ID SPT5H_HUMAN Reviewed; 1087 AA. AC O00267; O43279; Q59G52; Q99639; DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1997, sequence version 1. DT 27-MAR-2024, entry version 212. DE RecName: Full=Transcription elongation factor SPT5; DE Short=hSPT5; DE AltName: Full=DRB sensitivity-inducing factor 160 kDa subunit; DE Short=DSIF p160; DE AltName: Full=DRB sensitivity-inducing factor large subunit; DE Short=DSIF large subunit; DE AltName: Full=Tat-cotransactivator 1 protein; DE Short=Tat-CT1 protein; GN Name=SUPT5H; Synonyms=SPT5, SPT5H; 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 [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=8975720; DOI=10.1006/geno.1996.0646; RA Chiang P.-W., Fogel E., Jackson C.L., Lieuallen K., Lennon G., Qu X., RA Wang S.-Q., Kurnit D.M.; RT "Isolation, sequencing, and mapping of the human homologue of the yeast RT transcription factor, SPT5."; RL Genomics 38:421-424(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 116-152; RP 288-319; 461-471; 529-542; 580-587; 746-761; 795-809; 841-885; 888-922 AND RP 1068-1087, DOMAINS CTR1 AND CTR2, AND PHOSPHORYLATION. RX PubMed=9199507; DOI=10.1016/s0014-5793(97)00486-9; RA Stachora A.A., Schaefer R.E., Pohlmeier M., Maier G., Ponstingl H.; RT "Human Supt5h protein, a putative modulator of chromatin structure, is RT reversibly phosphorylated in mitosis."; RL FEBS Lett. 409:74-78(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 277-282; RP 324-328; 459-470 AND 580-597, FUNCTION, AND INTERACTION WITH SUPT4H1 AND RP RNA POLYMERASE II. RX PubMed=9450929; DOI=10.1101/gad.12.3.343; RA Wada T., Takagi T., Yamaguchi Y., Ferdous A., Imai T., Hirose S., RA Sugimoto S., Yano K., Hartzog G.A., Winston F., Buratowski S., Handa H.; RT "DSIF, a novel transcription elongation factor that regulates RNA RT polymerase II processivity, is composed of human Spt4 and Spt5 homologs."; RL Genes Dev. 12:343-356(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 199-213; RP 247-258 AND 799-811, AND FUNCTION. RX PubMed=9514752; DOI=10.1006/jmbi.1997.1601; RA Wu-Baer F., Lane W.S., Gaynor R.B.; RT "Role of the human homolog of the yeast transcription factor SPT5 in HIV-1 RT Tat-activation."; RL J. Mol. Biol. 277:179-197(1998). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Muscle; 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 [7] RP FUNCTION, AND INTERACTION WITH RNA POLYMERASE II. RX PubMed=9857195; DOI=10.1093/emboj/17.24.7395; RA Wada T., Takagi T., Yamaguchi Y., Watanabe D., Handa H.; RT "Evidence that P-TEFb alleviates the negative effect of DSIF on RNA RT polymerase II-dependent transcription in vitro."; RL EMBO J. 17:7395-7403(1998). RN [8] RP FUNCTION, AND INTERACTION WITH THE NELF COMPLEX. RX PubMed=10199401; DOI=10.1016/s0092-8674(00)80713-8; RA Yamaguchi Y., Takagi T., Wada T., Yano K., Furuya A., Sugimoto S., RA Hasegawa J., Handa H.; RT "NELF, a multisubunit complex containing RD, cooperates with DSIF to RT repress RNA polymerase II elongation."; RL Cell 97:41-51(1999). RN [9] RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH NCL; CCNT1; RNA POL II; RP HTATSF1 AND CDK9. RX PubMed=10393184; DOI=10.1093/emboj/18.13.3688; RA Parada C.A., Roeder R.G.; RT "A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV- RT 1 transcription."; RL EMBO J. 18:3688-3701(1999). RN [10] RP FUNCTION, AND INTERACTION WITH RNGTT. RX PubMed=10421630; DOI=10.1101/gad.13.14.1774; RA Wen Y., Shatkin A.J.; RT "Transcription elongation factor hSPT5 stimulates mRNA capping."; RL Genes Dev. 13:1774-1779(1999). RN [11] RP FUNCTION, INTERACTION WITH RNA POLYMERASE II AND SUPT4H1, SUBCELLULAR RP LOCATION, AND TISSUE SPECIFICITY. RX PubMed=10075709; DOI=10.1074/jbc.274.12.8085; RA Yamaguchi Y., Wada T., Watanabe D., Takagi T., Hasegawa J., Handa H.; RT "Structure and function of the human transcription elongation factor RT DSIF."; RL J. Biol. Chem. 274:8085-8092(1999). RN [12] RP FUNCTION, AND INTERACTION WITH HTATSF1 AND RNA POLYMERASE II. RX PubMed=10454543; DOI=10.1128/mcb.19.9.5960; RA Kim J.B., Yamaguchi Y., Wada T., Handa H., Sharp P.A.; RT "Tat-SF1 protein associates with RAP30 and human SPT5 proteins."; RL Mol. Cell. Biol. 19:5960-5968(1999). RN [13] RP FUNCTION. RX PubMed=10912001; DOI=10.1016/s1097-2765(00)80272-5; RA Wada T., Orphanides G., Hasegawa J., Kim D.-K., Shima D., Yamaguchi Y., RA Fukuda A., Hisatake K., Oh S., Reinberg D., Handa H.; RT "FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation RT and reveals functional differences between P-TEFb and TFIIH."; RL Mol. Cell 5:1067-1072(2000). RN [14] RP FUNCTION, INTERACTION WITH RNA POLYMERASE II AND SUPT4H1, AND RP PHOSPHORYLATION AT THR-775 AND THR-784. RX PubMed=10757782; DOI=10.1128/mcb.20.9.2970-2983.2000; RA Ivanov D., Kwak Y.T., Guo J., Gaynor R.B.; RT "Domains in the SPT5 protein that modulate its transcriptional regulatory RT properties."; RL Mol. Cell. Biol. 20:2970-2983(2000). RN [15] RP PHOSPHORYLATION BY CDK9. RX PubMed=11145967; DOI=10.1074/jbc.m010908200; RA Kim J.B., Sharp P.A.; RT "Positive transcription elongation factor B phosphorylates hSPT5 and RNA RT polymerase II carboxyl-terminal domain independently of cyclin-dependent RT kinase-activating kinase."; RL J. Biol. Chem. 276:12317-12323(2001). RN [16] RP FUNCTION, AND PHOSPHORYLATION BY CDK9. RX PubMed=11112772; DOI=10.1074/jbc.m006130200; RA Ping Y.