MEPCE_HUMAN
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 03-AUG-2022, entry version 170.
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};
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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 SMR; Q7L2J0; -.
DR BioGRID; 121122; 840.
DR IntAct; Q7L2J0; 64.
DR MINT; Q7L2J0; -.
DR STRING; 9606.ENSP00000308546; -.
DR GlyGen; Q7L2J0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q7L2J0; -.
DR PhosphoSitePlus; Q7L2J0; -.
DR BioMuta; MEPCE; -.
DR DMDM; 74758999; -.
DR EPD; Q7L2J0; -.
DR jPOST; Q7L2J0; -.
DR MassIVE; Q7L2J0; -.
DR MaxQB; Q7L2J0; -.
DR PaxDb; Q7L2J0; -.
DR PeptideAtlas; Q7L2J0; -.
DR PRIDE; Q7L2J0; -.
DR ProteomicsDB; 15164; -.
DR ProteomicsDB; 68762; -. [Q7L2J0-1]
DR Antibodypedia; 30703; 202 antibodies from 31 providers.
DR DNASU; 56257; -.
DR Ensembl; ENST00000310512.4; ENSP00000308546.2; ENSG00000146834.14. [Q7L2J0-1]
DR Ensembl; ENST00000414441.5; ENSP00000400875.1; ENSG00000146834.14. [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 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; 1185441at2759; -.
DR PhylomeDB; Q7L2J0; -.
DR TreeFam; TF324061; -.
DR PathwayCommons; Q7L2J0; -.
DR SignaLink; Q7L2J0; -.
DR SIGNOR; Q7L2J0; -.
DR BioGRID-ORCS; 56257; 754 hits in 1056 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 201 other 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:0035562; P:negative regulation of chromatin binding; IEA:Ensembl.
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 DisProt; DP02832; -.
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 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
