NELFE_HUMAN
ID NELFE_HUMAN Reviewed; 380 AA.
AC P18615; A2BE08; B4DUN1; B4DYX9; Q5JP74; Q5JP75; Q96F56; Q9NPK2;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 3.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=Negative elongation factor E;
DE Short=NELF-E;
DE AltName: Full=RNA-binding protein RD {ECO:0000303|PubMed:14701750};
GN Name=NELFE; Synonyms=RD {ECO:0000303|PubMed:14701750}, RDBP;
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 [GENOMIC DNA].
RX PubMed=2612324; DOI=10.1089/dna.1989.8.745;
RA Speiser P.W., White P.C.;
RT "Structure of the human RD gene: a highly conserved gene in the class III
RT region of the major histocompatibility complex.";
RL DNA 8:745-751(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=T-cell;
RX PubMed=8373374; DOI=10.1042/bj2940589;
RA Cheng J., Macon K.J., Volanakis J.E.;
RT "cDNA cloning and characterization of the protein encoded by RD, a gene
RT located in the class III region of the human major histocompatibility
RT complex.";
RL Biochem. J. 294:589-593(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14656967; DOI=10.1101/gr.1736803;
RA Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D.,
RA Hood L.;
RT "Analysis of the gene-dense major histocompatibility complex class III
RT region and its comparison to mouse.";
RL Genome Res. 13:2621-2636(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Retinal pigment epithelium, and Skin;
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 [8]
RP PROTEIN SEQUENCE OF 48-65 AND 362-373, IDENTIFICATION IN THE NELF COMPLEX,
RP AND FUNCTION OF 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 NUCLEOTIDE SEQUENCE [MRNA] OF 56-380 (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=2119325; DOI=10.1016/0378-1119(90)90194-v;
RA Surowy C.S., Hoganson G., Gosink J., Strunk K., Spritz R.A.;
RT "The human RD protein is closely related to nuclear RNA-binding proteins
RT and has been highly conserved.";
RL Gene 90:299-302(1990).
RN [10]
RP FUNCTION, RNA-BINDING, DOMAIN, AND MUTAGENESIS OF 295-ARG--PHE-299.
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 [11]
RP FUNCTION, AND TISSUE SPECIFICITY.
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 [12]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-181; SER-185; SER-187 AND
RP SER-191, AND MUTAGENESIS OF 181-SER--SER-191.
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 [13]
RP SUMOYLATION.
RX PubMed=15561718; DOI=10.1074/jbc.m411718200;
RA Gocke C.B., Yu H., Kang J.;
RT "Systematic identification and analysis of mammalian small ubiquitin-like
RT modifier substrates.";
RL J. Biol. Chem. 280:5004-5012(2005).
RN [14]
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-115 AND SER-353, AND
RP IDENTIFICATION BY 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-281, AND IDENTIFICATION BY
RP 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 [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113; SER-131; SER-251;
RP THR-272; THR-274; SER-281 AND SER-353, AND IDENTIFICATION BY MASS
RP 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 [19]
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 [20]
RP IDENTIFICATION BY 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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131 AND SER-353, AND
RP IDENTIFICATION BY 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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-115; SER-131; SER-281 AND
RP SER-353, AND 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 [23]
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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-115; SER-181; SER-185 AND
RP SER-251, AND IDENTIFICATION BY 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 [25]
RP FUNCTION OF THE NELF COMPLEX IN HIV-1 LATENCY (MICROBIAL INFECTION).
RX PubMed=23884411; DOI=10.1074/jbc.m113.496489;
RA Natarajan M., Schiralli Lester G.M., Lee C., Missra A., Wasserman G.A.,
RA Steffen M., Gilmour D.S., Henderson A.J.;
RT "Negative elongation factor (NELF) coordinates RNA polymerase II pausing,
RT premature termination, and chromatin remodeling to regulate HIV
RT transcription.";
RL J. Biol. Chem. 288:25995-26003(2013).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-115; SER-131;
RP SER-139; SER-165; SER-249; SER-251 AND SER-353, 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 [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179, AND IDENTIFICATION BY
RP 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 [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-78, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [29]
RP RECONSTITUTION OF THE NELF COMPLEX, AND RNA BINDING.
