ID MEPCE_HUMAN Reviewed; 689 AA. AC Q7L2J0; B3KP86; D6W5V7; Q9NPD4; DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 27-MAR-2024, entry version 179. DE RecName: Full=7SK snRNA methylphosphate capping enzyme {ECO:0000303|PubMed:30559425}; DE Short=MePCE {ECO:0000303|PubMed:30559425}; DE EC=2.1.1.- {ECO:0000269|PubMed:17643375, ECO:0000269|PubMed:19906723, ECO:0000269|PubMed:30559425}; DE AltName: Full=Bicoid-interacting protein 3 homolog {ECO:0000303|PubMed:17643375}; DE Short=Bin3 homolog {ECO:0000303|PubMed:17643375}; GN Name=MEPCE {ECO:0000303|PubMed:30559425, ECO:0000312|HGNC:HGNC:20247}; GN Synonyms=BCDIN3 {ECO:0000303|PubMed:17643375}; 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 [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 320-689 (ISOFORM 1). RC TISSUE=Colon mucosa; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 73-689, AND TISSUE SPECIFICITY. RX PubMed=12358911; DOI=10.1046/j.1365-2141.2002.03775.x; RA Rogers S.A., Bowen D.J., Ling M., Thomson P., Wang Z., Lim S.H.; RT "Identification and characterization of a novel gene encoding a SEREX RT antigen in chronic myeloid leukaemia."; RL Br. J. Haematol. 119:112-114(2002). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-69 AND SER-175, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-217, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [9] RP FUNCTION, IDENTIFICATION IN THE 7SK RNP COMPLEX, AND CATALYTIC ACTIVITY. RX PubMed=17643375; DOI=10.1016/j.molcel.2007.06.027; RA Jeronimo C., Forget D., Bouchard A., Li Q., Chua G., Poitras C., RA Therien C., Bergeron D., Bourassa S., Greenblatt J., Chabot B., RA Poirier G.G., Hughes T.R., Blanchette M., Price D.H., Coulombe B.; RT "Systematic analysis of the protein interaction network for the human RT transcription machinery reveals the identity of the 7SK capping enzyme."; RL Mol. Cell 27:262-274(2007). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-175 AND SER-179, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-57; SER-60; SER-69; SER-152; RP SER-175; SER-254 AND SER-330, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60; SER-69; THR-213; SER-216; RP SER-217 AND SER-254, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-254, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-213, 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 [16] RP FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, IDENTIFICATION IN THE RP 7SK RNP COMPLEX, AND MUTAGENESIS OF 447-VAL--ASP-449. RX PubMed=19906723; DOI=10.1093/nar/gkp977; RA Xue Y., Yang Z., Chen R., Zhou Q.; RT "A capping-independent function of MePCE in stabilizing 7SK snRNA and RT facilitating the assembly of 7SK snRNP."; RL Nucleic Acids Res. 38:360-369(2010). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-69; SER-101; THR-213; RP SER-216; SER-217; SER-254 AND SER-390, AND IDENTIFICATION BY MASS RP 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 [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-213, AND IDENTIFICATION BY RP 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 [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60; SER-69; SER-101; SER-152; RP THR-213; SER-216; SER-217 AND SER-254, AND IDENTIFICATION BY MASS RP 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 [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60; SER-69; SER-152; THR-213; RP SER-217; SER-254; THR-291 AND SER-344, AND IDENTIFICATION BY MASS RP 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 [22] RP FUNCTION. RX PubMed=28254838; DOI=10.15252/embj.201695740; RA Egloff S., Vitali P., Tellier M., Raffel R., Murphy S., Kiss T.; RT "The 7SK snRNP associates with the little elongation complex