DCP2_MOUSE
ID DCP2_MOUSE Reviewed; 422 AA.
AC Q9CYC6; Q3TLD9;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=m7GpppN-mRNA hydrolase {ECO:0000305};
DE EC=3.6.1.62 {ECO:0000269|PubMed:21070968};
DE AltName: Full=mRNA-decapping enzyme 2;
GN Name=Dcp2;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
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 [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246; SER-247 AND SER-249, AND
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246; SER-247 AND SER-249, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, 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 [4]
RP FUNCTION AS A DECAPPING ENZYME, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
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).
CC -!- FUNCTION: Decapping metalloenzyme that catalyzes the cleavage of the
CC cap structure on mRNAs (PubMed:21070968). Removes the 7-methyl guanine
CC cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA
CC fragment and 7m-GDP (PubMed:21070968). Necessary for the degradation of
CC mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay
CC (By similarity). Plays a role in replication-dependent histone mRNA
CC degradation. Has 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 (By similarity). Blocks autophagy in nutrient-rich conditions
CC by repressing the expression of ATG-related genes through degradation
CC of their transcripts (By similarity). {ECO:0000250|UniProtKB:Q8IU60,
CC ECO:0000269|PubMed:21070968}.
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:21070968};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67485;
CC Evidence={ECO:0000269|PubMed:21070968};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q8IU60};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8IU60};
CC Note=Mn(2+) ion is required for highest activity. Can also utilize
CC magnesium ions. {ECO:0000250|UniProtKB:Q8IU60};
CC -!- SUBUNIT: Found in a mRNA decay complex with LSM1, LSM3, LSM4, EXOSC2,
CC EXOSC4, EXOSC10, PARN, XRN1, CNOT6, UPF1, UPF2 and UPF3B. Forms a
CC complex with DCP1A, EDC3, DDX6 and EDC4/HEDLS, within this complex
CC directly interacts with EDC4/HEDLS. Interacts with DPC1B, UPF1, UPF2
CC and UPF3B. Associates with polysomes. Interacts (via N-terminus and C-
CC terminus) with TRIM21 (via N-terminus and C-terminus). Interacts with
CC LIMD1, WTIP and AJUBA. Interacts with DDX17 in an RNA-dependent manner.
CC Interacts with ZC3HAV1. Interacts with APOBEC3G in an RNA-dependent
CC manner. Interacts with ZFP36L1 (via N-terminus). Interacts with NBDY.
CC {ECO:0000250|UniProtKB:Q8IU60}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000250|UniProtKB:Q8IU60}.
CC Nucleus {ECO:0000250|UniProtKB:Q8IU60}. Note=Predominantly cytoplasmic,
CC in processing bodies (PB) (By similarity). A minor amount is nuclear
CC (By similarity). {ECO:0000250|UniProtKB:Q8IU60}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in brain and testis. Weakly
CC expressed in lung. Not detected in heart, liver, kidney and muscle (at
CC protein level). {ECO:0000269|PubMed:21070968}.
CC -!- DEVELOPMENTAL STAGE: Strongly expressed in brain, heart, liver at 14.5
CC and 16.5 dpc. Strongly expressed in brain at 20 dpc. Weakly expressed
CC in heart and liver at 20 dpc (at protein level).
CC {ECO:0000269|PubMed:21070968}.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. DCP2 subfamily.
CC {ECO:0000305}.
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DR EMBL; AK017809; BAB30946.1; -; mRNA.
DR EMBL; AK166560; BAE38853.1; -; mRNA.
DR CCDS; CCDS50275.1; -.
DR RefSeq; NP_081766.1; NM_027490.1.
DR AlphaFoldDB; Q9CYC6; -.
DR SMR; Q9CYC6; -.
DR STRING; 10090.ENSMUSP00000025350; -.
DR iPTMnet; Q9CYC6; -.
DR PhosphoSitePlus; Q9CYC6; -.
DR EPD; Q9CYC6; -.
DR MaxQB; Q9CYC6; -.
DR PaxDb; Q9CYC6; -.
DR PRIDE; Q9CYC6; -.
DR ProteomicsDB; 279392; -.
DR Antibodypedia; 25376; 230 antibodies from 27 providers.