RX PubMed=27282391; DOI=10.7554/elife.14981;
RA Vos S.M., Pollmann D., Caizzi L., Hofmann K.B., Rombaut P., Zimniak T.,
RA Herzog F., Cramer P.;
RT "Architecture and RNA binding of the human negative elongation factor.";
RL Elife 5:0-0(2016).
RN [30]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-78 AND LYS-82, AND IDENTIFICATION
RP 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 [31]
RP STRUCTURE BY NMR OF 244-343, AND RNA-BINDING (MICROBIAL INFECTION).
RX PubMed=16898873; DOI=10.1042/bj20060421;
RA Rao J.N., Neumann L., Wenzel S., Schweimer K., Rosch P., Wohrl B.M.;
RT "Structural studies on the RNA-recognition motif of NELF E, a cellular
RT negative transcription elongation factor involved in the regulation of HIV
RT transcription.";
RL Biochem. J. 400:449-456(2006).
RN [32]
RP STRUCTURE BY NMR OF 244-343, AND RNA-BINDING.
RX PubMed=18303858; DOI=10.1021/bi702429m;
RA Rao J.N., Schweimer K., Wenzel S., Wohrl B.M., Rosch P.;
RT "NELF-E RRM undergoes major structural changes in flexible protein regions
RT on target RNA binding.";
RL Biochemistry 47:3756-3761(2008).
RN [33]
RP STRUCTURE BY NMR OF 254-337.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RRM domain in PARP14.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: Essential component of the NELF complex, a complex that
CC negatively regulates the elongation of transcription by RNA polymerase
CC II (PubMed:10199401). The NELF complex, which acts via an association
CC with the DSIF complex and causes transcriptional pausing, is
CC counteracted by the P-TEFb kinase complex (PubMed:11940650,
CC PubMed:12612062). Provides the strongest RNA binding activity of the
CC NELF complex and may initially recruit the NELF complex to RNA
CC (PubMed:18303858, PubMed:27282391). {ECO:0000269|PubMed:10199401,
CC ECO:0000269|PubMed:11940650, ECO:0000269|PubMed:12612062,
CC ECO:0000269|PubMed:18303858, ECO:0000269|PubMed:27282391}.
CC -!- FUNCTION: (Microbial infection) The NELF complex is involved in HIV-1
CC latency possibly involving recruitment of PCF11 to paused RNA
CC polymerase II. {ECO:0000269|PubMed:23884411}.
CC -!- SUBUNIT: The NELF complex is composed of NELFA, NELFB, NELFCD (isoform
CC NELF-C or isoform NELF-D) and NELFE (PubMed:10199401, PubMed:27282391).
CC Interacts with NELFB (By similarity). {ECO:0000250|UniProtKB:P19426,
CC ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:27282391}.
CC -!- SUBUNIT: (Microbial infection) Binds to the HIV-1 TAR RNA which is
CC located in the long terminal repeat (LTR) of HIV-1.
CC {ECO:0000269|PubMed:16898873}.
CC -!- INTERACTION:
CC P18615; Q2TAC2: CCDC57; NbExp=3; IntAct=EBI-348444, EBI-2808286;
CC P18615; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-348444, EBI-2556193;
CC P18615; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-348444, EBI-742948;
CC P18615; Q8WX92: NELFB; NbExp=7; IntAct=EBI-348444, EBI-347721;
CC P18615; Q8WX92-2: NELFB; NbExp=7; IntAct=EBI-348444, EBI-22734860;
CC P18615; P14373: TRIM27; NbExp=3; IntAct=EBI-348444, EBI-719493;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14701750}. Chromosome
CC {ECO:0000269|PubMed:14701750}. Note=Localizes to chromatin
CC (PubMed:14701750). Phosphorylation by the P-TEFb complex promotes its
CC release from chromatin (PubMed:14701750).
CC {ECO:0000269|PubMed:14701750}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P18615-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P18615-3; Sequence=VSP_056151;
CC Name=3;
CC IsoId=P18615-4; Sequence=VSP_056152;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in heart, brain, lung,
CC placenta, liver, skeletal muscle, kidney and pancreas.
CC {ECO:0000269|PubMed:12612062}.
