ID DCP2_HUMAN Reviewed; 420 AA. AC Q8IU60; C9J778; Q6P2D4; Q7Z5W5; Q8NBG5; DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 12-SEP-2018, sequence version 3. DT 24-JAN-2024, entry version 179. DE RecName: Full=m7GpppN-mRNA hydrolase {ECO:0000305}; DE EC=3.6.1.62 {ECO:0000269|PubMed:12486012, ECO:0000269|PubMed:12923261, ECO:0000269|PubMed:21070968, ECO:0000269|PubMed:28002401, ECO:0000269|PubMed:31875550}; DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 20; DE Short=Nudix motif 20; DE AltName: Full=mRNA-decapping enzyme 2; DE Short=hDpc; GN Name=DCP2; Synonyms=NUDT20; 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 [MRNA] (ISOFORM 1), FUNCTION, MUTAGENESIS OF GLU-148, RP SUBCELLULAR LOCATION, AND INTERACTION WITH DCP1A AND UPF1. RX PubMed=12417715; DOI=10.1128/mcb.22.23.8114-8121.2002; RA Lykke-Andersen J.; RT "Identification of a human decapping complex associated with hUpf proteins RT in nonsense-mediated decay."; RL Mol. Cell. Biol. 22:8114-8121(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, MUTAGENESIS OF RP 147-GLU-GLU-148, SUBCELLULAR LOCATION, AND ASSOCIATION WITH POLYSOMES. RC TISSUE=Erythroleukemia; RX PubMed=12218187; DOI=10.1073/pnas.192445599; RA Wang Z., Jiao X., Carr-Schmid A., Kiledjian M.; RT "The hDcp2 protein is a mammalian mRNA decapping enzyme."; RL Proc. Natl. Acad. Sci. U.S.A. 99:12663-12668(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PHE-16. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Blood, and Uterus; 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 FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=12486012; DOI=10.1093/emboj/cdf678; RA van Dijk E., Cougot N., Meyer S., Babajko S., Wahle E., Seraphin B.; RT "Human Dcp2: a catalytically active mRNA decapping enzyme located in RT specific cytoplasmic structures."; RL EMBO J. 21:6915-6924(2002). RN [7] RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH A COMPLEX CONTAINING ENZYMES RP INVOLVED IN MRNA DECAY. RX PubMed=12515382; RA Ingelfinger D., Arndt-Jovin D.J., Luehrmann R., Achsel T.; RT "The human LSm1-7 proteins colocalize with the mRNA-degrading enzymes RT Dcp1/2 and Xrnl in distinct cytoplasmic foci."; RL RNA 8:1489-1501(2002). RN [8] RP FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, IDENTIFICATION IN A MRNA DECAY RP COMPLEX WITH UPF1; UPF2 AND UPF3B, AND SUBCELLULAR LOCATION. RX PubMed=14527413; DOI=10.1016/s1097-2765(03)00349-6; RA Lejeune F., Li X., Maquat L.E.; RT "Nonsense-mediated mRNA decay in mammalian cells involves decapping, RT deadenylating, and exonucleolytic activities."; RL Mol. Cell 12:675-687(2003). RN [9] RP FUNCTION, RNA-BINDING, CATALYTIC ACTIVITY, AND COFACTOR. RX PubMed=12923261; DOI=10.1261/rna.5690503; RA Piccirillo C., Khanna R., Kiledjian M.; RT "Functional characterization of the mammalian mRNA decapping enzyme RT hDcp2."; RL RNA 9:1138-1147(2003). RN [10] RP INTERACTION WITH DCP1A AND DCP1B. RX PubMed=15231747; DOI=10.1101/gr.2122004; RA Lehner B., Sanderson C.M.; RT "A protein interaction framework for human mRNA degradation."; RL Genome Res. 14:1315-1323(2004). RN [11] RP SUBCELLULAR LOCATION, AND INTERACTION WITH DCP1A. RX PubMed=15067023; DOI=10.1083/jcb.200309008; RA Cougot N., Babajko S., Seraphin B.; RT "Cytoplasmic foci are sites of mRNA decay in human cells."; RL J. Cell Biol. 165:31-40(2004). RN [12] RP SUBCELLULAR LOCATION. 