DR Ensembl; ENSMUST00000025350; ENSMUSP00000025350; ENSMUSG00000024472.
DR GeneID; 70640; -.
DR KEGG; mmu:70640; -.
DR UCSC; uc008eux.2; mouse.
DR CTD; 167227; -.
DR MGI; MGI:1917890; Dcp2.
DR VEuPathDB; HostDB:ENSMUSG00000024472; -.
DR eggNOG; KOG2937; Eukaryota.
DR GeneTree; ENSGT00390000018878; -.
DR HOGENOM; CLU_008108_0_0_1; -.
DR InParanoid; Q9CYC6; -.
DR OMA; RDRICKD; -.
DR OrthoDB; 1230808at2759; -.
DR PhylomeDB; Q9CYC6; -.
DR TreeFam; TF314180; -.
DR BRENDA; 3.6.1.62; 3474.
DR Reactome; R-MMU-430039; mRNA decay by 5' to 3' exoribonuclease.
DR Reactome; R-MMU-450385; Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
DR Reactome; R-MMU-450513; Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA.
DR Reactome; R-MMU-450604; KSRP (KHSRP) binds and destabilizes mRNA.
DR BioGRID-ORCS; 70640; 17 hits in 73 CRISPR screens.
DR ChiTaRS; Dcp2; mouse.
DR PRO; PR:Q9CYC6; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q9CYC6; protein.
DR Bgee; ENSMUSG00000024472; Expressed in metanephric mesenchyme and 224 other tissues.
DR ExpressionAtlas; Q9CYC6; baseline and differential.
DR Genevisible; Q9CYC6; MM.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0000932; C:P-body; ISO:MGI.
DR GO; GO:0016442; C:RISC complex; ISO:MGI.
DR GO; GO:0004534; F:5'-3' exoribonuclease activity; ISO:MGI.
DR GO; GO:0050072; F:m7G(5')pppN diphosphatase activity; ISS:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0000290; P:deadenylation-dependent decapping of nuclear-transcribed mRNA; IBA:GO_Central.
DR GO; GO:0071044; P:histone mRNA catabolic process; ISS:UniProtKB.
DR GO; GO:0006402; P:mRNA catabolic process; IMP:UniProtKB.
DR GO; GO:0032211; P:negative regulation of telomere maintenance via telomerase; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:1904872; P:regulation of telomerase RNA localization to Cajal body; ISO:MGI.
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 Cytoplasm; Hydrolase; Manganese; Metal-binding;
KW Nonsense-mediated mRNA decay; Nucleus; Phosphoprotein; Reference proteome;
KW RNA-binding.
FT CHAIN 1..422
FT /note="m7GpppN-mRNA hydrolase"
FT /id="PRO_0000057052"
FT DOMAIN 95..226
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT REGION 247..347
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 129..150
FT /note="Nudix box"
FT COMPBIAS 247..265
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 274..304
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 314..344
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:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 247
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 276
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IU60"
FT MOD_RES 284
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IU60"
FT CONFLICT 226
FT /note="F -> Y (in Ref. 1; BAB30946)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 422 AA; 48380 MW; 80FE791B05E4C8FD CRC64;
MEPKRLEIPG SVLDDLCSRF ILHIPSEERD NAIRVCFQIE LAHWFYLDFY MQNTPGLPQC
GIRDFAKAVF SHCPFLLPQG EDVEKILDEW KEYKMGVPTY GAIILDETLE NVLLVQGYLA
KSGWGFPKGK VNKEEAPHDC AAREVFEETG FDIKDYICKD DYIELRINDQ LARLYIIPGV
PKDTKFNPKT RREIRNIEWF SIEKLPCHRN DMTPKSKLGL APNKFFMAIP FIRPLRDWLS
RRFGDSSDSD NGFSSAGSTP ARPTVEKLSR TKFRHSQQLF PEGSPSDQWV KHRQPLQQKS
HSNHGEVSDL LKAKNQNMRG NGRKQYQDSP NQKKRANGVH GQPAKQQNPL VKCEKKLHPR
KLQDNFETDA TCDLPCSGEE PSVEHAEGHS VACNGHCKFP FSSRAFLSFK FDQNAIMKIL
DL