to promote RT snRNA gene expression."; RL EMBO J. 36:934-948(2017). RN [23] RP INTERACTION WITH METTL16. RX PubMed=29051200; DOI=10.15252/embr.201744940; RA Warda A.S., Kretschmer J., Hackert P., Lenz C., Urlaub H., Hoebartner C., RA Sloan K.E., Bohnsack M.T.; RT "Human METTL16 is a N6-methyladenosine (m6A) methyltransferase that targets RT pre-mRNAs and various non-coding RNAs."; RL EMBO Rep. 18:2004-2014(2017). RN [24] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-643, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [25] RP INTERACTION WITH RBM7. RX PubMed=30824372; DOI=10.1016/j.molcel.2019.01.033; RA Bugai A., Quaresma A.J.C., Friedel C.C., Lenasi T., Duester R., RA Sibley C.R., Fujinaga K., Kukanja P., Hennig T., Blasius M., Geyer M., RA Ule J., Doelken L., Barboric M.; RT "P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response RT to Genotoxic Stress."; RL Mol. Cell 74:254-267(2019). RN [26] RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 400-689 IN COMPLEX WITH RP S-ADENOSYL-L-METHIONINE. RG Structural genomics consortium (SGC); RT "Methyltransferase domain of human bicoid-interacting protein 3 homolog RT (drosophila)."; RL Submitted (MAY-2009) to the PDB data bank. RN [27] {ECO:0007744|PDB:6DCB, ECO:0007744|PDB:6DCC} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 400-689 IN COMPLEX WITH 7SK RNA RP AND S-ADENOSYL-L-METHIONINE, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS RP OF TYR-421; LYS-585 AND PHE-674. RX PubMed=30559425; DOI=10.1038/s41589-018-0188-z; RA Yang Y., Eichhorn C.D., Wang Y., Cascio D., Feigon J.; RT "Structural basis of 7SK RNA 5'-gamma-phosphate methylation and retention RT by MePCE."; RL Nat. Chem. Biol. 15:132-140(2019). 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 (PubMed:17643375, PubMed:19906723, PubMed:30559425). Also CC has a non-enzymatic function as part of the 7SK RNP complex: the 7SK CC RNP complex sequesters the positive transcription elongation factor b CC (P-TEFb) in a large inactive 7SK RNP complex preventing RNA polymerase CC II phosphorylation and subsequent transcriptional elongation CC (PubMed:17643375). The 7SK RNP complex also promotes snRNA gene CC transcription by RNA polymerase II via interaction with the little CC elongation complex (LEC) (PubMed:28254838). In the 7SK RNP complex, CC MEPCE is required to stabilize 7SK RNA and facilitate the assembly of CC 7SK RNP complex (PubMed:19906723). MEPCE has a non-enzymatic function CC in the 7SK RNP complex; interaction with LARP7 within the 7SK RNP CC complex occluding its catalytic center (PubMed:19906723). CC {ECO:0000269|PubMed:17643375, ECO:0000269|PubMed:19906723, CC ECO:0000269|PubMed:28254838, ECO:0000269|PubMed:30559425}. 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:0000269|PubMed:17643375, CC ECO:0000269|PubMed:19906723, ECO:0000269|PubMed:30559425}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58781; CC Evidence={ECO:0000269|PubMed:17643375, ECO:0000269|PubMed:19906723, CC ECO:0000269|PubMed:30559425}; 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) (PubMed:17643375, PubMed:19906723). Interacts with CC METTL16 (PubMed:29051200). Interacts with RBM7; upon genotoxic stress CC this interaction is enhanced, triggering the release of inactive P-TEFb CC complex from the core, yielding to P-TEFb complex activation CC (PubMed:30824372). {ECO:0000269|PubMed:17643375, CC ECO:0000269|PubMed:19906723, ECO:0000269|PubMed:29051200, CC ECO:0000269|PubMed:30824372}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19906723}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q7L2J0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q7L2J0-2; Sequence=VSP_044512; CC -!