ID DCPS_MOUSE Reviewed; 338 AA. AC Q9DAR7; Q8C5I7; DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 24-JAN-2024, entry version 158. DE RecName: Full=m7GpppX diphosphatase; DE EC=3.6.1.59 {ECO:0000250|UniProtKB:Q96C86}; 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; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=BALB/cJ; TISSUE=Brain; 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 [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Olfactory bulb, and Testis; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Eye; 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 [4] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-100, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [6] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-137, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001; RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.; RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic RT pathways."; RL Mol. Cell 50:919-930(2013). RN [7] RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS). RG Joint center for structural genomics (JCSG); RT "Crystal structure of mRNA decapping enzyme (DCPS) from Mus musculus at RT 1.83 A resolution."; RL Submitted (AUG-2004) to the PDB data bank. 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. May also play a role in CC the 5'->3 mRNA decay pathway; m7GDP, the downstream product released by CC the 5'->3' mRNA mediated decapping activity, may be also converted by CC DCPS to m7GMP. Binds to m7GpppG and strongly to m7GDP. Plays a role in CC first intron splicing of pre-mRNAs. Inhibits activation-induced cell CC death. {ECO:0000250}. 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:0000250|UniProtKB:Q96C86}; 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:0000250}. CC -!- SUBUNIT: Homodimer. Associates with components of the exosome CC multienzyme ribonuclease complex, such as EXOSC3 and EXOSC4. Interacts CC with NDOR1. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. CC Note=Predominantly localized in the nucleus. Nucleocytoplasmic CC shuttling protein that can transiently enter the cytoplasm in mammalian CC cells in a XPO1/CRM1-dependent manner. {ECO:0000250}. 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. {ECO:0000250}. 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; AY040775; AAK91764.1; -; mRNA. DR EMBL; AK005584; BAB24138.1; -; mRNA. DR EMBL; AK078253; BAC37194.1; -; mRNA. DR EMBL; BC016273; AAH16273.1; -; mRNA. DR CCDS; CCDS22957.1; -. DR RefSeq; NP_081306.1; NM_027030.2. DR PDB; 1VLR; X-ray; 1.83 A; A/B=1-338. DR PDBsum; 1VLR; -. DR AlphaFoldDB; Q9DAR7; -. DR SMR; Q9DAR7; -. DR BioGRID; 213348; 13. DR IntAct; Q9DAR7; 1. DR MINT; Q9DAR7; -. DR STRING; 10090.ENSMUSP00000034539; -. DR ChEMBL; CHEMBL4105708; -. DR iPTMnet; Q9DAR7; -. DR PhosphoSitePlus; Q9DAR7; -. DR SwissPalm; Q9DAR7; -. DR EPD; Q9DAR7; -. DR jPOST; Q9DAR7; -. DR MaxQB; Q9DAR7; -. DR PaxDb; 10090-ENSMUSP00000034539; -. DR PeptideAtlas; Q9DAR7; -. DR ProteomicsDB; 279393; -. DR Pumba; Q9DAR7; -. DR Antibodypedia; 32998; 259 antibodies from 24 providers. DR DNASU; 69305; -. DR Ensembl; ENSMUST00000034539.12; ENSMUSP00000034539.6; ENSMUSG00000032040.16. DR GeneID; 69305; -. DR KEGG; mmu:69305; -. DR UCSC; uc009osp.1; mouse. DR AGR; MGI:1916555; -. DR CTD; 28960; -. DR MGI; MGI:1916555; Dcps. DR VEuPathDB; HostDB:ENSMUSG00000032040; -. DR eggNOG; KOG3969; Eukaryota. DR GeneTree; ENSGT00390000003924; -. DR HOGENOM; CLU_041045_2_0_1; -. DR InParanoid; Q9DAR7; -. DR OMA; HVHINPI; -. DR OrthoDB; 5490768at2759; -. DR PhylomeDB; Q9DAR7; -. DR TreeFam; TF105622; -. DR BRENDA; 3.6.1.59; 3474. DR Reactome; R-MMU-429958; mRNA decay by 3' to 5' exoribonuclease. DR BioGRID-ORCS; 69305; 22 hits in 82 CRISPR screens. DR ChiTaRS; Dcps; mouse. DR EvolutionaryTrace; Q9DAR7; -. DR PRO; PR:Q9DAR7; -. DR Proteomes; UP000000589; Chromosome 9. DR RNAct; Q9DAR7; Protein. DR Bgee; ENSMUSG00000032040; Expressed in spinal cord lateral wall and 246 other cell types or tissues. DR ExpressionAtlas; Q9DAR7; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0005739; C:mitochondrion; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; ISS: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; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0000340; F:RNA 7-methylguanosine cap binding; ISS:UniProtKB. DR GO; GO:0000290; P:deadenylation-dependent decapping of nuclear-transcribed mRNA; IBA:GO_Central. DR GO; GO:0110156; P:methylguanosine-cap decapping; ISO:MGI. DR GO; GO:0045292; P:mRNA cis splicing, via spliceosome; ISS: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; Q9DAR7; MM. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Hydrolase; mRNA processing; KW mRNA splicing; Nucleus; Phosphoprotein; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:Q96C86" FT CHAIN 2..338 FT /note="m7GpppX diphosphatase" FT /id="PRO_0000109795" FT REGION 1..36 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 9..12 FT /note="nuclear localization signal (NLS)" FT /evidence="ECO:0000250" FT MOTIF 141..153 FT /note="nuclear export sequence (NES)" FT /evidence="ECO:0000250" FT MOTIF 274..278 FT /note="Histidine triad motif" FT /evidence="ECO:0000250" FT COMPBIAS 1..18 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 276 FT /note="Nucleophile" FT /evidence="ECO:0000250" FT BINDING 174 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 184 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 204 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 206 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 267..278 FT /ligand="substrate" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:Q96C86" FT MOD_RES 23 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q96C86" FT MOD_RES 100 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 137 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 141 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q96C86" FT CONFLICT 141 FT /note="K -> E (in Ref. 2; BAC37194)" FT /evidence="ECO:0000305" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 47..55 FT /evidence="ECO:0007829|PDB:1VLR" FT TURN 56..59 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 60..67 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 77..85 FT /evidence="ECO:0007829|PDB:1VLR" FT HELIX 90..97 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 102..108 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 110..118 FT /evidence="ECO:0007829|PDB:1VLR" FT HELIX 121..124 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 126..133 FT /evidence="ECO:0007829|PDB:1VLR" FT HELIX 136..142 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 147..152 FT /evidence="ECO:0007829|PDB:1VLR" FT HELIX 154..159 FT /evidence="ECO:0007829|PDB:1VLR" FT HELIX 161..168 FT /evidence="ECO:0007829|PDB:1VLR" FT HELIX 173..179 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 182..184 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 189..192 FT /evidence="ECO:0007829|PDB:1VLR" FT TURN 195..197 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 199..203 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 216..224 FT /evidence="ECO:0007829|PDB:1VLR" FT HELIX 229..231 FT /evidence="ECO:0007829|PDB:1VLR" FT HELIX 234..236 FT /evidence="ECO:0007829|PDB:1VLR" FT HELIX 237..255 FT /evidence="ECO:0007829|PDB:1VLR" FT HELIX 259..261 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 262..269 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 271..274 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 276..281 FT /evidence="ECO:0007829|PDB:1VLR" FT TURN 291..293 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 294..296 FT /evidence="ECO:0007829|PDB:1VLR" FT HELIX 297..306 FT /evidence="ECO:0007829|PDB:1VLR" FT HELIX 310..313 FT /evidence="ECO:0007829|PDB:1VLR" FT STRAND 316..321 FT /evidence="ECO:0007829|PDB:1VLR" FT HELIX 325..336 FT /evidence="ECO:0007829|PDB:1VLR" SQ SEQUENCE 338 AA; 38988 MW; A9520CBE48293DFC CRC64; MADTAPQLKR KREQEAEEAE TPSTEEKEAG VGNGTSAPVR LPFSGFRVQK VLRESARDKI IFLHGKVNED SGDTHGEDAV VILEKTPFQV EHVAQLLTGS PELKLQFSND IYSTYNLFPP RHLSDIKTTV VYPATEKHLQ KYMRQDLRLI RETGDDYRTI TLPYLESQSL SIQWVYNILD KKAEADRIVF ENPDPSDGFV LIPDLKWNQQ QLDDLYLIAI CHRRGIRSLR DLTPEHLPLL RNILREGQEA ILKRYQVTGD RLRVYLHYLP SYYHLHVHFT ALGFEAPGSG VERAHLLAQV IENLECDPKH YQQRTLTFAL RTDDPLLQLL QKAQQERN //