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 [13] RP INTERACTION WITH ZFP36L1. RX PubMed=15687258; DOI=10.1101/gad.1282305; RA Lykke-Andersen J., Wagner E.; RT "Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay RT activation domains in the proteins TTP and BRF-1."; RL Genes Dev. 19:351-361(2005). RN [14] RP INTERACTION WITH DCP1A; EDC3; EDC4 AND DDX6, AND SUBCELLULAR LOCATION. RX PubMed=16364915; DOI=10.1016/j.molcel.2005.10.031; RA Fenger-Groen M., Fillman C., Norrild B., Lykke-Andersen J.; RT "Multiple processing body factors and the ARE binding protein TTP activate RT mRNA decapping."; RL Mol. Cell 20:905-915(2005). RN [15] RP INTERACTION WITH APOBEC3G. RX PubMed=16699599; DOI=10.1371/journal.ppat.0020041; RA Wichroski M.J., Robb G.B., Rana T.M.; RT "Human retroviral host restriction factors APOBEC3G and APOBEC3F localize RT to mRNA processing bodies."; RL PLoS Pathog. 2:E41-E41(2006). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-276 AND SER-284, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [17] RP INTERACTION WITH TRIM21. RX PubMed=18361920; DOI=10.1016/j.bbrc.2008.03.075; RA Yamochi T., Ohnuma K., Hosono O., Tanaka H., Kanai Y., Morimoto C.; RT "SSA/Ro52 autoantigen interacts with Dcp2 to enhance its decapping RT activity."; RL Biochem. Biophys. Res. Commun. 370:195-199(2008). RN [18] RP FUNCTION IN HISTONE MRNA DEGRADATION ACTIVITY. RX PubMed=18172165; DOI=10.1101/gad.1622708; RA Mullen T.E., Marzluff W.F.; RT "Degradation of histone mRNA requires oligouridylation followed by RT decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to RT 5'."; RL Genes Dev. 22:50-65(2008). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246; SER-247; SER-249 AND RP SER-284, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [21] RP FUNCTION AS A DECAPPING ENZYME, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY. RX PubMed=21070968; DOI=10.1016/j.molcel.2010.10.010; RA Song M.G., Li Y., Kiledjian M.; RT "Multiple mRNA decapping enzymes in mammalian cells."; RL Mol. Cell 40:423-432(2010). RN [22] RP SUBCELLULAR LOCATION, AND INTERACTION WITH LIMD1; WTIP AND AJUBA. RX PubMed=20616046; DOI=10.1073/pnas.0914987107; RA James V., Zhang Y., Foxler D.E., de Moor C.H., Kong Y.W., Webb T.M., RA Self T.J., Feng Y., Lagos D., Chu C.Y., Rana T.M., Morley S.J., RA Longmore G.D., Bushell M., Sharp T.V.; RT "LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA- RT mediated gene silencing."; RL Proc. Natl. Acad. Sci. U.S.A. 107:12499-12504(2010). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [24] RP INTERACTION WITH ZC3HAV1 AND DDX17. RX PubMed=21876179; DOI=10.1073/pnas.1101676108; RA Zhu Y., Chen G., Lv F., Wang X., Ji X., Xu Y., Sun J., Wu L., Zheng Y.T., RA Gao G.; RT "Zinc-finger antiviral protein inhibits HIV-1 infection by selectively RT targeting multiply spliced viral mRNAs for degradation."; RL Proc. Natl. Acad. Sci. U.S.A. 108:15834-15839(2011). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246; SER-247 AND SER-249, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249 AND SER-284, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and 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 [27] 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 [28] RP FUNCTION, MUTAGENESIS OF SER-249, AND PHOSPHORYLATION AT SER-249. RX PubMed=26098573; DOI=10.1038/ncb3189; RA Hu G., McQuiston T., Bernard A., Park Y.D., Qiu J., Vural A., Zhang N., RA Waterman S.R., Blewett N.H., Myers T.G., Maraia R.J., Kehrl J.H., Uzel G., RA Klionsky D.J., Williamson P.R.; RT "A conserved mechanism of TOR-dependent RCK-mediated mRNA degradation RT regulates autophagy."; RL Nat. Cell Biol. 17:930-942(2015). RN [29] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=28002401; DOI=10.1038/nature21022; RA Mauer J., Luo X., Blanjoie A., Jiao X., Grozhik A.V., Patil D.P., RA Linder B., Pickering B.F., Vasseur J.J., Chen Q., Gross S.S., Elemento O., RA Debart F., Kiledjian M., Jaffrey S.R.; RT "Reversible methylation of m6Am in the 5' cap controls mRNA stability."; RL Nature 541:371-375(2017). RN [30] RP INTERACTION WITH NBDY. RX PubMed=27918561; DOI=10.1038/nchembio.2249; RA D'Lima N.G., Ma J., Winkler L., Chu Q., Loh K.H., Corpuz E.O., Budnik B.A., RA Lykke-Andersen J., Saghatelian A., Slavoff S.A.; RT "A human microprotein that interacts with the mRNA decapping complex."; RL Nat. Chem. Biol. 13:174-180(2017). RN [31] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=31875550; DOI=10.1016/j.celrep.2019.11.108; RA Wu H., Li L., Chen K.M., Homolka D., Gos P., Fleury-Olela F., RA McCarthy A.A., Pillai R.S.; RT "Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of RT NAD-Capped RNAs."; RL Cell Rep. 29:4422-4434(2019). CC -!- FUNCTION: Decapping metalloenzyme that catalyzes the cleavage of the CC cap structure on mRNAs (PubMed:12417715, PubMed:12218187, CC PubMed:12923261, PubMed:21070968, PubMed:28002401, PubMed:31875550). CC Removes the 7-methyl guanine cap structure from mRNA molecules, CC yielding a 5'-phosphorylated mRNA fragment and 7m-GDP (PubMed:12486012, CC PubMed:12923261, PubMed:21070968, PubMed:28002401, PubMed:31875550). CC Necessary for the degradation of mRNAs, both in normal mRNA turnover CC and in nonsense-mediated mRNA decay (PubMed:14527413). Plays a role in CC replication-dependent histone mRNA degradation (PubMed:18172165). Has CC higher activity towards mRNAs that lack a poly(A) tail CC (PubMed:21070968). Has no activity towards a cap structure lacking an CC RNA moiety (PubMed:21070968). The presence of a N(6)-methyladenosine CC methylation at the second transcribed position of mRNAs (N(6),2'-O- CC dimethyladenosine cap; m6A(m)) provides resistance to DCP2-mediated CC decapping (PubMed:28002401). Blocks autophagy in nutrient-rich CC conditions by repressing the expression of ATG-related genes through CC degradation of their transcripts (PubMed:26098573). CC {ECO:0000269|PubMed:12218187, ECO:0000269|PubMed:12417715, CC ECO:0000269|PubMed:12486012, ECO:0000269|PubMed:12923261, CC ECO:0000269|PubMed:14527413, ECO:0000269|PubMed:18172165, CC ECO:0000269|PubMed:21070968, ECO:0000269|PubMed:26098573, CC ECO:0000269|PubMed:28002401}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside CC in mRNA + H2O = a 5'-end phospho-ribonucleoside in mRNA + 2 H(+) + CC N(7)-methyl-GDP; Xref=Rhea:RHEA:67484, Rhea:RHEA-COMP:15692, CC