CC -!- DOMAIN: The RRM domain interacts with RNA, and is essential for NELF
CC complex function. It is however not required for the NELF complex
CC formation. {ECO:0000269|PubMed:11940650}.
CC -!- PTM: Phosphorylated by the P-TEFb complex at sites next to its RNA
CC recognition motif, promoting its release from chromatin.
CC {ECO:0000269|PubMed:14701750}.
CC -!- PTM: Sumoylated. {ECO:0000269|PubMed:15561718}.
CC -!- SIMILARITY: Belongs to the RRM NELF-E family. {ECO:0000305}.
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DR EMBL; M33231; AAA36308.1; -; Genomic_DNA.
DR EMBL; M32274; AAA36308.1; JOINED; Genomic_DNA.
DR EMBL; M32275; AAA36308.1; JOINED; Genomic_DNA.
DR EMBL; M32276; AAA36308.1; JOINED; Genomic_DNA.
DR EMBL; M33230; AAA36308.1; JOINED; Genomic_DNA.
DR EMBL; L03411; AAC37523.1; -; mRNA.
DR EMBL; AF019413; AAB67979.1; -; Genomic_DNA.
DR EMBL; AK300717; BAG62393.1; -; mRNA.
DR EMBL; AK302652; BAG63891.1; -; mRNA.
DR EMBL; AL049547; CAB89308.1; -; Genomic_DNA.
DR EMBL; AL662849; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL844853; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX005143; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR759782; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR388219; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL645922; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR753845; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03553.1; -; Genomic_DNA.
DR EMBL; BC025235; AAH25235.1; -; mRNA.
DR EMBL; BC050617; AAH50617.1; -; mRNA.
DR EMBL; X16105; CAA34231.1; -; mRNA.
DR CCDS; CCDS4730.1; -. [P18615-1]
DR PIR; S36789; S36789.
DR RefSeq; NP_002895.3; NM_002904.5. [P18615-1]
DR PDB; 1X5P; NMR; -; A=254-337.
DR PDB; 2BZ2; NMR; -; A=244-343.
DR PDB; 2JX2; NMR; -; A=244-343.
DR PDB; 5OOB; X-ray; 2.79 A; E/K/Z=360-380.
DR PDB; 6GML; EM; 3.20 A; X=1-380.
DR PDBsum; 1X5P; -.
DR PDBsum; 2BZ2; -.
DR PDBsum; 2JX2; -.
DR PDBsum; 5OOB; -.
DR PDBsum; 6GML; -.
DR AlphaFoldDB; P18615; -.
DR BMRB; P18615; -.
DR SMR; P18615; -.
DR BioGRID; 113662; 66.
DR ComplexPortal; CPX-6267; NELF negative elongation factor complex.
DR CORUM; P18615; -.
DR DIP; DIP-32669N; -.
DR IntAct; P18615; 31.
DR MINT; P18615; -.
DR STRING; 9606.ENSP00000364578; -.
DR GlyGen; P18615; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P18615; -.
DR MetOSite; P18615; -.
DR PhosphoSitePlus; P18615; -.
DR BioMuta; NELFE; -.
DR DMDM; 1350554; -.
DR CPTAC; CPTAC-999; -.
DR EPD; P18615; -.
DR jPOST; P18615; -.
DR MassIVE; P18615; -.
DR MaxQB; P18615; -.
DR PaxDb; P18615; -.
DR PeptideAtlas; P18615; -.
DR PRIDE; P18615; -.
DR ProteomicsDB; 5199; -.
DR ProteomicsDB; 53602; -. [P18615-1]
DR ProteomicsDB; 5554; -.
DR Antibodypedia; 1924; 160 antibodies from 27 providers.
DR DNASU; 7936; -.
DR Ensembl; ENST00000375425.9; ENSP00000364574.5; ENSG00000204356.14. [P18615-3]
DR Ensembl; ENST00000375429.8; ENSP00000364578.3; ENSG00000204356.14. [P18615-1]
DR Ensembl; ENST00000383174.8; ENSP00000372660.4; ENSG00000206268.11. [P18615-1]
DR Ensembl; ENST00000383343.8; ENSP00000372834.4; ENSG00000206357.11. [P18615-1]
DR Ensembl; ENST00000429857.6; ENSP00000403623.2; ENSG00000231044.10. [P18615-1]
DR Ensembl; ENST00000444811.6; ENSP00000388400.2; ENSG00000204356.14. [P18615-4]
DR Ensembl; ENST00000448628.6; ENSP00000394879.2; ENSG00000229363.9. [P18615-1]
DR Ensembl; ENST00000457397.6; ENSP00000393005.2; ENSG00000233801.9. [P18615-1]
DR GeneID; 7936; -.
