MCE1_MOUSE
ID MCE1_MOUSE Reviewed; 597 AA.
AC O55236;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=mRNA-capping enzyme;
DE AltName: Full=HCE;
DE AltName: Full=MCE1;
DE Includes:
DE RecName: Full=mRNA 5'-triphosphate monophosphatase;
DE EC=3.6.1.74 {ECO:0000269|PubMed:21683636};
DE AltName: Full=mRNA 5'-phosphatase;
DE Includes:
DE RecName: Full=mRNA guanylyltransferase;
DE EC=2.7.7.50 {ECO:0000269|PubMed:21683636};
DE AltName: Full=GTP--RNA guanylyltransferase;
DE Short=GTase;
GN Name=Rngtt; Synonyms=Cap1a;
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], MUTAGENESIS OF LYS-294, FUNCTION, AND SUBUNIT.
RX PubMed=9371772; DOI=10.1073/pnas.94.24.12898;
RA Yue Z., Maldonado E., Pillutla R., Cho H., Reinberg D., Shatkin A.J.;
RT "Mammalian capping enzyme complements mutant Saccharomyces cerevisiae
RT lacking mRNA guanylyltransferase and selectively binds the elongating form
RT of RNA polymerase II.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:12898-12903(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBUNIT.
RX PubMed=9407024; DOI=10.1101/gad.11.24.3306;
RA McCracken S., Fong N., Rosonina E., Yankulov K., Brothers G.,
RA Siderovski D., Hessel A., Foster S., Shuman S., Bentley D.L.;
RT "5'-Capping enzymes are targeted to pre-mRNA by binding to the
RT phosphorylated carboxy-terminal domain of RNA polymerase II.";
RL Genes Dev. 11:3306-3318(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 CHARACTERIZATION, AND MUTAGENESIS.
RX PubMed=9770468; DOI=10.1073/pnas.95.21.12226;
RA Wen Y., Yue Z., Shatkin A.J.;
RT "Mammalian capping enzyme binds RNA and uses protein tyrosine phosphatase
RT mechanism.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:12226-12231(1998).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, 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 X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
RX PubMed=11350947; DOI=10.1093/emboj/20.10.2575;
RA Changela A., Ho C.K., Martins A., Shuman S., Mondragon A.;
RT "Structure and mechanism of the RNA triphosphatase component of mammalian
RT mRNA capping enzyme.";
RL EMBO J. 20:2575-2586(2001).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) OF 226-567 IN COMPLEX WITH GUANINE
RP AND POLR2A PEPTIDE, INTERACTION WITH POLR2A, CATALYTIC ACTIVITY, FUNCTION,
RP AND MUTAGENESIS OF CYS-375.
RX PubMed=21683636; DOI=10.1016/j.molcel.2011.06.001;
RA Ghosh A., Shuman S., Lima C.D.;
RT "Structural insights to how mammalian capping enzyme reads the CTD code.";
RL Mol. Cell 43:299-310(2011).
CC -!- FUNCTION: Bifunctional mRNA-capping enzyme exhibiting RNA 5'-
CC triphosphate monophosphatase activity in the N-terminal part and mRNA
CC guanylyltransferase activity in the C-terminal part. Catalyzes the
CC first two steps of cap formation: by removing the gamma-phosphate from
CC the 5'-triphosphate end of nascent mRNA to yield a diphosphate end, and
CC by transferring the GMP moiety of GTP to the 5'-diphosphate terminus of
CC RNA via a covalent enzyme-GMP reaction intermediate.
CC {ECO:0000269|PubMed:21683636, ECO:0000269|PubMed:9371772}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end triphospho-ribonucleoside in mRNA + H2O = a 5'-end
CC diphospho-ribonucleoside in mRNA + H(+) + phosphate;
CC Xref=Rhea:RHEA:67004, Rhea:RHEA-COMP:17164, Rhea:RHEA-COMP:17165,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:167616, ChEBI:CHEBI:167618; EC=3.6.1.74;
CC Evidence={ECO:0000269|PubMed:21683636};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67005;
CC Evidence={ECO:0000305|PubMed:21683636};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end diphospho-ribonucleoside in mRNA + GTP + H(+) = a 5'-
CC end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA + diphosphate;
CC Xref=Rhea:RHEA:67012, Rhea:RHEA-COMP:17165, Rhea:RHEA-COMP:17166,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:167616, ChEBI:CHEBI:167617; EC=2.7.7.50;
CC Evidence={ECO:0000269|PubMed:21683636};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67013;
CC Evidence={ECO:0000305|PubMed:21683636};
CC -!- ACTIVITY REGULATION: RNA triphosphatase activity is inhibited by
CC vanadate, iodoacetate and magnesium.