-H., Rana T.M.; RT "DSIF and NELF interact with RNA polymerase II elongation complex and HIV-1 RT Tat stimulates P-TEFb-mediated phosphorylation of RNA polymerase II and RT DSIF during transcription elongation."; RL J. Biol. Chem. 276:12951-12958(2001). RN [17] RP FUNCTION. RX PubMed=11553615; DOI=10.1074/jbc.m104967200; RA Renner D.B., Yamaguchi Y., Wada T., Handa H., Price D.H.; RT "A highly purified RNA polymerase II elongation control system."; RL J. Biol. Chem. 276:42601-42609(2001). RN [18] RP INTERACTION WITH PIN1, AND PHOSPHORYLATION. RX PubMed=11575923; DOI=10.1006/jmbi.2001.4991; RA Lavoie S.B., Albert A.L., Handa H., Vincent M., Bensaude O.; RT "The peptidyl-prolyl isomerase Pin1 interacts with hSpt5 phosphorylated by RT Cdk9."; RL J. Mol. Biol. 312:675-685(2001). RN [19] RP FUNCTION, AND PHOSPHORYLATION BY CDK9. RX PubMed=11809800; DOI=10.1128/mcb.22.4.1079-1093.2002; RA Bourgeois C.F., Kim Y.K., Churcher M.J., West M.J., Karn J.; RT "Spt5 cooperates with human immunodeficiency virus type 1 Tat by preventing RT premature RNA release at terminator sequences."; RL Mol. Cell. Biol. 22:1079-1093(2002). RN [20] RP INTERACTION WITH THE NELF COMPLEX. RX PubMed=11940650; DOI=10.1128/mcb.22.9.2918-2927.2002; RA Yamaguchi Y., Inukai N., Narita T., Wada T., Handa H.; RT "Evidence that negative elongation factor represses transcription RT elongation through binding to a DRB sensitivity-inducing factor/RNA RT polymerase II complex and RNA."; RL Mol. Cell. Biol. 22:2918-2927(2002). RN [21] RP FUNCTION, AND INTERACTION WITH SUPT4H1. RX PubMed=12653964; DOI=10.1046/j.1365-2443.2003.00638.x; RA Kim D.-K., Inukai N., Yamada T., Furuya A., Sato H., Yamaguchi Y., Wada T., RA Handa H.; RT "Structure-function analysis of human Spt4: evidence that hSpt4 and hSpt5 RT exert their roles in transcriptional elongation as parts of the DSIF RT complex."; RL Genes Cells 8:371-378(2003). RN [22] RP FUNCTION, INTERACTION WITH CDK9; PRMT1; RNA POLYMERASE II; PRMT5 AND RP SUPT4H1, METHYLATION AT ARG-681; ARG-696 AND ARG-698, AND MUTAGENESIS OF RP ARG-681; ARG-696 AND ARG-698. RX PubMed=12718890; DOI=10.1016/s1097-2765(03)00101-1; RA Kwak Y.T., Guo J., Prajapati S., Park K.-J., Surabhi R.M., Miller B., RA Gehrig P., Gaynor R.B.; RT "Methylation of SPT5 regulates its interaction with RNA polymerase II and RT transcriptional elongation properties."; RL Mol. Cell 11:1055-1066(2003). RN [23] RP INTERACTION WITH THE NELF COMPLEX. RX PubMed=12612062; DOI=10.1128/mcb.23.6.1863-1873.2003; RA Narita T., Yamaguchi Y., Yano K., Sugimoto S., Chanarat S., Wada T., RA Kim D.-K., Hasegawa J., Omori M., Inukai N., Endoh M., Yamada T., Handa H.; RT "Human transcription elongation factor NELF: identification of novel RT subunits and reconstitution of the functionally active complex."; RL Mol. Cell. Biol. 23:1863-1873(2003). RN [24] RP FUNCTION, AND MUTAGENESIS OF GLY-1002. RX PubMed=15380072; DOI=10.1016/j.cub.2004.08.066; RA Jennings B.H., Shah S., Yamaguchi Y., Seki M., Phillips R.G., Handa H., RA Ish-Horowicz D.; RT "Locus-specific requirements for Spt5 in transcriptional activation and RT repression in Drosophila."; RL Curr. Biol. 14:1680-1684(2004). RN [25] RP PHOSPHORYLATION BY CDK9. RX PubMed=15564463; DOI=10.1128/jvi.78.24.13522-13533.2004; RA Zhou M., Deng L., Lacoste V., Park H.U., Pumfery A., Kashanchi F., RA Brady J.N., Kumar A.; RT "Coordination of transcription factor phosphorylation and histone RT methylation by the P-TEFb kinase during human immunodeficiency virus type 1 RT transcription."; RL J. Virol. 78:13522-13533(2004). RN [26] RP FUNCTION. RX PubMed=14701750; DOI=10.1128/mcb.24.2.787-795.2004; RA Fujinaga K., Irwin D., Huang Y., Taube R., Kurosu T., Peterlin B.M.; RT "Dynamics of human immunodeficiency virus transcription: P-TEFb RT phosphorylates RD and dissociates negative effectors from the RT transactivation response element."; RL Mol. Cell. Biol. 24:787-795(2004). RN [27] RP INTERACTION WITH RNA POLYMERASE II; SUPT4H1 AND SUPT6H. RX PubMed=15060154; DOI=10.1128/mcb.24.8.3324-3336.2004; RA Endoh M., Zhu W., Hasegawa J., Watanabe H., Kim D.-K., Aida M., Inukai N., RA Narita T., Yamada T., Furuya A., Sato H., Yamaguchi Y., Mandal S.S., RA Reinberg D., Wada T., Handa H.; RT "Human Spt6 stimulates transcription elongation by RNA polymerase II in RT vitro."; RL Mol. Cell. Biol. 24:3324-3336(2004). RN [28] RP FUNCTION. RX PubMed=15136722; DOI=10.1073/pnas.0401493101; RA Mandal S.S., Chu C., Wada T., Handa H., Shatkin A.J., Reinberg D.; RT "Functional interactions of RNA-capping enzyme with factors that positively RT and negatively regulate promoter escape by RNA polymerase II."; RL Proc. Natl. Acad. Sci. U.S.A. 101:7572-7577(2004). RN [29] RP FUNCTION. RX PubMed=16214896; DOI=10.1073/pnas.0409405102; RA Palangat M., Renner D.B., Price D.H., Landick R.; RT "A negative elongation factor for human RNA polymerase II inhibits the RT anti-arrest transcript-cleavage factor TFIIS."; RL Proc. Natl. Acad. Sci. U.S.A. 102:15036-15041(2005). