MEPCE_MOUSE
ID MEPCE_MOUSE Reviewed; 666 AA.
AC Q8K3A9; Q2YFS5; Q3U465; Q3UT64; Q91W35;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=7SK snRNA methylphosphate capping enzyme {ECO:0000303|PubMed:23154982};
DE Short=MePCE {ECO:0000303|PubMed:23154982};
DE EC=2.1.1.- {ECO:0000250|UniProtKB:Q7L2J0};
GN Name=Mepce {ECO:0000303|PubMed:23154982, ECO:0000312|MGI:MGI:106477};
GN Synonyms=Bcdin3 {ECO:0000312|MGI:MGI:106477},
GN Bipl1 {ECO:0000303|PubMed:16926269}, D5Wsu46e {ECO:0000312|MGI:MGI:106477};
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 [GENOMIC DNA].
RC STRAIN=129/Sv;
RX PubMed=16926269; DOI=10.1152/physiolgenomics.00284.2005;
RA Wilson M.D., Cheung J., Martindale D.W., Scherer S.W., Koop B.F.;
RT "Comparative analysis of the paired immunoglobulin-like receptor (PILR)
RT locus in six mammalian genomes: duplication, conversion, and the birth of
RT new genes.";
RL Physiol. Genomics 27:201-218(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Egg;
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=Czech II, and FVB/N; TISSUE=Mammary tumor, and Salivary 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-188 AND SER-192, 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-188 AND SER-192, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC 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 FUNCTION.
RX PubMed=23154982; DOI=10.1101/gad.202242.112;
RA Okamura D., Maeda I., Taniguchi H., Tokitake Y., Ikeda M., Ozato K.,
RA Mise N., Abe K., Noce T., Izpisua Belmonte J.C., Matsui Y.;
RT "Cell cycle gene-specific control of transcription has a critical role in
RT proliferation of primordial germ cells.";
RL Genes Dev. 26:2477-2482(2012).
RN [7]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-91, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: S-adenosyl-L-methionine-dependent methyltransferase that adds
CC a methylphosphate cap at the 5'-end of 7SK snRNA (7SK RNA), leading to
CC stabilize it (By similarity). Also has a non-enzymatic function as part
CC of the 7SK RNP complex: the 7SK RNP complex sequesters the positive
CC transcription elongation factor b (P-TEFb) in a large inactive 7SK RNP
CC complex preventing RNA polymerase II phosphorylation and subsequent
CC transcriptional elongation (PubMed:23154982). The 7SK RNP complex also
CC promotes snRNA gene transcription by RNA polymerase II via interaction
CC with the little elongation complex (LEC) (By similarity). In the 7SK
CC RNP complex, MEPCE is required to stabilize 7SK RNA and facilitate the
CC assembly of 7SK RNP complex (By similarity). MEPCE has a non-enzymatic
CC function in the 7SK RNP complex; it has a non-enzymatic function;
CC interaction with LARP7 within the 7SK RNP complex occluding its
CC catalytic center (By similarity). {ECO:0000250|UniProtKB:Q7L2J0,
CC ECO:0000269|PubMed:23154982}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end triphospho-guanosine-ribonucleotide-snRNA + S-
CC adenosyl-L-methionine = a 5'-end methyltriphosphate-guanosine-
CC ribonucleotide-snRNA + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:58780, Rhea:RHEA-COMP:15220, Rhea:RHEA-COMP:15221,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:138278,
CC ChEBI:CHEBI:142789; Evidence={ECO:0000250|UniProtKB:Q7L2J0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58781;
CC Evidence={ECO:0000250|UniProtKB:Q7L2J0};
CC -!- SUBUNIT: Core component of the 7SK RNP complex, at least composed of
CC 7SK RNA, LARP7, MEPCE, HEXIM1 (or HEXIM2) and P-TEFb (composed of CDK9
CC and CCNT1/cyclin-T1). Interacts with METTL16. Interacts with RBM7; upon
CC genotoxic stress this interaction is enhanced, triggering the release
CC of inactive P-TEFb complex from the core, yielding to P-TEFb complex
CC activation. {ECO:0000250|UniProtKB:Q7L2J0}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q7L2J0}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH17157.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAX39492.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY823670; AAX39492.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AK139731; BAE24116.1; -; mRNA.
DR EMBL; AK154415; BAE32569.1; -; mRNA.
DR EMBL; BC017157; AAH17157.2; ALT_INIT; mRNA.
DR EMBL; BC026876; AAH26876.1; -; mRNA.
DR CCDS; CCDS39337.1; -.
DR RefSeq; NP_659162.3; NM_144913.3.
DR AlphaFoldDB; Q8K3A9; -.
DR SMR; Q8K3A9; -.
DR BioGRID; 231168; 3.
DR IntAct; Q8K3A9; 1.
DR STRING; 10090.ENSMUSP00000031740; -.
DR iPTMnet; Q8K3A9; -.
DR PhosphoSitePlus; Q8K3A9; -.
DR EPD; Q8K3A9; -.
DR jPOST; Q8K3A9; -.
DR MaxQB; Q8K3A9; -.
DR PaxDb; Q8K3A9; -.
DR PeptideAtlas; Q8K3A9; -.
DR PRIDE; Q8K3A9; -.
DR ProteomicsDB; 295927; -.
DR Antibodypedia; 30703; 202 antibodies from 31 providers.
DR DNASU; 231803; -.