CC -!- SUBUNIT: Interacts with SUPT5H and RNMT (By similarity). Interacts with
CC POLR2A (via C-terminus); this enhances guanylyltransferase activity.
CC Binds (via GTase domain) to the elongating phosphorylated form of RNA
CC polymerase II; can form direct interactions with the phosphorylated
CC POLR2A C-terminal domain and indirect interactions via bound RNA.
CC {ECO:0000250, ECO:0000269|PubMed:21683636, ECO:0000269|PubMed:9371772,
CC ECO:0000269|PubMed:9407024}.
CC -!- INTERACTION:
CC O55236; P16333-1: NCK1; Xeno; NbExp=3; IntAct=EBI-16118241, EBI-15578122;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- SIMILARITY: In the N-terminal section; belongs to the non-receptor
CC class of the protein-tyrosine phosphatase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the eukaryotic GTase
CC family. {ECO:0000305}.
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DR EMBL; AF025653; AAB91558.1; -; mRNA.
DR EMBL; AF034568; AAB88903.1; -; mRNA.
DR EMBL; BC043657; AAH43657.1; -; mRNA.
DR CCDS; CCDS38705.1; -.
DR RefSeq; NP_036014.1; NM_011884.3.
DR PDB; 1I9S; X-ray; 1.65 A; A=1-210.
DR PDB; 1I9T; X-ray; 1.70 A; A=1-210.
DR PDB; 3RTX; X-ray; 2.81 A; A/B=226-567.
DR PDBsum; 1I9S; -.
DR PDBsum; 1I9T; -.
DR PDBsum; 3RTX; -.
DR AlphaFoldDB; O55236; -.
DR SMR; O55236; -.
DR BioGRID; 204857; 2.
DR DIP; DIP-61013N; -.
DR IntAct; O55236; 2.
DR MINT; O55236; -.
DR STRING; 10090.ENSMUSP00000103788; -.
DR iPTMnet; O55236; -.
DR PhosphoSitePlus; O55236; -.
DR EPD; O55236; -.
DR PaxDb; O55236; -.
DR PeptideAtlas; O55236; -.
DR PRIDE; O55236; -.
DR ProteomicsDB; 287328; -.
DR Antibodypedia; 1158; 166 antibodies from 30 providers.
DR DNASU; 24018; -.
DR Ensembl; ENSMUST00000108153; ENSMUSP00000103788; ENSMUSG00000028274.
DR GeneID; 24018; -.
DR KEGG; mmu:24018; -.
DR UCSC; uc008sfv.2; mouse.
DR CTD; 8732; -.
DR MGI; MGI:1329041; Rngtt.
DR VEuPathDB; HostDB:ENSMUSG00000028274; -.
DR eggNOG; KOG2386; Eukaryota.
DR GeneTree; ENSGT00940000156953; -.
DR HOGENOM; CLU_021710_3_0_1; -.
DR InParanoid; O55236; -.
DR OMA; WMSARLL; -.
DR OrthoDB; 1544021at2759; -.
DR PhylomeDB; O55236; -.
DR TreeFam; TF314914; -.
DR BRENDA; 2.7.7.50; 3474.
DR Reactome; R-MMU-72086; mRNA Capping.
DR Reactome; R-MMU-77075; RNA Pol II CTD phosphorylation and interaction with CE.
DR BioGRID-ORCS; 24018; 25 hits in 60 CRISPR screens.
DR ChiTaRS; Rngtt; mouse.
DR EvolutionaryTrace; O55236; -.
DR PRO; PR:O55236; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; O55236; protein.
DR Bgee; ENSMUSG00000028274; Expressed in embryonic post-anal tail and 246 other tissues.
DR ExpressionAtlas; O55236; baseline and differential.
DR Genevisible; O55236; MM.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0004484; F:mRNA guanylyltransferase activity; ISS:UniProtKB.
DR GO; GO:0004651; F:polynucleotide 5'-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IEA:InterPro.