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-666, AND IDENTIFICATION BY RP 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 [31] RP PHOSPHORYLATION BY CDK7. RX PubMed=16327805; DOI=10.1038/nsmb1028; RA Larochelle S., Batliner J., Gamble M.J., Barboza N.M., Kraybill B.C., RA Blethrow J.D., Shokat K.M., Fisher R.P.; RT "Dichotomous but stringent substrate selection by the dual-function Cdk7 RT complex revealed by chemical genetics."; RL Nat. Struct. Mol. Biol. 13:55-62(2006). RN [32] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17924679; DOI=10.1021/pr070152u; RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells RT and high confident phosphopeptide identification by cross-validation of RT MS/MS and MS/MS/MS spectra."; RL J. Proteome Res. 6:4150-4162(2007). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-666 AND THR-1034, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [34] RP IDENTIFICATION BY MASS 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 [35] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-666 AND THR-1034, AND RP IDENTIFICATION BY MASS 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 [36] 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 [37] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-666; SER-686; SER-789; RP THR-791; SER-804; THR-806 AND THR-1034, 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 [38] RP INTERACTION WITH MCM3AP. RX PubMed=23652018; DOI=10.1038/ncomms2823; RA Singh S.K., Maeda K., Eid M.M., Almofty S.A., Ono M., Pham P., RA Goodman M.F., Sakaguchi N.; RT "GANP regulates recruitment of AID to immunoglobulin variable regions by RT modulating transcription and nucleosome occupancy."; RL Nat. Commun. 4:1830-1830(2013). RN [39] RP IDENTIFICATION BY MASS 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 [40] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-143, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [41] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-143, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25755297; DOI=10.1074/mcp.o114.044792; RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V., RA Vertegaal A.C.; RT "System-wide analysis of SUMOylation dynamics in response to replication RT stress reveals novel small ubiquitin-like modified target proteins and RT acceptor lysines relevant for genome stability."; RL Mol. Cell. Proteomics 14:1419-1434(2015). RN [42] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-143 AND LYS-1037, AND RP IDENTIFICATION BY MASS 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 [43] RP STRUCTURE BY NMR OF 420-523 AND 690-757. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of KOW motifs of human transcription elongation factor RT SPT5."; RL Submitted (JUL-2007) to the PDB data bank. RN [44] RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 176-273 IN COMPLEX WITH SPT4H1. RX PubMed=19860741; DOI=10.1042/bj20091422; RA Wenzel S., Martins B.M., Rosch P., Wohrl B.M.; RT "Crystal structure of the human transcription elongation factor DSIF hSpt4 RT subunit in complex with the hSpt5 dimerization interface."; RL Biochem. J. 425:373-380(2010). RN [45] RP X-RAY CRYSTALLOGRAPHY (1.10 ANGSTROMS) OF 979-1087 IN COMPLEX WITH DNA-RNA RP HYBRID, SUBUNIT, AND MUTAGENESIS OF ARG-246; LEU-247; TYR-249; TRP-250; RP ASN-251; ARG-577; LYS-578; LYS-579 AND ARG-582. RX PubMed=28892040; DOI=10.1038/nsmb.3465; RA Bernecky C., Plitzko J.M., Cramer P.; RT "Structure of a transcribing RNA polymerase II-DSIF complex reveals a RT multidentate DNA-RNA clamp."; RL Nat. Struct. Mol. Biol. 24:809-815(2017). CC -!- FUNCTION: Component of the DRB sensitivity-inducing factor complex CC (DSIF complex), which regulates mRNA processing and transcription CC elongation by RNA polymerase II. DSIF positively regulates mRNA capping CC by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A. CC DSIF also acts cooperatively with the negative elongation factor CC complex (NELF complex) to enhance transcriptional pausing at sites CC proximal to the promoter. Transcriptional pausing may facilitate the CC assembly of an elongation competent RNA polymerase II complex. DSIF and CC NELF promote pausing by inhibition of the transcription elongation CC factor TFIIS/S-II. TFIIS/S-II binds to RNA polymerase II at CC transcription pause sites and stimulates the weak intrinsic nuclease CC activity of the enzyme. Cleavage of blocked transcripts by RNA CC polymerase II promotes the resumption of transcription from the new 3' CC terminus and may allow repeated attempts at transcription through CC natural pause sites. DSIF can also positively regulate transcriptional CC elongation and is required for the efficient activation of CC transcriptional elongation by the HIV-1 nuclear transcriptional CC activator, Tat. DSIF acts to suppress transcriptional pausing in CC transcripts derived from the HIV-1 LTR and blocks premature release of CC HIV-1 transcripts at terminator sequences. CC {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, CC ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10421630, CC ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10757782, CC ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, CC ECO:0000269|PubMed:11553615, ECO:0000269|PubMed:11809800, CC ECO:0000269|PubMed:12653964, ECO:0000269|PubMed:12718890, CC ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15136722, CC ECO:0000269|PubMed:15380072, ECO:0000269|PubMed:16214896, CC ECO:0000269|PubMed:9450929, ECO:0000269|PubMed:9514752, CC ECO:0000269|PubMed:9857195}. CC -!