NELFA_HUMAN
ID NELFA_HUMAN Reviewed; 528 AA.
AC Q9H3P2; A2A2T1; O95392;
DT 14-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 3.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Negative elongation factor A;
DE Short=NELF-A;
DE AltName: Full=Wolf-Hirschhorn syndrome candidate 2 protein;
GN Name=NELFA; Synonyms=WHSC2; ORFNames=P/OKcl.15;
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.
RC TISSUE=Brain;
RX PubMed=10409432; DOI=10.1006/geno.1999.5871;
RA Wright T.J., Costa J.L., Naranjo C., Francis-West P., Altherr M.R.;
RT "Comparative analysis of a novel gene from the Wolf-Hirschhorn/Pitt-Rogers-
RT Danks syndrome critical region.";
RL Genomics 59:203-212(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Pancreatic cancer;
RX PubMed=11280764;
RA Ito M., Shichijo S., Tsuda N., Ochi M., Harashima N., Saito N., Itoh K.;
RT "Molecular basis of T cell-mediated recognition of pancreatic cancer
RT cells.";
RL Cancer Res. 61:2038-2046(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Mei G., Yu W., Gibbs R.A.;
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 212-221; 309-321 AND 503-513, AND IDENTIFICATION IN THE
RP NELF COMPLEX.
RX PubMed=11387440; DOI=10.1126/science.1057925;
RA Yamaguchi Y., Filipovska J., Yano K., Furuya A., Inukai N., Narita T.,
RA Wada T., Sugimoto S., Konarska M.M., Handa H.;
RT "Stimulation of RNA polymerase II elongation by hepatitis delta antigen.";
RL Science 293:124-127(2001).
RN [9]
RP FUNCTION OF THE NELF COMPLEX, AND INTERACTION WITH RNA POLYMERASE II
RP 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 [10]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11150502; DOI=10.1016/s0014-5793(00)02335-8;
RA Mariotti M., Manganini M., Maier J.A.M.;
RT "Modulation of WHSC2 expression in human endothelial cells.";
RL FEBS Lett. 487:166-170(2000).
RN [11]
RP FUNCTION.
RX PubMed=12563561; DOI=10.1086/367925;
RA Zollino M., Lecce R., Fischetto R., Murdolo M., Faravelli F., Selicorni A.,
RA Butte C., Memo L., Capovilla G., Neri G.;
RT "Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently
RT accepted WHS critical region and defining a new critical region, WHSCR-2.";
RL Am. J. Hum. Genet. 72:590-597(2003).
RN [12]
RP FUNCTION, TISSUE SPECIFICITY, AND DOMAIN.
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-157, 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363, AND IDENTIFICATION BY
RP 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 [15]
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-157, 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-157; THR-277 AND SER-363, 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 [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 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-157; SER-225; SER-233;
RP THR-277 AND SER-363, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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-363, 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 [22]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 6-182 IN COMPLEX WITH NELFCD, AND
RP RECONSTITUTION OF THE NELF COMPLEX.
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).
CC -!- FUNCTION: Essential component of the NELF complex, a complex that
CC negatively regulates the elongation of transcription by RNA polymerase
CC II. The NELF complex, which acts via an association with the DSIF
CC complex and causes transcriptional pausing, is counteracted by the P-
CC TEFb kinase complex. {ECO:0000269|PubMed:10199401,
CC ECO:0000269|PubMed:12563561, ECO:0000269|PubMed:12612062}.
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; NELFA and NELFCD form a stable
CC subcomplex that binds to the N-terminus of NELFB (PubMed:11387440). In
CC vitro, the NELFA:NELFCD subcomplex binds to ssDNA and ssRNA in a
CC sequence- and structure-dependent manner (PubMed:27282391). Interacts
CC with the RNA polymerase II complex when it is not phosphorylated by P-
CC TEFb (PubMed:10199401). {ECO:0000269|PubMed:10199401,
CC ECO:0000269|PubMed:11387440, ECO:0000269|PubMed:27282391}.