Rhea:RHEA-COMP:17167, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:63714, ChEBI:CHEBI:138282, ChEBI:CHEBI:156461; CC EC=3.6.1.62; Evidence={ECO:0000269|PubMed:12486012, CC ECO:0000269|PubMed:12923261, ECO:0000269|PubMed:21070968, CC ECO:0000269|PubMed:28002401}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67485; CC Evidence={ECO:0000269|PubMed:12486012, ECO:0000269|PubMed:12923261, CC ECO:0000269|PubMed:21070968, ECO:0000269|PubMed:28002401}; CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000269|PubMed:12923261}; CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:12923261}; CC Note=Mn(2+) ion is required for highest activity. Can also utilize CC magnesium ions. {ECO:0000269|PubMed:12923261}; CC -!- SUBUNIT: Found in a mRNA decay complex with LSM1, LSM3, LSM4, EXOSC2, CC EXOSC4, EXOSC10, PARN, XRN1, CNOT6, UPF1, UPF2 and UPF3B CC (PubMed:12417715, PubMed:12515382, PubMed:14527413). Forms a complex CC with DCP1A, EDC3, DDX6 and EDC4/HEDLS, within this complex directly CC interacts with EDC4/HEDLS (PubMed:15231747, PubMed:15067023, CC PubMed:16364915). Interacts with DPC1B (PubMed:15231747). Interacts CC (via N-terminus and C-terminus) with TRIM21 (via N-terminus and C- CC terminus) (PubMed:18361920). Associates with polysomes CC (PubMed:12218187). Interacts with LIMD1, WTIP and AJUBA CC (PubMed:20616046). Interacts with DDX17 in an RNA-dependent manner CC (PubMed:21876179). Interacts with ZC3HAV1 (PubMed:21876179). Interacts CC with APOBEC3G in an RNA-dependent manner (PubMed:16699599). Interacts CC with ZFP36L1 (via N-terminus) (PubMed:15687258). Interacts with NBDY CC (PubMed:27918561). {ECO:0000269|PubMed:12218187, CC ECO:0000269|PubMed:12417715, ECO:0000269|PubMed:12515382, CC ECO:0000269|PubMed:14527413, ECO:0000269|PubMed:15067023, CC ECO:0000269|PubMed:15231747, ECO:0000269|PubMed:15687258, CC ECO:0000269|PubMed:16364915, ECO:0000269|PubMed:16699599, CC ECO:0000269|PubMed:18361920, ECO:0000269|PubMed:20616046, CC ECO:0000269|PubMed:21876179, ECO:0000269|PubMed:27918561}. CC -!- INTERACTION: CC Q8IU60; Q9NPI6: DCP1A; NbExp=16; IntAct=EBI-521577, EBI-374238; CC Q8IU60; Q8IZD4: DCP1B; NbExp=3; IntAct=EBI-521577, EBI-521595; CC Q8IU60; Q6P2E9: EDC4; NbExp=8; IntAct=EBI-521577, EBI-1006038; CC Q8IU60; Q92900: UPF1; NbExp=3; IntAct=EBI-521577, EBI-373471; CC Q8IU60-2; Q6P2E9: EDC4; NbExp=2; IntAct=EBI-521590, EBI-1006038; CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000269|PubMed:15067023, CC ECO:0000269|PubMed:15273322, ECO:0000269|PubMed:16364915, CC ECO:0000269|PubMed:20616046}. Nucleus {ECO:0000269|PubMed:15273322}. CC Note=Predominantly cytoplasmic, in processing bodies (PB) CC (PubMed:15273322). A minor amount is nuclear (PubMed:15273322). CC {ECO:0000269|PubMed:15273322, ECO:0000269|PubMed:16364915, CC ECO:0000269|PubMed:20616046}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8IU60-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8IU60-2; Sequence=VSP_012908; CC -!- TISSUE SPECIFICITY: Expressed in brain and testis. Not detected in CC heart (at protein level). {ECO:0000269|PubMed:21070968}. CC -!