- SUBUNIT: Interacts with SUPT4H1 to form DSIF. DSIF interacts with the CC positive transcription elongation factor b complex (P-TEFb complex), CC which is composed of CDK9 and cyclin-T (CCNT1 or CCNT2). DSIF interacts CC with RNA polymerase II (Pol II); forms DNA and RNA clamps that CC stabilize Pol II elongation complex while maintaining the nontemplate CC DNA strand in the transcription bubble and nascent RNA in the exit CC channel. This interaction is reduced by phosphorylation of the C- CC terminal domain (CTD) of POLR2A by P-TEFb. DSIF also interacts with the CC NELF complex, which is composed of NELFA, NELFB, NELFD and NELFE, and CC this interaction occurs following prior binding of DSIF to RNA CC polymerase II. DSIF also interacts with PRMT1/HRMT1L2, HTATSF1/TATSF1, CC RNGTT/CAP1A, PRMT5/SKB1, SUPT6H, and can interact with PIN1. Component CC of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb CC complex components CDK9 and CCNT1, RNA polymerase II, SUPT5H, and CC NCL/nucleolin. Interacts with MCM3AP isoform GANP (PubMed:23652018). CC {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, CC ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10421630, CC ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10757782, CC ECO:0000269|PubMed:11575923, ECO:0000269|PubMed:11940650, CC ECO:0000269|PubMed:12612062, ECO:0000269|PubMed:12653964, CC ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:15060154, CC ECO:0000269|PubMed:19860741, ECO:0000269|PubMed:23652018, CC ECO:0000269|PubMed:28892040, ECO:0000269|PubMed:9450929, CC ECO:0000269|PubMed:9857195}. CC -!- INTERACTION: CC O00267; P50613: CDK7; NbExp=3; IntAct=EBI-710464, EBI-1245958; CC O00267; Q13526: PIN1; NbExp=4; IntAct=EBI-710464, EBI-714158; CC O00267; P24928: POLR2A; NbExp=5; IntAct=EBI-710464, EBI-295301; CC O00267; P62937: PPIA; NbExp=2; IntAct=EBI-710464, EBI-437708; CC O00267; P63272: SUPT4H1; NbExp=15; IntAct=EBI-710464, EBI-727250; CC O00267; P54274: TERF1; NbExp=2; IntAct=EBI-710464, EBI-710997; CC O00267; Q5EP34: PA; Xeno; NbExp=3; IntAct=EBI-710464, EBI-25772799; CC O00267; G3MZY8: POLR2A; Xeno; NbExp=2; IntAct=EBI-710464, EBI-6551200; CC O00267; A5PJW8: POLR2B; Xeno; NbExp=8; IntAct=EBI-710464, EBI-15586776; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10075709}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O00267-1; Sequence=Displayed; CC Name=2; CC IsoId=O00267-2; Sequence=VSP_016282; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:8975720}. CC -!- PTM: Methylated by PRMT1/HRMT1L2 and PRMT5/SKB1. Methylation negatively CC regulates interaction with P-TEFb and RNA polymerase II. CC {ECO:0000269|PubMed:12718890}. CC -!- PTM: Phosphorylated by CDK7 and CDK9. Phosphorylation by P-TEFb CC alleviates transcriptional pausing and can stimulate transcriptional CC elongation from the HIV-1 LTR. P-TEFb dependent phosphorylation is CC stimulated by the HIV-1 Tat protein. Phosphorylation may also stimulate CC interaction with PIN1. Bulk phosphorylation occurs predominantly in CC mitosis. {ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:11112772, CC ECO:0000269|PubMed:11145967, ECO:0000269|PubMed:11575923, CC ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:15564463, CC ECO:0000269|PubMed:16327805, ECO:0000269|PubMed:9199507}. CC -!- SIMILARITY: Belongs to the SPT5 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD92494.1; 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; U56402; AAC51102.1; -; mRNA. DR EMBL; Y12790; CAA73326.1; -; mRNA. DR EMBL; AB000516; BAA24075.1; -; mRNA. DR EMBL; AF040253; AAD02179.1; -; mRNA. DR EMBL; AB209257; BAD92494.1; ALT_INIT; mRNA. DR EMBL; BC024203; AAH24203.1; -; mRNA. DR CCDS; CCDS12536.1; -. [O00267-1] DR CCDS; CCDS46072.1; -. [O00267-2] DR RefSeq; NP_001104490.1; NM_001111020.2. [O00267-1] DR RefSeq; NP_001124296.1; NM_001130824.1. [O00267-1] DR RefSeq; NP_001124297.1; NM_001130825.1. [O00267-2] DR RefSeq; NP_001306919.1; NM_001319990.1. [O00267-1] DR RefSeq; NP_001306920.1; NM_001319991.1. [O00267-2] DR RefSeq; NP_003160.2; NM_003169.3. [O00267-1] DR PDB; 2DO3; NMR; -; A=462-523. DR PDB; 2E6Z; NMR; -; A=420-471. DR PDB; 2E70; NMR; -; A=694-757. DR PDB; 3H7H; X-ray; 1.55 A; B=176-273. DR PDB; 4L1U; X-ray; 2.42 A; G/H/I/J=778-790. DR PDB; 5OHO; X-ray; 1.60 A; A/B=536-646. DR PDB; 5OHQ; X-ray; 1.10 A; A=979-1087. DR PDB; 5OIK; EM; 3.70 A; Z=1-1087. DR PDB; 5U98; X-ray; 2.00 A; C/F=980-988. DR PDB; 6EQY; NMR; -; A=522-647. DR PDB; 6ER0; NMR; -; A=961-1087. DR PDB; 6GMH; EM; 3.10 A; Z=1-1087. DR PDB; 6GML; EM; 3.20 A; Z=1-1087. DR PDB; 6TED; EM; 3.10 A; Z=1-1087. DR PDB; 7OKX; EM; 3.30 A; Z=1-1087. DR PDB; 7OKY; EM; 4.14 A; Z=1-1087. DR PDB; 7OL0; EM; 3.00 A; Z=1-1087. DR PDB; 7PKS; EM; 3.60 A; Z=1-1087. DR PDB; 7UNC; EM; 3.00 A; Z=1-1087. DR PDB; 7UND; EM; 3.00 A; Z=1-1087. DR PDB; 7YCX; EM; 4.18 A; j=1-1087. DR PDB; 8P4C; EM; 3.80 A; Z=1-1087. DR PDB; 8P4D; EM; 3.60 A; Z=1-1087. DR PDB; 8P4E; EM; 3.90 A; Z=1-1087. DR PDB; 8P4F; EM; 4.00 A; Z=1-1087. DR PDBsum; 2DO3; -. DR