DR Ensembl; ENSMUST00000031740; ENSMUSP00000031740; ENSMUSG00000029726.
DR GeneID; 231803; -.
DR KEGG; mmu:231803; -.
DR UCSC; uc009ady.1; mouse.
DR CTD; 56257; -.
DR MGI; MGI:106477; Mepce.
DR VEuPathDB; HostDB:ENSMUSG00000029726; -.
DR eggNOG; KOG2899; Eukaryota.
DR GeneTree; ENSGT00940000153993; -.
DR HOGENOM; CLU_004729_3_3_1; -.
DR InParanoid; Q8K3A9; -.
DR OMA; CTDEAHV; -.
DR OrthoDB; 1185441at2759; -.
DR PhylomeDB; Q8K3A9; -.
DR TreeFam; TF324061; -.
DR BioGRID-ORCS; 231803; 26 hits in 71 CRISPR screens.
DR PRO; PR:Q8K3A9; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8K3A9; protein.
DR Bgee; ENSMUSG00000029726; Expressed in embryonic post-anal tail and 256 other tissues.
DR ExpressionAtlas; Q8K3A9; baseline and differential.
DR Genevisible; Q8K3A9; MM.
DR GO; GO:0120259; C:7SK snRNP; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISS:UniProtKB.
DR GO; GO:0097322; F:7SK snRNA binding; ISO:MGI.
DR GO; GO:0008171; F:O-methyltransferase activity; IBA:GO_Central.
DR GO; GO:1990276; F:RNA 5'-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0008173; F:RNA methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0017069; F:snRNA binding; IBA:GO_Central.
DR GO; GO:0035562; P:negative regulation of chromatin binding; IGI:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IMP:MGI.
DR GO; GO:1904871; P:positive regulation of protein localization to Cajal body; ISS:UniProtKB.
DR GO; GO:1905382; P:positive regulation of snRNA transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0001510; P:RNA methylation; ISS:UniProtKB.
DR GO; GO:0016073; P:snRNA metabolic process; ISS:UniProtKB.
DR GO; GO:0040031; P:snRNA modification; ISS:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR039772; Bin3-like.
DR InterPro; IPR010675; Bin3_C.
DR InterPro; IPR024160; BIN3_SAM-bd_dom.
DR InterPro; IPR025714; Methyltranfer_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR12315; PTHR12315; 1.
DR Pfam; PF06859; Bin3; 1.
DR Pfam; PF13847; Methyltransf_31; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51515; BIN3_SAM; 1.
PE 1: Evidence at protein level;
KW Acetylation; Isopeptide bond; Methylation; Methyltransferase; Nucleus;
KW Phosphoprotein; Reference proteome; S-adenosyl-L-methionine; Transferase;
KW Ubl conjugation.
FT CHAIN 1..666
FT /note="7SK snRNA methylphosphate capping enzyme"
FT /id="PRO_0000289263"
FT DOMAIN 408..663
FT /note="Bin3-type SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00848"
FT REGION 1..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 235..291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 309..383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 246..264
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..291
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 310..336
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 399
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT BINDING 410
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT BINDING 428..430
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT BINDING 451..452
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT BINDING 536..537
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT BINDING 558
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT MOD_RES 91
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 126
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT MOD_RES 154
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT MOD_RES 188
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 191
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT MOD_RES 192
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 229
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT MOD_RES 268
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT CROSSLNK 620
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q7L2J0"
FT CONFLICT 80
FT /note="Missing (in Ref. 1; AAX39492)"
FT /evidence="ECO:0000305"
FT CONFLICT 246
FT /note="Missing (in Ref. 3; AAH26876)"
FT /evidence="ECO:0000305"
FT CONFLICT 441
FT /note="K -> M (in Ref. 3; AAH17157)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 666 AA; 72050 MW; 872F17A84E049AD9 CRC64;
MIEMAAEKEP FLVPAPPPPL KDESGGGGGP EVQSHQEAAS GELRDGTEHG PGPRAHSAGA
AASGGGGPQA QAHGEPHGRA AAPADVGEER RGGGGTDLGP PAPPRPRNGY QPHRPPGGGG
GKRRNSCNVG GGSGGSFKHP AFKRRRRVNS DCDSVLPSNF LLGGNIFDPL NLNSLLDEEV
SRALNAETPK SSPLPAKGRD PVEILIPKDI TDPLSLNTCT DEAHVVLASP LKIGRKRHRH
RGPHHQQQQQ ASGGNDSNAA VLPTDPLTPS LHGEGATQQQ QNRGQNRDAP QPYELNTAIN
CRDEVVSPLP SALQGSSGSL SAPPAASVTS APSTSSSSRH RKRRRTSSKS EAGARGGSQG
SKEKGRGSGG GRHHHHPLPA TGFKKQQLKF QYGNYCKYYG YRNPSCEDVR LRVLKPEWFQ
GRDVLDLGCN VGHLTLSIAC KWGPARMVGL DIDPRLIHSA RQNIRHYLSE ELRLQAQTSE
GDPGTEGEEG TITVRKRSCF PASLTASRGP IAAPQVPLDG ADTSVFPNNV VFVTGNYVLD
RDELVDAQRP EYDVVLCFSL TKWVHLNWGD EGLKRMFRRI YRHLRPGGIL VLEPQPWSSY
CKRKSLTETI YKNYFRIQLK PEQFSSYLTS PEVGFSSYEL VATPNNTSRG FQRPVYLFHK
ARSPSH