- PTM: Phosphorylated at ser-249 in a MTOR-dependent manner CC (PubMed:26098573). CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. DCP2 subfamily. CC {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; AY146650; AAN62762.1; -; mRNA. DR EMBL; AY135173; AAN08884.1; -; mRNA. DR EMBL; AK090564; BAC03479.1; -; mRNA. DR EMBL; AC008536; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC045596; AAH45596.1; -; mRNA. DR EMBL; BC064593; AAH64593.1; -; mRNA. DR CCDS; CCDS34210.1; -. [Q8IU60-1] DR CCDS; CCDS56377.1; -. [Q8IU60-2] DR RefSeq; NP_001229306.1; NM_001242377.1. [Q8IU60-2] DR RefSeq; NP_689837.2; NM_152624.5. [Q8IU60-1] DR PDB; 5MP0; X-ray; 1.63 A; D=95-260. DR PDB; 5QOH; X-ray; 1.93 A; A=95-260. DR PDB; 5QOI; X-ray; 1.99 A; A=95-260. DR PDB; 5QOJ; X-ray; 2.05 A; A=95-260. DR PDB; 5QOK; X-ray; 2.28 A; A=95-260. DR PDB; 5QOL; X-ray; 1.85 A; A=95-260. DR PDB; 5QOM; X-ray; 1.87 A; A=95-260. DR PDB; 5QON; X-ray; 1.80 A; A=95-260. DR PDB; 5QOO; X-ray; 1.56 A; A=95-260. DR PDB; 5QOP; X-ray; 1.86 A; A=95-260. DR PDB; 5QOQ; X-ray; 1.49 A; A=95-260. DR PDB; 5QOR; X-ray; 1.95 A; A=95-260. DR PDB; 5QOS; X-ray; 1.70 A; A=95-260. DR PDB; 5QOT; X-ray; 1.68 A; A=95-260. DR PDB; 5QOU; X-ray; 2.19 A; A=95-260. DR PDB; 5QOV; X-ray; 1.65 A; A=95-260. DR PDB; 5QOW; X-ray; 1.82 A; A=95-260. DR PDB; 5QOX; X-ray; 1.95 A; A=95-260. DR PDB; 5QOY; X-ray; 1.69 A; A=95-260. DR PDB; 5QOZ; X-ray; 1.70 A; A=95-260. DR PDB; 5QP0; X-ray; 2.00 A; A=95-260. DR PDB; 5QP1; X-ray; 1.79 A; A=95-260. DR PDB; 5QP2; X-ray; 1.83 A; A=95-260. DR PDB; 5QP3; X-ray; 1.75 A; A=95-260. DR PDB; 5QP4; X-ray; 1.71 A; A=95-260. DR PDB; 5QP5; X-ray; 1.90 A; A=95-260. DR PDB; 5QP6; X-ray; 1.65 A; A=95-260. DR PDB; 5QP7; X-ray; 1.88 A; A=95-260. DR PDB; 5QP8; X-ray; 1.64 A; A=95-260. DR PDB; 5QP9; X-ray; 1.72 A; A=95-260. DR PDB; 5QPA; X-ray; 1.61 A; A=95-260. DR PDB; 5QPB; X-ray; 1.68 A; A=95-260. DR PDB; 5QPC; X-ray; 1.66 A; A=95-260. DR PDBsum; 5MP0; -. DR PDBsum; 5QOH; -. DR PDBsum; 5QOI; -. DR PDBsum; 5QOJ; -. DR PDBsum; 5QOK; -. DR PDBsum; 5QOL; -. DR PDBsum; 5QOM; -. DR PDBsum; 5QON; -. DR PDBsum; 5QOO; -. DR PDBsum; 5QOP; -. DR PDBsum; 5QOQ; -. DR PDBsum; 5QOR; -. DR PDBsum; 5QOS; -. DR PDBsum; 5QOT; -. DR PDBsum; 5QOU; -. DR PDBsum; 5QOV; -. DR PDBsum; 5QOW; -. DR PDBsum; 5QOX; -. DR PDBsum; 5QOY; -. DR PDBsum; 5QOZ; -. DR PDBsum; 5QP0; -. DR PDBsum; 5QP1; -. DR PDBsum; 5QP2; -. DR PDBsum; 5QP3; -. DR PDBsum; 5QP4; -. DR PDBsum; 5QP5; -. DR PDBsum; 5QP6; -. DR PDBsum; 5QP7; -. DR PDBsum; 5QP8; -. DR PDBsum; 5QP9; -. DR PDBsum; 5QPA; -. DR PDBsum; 5QPB; -. DR PDBsum; 5QPC; -. DR AlphaFoldDB; Q8IU60; -. DR SMR; Q8IU60; -. DR BioGRID; 127944; 93. DR ComplexPortal; CPX-2870; RNA decapping and exonuclease complex, DCP1A variant. DR ComplexPortal; CPX-7341; RNA decapping and exonuclease complex, DCP1B variant. DR CORUM; Q8IU60; -. DR DIP; DIP-31126N; -. DR IntAct; Q8IU60; 38. DR STRING; 9606.ENSP00000373715; -. DR iPTMnet; Q8IU60; -. DR PhosphoSitePlus; Q8IU60; -. DR BioMuta; DCP2; -. DR DMDM; 269849560; -. DR EPD; Q8IU60; -. DR jPOST; Q8IU60; -. DR MassIVE; Q8IU60; -. DR PaxDb; 9606-ENSP00000373715; -. DR PeptideAtlas; Q8IU60; -. DR ProteomicsDB; 70509; -. [Q8IU60-1] DR ProteomicsDB; 70510; -. [Q8IU60-2] DR Pumba; Q8IU60; -. DR Antibodypedia; 25376; 256 antibodies from 27 providers. DR DNASU; 167227; -. DR Ensembl; ENST00000389063.3; ENSP00000373715.2; ENSG00000172795.17. [Q8IU60-1] DR Ensembl; ENST00000515408.5; ENSP00000425770.1; ENSG00000172795.17. [Q8IU60-2] DR