PDBsum; 2E6Z; -. DR PDBsum; 2E70; -. DR PDBsum; 3H7H; -. DR PDBsum; 4L1U; -. DR PDBsum; 5OHO; -. DR PDBsum; 5OHQ; -. DR PDBsum; 5OIK; -. DR PDBsum; 5U98; -. DR PDBsum; 6EQY; -. DR PDBsum; 6ER0; -. DR PDBsum; 6GMH; -. DR PDBsum; 6GML; -. DR PDBsum; 6TED; -. DR PDBsum; 7OKX; -. DR PDBsum; 7OKY; -. DR PDBsum; 7OL0; -. DR PDBsum; 7PKS; -. DR PDBsum; 7UNC; -. DR PDBsum; 7UND; -. DR PDBsum; 7YCX; -. DR PDBsum; 8P4C; -. DR PDBsum; 8P4D; -. DR PDBsum; 8P4E; -. DR PDBsum; 8P4F; -. DR AlphaFoldDB; O00267; -. DR EMDB; EMD-0031; -. DR EMDB; EMD-0038; -. DR EMDB; EMD-10480; -. DR EMDB; EMD-12966; -. DR EMDB; EMD-12967; -. DR EMDB; EMD-12968; -. DR EMDB; EMD-12969; -. DR EMDB; EMD-12970; -. DR EMDB; EMD-12971; -. DR EMDB; EMD-12972; -. DR EMDB; EMD-12973; -. DR EMDB; EMD-12974; -. DR EMDB; EMD-13479; -. DR EMDB; EMD-17405; -. DR EMDB; EMD-17406; -. DR EMDB; EMD-17407; -. DR EMDB; EMD-17408; -. DR EMDB; EMD-26620; -. DR EMDB; EMD-26621; -. DR EMDB; EMD-33741; -. DR EMDB; EMD-3817; -. DR SMR; O00267; -. DR BioGRID; 112697; 394. DR ComplexPortal; CPX-891; DSIF transcription elongation factor complex. DR CORUM; O00267; -. DR DIP; DIP-29014N; -. DR IntAct; O00267; 128. DR MINT; O00267; -. DR STRING; 9606.ENSP00000470252; -. DR GlyCosmos; O00267; 2 sites, 1 glycan. DR GlyGen; O00267; 7 sites, 2 O-linked glycans (7 sites). DR iPTMnet; O00267; -. DR MetOSite; O00267; -. DR PhosphoSitePlus; O00267; -. DR SwissPalm; O00267; -. DR BioMuta; SUPT5H; -. DR EPD; O00267; -. DR jPOST; O00267; -. DR MassIVE; O00267; -. DR MaxQB; O00267; -. DR PaxDb; 9606-ENSP00000470252; -. DR PeptideAtlas; O00267; -. DR ProteomicsDB; 47816; -. [O00267-1] DR ProteomicsDB; 47817; -. [O00267-2] DR Pumba; O00267; -. DR Antibodypedia; 16797; 219 antibodies from 29 providers. DR DNASU; 6829; -. DR Ensembl; ENST00000359191.10; ENSP00000352117.6; ENSG00000196235.14. [O00267-2] DR Ensembl; ENST00000402194.6; ENSP00000384505.2; ENSG00000196235.14. [O00267-2] DR Ensembl; ENST00000432763.7; ENSP00000404029.4; ENSG00000196235.14. [O00267-1] DR Ensembl; ENST00000598725.5; ENSP00000469090.1; ENSG00000196235.14. [O00267-1] DR Ensembl; ENST00000599117.5; ENSP00000470252.1; ENSG00000196235.14. [O00267-1] DR GeneID; 6829; -. DR KEGG; hsa:6829; -. DR MANE-Select; ENST00000432763.7; ENSP00000404029.4; NM_001111020.3; NP_001104490.1. DR UCSC; uc002olo.5; human. [O00267-1] DR AGR; HGNC:11469; -. DR CTD; 6829; -. DR DisGeNET; 6829; -. DR GeneCards; SUPT5H; -. DR HGNC; HGNC:11469; SUPT5H. DR HPA; ENSG00000196235; Low tissue specificity. DR MIM; 602102; gene. DR neXtProt; NX_O00267; -. DR OpenTargets; ENSG00000196235; -. DR PharmGKB; PA36255; -. DR VEuPathDB; HostDB:ENSG00000196235; -. DR eggNOG; KOG1999; Eukaryota. DR GeneTree; ENSGT00440000037640; -. DR HOGENOM; CLU_003537_0_0_1; -. DR InParanoid; O00267; -. DR OMA; PYPVGYM; -. DR OrthoDB; 24955at2759; -. DR PhylomeDB; O00267; -. DR TreeFam; TF105730; -. DR BioCyc; MetaCyc:G66-31601-MONOMER; -. DR PathwayCommons; O00267; -. DR Reactome; R-HSA-112382; Formation of RNA Pol II elongation complex. DR Reactome; R-HSA-113418; Formation of the Early Elongation Complex. DR Reactome; R-HSA-167152; Formation of HIV elongation complex in the absence of HIV Tat. DR Reactome; R-HSA-167158; Formation of the HIV-1 Early Elongation Complex. DR Reactome; R-HSA-167160; RNA Pol II CTD phosphorylation and interaction with CE during HIV infection. DR Reactome; R-HSA-167200; Formation of HIV-1 elongation complex containing HIV-1 Tat. DR Reactome; R-HSA-167238; Pausing and recovery of Tat-mediated HIV elongation. DR Reactome; R-HSA-167242; Abortive elongation of HIV-1 transcript in the absence of Tat. DR Reactome; R-HSA-167243; Tat-mediated HIV elongation arrest and recovery. DR Reactome; R-HSA-167246; Tat-mediated elongation of the HIV-1 transcript. DR Reactome; R-HSA-167287; HIV elongation arrest and recovery. DR Reactome; R-HSA-167290; Pausing and recovery of HIV elongation. DR Reactome; R-HSA-674695; RNA Polymerase II Pre-transcription Events. DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes. DR Reactome; R-HSA-6807505; RNA polymerase II transcribes snRNA genes. DR Reactome; R-HSA-72086; mRNA Capping. DR Reactome; R-HSA-75955; RNA Polymerase II Transcription Elongation. DR Reactome; R-HSA-77075; RNA Pol II CTD phosphorylation and interaction with CE. DR SignaLink; O00267; -. DR SIGNOR; O00267; -. DR BioGRID-ORCS; 6829; 763 hits in 1157 CRISPR screens. DR ChiTaRS; SUPT5H; human. DR EvolutionaryTrace; O00267; -. DR GeneWiki; SUPT5H; -. DR GenomeRNAi; 6829; -. DR Pharos; O00267; Tbio. DR PRO; PR:O00267; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; O00267; Protein. DR Bgee; ENSG00000196235; Expressed in right testis and 203 other cell types or tissues. DR ExpressionAtlas; O00267; baseline and differential. DR GO; GO:0032044; C:DSIF complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0032785; P:negative regulation of DNA-templated transcription, elongation; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0032786; P:positive regulation of DNA-templated transcription, elongation; IDA:UniProtKB. DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0034243; P:regulation of transcription elongation by RNA polymerase II; IDA:ComplexPortal. DR