DR KEGG; hsa:7936; -.
DR MANE-Select; ENST00000375429.8; ENSP00000364578.3; NM_002904.6; NP_002895.3.
DR UCSC; uc003nyk.4; human. [P18615-1]
DR CTD; 7936; -.
DR DisGeNET; 7936; -.
DR GeneCards; NELFE; -.
DR HGNC; HGNC:13974; NELFE.
DR HPA; ENSG00000204356; Low tissue specificity.
DR MIM; 154040; gene.
DR neXtProt; NX_P18615; -.
DR OpenTargets; ENSG00000204356; -.
DR PharmGKB; PA134974984; -.
DR VEuPathDB; HostDB:ENSG00000204356; -.
DR eggNOG; ENOG502QQQ4; Eukaryota.
DR GeneTree; ENSGT00630000089917; -.
DR HOGENOM; CLU_055643_0_0_1; -.
DR InParanoid; P18615; -.
DR PhylomeDB; P18615; -.
DR TreeFam; TF324087; -.
DR PathwayCommons; P18615; -.
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-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-75955; RNA Polymerase II Transcription Elongation.
DR SignaLink; P18615; -.
DR BioGRID-ORCS; 7936; 374 hits in 1081 CRISPR screens.
DR EvolutionaryTrace; P18615; -.
DR GeneWiki; RDBP; -.
DR GenomeRNAi; 7936; -.
DR Pharos; P18615; Tbio.
DR PRO; PR:P18615; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P18615; protein.
DR Bgee; ENSG00000204356; Expressed in left testis and 95 other tissues.
DR ExpressionAtlas; P18615; baseline and differential.
DR Genevisible; P18615; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0032021; C:NELF complex; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; IDA:ComplexPortal.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR CDD; cd12305; RRM_NELFE; 1.
DR DisProt; DP02713; -.
DR Gene3D; 3.30.70.330; -; 1.
DR IDEAL; IID00030; -.
DR InterPro; IPR033102; NELFE.
DR InterPro; IPR034637; NELFE_RRM.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR PANTHER; PTHR17250; PTHR17250; 2.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM00360; RRM; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosome; Coiled coil;
KW Direct protein sequencing; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; RNA-binding; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..380
FT /note="Negative elongation factor E"
FT /id="PRO_0000081802"
FT REPEAT 184..185
FT /note="1"
FT REPEAT 186..187
FT /note="2"
FT REPEAT 188..189
FT /note="3"
FT REPEAT 190..191
FT /note="4"
FT REPEAT 192..193
FT /note="5; approximate"
FT REPEAT 194..195
FT /note="6"
FT REPEAT 196..197
FT /note="7"
FT REPEAT 198..199
FT /note="8"
FT REPEAT 200..201
FT /note="9"
FT REPEAT 202..203
FT /note="10"
FT REPEAT 204..205
FT /note="11"
FT REPEAT 206..207
FT /note="12"
FT REPEAT 208..209
FT /note="13"
FT REPEAT 210..211
FT /note="14"
FT REPEAT 212..213
FT /note="15"
FT REPEAT 214..215
FT /note="16"
FT REPEAT 216..217
FT /note="17"
FT REPEAT 218..219
FT /note="18"
FT REPEAT 220..221
FT /note="19"
FT REPEAT 222..223
FT /note="20"
FT REPEAT 224..225
FT /note="21"
FT REPEAT 226..227
FT /note="22"
FT REPEAT 228..229
FT /note="23"
FT REPEAT 230..231
FT /note="24"
FT REPEAT 232..233
FT /note="25"
FT REPEAT 234..235
FT /note="26"
FT REPEAT 236..237
FT /note="27"
FT REPEAT 238..239
FT /note="28"
FT REPEAT 240..241
FT /note="29"
FT REPEAT 242..243
FT /note="30"
FT DOMAIN 262..332
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 30..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 79..258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 184..243
FT /note="30 X 2 AA approximate tandem repeats of R-[DSNE]"
FT COILED 7..36
FT /evidence="ECO:0000255"
FT COMPBIAS 32..67
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 83..100
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 183..257
