DCP2_HUMAN
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 03-AUG-2022, entry version 171.
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}.
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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; 82.
DR CORUM; Q8IU60; -.
DR DIP; DIP-31126N; -.
DR IntAct; Q8IU60; 36.
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; Q8IU60; -.
DR PeptideAtlas; Q8IU60; -.
DR PRIDE; Q8IU60; -.
DR ProteomicsDB; 70509; -. [Q8IU60-1]
DR ProteomicsDB; 70510; -. [Q8IU60-2]
DR Antibodypedia; 25376; 230 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 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; 1230808at2759; -.
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; 134 hits in 1078 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 209 other tissues.
DR ExpressionAtlas; Q8IU60; baseline and differential.
DR Genevisible; Q8IU60; HS.
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:0004534; F:5'-3' exoribonuclease activity; IMP:BHF-UCL.
DR GO; GO:0016896; F:exoribonuclease activity, producing 5'-phosphomonoesters; TAS:Reactome.
DR GO; GO:0050072; F:m7G(5')pppN diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; IEA:InterPro.
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; -; 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 Pfam; PF05026; DCP2; 1.
DR Pfam; PF00293; NUDIX; 1.
DR SMART; SM01125; DCP2; 1.
DR SUPFAM; SSF140586; SSF140586; 1.
DR SUPFAM; SSF55811; SSF55811; 1.
DR PROSITE; PS51462; NUDIX; 1.
DR PROSITE; PS00893; NUDIX_BOX; 1.
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