GO; GO:0006368; P:transcription elongation by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0140673; P:transcription elongation-coupled chromatin remodeling; IEA:InterPro. DR CDD; cd06081; KOW_Spt5_1; 1. DR CDD; cd06082; KOW_Spt5_2; 1. DR CDD; cd06083; KOW_Spt5_3; 1. DR CDD; cd06084; KOW_Spt5_4; 1. DR CDD; cd06085; KOW_Spt5_5; 1. DR CDD; cd06086; KOW_Spt5_6; 1. DR CDD; cd09888; NGN_Euk; 1. DR Gene3D; 2.30.30.30; -; 3. DR Gene3D; 3.30.70.940; NusG, N-terminal domain; 1. DR IDEAL; IID00641; -. DR InterPro; IPR005824; KOW. DR InterPro; IPR041973; KOW_Spt5_1. DR InterPro; IPR041975; KOW_Spt5_2. DR InterPro; IPR041976; KOW_Spt5_3. DR InterPro; IPR041977; KOW_Spt5_4. DR InterPro; IPR041978; KOW_Spt5_5. DR InterPro; IPR041980; KOW_Spt5_6. DR InterPro; IPR005100; NGN-domain. DR InterPro; IPR006645; NGN-like_dom. DR InterPro; IPR036735; NGN_dom_sf. DR InterPro; IPR039385; NGN_Euk. DR InterPro; IPR014722; Rib_uL2_dom2. DR InterPro; IPR039659; SPT5. DR InterPro; IPR024945; Spt5_C_dom. DR InterPro; IPR022581; Spt5_N. DR InterPro; IPR017071; TF_Spt5_eukaryote. DR InterPro; IPR008991; Translation_prot_SH3-like_sf. DR PANTHER; PTHR11125; SUPPRESSOR OF TY 5; 1. DR PANTHER; PTHR11125:SF7; TRANSCRIPTION ELONGATION FACTOR SPT5; 1. DR Pfam; PF00467; KOW; 2. DR Pfam; PF03439; Spt5-NGN; 1. DR Pfam; PF11942; Spt5_N; 1. DR PIRSF; PIRSF036945; Spt5; 1. DR SMART; SM01104; CTD; 1. DR SMART; SM00739; KOW; 6. DR SMART; SM00738; NGN; 1. DR SUPFAM; SSF50104; Translation proteins SH3-like domain; 1. DR Genevisible; O00267; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW Direct protein sequencing; Isopeptide bond; Methylation; Nucleus; KW Phosphoprotein; Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation; Ubl conjugation. FT CHAIN 1..1087 FT /note="Transcription elongation factor SPT5" FT /id="PRO_0000208468" FT DOMAIN 273..306 FT /note="KOW 1" FT DOMAIN 420..451 FT /note="KOW 2" FT DOMAIN 472..503 FT /note="KOW 3" FT DOMAIN 594..627 FT /note="KOW 4" FT DOMAIN 704..737 FT /note="KOW 5" FT REPEAT 754..759 FT /note="CTR1-1; approximate" FT REPEAT 760..765 FT /note="CTR1-2" FT REPEAT 766..771 FT /note="CTR1-3" FT REPEAT 772..778 FT /note="CTR1-4" FT REPEAT 781..787 FT /note="CTR1-5" FT REPEAT 788..794 FT /note="CTR1-6" FT REPEAT 796..802 FT /note="CTR1-7" FT REPEAT 803..809 FT /note="CTR1-8" FT REPEAT 811..817 FT /note="CTR1-9" FT REPEAT 844..851 FT /note="CTR2-1" FT REPEAT 854..862 FT /note="CTR2-2; approximate" FT REPEAT 863..869 FT /note="CTR2-3; approximate" FT REPEAT 881..885 FT /note="CTR2-4; half-length" FT REPEAT 896..902 FT /note="CTR2-5; approximate" FT REPEAT 904..911 FT /note="CTR2-6" FT REPEAT 916..921 FT /note="CTR2-7; approximate" FT REPEAT 924..930 FT /note="CTR2-8" FT REPEAT 932..939 FT /note="CTR2-9" FT REPEAT 943..950 FT /note="CTR2-10" FT REGION 1..92 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 176..270 FT /note="Interaction with SUPT4H1" FT REGION 313..420 FT /note="Interaction with RNA polymerase II" FT REGION 670..700 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 747..978 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 754..817 FT /note="9 X 7 AA approximate tandem repeats of G-S-[QR]-T-P- FT X-[YQ], motif CTR1" FT REGION 844..950 FT /note="10 X 8 AA approximate tandem repeats of P-[TS]-P-S- FT P-[QA]-[SG]-Y, motif CTR2" FT COMPBIAS 1..23 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 24..38 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 39..63 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 64..79 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 747..831 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 850..872 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 873..947 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 948..962 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 579 FT /ligand="RNA" FT /ligand_id="ChEBI:CHEBI:33697" FT /evidence="ECO:0000269|PubMed:28892040, FT ECO:0007744|PDB:5OIK" FT BINDING 619 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /evidence="ECO:0000269|PubMed:28892040, FT ECO:0007744|PDB:5OIK" FT MOD_RES 32 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O55201" FT MOD_RES 36 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O55201" FT MOD_RES 666 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 681 FT /note="Asymmetric dimethylarginine; by PRMT1; alternate" FT /evidence="ECO:0000269|PubMed:12718890" FT MOD_RES 681 FT /note="Omega-N-methylarginine; by PRMT1; alternate" FT /evidence="ECO:0000269|PubMed:12718890" FT MOD_RES 686 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 696 FT /note="Asymmetric dimethylarginine; by PRMT1; alternate" FT /evidence="ECO:0000269|PubMed:12718890" FT MOD_RES 696 FT /note="Omega-N-methylarginine; by PRMT1; alternate" FT /evidence="ECO:0000269|PubMed:12718890" FT MOD_RES 698 FT /note="Asymmetric dimethylarginine; by PRMT1; alternate" FT /evidence="ECO:0000269|PubMed:12718890" FT MOD_RES 698 FT /note="Omega-N-methylarginine; by PRMT1 and PRMT5; FT alternate" FT /evidence="ECO:0000269|PubMed:12718890" FT MOD_RES 698 FT /note="Symmetric dimethylarginine; by PRMT5; alternate" FT /evidence="ECO:0000269|PubMed:12718890" FT MOD_RES 718 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:O55201" FT