GeneID; 167227; -. DR KEGG; hsa:167227; -. DR MANE-Select; ENST00000389063.3; ENSP00000373715.2; NM_152624.6; NP_689837.2. DR UCSC; uc003kqh.4; human. [Q8IU60-1] DR AGR; HGNC:24452; -. DR CTD; 167227; -. DR GeneCards; DCP2; -. DR HGNC; HGNC:24452; DCP2. DR HPA; ENSG00000172795; Low tissue specificity. DR MIM; 609844; gene. DR neXtProt; NX_Q8IU60; -. DR OpenTargets; ENSG00000172795; -. DR PharmGKB; PA134898646; -. DR VEuPathDB; HostDB:ENSG00000172795; -. DR eggNOG; KOG2937; Eukaryota. DR GeneTree; ENSGT00390000018878; -. DR HOGENOM; CLU_008108_0_0_1; -. DR InParanoid; Q8IU60; -. DR OMA; RDRICKD; -. DR OrthoDB; 1472at2759; -. DR PhylomeDB; Q8IU60; -. DR TreeFam; TF314180; -. DR BRENDA; 3.6.1.62; 2681. DR PathwayCommons; Q8IU60; -. DR Reactome; R-HSA-380994; ATF4 activates genes in response to endoplasmic reticulum stress. DR Reactome; R-HSA-430039; mRNA decay by 5' to 3' exoribonuclease. DR Reactome; R-HSA-450385; Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA. DR Reactome; R-HSA-450513; Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA. DR Reactome; R-HSA-450604; KSRP (KHSRP) binds and destabilizes mRNA. DR SignaLink; Q8IU60; -. DR BioGRID-ORCS; 167227; 143 hits in 1158 CRISPR screens. DR ChiTaRS; DCP2; human. DR GeneWiki; DCP2; -. DR GenomeRNAi; 167227; -. DR Pharos; Q8IU60; Tbio. DR PRO; PR:Q8IU60; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q8IU60; Protein. DR Bgee; ENSG00000172795; Expressed in oocyte and 211 other cell types or tissues. DR ExpressionAtlas; Q8IU60; baseline and differential. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0000932; C:P-body; IDA:MGI. DR GO; GO:0016442; C:RISC complex; IDA:MGI. DR GO; GO:0140933; F:5'-(N(7)-methylguanosine 5'-triphospho)-[mRNA] hydrolase activity; IDA:UniProtKB. DR GO; GO:0004534; F:5'-3' RNA exonuclease activity; IMP:BHF-UCL. DR GO; GO:0030145; F:manganese ion binding; IEA:InterPro. DR GO; GO:0016896; F:RNA exonuclease activity, producing 5'-phosphomonoesters; TAS:Reactome. DR GO; GO:0070034; F:telomerase RNA binding; IC:BHF-UCL. 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:0071044; P:histone mRNA catabolic process; IMP:UniProtKB. DR GO; GO:0006402; P:mRNA catabolic process; IDA:UniProtKB. DR GO; GO:0032211; P:negative regulation of telomere maintenance via telomerase; IMP:BHF-UCL. DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IEA:UniProtKB-KW. DR GO; GO:0043488; P:regulation of mRNA stability; IDA:UniProtKB. DR GO; GO:1904872; P:regulation of telomerase RNA localization to Cajal body; IMP:BHF-UCL. DR CDD; cd03672; Dcp2p; 1. DR Gene3D; 1.10.10.1050; Dcp2, box A domain; 1. DR Gene3D; 3.90.79.10; Nucleoside Triphosphate Pyrophosphohydrolase; 1. DR InterPro; IPR007722; DCP2_BoxA. DR InterPro; IPR036189; DCP2_BoxA_sf. DR InterPro; IPR044099; Dcp2_NUDIX. DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf. DR InterPro; IPR020084; NUDIX_hydrolase_CS. DR InterPro; IPR000086; NUDIX_hydrolase_dom. DR PANTHER; PTHR23114; M7GPPPN-MRNA HYDROLASE; 1. DR PANTHER; PTHR23114:SF17; M7GPPPN-MRNA HYDROLASE; 1. DR Pfam; PF05026; DCP2; 1. DR Pfam; PF00293; NUDIX; 1. DR SMART; SM01125; DCP2; 1. DR SUPFAM; SSF140586; Dcp2 domain-like; 1. DR SUPFAM; SSF55811; Nudix; 1. DR PROSITE; PS51462; NUDIX; 1. DR PROSITE; PS00893; NUDIX_BOX; 