 FT /note="Y->F: Activates decapping activity to 120% of FT wild-type." FT /evidence="ECO:0000269|PubMed:15769464" FT MUTAGEN 277 FT /note="H->N: Loss of decapping activity. Does not inhibit FT cap structure and capped RNA binding. Preferentially FT hydrolyzes cap structure (m7GpppG) at least 2500-fold more FT efficiently than capped RNA (m7Gppp-RNA)." FT /evidence="ECO:0000269|PubMed:12198172, FT ECO:0000269|PubMed:15068804, ECO:0000269|PubMed:15273322" FT MUTAGEN 279 FT /note="H->N: Loss of decapping activity." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 294 FT /note="R->A,K: No effect." FT /evidence="ECO:0000269|PubMed:15068804" FT MUTAGEN 322 FT /note="R->A: No effect." FT /evidence="ECO:0000269|PubMed:15068804" FT CONFLICT 69 FT /note="N -> K (in Ref. 1; AAK91763)" FT /evidence="ECO:0000305" FT STRAND 43..45 FT /evidence="ECO:0007829|PDB:1ST0" FT STRAND 48..56 FT /evidence="ECO:0007829|PDB:3BL9" FT TURN 57..60 FT /evidence="ECO:0007829|PDB:3BL9" FT STRAND 61..67 FT /evidence="ECO:0007829|PDB:3BL9" FT STRAND 79..86 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 91..98 FT /evidence="ECO:0007829|PDB:3BL9" FT STRAND 103..110 FT /evidence="ECO:0007829|PDB:3BL9" FT STRAND 113..119 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 122..124 FT /evidence="ECO:0007829|PDB:3BL9" FT STRAND 127..132 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 137..143 FT /evidence="ECO:0007829|PDB:3BL9" FT STRAND 148..153 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 155..160 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 162..167 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 174..180 FT /evidence="ECO:0007829|PDB:3BL9" FT STRAND 183..185 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 186..188 FT /evidence="ECO:0007829|PDB:3BL9" FT STRAND 191..193 FT /evidence="ECO:0007829|PDB:3BL9" FT TURN 196..198 FT /evidence="ECO:0007829|PDB:3BL9" FT STRAND 200..204 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 213..215 FT /evidence="ECO:0007829|PDB:1XML" FT STRAND 217..225 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 230..232 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 235..237 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 238..256 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 260..262 FT /evidence="ECO:0007829|PDB:3BL9" FT STRAND 263..270 FT /evidence="ECO:0007829|PDB:3BL9" FT STRAND 272..275 FT /evidence="ECO:0007829|PDB:3BL9" FT STRAND 277..282 FT /evidence="ECO:0007829|PDB:3BL9" FT TURN 292..294 FT /evidence="ECO:0007829|PDB:3BL9" FT STRAND 295..297 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 298..307 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 311..314 FT /evidence="ECO:0007829|PDB:3BL9" FT STRAND 317..322 FT /evidence="ECO:0007829|PDB:3BL9" FT HELIX 326..333 FT /evidence="ECO:0007829|PDB:3BL9" SQ SEQUENCE 337 AA; 38609 MW; C9C5A33C212D7A52 CRC64; MADAAPQLGK RKRELDVEEA HAASTEEKEA GVGNGTCAPV RLPFSGFRLQ KVLRESARDK IIFLHGKVNE ASGDGDGEDA VVILEKTPFQ VEQVAQLLTG SPELQLQFSN DIYSTYHLFP PRQLNDVKTT VVYPATEKHL QKYLRQDLRL IRETGDDYRN ITLPHLESQS LSIQWVYNIL DKKAEADRIV FENPDPSDGF VLIPDLKWNQ QQLDDLYLIA ICHRRGIRSL RDLTPEHLPL LRNILHQGQE AILQRYRMKG DHLRVYLHYL PSYYHLHVHF TALGFEAPGS GVERAHLLAE VIENLECDPR HYQQRTLTFA LRADDPLLKL LQEAQQS //