DCPS_HUMAN
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 03-AUG-2022, entry version 176.
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; 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}.
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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; 385.
DR IntAct; Q96C86; 7.
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 BioMuta; DCPS; -.
DR DMDM; 116241325; -.
DR REPRODUCTION-2DPAGE; IPI00335385; -.
DR EPD; Q96C86; -.
DR jPOST; Q96C86; -.
DR MassIVE; Q96C86; -.
DR MaxQB; Q96C86; -.
DR PaxDb; Q96C86; -.
DR PeptideAtlas; Q96C86; -.
DR PRIDE; Q96C86; -.
DR ProteomicsDB; 76164; -.
DR Antibodypedia; 32998; 233 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 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; LIYPCTD; -.
DR OrthoDB; 930557at2759; -.
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; 237 hits in 1090 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 154 other tissues.
DR ExpressionAtlas; Q96C86; baseline and differential.
DR Genevisible; Q96C86; HS.
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:0004532; F:exoribonuclease activity; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0050072; F:m7G(5')pppN diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0000340; F:RNA 7-methylguanosine cap binding; IDA:UniProtKB.
DR GO; GO:0036245; P:cellular response to menadione; IDA:UniProtKB.
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:0043069; P:negative regulation of programmed cell death; IDA:UniProtKB.
DR GO; GO:0000288; P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; TAS:UniProtKB.
DR Gene3D; 3.30.200.40; -; 1.
DR Gene3D; 3.30.428.10; -; 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; PTHR12978; 1.
DR Pfam; PF05652; DcpS; 1.
DR PIRSF; PIRSF028973; Scavenger_mRNA_decap_enz; 1.
DR SUPFAM; SSF102860; SSF102860; 1.
DR SUPFAM; SSF54197; SSF54197; 1.
DR PROSITE; PS00892; HIT_1; 1.
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 wild-
FT 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 wild-
FT type."
FT /evidence="ECO:0000269|PubMed:15068804"
FT MUTAGEN 145
FT /note="R->A: Increases decapping activity to 180% of wild-
FT type."
FT /evidence="ECO:0000269|PubMed:15068804"
FT MUTAGEN 146
FT /note="Q->P: Increases decapping activity to 140% of wild-
FT 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 wild-
FT 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