1. DR Genevisible; Q8IU60; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Hydrolase; Manganese; KW Metal-binding; Nonsense-mediated mRNA decay; Nucleus; Phosphoprotein; KW Reference proteome; RNA-binding. FT CHAIN 1..420 FT /note="m7GpppN-mRNA hydrolase" FT /id="PRO_0000057051" FT DOMAIN 95..226 FT /note="Nudix hydrolase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794" FT REGION 246..266 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 313..344 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 129..150 FT /note="Nudix box" FT COMPBIAS 246..265 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 144 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000250" FT BINDING 148 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000250" FT MOD_RES 246 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 247 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 249 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 276 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332" FT MOD_RES 284 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT VAR_SEQ 315..349 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_012908" FT VARIANT 16 FT /note="L -> F (in dbSNP:rs33555)" FT /evidence="ECO:0000269|PubMed:15372022" FT /id="VAR_059528" FT MUTAGEN 147 FT /note="E->Q: Loss of decapping activity; when associated FT with Q-148." FT MUTAGEN 148 FT /note="E->Q: Strongly reduced decapping activity." FT /evidence="ECO:0000269|PubMed:12417715" FT MUTAGEN 249 FT /note="S->A: Leads to the accumulation of autophagosomes FT under normal growth conditions." FT /evidence="ECO:0000269|PubMed:26098573" FT MUTAGEN 249 FT /note="S->D: Leads to reduced autophagosome formation under FT autophagy-inducing conditions." FT /evidence="ECO:0000269|PubMed:26098573" FT CONFLICT 103 FT /note="I -> V (in Ref. 3; BAC03479)" FT /evidence="ECO:0000305" FT STRAND 99..105 FT /evidence="ECO:0007829|PDB:5QOQ" FT STRAND 109..116 FT /evidence="ECO:0007829|PDB:5QOQ" FT HELIX 119..121 FT /evidence="ECO:0007829|PDB:5QOQ" FT STRAND 123..125 FT /evidence="ECO:0007829|PDB:5QOQ" FT STRAND 127..130 FT /evidence="ECO:0007829|PDB:5QOQ" FT HELIX 137..149 FT /evidence="ECO:0007829|PDB:5QOQ" FT TURN 154..156 FT /evidence="ECO:0007829|PDB:5QOQ" FT STRAND 162..167 FT /evidence="ECO:0007829|PDB:5QOQ" FT STRAND 170..177 FT /evidence="ECO:0007829|PDB:5QOQ" FT TURN 191..193 FT /evidence="ECO:0007829|PDB:5QOQ" FT STRAND 196..201 FT /evidence="ECO:0007829|PDB:5QOQ" FT HELIX 202..204 FT /evidence="ECO:0007829|PDB:5QOQ" FT HELIX 213..215 FT /evidence="ECO:0007829|PDB:5QOQ" FT STRAND 217..220 FT /evidence="ECO:0007829|PDB:5QPA" FT TURN 224..228 FT /evidence="ECO:0007829|PDB:5QOQ" FT HELIX 229..242 FT /evidence="ECO:0007829|PDB:5QOQ" SQ SEQUENCE 420 AA; 48423 MW; C0FA503A0C797967 CRC64; METKRVEIPG SVLDDLCSRF ILHIPSEERD NAIRVCFQIE LAHWFYLDFY MQNTPGLPQC GIRDFAKAVF SHCPFLLPQG EDVEKVLDEW KEYKMGVPTY GAIILDETLE NVLLVQGYLA KSGWGFPKGK VNKEEAPHDC AAREVFEETG FDIKDYICKD DYIELRINDQ LARLYIIPGI PKDTKFNPKT RREIRNIEWF SIEKLPCHRN DMTPKSKLGL APNKFFMAIP FIRPLRDWLS RRFGDSSDSD NGFSSTGSTP AKPTVEKLSR TKFRHSQQLF PDGSPGDQWV KHRQPLQQKP YNNHSEMSDL LKGKNQSMRG NGRKQYQDSP NQKKRTNGLQ PAKQQNSLMK CEKKLHPRKL QDNFETDAVY DLPSSSEDQL LEHAEGQPVA CNGHCKFPFS SRAFLSFKFD HNAIMKILDL //