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 51
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 115
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 131
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 179
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 181
FT /note="Phosphoserine; by CDK9"
FT /evidence="ECO:0000305|PubMed:14701750,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 185
FT /note="Phosphoserine; by CDK9"
FT /evidence="ECO:0000305|PubMed:14701750,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 187
FT /note="Phosphoserine; by CDK9"
FT /evidence="ECO:0000305|PubMed:14701750"
FT MOD_RES 191
FT /note="Phosphoserine; by CDK9"
FT /evidence="ECO:0000305|PubMed:14701750"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 251
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 272
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 274
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 281
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231"
FT MOD_RES 353
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT CROSSLNK 78
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 78
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 82
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1
FT /note="M -> MVPKGATM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056151"
FT VAR_SEQ 135..164
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056152"
FT MUTAGEN 181..191
FT /note="SPPRSRSRDRS->APPRARARDRA: Decreased
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:14701750"
FT MUTAGEN 181..191
FT /note="SPPRSRSRDRS->EPPRERERDRE: Mimics phosphorylation,
FT promoting its release from chromatin."
FT /evidence="ECO:0000269|PubMed:14701750"
FT MUTAGEN 295..299
FT /note="RNCAF->EQMAT: Abolishes interaction with RNA but not
FT the interaction with other proteins of the NELF complex."
FT /evidence="ECO:0000269|PubMed:11940650"
FT CONFLICT 119
FT /note="D -> DD (in Ref. 1; AAA36308)"
FT /evidence="ECO:0000305"
FT CONFLICT 174
FT /note="S -> M (in Ref. 9; CAA34231)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="Y -> YD (in Ref. 1; AAA36308)"
FT /evidence="ECO:0000305"
FT CONFLICT 312
FT /note="V -> A (in Ref. 1; AAA36308)"
FT /evidence="ECO:0000305"
FT CONFLICT 327
FT /note="V -> D (in Ref. 1; AAA36308)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="S -> A (in Ref. 1; AAA36308)"
FT /evidence="ECO:0000305"
FT STRAND 262..267
FT /evidence="ECO:0007829|PDB:1X5P"
FT HELIX 273..280
FT /evidence="ECO:0007829|PDB:1X5P"
FT TURN 281..283
FT /evidence="ECO:0007829|PDB:1X5P"
FT STRAND 286..292
FT /evidence="ECO:0007829|PDB:1X5P"
FT TURN 293..296
FT /evidence="ECO:0007829|PDB:1X5P"
FT STRAND 297..304
FT /evidence="ECO:0007829|PDB:1X5P"
FT HELIX 305..314
FT /evidence="ECO:0007829|PDB:1X5P"
FT TURN 315..317
FT /evidence="ECO:0007829|PDB:1X5P"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:1X5P"
FT STRAND 323..328
FT /evidence="ECO:0007829|PDB:1X5P"
FT TURN 334..337
FT /evidence="ECO:0007829|PDB:2JX2"
SQ SEQUENCE 380 AA; 43240 MW; 95EB422B5E07410B CRC64;
MLVIPPGLSE EEEALQKKFN KLKKKKKALL ALKKQSSSST TSQGGVKRSL SEQPVMDTAT
ATEQAKQLVK SGAISAIKAE TKNSGFKRSR TLEGKLKDPE KGPVPTFQPF QRSISADDDL
QESSRRPQRK SLYESFVSSS DRLRELGPDG EEAEGPGAGD GPPRSFDWGY EERSGAHSSA
SPPRSRSRDR SHERNRDRDR DRERDRDRDR DRDRERDRDR DRDRDRDRER DRDRERDRDR
DREGPFRRSD SFPERRAPRK GNTLYVYGED MTPTLLRGAF SPFGNIIDLS MDPPRNCAFV
TYEKMESADQ AVAELNGTQV ESVQLKVNIA RKQPMLDAAT GKSVWGSLAV QNSPKGCHRD
KRTQIVYSDD VYKENLVDGF