CC -!- INTERACTION:
CC Q9H3P2; Q00526: CDK3; NbExp=3; IntAct=EBI-5461341, EBI-1245761;
CC Q9H3P2; P40692: MLH1; NbExp=3; IntAct=EBI-5461341, EBI-744248;
CC Q9H3P2; O43639: NCK2; NbExp=3; IntAct=EBI-5461341, EBI-713635;
CC Q9H3P2; Q8IXH7: NELFCD; NbExp=12; IntAct=EBI-5461341, EBI-536725;
CC Q9H3P2; Q8IXH7-4: NELFCD; NbExp=5; IntAct=EBI-5461341, EBI-6109710;
CC Q9H3P2; P35372: OPRM1; NbExp=2; IntAct=EBI-5461341, EBI-2624570;
CC Q9H3P2; Q13526: PIN1; NbExp=3; IntAct=EBI-5461341, EBI-714158;
CC Q9H3P2; Q96B97: SH3KBP1; NbExp=3; IntAct=EBI-5461341, EBI-346595;
CC Q9H3P2; Q8IUQ4: SIAH1; NbExp=3; IntAct=EBI-5461341, EBI-747107;
CC Q9H3P2; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-5461341, EBI-358489;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11150502}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H3P2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H3P2-7; Sequence=VSP_035589;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in heart, brain, placenta,
CC liver, skeletal muscle, kidney and pancreas. Expressed at lower level
CC in adult lung. Expressed in fetal brain, lung, liver and kidney.
CC {ECO:0000269|PubMed:10409432, ECO:0000269|PubMed:11150502,
CC ECO:0000269|PubMed:12612062}.
CC -!- DOMAIN: The HDAg-like domain is essential for transcriptional
CC repression, and mediates the interaction with the RNA polymerase II
CC complex. {ECO:0000269|PubMed:12612062}.
CC -!- SIMILARITY: Belongs to the NELF-A family. {ECO:0000305}.
CC -!- CAUTION: PubMed:12612062 has shown that it is not involved in Wolf-
CC Hirschhorn syndrome. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC72982.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG54283.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAW82546.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF101434; AAC72982.1; ALT_INIT; mRNA.
DR EMBL; AB044549; BAB18651.1; -; mRNA.
DR EMBL; AF131751; AAD20034.1; -; mRNA.
DR EMBL; AK126056; BAG54283.1; ALT_INIT; mRNA.
DR EMBL; AL132868; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471131; EAW82546.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC002764; AAH02764.2; -; mRNA.
DR CCDS; CCDS3358.2; -. [Q9H3P2-1]
DR RefSeq; NP_005654.3; NM_005663.4. [Q9H3P2-1]
DR PDB; 5L3X; X-ray; 2.75 A; A=6-182.
DR PDB; 6GML; EM; 3.20 A; U=1-528.
DR PDB; 7PKS; EM; 3.60 A; U=1-528.
DR PDBsum; 5L3X; -.
DR PDBsum; 6GML; -.
DR PDBsum; 7PKS; -.
DR AlphaFoldDB; Q9H3P2; -.
DR SMR; Q9H3P2; -.
DR BioGRID; 113307; 94.
DR ComplexPortal; CPX-6267; NELF negative elongation factor complex.
DR CORUM; Q9H3P2; -.
DR DIP; DIP-48478N; -.
DR IntAct; Q9H3P2; 34.
DR MINT; Q9H3P2; -.
DR STRING; 9606.ENSP00000372335; -.
DR GlyGen; Q9H3P2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H3P2; -.
DR MetOSite; Q9H3P2; -.
DR PhosphoSitePlus; Q9H3P2; -.
DR BioMuta; NELFA; -.
DR DMDM; 212276499; -.
DR EPD; Q9H3P2; -.
DR jPOST; Q9H3P2; -.
DR MassIVE; Q9H3P2; -.
DR MaxQB; Q9H3P2; -.
DR PaxDb; Q9H3P2; -.
DR PeptideAtlas; Q9H3P2; -.
DR PRIDE; Q9H3P2; -.
DR ProteomicsDB; 80736; -. [Q9H3P2-1]
DR ProteomicsDB; 80737; -. [Q9H3P2-7]
DR Antibodypedia; 4097; 197 antibodies from 26 providers.
DR DNASU; 7469; -.
DR Ensembl; ENST00000382882.9; ENSP00000372335.4; ENSG00000185049.16. [Q9H3P2-1]
DR GeneID; 7469; -.
DR KEGG; hsa:7469; -.
DR MANE-Select; ENST00000382882.9; ENSP00000372335.4; NM_005663.5; NP_005654.4.
DR UCSC; uc003gem.4; human. [Q9H3P2-1]
DR CTD; 7469; -.
DR DisGeNET; 7469; -.
DR GeneCards; NELFA; -.
DR HGNC; HGNC:12768; NELFA.
DR HPA; ENSG00000185049; Low tissue specificity.
DR MalaCards; NELFA; -.
DR MIM; 606026; gene.
DR neXtProt; NX_Q9H3P2; -.
DR OpenTargets; ENSG00000185049; -.
DR Orphanet; 280; Wolf-Hirschhorn syndrome.
DR PharmGKB; PA37371; -.
DR VEuPathDB; HostDB:ENSG00000185049; -.