MOD_RES 775 FT /note="Phosphothreonine; by CDK9" FT /evidence="ECO:0000269|PubMed:10757782" FT MOD_RES 784 FT /note="Phosphothreonine; by CDK9" FT /evidence="ECO:0000269|PubMed:10757782" FT MOD_RES 789 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 791 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 804 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 806 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1034 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT CROSSLNK 143 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733" FT CROSSLNK 1037 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 103..106 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_016282" FT MUTAGEN 246 FT /note="R->A: Reduces the affinity for Pol II elongation FT complex; when associated with A-247, A-249, A-250 and FT A-251." FT /evidence="ECO:0000269|PubMed:28892040" FT MUTAGEN 247 FT /note="L->A: Reduces the affinity for Pol II elongation FT complex; when associated with A-246, A-249, A-250 and FT A-251." FT /evidence="ECO:0000269|PubMed:28892040" FT MUTAGEN 249 FT /note="Y->A: Reduces the affinity for Pol II elongation FT complex; when associated with A-246, A-247, A-250 and FT A-251." FT /evidence="ECO:0000269|PubMed:28892040" FT MUTAGEN 250 FT /note="W->A: Reduces the affinity for Pol II elongation FT complex; when associated with A-246, A-247, A-249 and FT A-251." FT /evidence="ECO:0000269|PubMed:28892040" FT MUTAGEN 251 FT /note="N->A: Reduces the affinity for Pol II elongation FT complex; when associated with A-246, A-247, A-249 and FT A-250." FT /evidence="ECO:0000269|PubMed:28892040" FT MUTAGEN 577 FT /note="R->A: Reduces the affinity for Pol II elongation FT complex; when associated with A-578, A-579 and A-582." FT /evidence="ECO:0000269|PubMed:28892040" FT MUTAGEN 577 FT /note="R->E: Reduces the affinity for Pol II elongation FT complex; when associated with E-578, E-579 and E-582." FT /evidence="ECO:0000269|PubMed:28892040" FT MUTAGEN 578 FT /note="K->A: Reduces the affinity for Pol II elongation FT complex; when associated with A-577, A-579 and A-582." FT /evidence="ECO:0000269|PubMed:28892040" FT MUTAGEN 578 FT /note="K->E: Reduces the affinity for Pol II elongation FT complex; when associated with E-577, E-579 and E-582." FT /evidence="ECO:0000269|PubMed:28892040" FT MUTAGEN 579 FT /note="K->A: Reduces the affinity for Pol II elongation FT complex; when associated with A-577, A-578 and A-582." FT /evidence="ECO:0000269|PubMed:28892040" FT MUTAGEN 579 FT /note="K->E: Reduces the affinity for Pol II elongation FT complex; when associated with E-577, E-578 and E-582." FT /evidence="ECO:0000269|PubMed:28892040" FT MUTAGEN 582 FT /note="R->A: Reduces the affinity for Pol II elongation FT complex; when associated with A-577, A-578 and A-579." FT /evidence="ECO:0000269|PubMed:28892040" FT MUTAGEN 582 FT /note="R->E: Reduces the affinity for Pol II elongation FT complex; when associated with E-577, E-578 and E-579." FT /evidence="ECO:0000269|PubMed:28892040" FT MUTAGEN 681 FT /note="R->A: Enhances interactions with CDK9 and RNA FT polymerase II and enhances transcriptional elongation; when FT associated with A-696 and A-698." FT /evidence="ECO:0000269|PubMed:12718890" FT MUTAGEN 681 FT /note="R->K: Increases promoter association and enhances FT transcriptional elongation; when associated with K-696 and FT K-698." FT /evidence="ECO:0000269|PubMed:12718890" FT MUTAGEN 696 FT /note="R->A: Enhances interactions with CDK9 and RNA FT polymerase II and enhances transcriptional elongation; when FT associated with A-681 and A-698." FT /evidence="ECO:0000269|PubMed:12718890" FT MUTAGEN 696 FT /note="R->K: Increases promoter association and enhances FT transcriptional elongation; when associated with K-681 and FT K-698." FT /evidence="ECO:0000269|PubMed:12718890" FT MUTAGEN 698 FT /note="R->A: Enhances transcriptional elongation. Enhances FT interactions with CDK9 and RNA polymerase II and enhances FT transcriptional elongation; when associated with A-681 and FT A-696." FT /evidence="ECO:0000269|PubMed:12718890" FT MUTAGEN 698 FT /note="R->K: Increases promoter association and enhances FT transcriptional elongation; when associated with K-681 and FT K-696." FT /evidence="ECO:0000269|PubMed:12718890" FT MUTAGEN 1002 FT /note="G->D: Defective in regulation of transcriptional FT elongation." FT /evidence="ECO:0000269|PubMed:15380072" FT CONFLICT 181 FT /note="T -> I (in Ref. 1; AAC51102)" FT /evidence="ECO:0000305" FT CONFLICT 483 FT /note="G -> A (in Ref. 1; AAC51102)" FT /evidence="ECO:0000305" FT CONFLICT 820 FT /note="A -> G (in Ref. 1; AAC51102)" FT /evidence="ECO:0000305" FT CONFLICT 846 FT /note="P -> R (in Ref. 3; BAA24075)" FT /evidence="ECO:0000305" FT STRAND 178..183 FT /evidence="ECO:0007829|PDB:3H7H" FT HELIX 189..203 FT /evidence="ECO:0007829|PDB:3H7H" FT STRAND 206..208 FT /evidence="ECO:0007829|PDB:3H7H" FT STRAND 214..217 FT /evidence="ECO:0007829|PDB:3H7H" FT STRAND 223..231 FT /evidence="ECO:0007829|PDB:3H7H" FT HELIX 232..239 FT /evidence="ECO:0007829|PDB:3H7H" FT HELIX 243..248 FT /evidence="ECO:0007829|PDB:3H7H" FT HELIX 257..259 FT /evidence="ECO:0007829|PDB:3H7H" FT HELIX 262..264 FT /evidence="ECO:0007829|PDB:3H7H" FT