DR GO; GO:0008192; F:RNA guanylyltransferase activity; ISO:MGI.
DR GO; GO:0050355; F:triphosphatase activity; ISS:UniProtKB.
DR GO; GO:0006370; P:7-methylguanosine mRNA capping; ISS:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
DR GO; GO:0006396; P:RNA processing; ISO:MGI.
DR CDD; cd07895; Adenylation_mRNA_capping; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR000340; Dual-sp_phosphatase_cat-dom.
DR InterPro; IPR017074; mRNA_cap_enz_bifunc.
DR InterPro; IPR001339; mRNA_cap_enzyme_adenylation.
DR InterPro; IPR013846; mRNA_cap_enzyme_C.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom.
DR Pfam; PF00782; DSPc; 1.
DR Pfam; PF03919; mRNA_cap_C; 1.
DR Pfam; PF01331; mRNA_cap_enzyme; 1.
DR PIRSF; PIRSF036958; mRNA_capping_HCE; 1.
DR SUPFAM; SSF50249; SSF50249; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; GTP-binding; Hydrolase; mRNA capping; mRNA processing;
KW Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase;
KW Nucleus; Protein phosphatase; Reference proteome; Transferase.
FT CHAIN 1..597
FT /note="mRNA-capping enzyme"
FT /id="PRO_0000210109"
FT DOMAIN 25..183
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 1..212
FT /note="TPase"
FT REGION 181..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 229..597
FT /note="GTase"
FT REGION 330..386
FT /note="Interaction with POLR2A"
FT /evidence="ECO:0000269|PubMed:21683636"
FT REGION 573..597
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 192..207
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 581..597
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 126
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT ACT_SITE 294
FT /note="N6-GMP-lysine intermediate"
FT BINDING 299
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 315
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT BINDING 343..345
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT BINDING 458..460
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT BINDING 528..533
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT MUTAGEN 36
FT /note="D->A: No effect."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 66
FT /note="D->A: Decrease of >90% of TPase activity."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 110
FT /note="C->S: No effect."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 125
FT /note="H->A: Decrease of 55-60% of TPase activity."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 126
FT /note="C->S: Loss of TPase activity."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 132
FT /note="R->A: Loss of TPase activity."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 133
FT /note="T->A: Decrease of 55-60% of TPase activity."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 138
FT /note="C->S: No effect."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 168
FT /note="D->A: No effect."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 290
FT /note="K->A: No effect."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 294
FT /note="K->A: Loss of GTase activity."
FT /evidence="ECO:0000269|PubMed:9371772"
FT MUTAGEN 315
FT /note="R->A: Almost complete loss of RNA-binding and loss
FT of GTase activity."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 315
FT /note="R->K: At least 60% of RNA-binding activity and loss
FT of GTase activity."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 375
FT /note="C->R: Increases stimulation of GTase activity by
FT POLR2A binding."
FT /evidence="ECO:0000269|PubMed:21683636"
FT MUTAGEN 530
FT /note="R->A: Almost complete loss of RNA-binding and loss
FT of GTase activity."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 530
FT /note="R->K: Loss of GTase activity."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 533
FT /note="K->A: Almost complete loss of RNA-binding and loss
FT of GTase activity."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 533
FT /note="K->R: At least 60% of RNA-binding activity and loss
FT of GTase activity."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 537
FT /note="N->A: Almost complete loss of RNA-binding and loss
FT of GTase activity."
FT /evidence="ECO:0000269|PubMed:9770468"
FT MUTAGEN 537
FT /note="N->Q: At least 60% of RNA binding activity and loss
FT of GTase activity."