DR eggNOG; ENOG502QTCD; Eukaryota.
DR GeneTree; ENSGT00390000005342; -.
DR HOGENOM; CLU_039060_1_0_1; -.
DR InParanoid; Q9H3P2; -.
DR OrthoDB; 1011916at2759; -.
DR PhylomeDB; Q9H3P2; -.
DR TreeFam; TF324956; -.
DR PathwayCommons; Q9H3P2; -.
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; Q9H3P2; -.
DR BioGRID-ORCS; 7469; 602 hits in 1090 CRISPR screens.
DR ChiTaRS; NELFA; human.
DR GeneWiki; WHSC2; -.
DR GenomeRNAi; 7469; -.
DR Pharos; Q9H3P2; Tbio.
DR PRO; PR:Q9H3P2; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9H3P2; protein.
DR Bgee; ENSG00000185049; Expressed in oocyte and 189 other tissues.
DR ExpressionAtlas; Q9H3P2; baseline and differential.
DR Genevisible; Q9H3P2; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
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:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; IDA:ComplexPortal.
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 DisProt; DP02712; -.
DR InterPro; IPR037517; HDAG_dom.
DR PROSITE; PS51838; HDAG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..528
FT /note="Negative elongation factor A"
FT /id="PRO_0000219126"
FT DOMAIN 89..248
FT /note="HDAg"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01183"
FT REGION 125..188
FT /note="NELF-C/D-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01183"
FT REGION 189..248
FT /note="RNAPII-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01183"
FT REGION 215..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 320..409
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 226..242
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 320..348
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 349..363
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 387..407
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 157
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 277
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 363
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..263
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_035589"
FT VARIANT 335
FT /note="S -> A (in dbSNP:rs2234569)"
FT /id="VAR_059459"
FT CONFLICT 37
FT /note="V -> I (in Ref. 2; BAB18651)"
FT /evidence="ECO:0000305"
FT CONFLICT 40
FT /note="N -> NIRLCFHGLSSASLLTAAVIDN (in Ref. 2; BAB18651)"
FT /evidence="ECO:0000305"
FT HELIX 9..17
FT /evidence="ECO:0007829|PDB:5L3X"
FT HELIX 29..32
FT /evidence="ECO:0007829|PDB:5L3X"
FT HELIX 35..44
FT /evidence="ECO:0007829|PDB:5L3X"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:5L3X"
FT HELIX 50..59
FT /evidence="ECO:0007829|PDB:5L3X"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:5L3X"
FT HELIX 65..70
FT /evidence="ECO:0007829|PDB:5L3X"
FT HELIX 72..82
FT /evidence="ECO:0007829|PDB:5L3X"
FT HELIX 88..96
FT /evidence="ECO:0007829|PDB:5L3X"
FT HELIX 100..103
FT /evidence="ECO:0007829|PDB:5L3X"
FT HELIX 115..130
FT /evidence="ECO:0007829|PDB:5L3X"
FT HELIX 139..143
FT /evidence="ECO:0007829|PDB:5L3X"
FT HELIX 146..153
FT /evidence="ECO:0007829|PDB:5L3X"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:5L3X"
FT HELIX 171..180
FT /evidence="ECO:0007829|PDB:5L3X"
SQ SEQUENCE 528 AA; 57277 MW; 4F33C3BC68BDC798 CRC64;
MASMRESDTG LWLHNKLGAT DELWAPPSIA SLLTAAVIDN IRLCFHGLSS AVKLKLLLGT
LHLPRRTVDE MKGALMEIIQ LASLDSDPWV LMVADILKSF PDTGSLNLEL EEQNPNVQDI
LGELREKVGE CEASAMLPLE CQYLNKNALT TLAGPLTPPV KHFQLKRKPK SATLRAELLQ
KSTETAQQLK RSAGVPFHAK GRGLLRKMDT TTPLKGIPKQ APFRSPTAPS VFSPTGNRTP
IPPSRTLLRK ERGVKLLDIS ELDMVGAGRE AKRRRKTLDA EVVEKPAKEE TVVENATPDY
AAGLVSTQKL GSLNNEPALP STSYLPSTPS VVPASSYIPS SETPPAPSSR EASRPPEEPS
APSPTLPAQF KQRAPMYNSG LSPATPTPAA PTSPLTPTTP PAVAPTTQTP PVAMVAPQTQ
APAQQQPKKN LSLTREQMFA AQEMFKTANK VTRPEKALIL GFMAGSRENP CQEQGDVIQI
KLSEHTEDLP KADGQGSTTM LVDTVFEMNY ATGQWTRFKK YKPMTNVS