- TISSUE SPECIFICITY: Expressed in chronic myeloid leukemia cells, CC adrenal gland, brain, cerebellum, kidney, lung, mammary gland and CC testis (PubMed:12358911). Weakly or not expressed in other tissues CC (PubMed:12358911). {ECO:0000269|PubMed:12358911}. CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF74767.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAH16396.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAA91040.1; Type=Erroneous initiation; Evidence={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; AK055964; BAG51598.1; -; mRNA. DR EMBL; AC092849; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471091; EAW76534.1; -; Genomic_DNA. DR EMBL; CH471091; EAW76535.1; -; Genomic_DNA. DR EMBL; CH471091; EAW76536.1; -; Genomic_DNA. DR EMBL; CH236956; EAL23834.1; -; Genomic_DNA. DR EMBL; BC000556; AAH00556.2; -; mRNA. DR EMBL; BC016396; AAH16396.1; ALT_INIT; mRNA. DR EMBL; BC018935; AAH18935.2; -; mRNA. DR EMBL; AF264752; AAF74767.1; ALT_INIT; Genomic_DNA. DR EMBL; AK000264; BAA91040.1; ALT_INIT; mRNA. DR CCDS; CCDS55136.1; -. [Q7L2J0-2] DR CCDS; CCDS5693.1; -. [Q7L2J0-1] DR RefSeq; NP_001181919.1; NM_001194990.1. [Q7L2J0-2] DR RefSeq; NP_001181920.1; NM_001194991.1. [Q7L2J0-2] DR RefSeq; NP_001181921.1; NM_001194992.1. [Q7L2J0-2] DR RefSeq; NP_062552.2; NM_019606.5. [Q7L2J0-1] DR RefSeq; XP_011514712.1; XM_011516410.2. DR PDB; 5UNA; X-ray; 2.55 A; A/B/C/D/E/F=400-689. DR PDB; 6DCB; X-ray; 2.00 A; A=400-689. DR PDB; 6DCC; X-ray; 2.10 A; A=400-689. DR PDB; 7SLP; EM; 4.10 A; A=400-689. DR PDB; 7SLQ; EM; 3.70 A; A=400-689. DR PDBsum; 5UNA; -. DR PDBsum; 6DCB; -. DR PDBsum; 6DCC; -. DR PDBsum; 7SLP; -. DR PDBsum; 7SLQ; -. DR AlphaFoldDB; Q7L2J0; -. DR EMDB; EMD-25197; -. DR EMDB; EMD-25198; -. DR SMR; Q7L2J0; -. DR BioGRID; 121122; 861. DR IntAct; Q7L2J0; 66. DR MINT; Q7L2J0; -. DR STRING; 9606.ENSP00000308546; -. DR GlyGen; Q7L2J0; 5 sites, 1 O-linked glycan (5 sites). DR iPTMnet; Q7L2J0; -. DR PhosphoSitePlus; Q7L2J0; -. DR SwissPalm; Q7L2J0; -. DR BioMuta; MEPCE; -. DR DMDM; 74758999; -. DR EPD; Q7L2J0; -. DR jPOST; Q7L2J0; -. DR MassIVE; Q7L2J0; -. DR MaxQB; Q7L2J0; -. DR PaxDb; 9606-ENSP00000308546; -. DR PeptideAtlas; Q7L2J0; -. DR ProteomicsDB; 15164; -. DR ProteomicsDB; 68762; -. [Q7L2J0-1] DR Pumba; Q7L2J0; -. DR Antibodypedia; 30703; 235 antibodies from 31 providers. DR DNASU; 56257; -. DR Ensembl; ENST00000310512.4; ENSP00000308546.2; ENSG00000146834.15. [Q7L2J0-1] DR Ensembl; ENST00000414441.5; ENSP00000400875.1; ENSG00000146834.15. [Q7L2J0-2] DR Ensembl; ENST00000479201.2; ENSP00000511704.1; ENSG00000146834.15. [Q7L2J0-2] DR Ensembl; ENST00000497759.2; ENSP00000511703.1; ENSG00000146834.15. [Q7L2J0-2] DR Ensembl; ENST00000695111.1; ENSP00000511702.1; ENSG00000146834.15. [Q7L2J0-2] DR GeneID; 56257; -. DR KEGG; hsa:56257; -. DR MANE-Select; ENST00000310512.4; ENSP00000308546.2; NM_019606.6; NP_062552.2. DR UCSC; uc003uuv.4; human. [Q7L2J0-1] DR AGR; HGNC:20247; -. DR CTD; 56257; -. DR DisGeNET; 56257; -. DR GeneCards; MEPCE; -. DR HGNC; HGNC:20247; MEPCE. DR HPA; ENSG00000146834; Low tissue specificity. DR MIM; 611478; gene. DR neXtProt; NX_Q7L2J0; -. DR OpenTargets; ENSG00000146834; -. DR PharmGKB; PA162395768; -. DR VEuPathDB; HostDB:ENSG00000146834; -. DR eggNOG; KOG2899; Eukaryota. DR GeneTree; ENSGT00940000153993; -. DR HOGENOM; CLU_004729_2_1_1; -. DR InParanoid; Q7L2J0; -. DR OMA; CTDEAHV; -. DR OrthoDB; 1130801at2759; -. DR PhylomeDB; Q7L2J0; -. DR TreeFam; TF324061; -. DR PathwayCommons; Q7L2J0; -. DR SignaLink; Q7L2J0; -. DR SIGNOR; Q7L2J0; -. DR BioGRID-ORCS; 56257; 787 hits in 1131 CRISPR screens. DR ChiTaRS; MEPCE; human. DR EvolutionaryTrace; Q7L2J0; -. DR GenomeRNAi; 56257; -. DR Pharos; Q7L2J0; Tbio. DR PRO; PR:Q7L2J0; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q7L2J0; Protein. DR Bgee; ENSG00000146834; Expressed in left testis and 203 other cell types or tissues. DR Genevisible; Q7L2J0; HS. DR GO; GO:0120259; C:7SK snRNP; IDA:FlyBase. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB. DR GO; GO:0097322; F:7SK snRNA binding; IDA:FlyBase. DR GO; GO:0008171; F:O-methyltransferase activity; IBA:GO_Central. DR GO; GO:1990276; F:RNA 5'-methyltransferase activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0008173; F:RNA methyltransferase activity; IDA:UniProtKB. DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; IDA:UniProtKB. DR GO; GO:0017069; F:snRNA binding; IBA:GO_Central. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl. DR GO; GO:1904871; P:positive regulation of protein localization to Cajal body; IDA:UniProtKB. DR GO; GO:1905382; P:positive regulation of snRNA transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0001510; P:RNA methylation; IDA:UniProtKB. DR GO; GO:0016073; P:snRNA metabolic process; IDA:UniProtKB. DR GO; GO:0040031; P:snRNA modification; IDA:UniProtKB. DR CDD; cd02440; AdoMet_MTases; 1. DR DisProt; DP02832; -. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR InterPro; IPR039772; Bin3-like. DR InterPro; IPR010675; Bin3_C. DR InterPro; IPR024160; BIN3_SAM-bd_dom. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR PANTHER; PTHR12315:SF0; 7SK SNRNA METHYLPHOSPHATE CAPPING ENZYME; 1. DR PANTHER; PTHR12315; BICOID-INTERACTING PROTEIN RELATED; 1. DR Pfam; PF06859; Bin3; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR PROSITE; PS51515; BIN3_SAM; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Isopeptide bond; KW Methylation; Methyltransferase; Nucleus; Phosphoprotein; KW Reference proteome; S-adenosyl-L-methionine; Transferase; Ubl conjugation. FT CHAIN 1..689 FT /note="7SK snRNA methylphosphate capping enzyme" FT /id="PRO_0000289262" FT DOMAIN 431..686 FT /note="Bin3-type SAM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00848" FT REGION 1..167 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 258..314 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 332..407 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 71..90 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 335..358 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 390..405 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 422 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:30559425, FT ECO:0007744|PDB:6DCB, ECO:0007744|PDB:6DCC" FT BINDING 433 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:30559425, FT ECO:0007744|PDB:6DCB, ECO:0007744|PDB:6DCC" FT BINDING 451..453 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:30559425, ECO:0000269|Ref.26, FT ECO:0007744|PDB:5UNA, ECO:0007744|PDB:6DCB, FT ECO:0007744|PDB:6DCC" FT BINDING 474..475 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:30559425, ECO:0000269|Ref.26, FT ECO:0007744|PDB:5UNA, ECO:0007744|PDB:6DCB, FT ECO:0007744|PDB:6DCC" FT BINDING 559..560 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:30559425, ECO:0000269|Ref.26, FT ECO:0007744|PDB:5UNA, ECO:0007744|PDB:6DCB, FT ECO:0007744|PDB:6DCC" FT BINDING 581 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:30559425, ECO:0000269|Ref.26, FT ECO:0007744|PDB:5UNA, ECO:0007744|PDB:6DCB, FT ECO:0007744|PDB:6DCC" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 57 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 60 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 69 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 101 