STRAND 278..284 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 290..296 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 300..307 FT /evidence="ECO:0007829|PDB:6GMH" FT TURN 313..315 FT /evidence="ECO:0007829|PDB:6GMH" FT HELIX 342..348 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 350..355 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 358..361 FT /evidence="ECO:0007829|PDB:6GMH" FT TURN 362..364 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 365..368 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 371..378 FT /evidence="ECO:0007829|PDB:6GMH" FT HELIX 390..395 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 425..428 FT /evidence="ECO:0007829|PDB:6GMH" FT TURN 432..435 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 437..439 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 445..447 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 461..464 FT /evidence="ECO:0007829|PDB:2E6Z" FT HELIX 465..467 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 468..470 FT /evidence="ECO:0007829|PDB:2E6Z" FT STRAND 477..480 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 481..483 FT /evidence="ECO:0007829|PDB:6TED" FT TURN 484..487 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 489..495 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 500..507 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 510..513 FT /evidence="ECO:0007829|PDB:6GMH" FT HELIX 515..517 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 518..520 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 531..533 FT /evidence="ECO:0007829|PDB:6GMH" FT STRAND 539..541 FT /evidence="ECO:0007829|PDB:5OHO" FT STRAND 543..545 FT /evidence="ECO:0007829|PDB:5OHO" FT STRAND 547..553 FT /evidence="ECO:0007829|PDB:5OHO" FT STRAND 555..562 FT /evidence="ECO:0007829|PDB:5OHO" FT TURN 563..565 FT /evidence="ECO:0007829|PDB:6EQY" FT STRAND 567..571 FT /evidence="ECO:0007829|PDB:5OHO" FT HELIX 572..574 FT /evidence="ECO:0007829|PDB:5OHO" FT STRAND 575..577 FT /evidence="ECO:0007829|PDB:5OHO" FT STRAND 585..587 FT /evidence="ECO:0007829|PDB:5OHO" FT TURN 589..591 FT /evidence="ECO:0007829|PDB:6EQY" FT STRAND 593..595 FT /evidence="ECO:0007829|PDB:5OHO" FT STRAND 599..602 FT /evidence="ECO:0007829|PDB:5OHO" FT TURN 606..609 FT /evidence="ECO:0007829|PDB:5OHO" FT STRAND 611..617 FT /evidence="ECO:0007829|PDB:5OHO" FT STRAND 619..625 FT /evidence="ECO:0007829|PDB:5OHO" FT HELIX 631..634 FT /evidence="ECO:0007829|PDB:5OHO" FT STRAND 635..639 FT /evidence="ECO:0007829|PDB:5OHO" FT HELIX 640..642 FT /evidence="ECO:0007829|PDB:5OHO" FT STRAND 643..645 FT /evidence="ECO:0007829|PDB:5OHO" FT TURN 704..707 FT /evidence="ECO:0007829|PDB:7OL0" FT STRAND 709..712 FT /evidence="ECO:0007829|PDB:7OL0" FT TURN 716..719 FT /evidence="ECO:0007829|PDB:7OL0" FT STRAND 721..727 FT /evidence="ECO:0007829|PDB:7OL0" FT STRAND 729..740 FT /evidence="ECO:0007829|PDB:7OL0" FT STRAND 742..746 FT /evidence="ECO:0007829|PDB:7OL0" FT HELIX 747..749 FT /evidence="ECO:0007829|PDB:7OL0" FT STRAND 750..752 FT /evidence="ECO:0007829|PDB:7OL0" FT STRAND 984..988 FT /evidence="ECO:0007829|PDB:5OHQ" FT TURN 995..999 FT /evidence="ECO:0007829|PDB:5OHQ" FT STRAND 1001..1008 FT /evidence="ECO:0007829|PDB:5OHQ" FT STRAND 1011..1016 FT /evidence="ECO:0007829|PDB:5OHQ" FT TURN 1017..1020 FT /evidence="ECO:0007829|PDB:5OHQ" FT STRAND 1021..1026 FT /evidence="ECO:0007829|PDB:5OHQ" FT HELIX 1027..1029 FT /evidence="ECO:0007829|PDB:5OHQ" FT STRAND 1030..1032 FT /evidence="ECO:0007829|PDB:5OHQ" FT STRAND 1040..1043 FT /evidence="ECO:0007829|PDB:5OHQ" FT TURN 1047..1050 FT /evidence="ECO:0007829|PDB:5OHQ" FT STRAND 1052..1059 FT /evidence="ECO:0007829|PDB:5OHQ" FT STRAND 1062..1067 FT /evidence="ECO:0007829|PDB:5OHQ" FT TURN 1068..1070 FT /evidence="ECO:0007829|PDB:5OHQ" FT STRAND 1073..1077 FT /evidence="ECO:0007829|PDB:5OHQ" FT HELIX 1078..1080 FT /evidence="ECO:0007829|PDB:5OHQ" FT STRAND 1081..1084 FT /evidence="ECO:0007829|PDB:5OHQ" SQ SEQUENCE 1087 AA; 121000 MW; EC3F402A670A5B7D CRC64; MSDSEDSNFS EEEDSERSSD GEEAEVDEER RSAAGSEKEE EPEDEEEEEE EEEYDEEEEE EDDDRPPKKP RHGGFILDEA DVDDEYEDED QWEDGAEDIL EKEEIEASNI DNVVLDEDRS GARRLQNLWR DQREEELGEY YMKKYAKSSV GETVYGGSDE LSDDITQQQL LPGVKDPNLW TVKCKIGEER ATAISLMRKF IAYQFTDTPL QIKSVVAPEH VKGYIYVEAY KQTHVKQAIE GVGNLRLGYW NQQMVPIKEM TDVLKVVKEV ANLKPKSWVR LKRGIYKDDI AQVDYVEPSQ NTISLKMIPR IDYDRIKARM SLKDWFAKRK KFKRPPQRLF DAEKIRSLGG DVASDGDFLI FEGNRYSRKG FLFKSFAMSA VITEGVKPTL SELEKFEDQP EGIDLEVVTE STGKEREHNF QPGDNVEVCE GELINLQGKI LSVDGNKITI MPKHEDLKDM LEFPAQELRK YFKMGDHVKV IAGRFEGDTG LIVRVEENFV ILFSDLTMHE LKVLPRDLQL CSETASGVDV GGQHEWGELV QLDPQTVGVI VRLERETFQV LNMYGKVVTV RHQAVTRKKD NRFAVALDSE QNNIHVKDIV KVIDGPHSGR EGEIRHLFRS FAFLHCKKLV ENGGMFVCKT RHLVLAGGSK PRDVTNFTVG GFAPMSPRIS SPMHPSAGGQ RGGFGSPGGG SGGMSRGRGR RDNELIGQTV RISQGPYKGY IGVVKDATES TARVELHSTC QTISVDRQRL TTVGSRRPGG MTSTYGRTPM YGSQTPMYGS GSRTPMYGSQ TPLQDGSRTP HYGSQTPLHD GSRTPAQSGA WDPNNPNTPS RAEEEYEYAF DDEPTPSPQA YGGTPNPQTP GYPDPSSPQV NPQYNPQTPG TPAMYNTDQF SPYAAPSPQG SYQPSPSPQS YHQVAPSPAG YQNTHSPASY HPTPSPMAYQ ASPSPSPVGY SPMTPGAPSP GGYNPHTPGS GIEQNSSDWV TTDIQVKVRD TYLDTQVVGQ TGVIRSVTGG MCSVYLKDSE KVVSISSEHL EPITPTKNNK VKVILGEDRE ATGVLLSIDG EDGIVRMDLD EQLKILNLRF LGKLLEA //