FT /evidence="ECO:0000269|PubMed:9770468"
FT TURN 21..23
FT /evidence="ECO:0007829|PDB:1I9S"
FT STRAND 24..27
FT /evidence="ECO:0007829|PDB:1I9S"
FT HELIX 33..35
FT /evidence="ECO:0007829|PDB:1I9S"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:1I9S"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:1I9S"
FT HELIX 47..56
FT /evidence="ECO:0007829|PDB:1I9S"
FT STRAND 61..66
FT /evidence="ECO:0007829|PDB:1I9S"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:1I9S"
FT HELIX 77..80
FT /evidence="ECO:0007829|PDB:1I9S"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:1I9S"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:1I9S"
FT HELIX 100..110
FT /evidence="ECO:0007829|PDB:1I9S"
FT TURN 111..115
FT /evidence="ECO:0007829|PDB:1I9T"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:1I9S"
FT STRAND 127..130
FT /evidence="ECO:0007829|PDB:1I9S"
FT HELIX 131..145
FT /evidence="ECO:0007829|PDB:1I9S"
FT HELIX 149..159
FT /evidence="ECO:0007829|PDB:1I9S"
FT HELIX 167..177
FT /evidence="ECO:0007829|PDB:1I9S"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:1I9S"
FT HELIX 191..194
FT /evidence="ECO:0007829|PDB:1I9S"
FT STRAND 232..236
FT /evidence="ECO:0007829|PDB:3RTX"
FT STRAND 241..243
FT /evidence="ECO:0007829|PDB:3RTX"
FT HELIX 249..260
FT /evidence="ECO:0007829|PDB:3RTX"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:3RTX"
FT STRAND 270..275
FT /evidence="ECO:0007829|PDB:3RTX"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:3RTX"
FT HELIX 283..286
FT /evidence="ECO:0007829|PDB:3RTX"
FT STRAND 289..294
FT /evidence="ECO:0007829|PDB:3RTX"
FT STRAND 298..304
FT /evidence="ECO:0007829|PDB:3RTX"
FT STRAND 310..313
FT /evidence="ECO:0007829|PDB:3RTX"
FT STRAND 319..322
FT /evidence="ECO:0007829|PDB:3RTX"
FT STRAND 332..336
FT /evidence="ECO:0007829|PDB:3RTX"
FT STRAND 339..367
FT /evidence="ECO:0007829|PDB:3RTX"
FT HELIX 372..374
FT /evidence="ECO:0007829|PDB:3RTX"
FT HELIX 377..387
FT /evidence="ECO:0007829|PDB:3RTX"
FT HELIX 389..398
FT /evidence="ECO:0007829|PDB:3RTX"
FT TURN 403..405
FT /evidence="ECO:0007829|PDB:3RTX"
FT STRAND 406..412
FT /evidence="ECO:0007829|PDB:3RTX"
FT HELIX 418..420
FT /evidence="ECO:0007829|PDB:3RTX"
FT HELIX 421..424
FT /evidence="ECO:0007829|PDB:3RTX"
FT STRAND 439..446
FT /evidence="ECO:0007829|PDB:3RTX"
FT STRAND 451..459
FT /evidence="ECO:0007829|PDB:3RTX"
FT HELIX 539..550
FT /evidence="ECO:0007829|PDB:3RTX"
FT HELIX 555..565
FT /evidence="ECO:0007829|PDB:3RTX"
SQ SEQUENCE 597 AA; 68684 MW; B2A9E711889D8EA7 CRC64;
MAYNKIPPRW LNCPRRGQPV AGRFLPLKTM LGPRYDSQVA EENRFHPSML SNYLKSLKVK
MSLLVDLTNT SRFYDRNDIE KEGIKYIKLQ CKGHGECPTT ENTETFIRLC ERFNERSPPE
LIGVHCTHGF NRTGFLICAF LVEKMDWSIE AAVATFAQAR PPGIYKGDYL KELFRRYGDI
EEAPPPPVLP DWCFEDEDEE DEDEDGKKDS EPGSSASFSK RRKERLKLGA IFLEGITVKG
VTQVTTQPKL GEVQQKCHQF CGWEGSGFPG AQPVSMDKQN IRLLEQKPYK VSWKADGTRY
MMLIDGTNEV FMIDRDNSVF HVSNLEFPFR KDLRMHLSNT LLDGEMIIDK VNGQAVPRYL
IYDIIKFNAQ PVGDCDFNIR LQCIEREIIS PRHEKMKTGL IDKTQEPFSV RPKQFFDINI
SRKLLEGNFA KEVSHEMDGL IFQPIGKYKP GRCDDILKWK PPSLNSVDFR LKITRMGGEG
LLPQNVGLLY VGGYERPFAQ IKVTKELKQY DNKIIECKFE NNSWVFMRQR IDKSFPNAYN
TAMAVCNSIS NPVTKEMLFE FIDRCAAAAQ GQKRKYPLDP DTELMPPPPP KRLHRPT