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 117 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q8K3A9" FT MOD_RES 152 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 175 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18691976" FT MOD_RES 179 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336" FT MOD_RES 213 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 216 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 217 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 254 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 291 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 330 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 344 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 390 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT CROSSLNK 643 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..469 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044512" FT MUTAGEN 421 FT /note="Y->A: Nearly abolished methyltransferase activity." FT /evidence="ECO:0000269|PubMed:30559425" FT MUTAGEN 447..449 FT /note="VLD->AAA: Abolished methyltransferase activity and FT reduced interaction with LARP7, without affecting FT interaction with P-TEFb." FT /evidence="ECO:0000269|PubMed:19906723" FT MUTAGEN 585 FT /note="K->A: Decreased methyltransferase activity." FT /evidence="ECO:0000269|PubMed:30559425" FT MUTAGEN 674 FT /note="F->A: Strongly reduced methyltransferase activity." FT /evidence="ECO:0000269|PubMed:30559425" FT CONFLICT 661 FT /note="Y -> N (in Ref. 1; BAG51598)" FT /evidence="ECO:0000305" FT HELIX 421..425 FT /evidence="ECO:0007829|PDB:6DCB" FT HELIX 432..435 FT /evidence="ECO:0007829|PDB:6DCB" FT HELIX 439..441 FT /evidence="ECO:0007829|PDB:6DCB" FT TURN 442..444 FT /evidence="ECO:0007829|PDB:6DCB" FT STRAND 446..450 FT /evidence="ECO:0007829|PDB:6DCB" FT HELIX 456..464 FT /evidence="ECO:0007829|PDB:6DCB" FT STRAND 468..475 FT /evidence="ECO:0007829|PDB:6DCB" FT HELIX 477..486 FT /evidence="ECO:0007829|PDB:6DCB" FT HELIX 487..490 FT /evidence="ECO:0007829|PDB:6DCB" FT TURN 549..552 FT /evidence="ECO:0007829|PDB:6DCB" FT STRAND 553..557 FT /evidence="ECO:0007829|PDB:6DCB" FT HELIX 565..569 FT /evidence="ECO:0007829|PDB:6DCB" FT STRAND 575..582 FT /evidence="ECO:0007829|PDB:6DCB" FT HELIX 584..606 FT /evidence="ECO:0007829|PDB:6DCB" FT STRAND 607..616 FT /evidence="ECO:0007829|PDB:6DCB" FT HELIX 620..622 FT /evidence="ECO:0007829|PDB:6DCB" FT HELIX 624..626 FT /evidence="ECO:0007829|PDB:6DCB" FT HELIX 631..639 FT /evidence="ECO:0007829|PDB:6DCB" FT HELIX 644..646 FT /evidence="ECO:0007829|PDB:6DCB" FT HELIX 647..651 FT /evidence="ECO:0007829|PDB:6DCB" FT TURN 654..656 FT /evidence="ECO:0007829|PDB:6DCB" FT STRAND 660..665 FT /evidence="ECO:0007829|PDB:6DCB" FT HELIX 672..674 FT /evidence="ECO:0007829|PDB:6DCB" FT STRAND 678..682 FT /evidence="ECO:0007829|PDB:6DCB" SQ SEQUENCE 689 AA; 74355 MW; CBB1D6BF144C923A CRC64; MIEMAAEKEP FLVPAPPPPL KDESGGGGGP TVPPHQEAAS GELRGGTERG PGRCAPSAGS PAAAVGRESP GAAATSSSGP QAQQHRGGGP QAQSHGEARL SDPPGRAAPP DVGEERRGGG GTELGPPAPP RPRNGYQPHR PPGGGGGKRR NSCNVGGGGG GFKHPAFKRR RRVNSDCDSV LPSNFLLGGN IFDPLNLNSL LDEEVSRTLN AETPKSSPLP AKGRDPVEIL IPKDITDPLS LNTCTDEGHV VLASPLKTGR KRHRHRGQHH QQQQAAGGSE SHPVPPTAPL TPLLHGEGAS QQPRHRGQNR DAPQPYELNT AINCRDEVVS PLPSALQGPS GSLSAPPAAS VISAPPSSSS RHRKRRRTSS KSEAGARGGG QGSKEKGRGS WGGRHHHHHP LPAAGFKKQQ RKFQYGNYCK YYGYRNPSCE DGRLRVLKPE WFRGRDVLDL GCNVGHLTLS IACKWGPSRM VGLDIDSRLI HSARQNIRHY LSEELRLPPQ TLEGDPGAEG EEGTTTVRKR SCFPASLTAS RGPIAAPQVP LDGADTSVFP NNVVFVTGNY VLDRDDLVEA QTPEYDVVLC LSLTKWVHLN WGDEGLKRMF RRIYRHLRPG GILVLEPQPW SSYGKRKTLT ETIYKNYYRI QLKPEQFSSY LTSPDVGFSS YELVATPHNT SKGFQRPVYL FHKARSPSH //