NELFB_MOUSE
ID NELFB_MOUSE Reviewed; 580 AA.
AC Q8C4Y3; A0A0X1KG62; Q69ZP4; Q99J41; Q9JJA5;
DT 14-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2003, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Negative elongation factor B;
DE Short=NELF-B;
DE AltName: Full=Cofactor of BRCA1 {ECO:0000303|PubMed:19340312};
GN Name=Nelfb; Synonyms=Cobra1 {ECO:0000303|PubMed:19340312};
GN ORFNames=MNCb-5210;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mammary tumor;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-580 (ISOFORMS 1/2).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 34-580 (ISOFORMS 1/2).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Osada N., Kusuda J., Tanuma R., Ito A., Hirata M., Sugano S., Hashimoto K.;
RT "Isolation of full-length cDNA clones from mouse brain cDNA library made by
RT oligo-capping method.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 61-580 (ISOFORMS 1/2).
RC TISSUE=Embryonic tail;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19340312; DOI=10.1371/journal.pone.0005034;
RA Amleh A., Nair S.J., Sun J., Sutherland A., Hasty P., Li R.;
RT "Mouse cofactor of BRCA1 (Cobra1) is required for early embryogenesis.";
RL PLoS ONE 4:E5034-E5034(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24656816; DOI=10.1016/j.celrep.2014.02.028;
RA Pan H., Qin K., Guo Z., Ma Y., April C., Gao X., Andrews T.G., Bokov A.,
RA Zhang J., Chen Y., Weintraub S.T., Fan J.B., Wang D., Hu Y., Aune G.J.,
RA Lindsey M.L., Li R.;
RT "Negative elongation factor controls energy homeostasis in
RT cardiomyocytes.";
RL Cell Rep. 7:79-85(2014).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25773599; DOI=10.1016/j.molcel.2015.02.003;
RA Williams L.H., Fromm G., Gokey N.G., Henriques T., Muse G.W.,
RA Burkholder A., Fargo D.C., Hu G., Adelman K.;
RT "Pausing of RNA polymerase II regulates mammalian developmental potential
RT through control of signaling networks.";
RL Mol. Cell 58:311-322(2015).
RN [11]
RP ALTERNATIVE INITIATION (ISOFORM 2), CTG START CODON (ISOFORM 2),
RP INTERACTION WITH NELFA; NELFCD AND NELFE, AND TISSUE SPECIFICITY.
RX PubMed=26010750; DOI=10.1371/journal.pone.0127422;
RA Pan H., Zhao X., Zhang X., Abouelsoud M., Sun J., April C., Amleh A.,
RA Fan J.B., Hu Y., Li R.;
RT "Translational initiation at a non-AUG start codon for human and mouse
RT negative elongation factor-B.";
RL PLoS ONE 10:E0127422-E0127422(2015).
CC -!- FUNCTION: Essential component of the NELF complex, a complex that
CC negatively regulates the elongation of transcription by RNA polymerase
CC II (Pol II) (PubMed:25773599). The NELF complex, which acts via an
CC association with the DSIF complex and causes transcriptional pausing,
CC is counteracted by the P-TEFb kinase complex (By similarity). May be
CC able to induce chromatin unfolding (By similarity). Essential for early
CC embryogenesis; plays an important role in maintaining the
CC undifferentiated state of embryonic stem cells (ESCs) by preventing
CC unscheduled expression of developmental genes (PubMed:19340312). Plays
CC a key role in establishing the responsiveness of stem cells to
CC developmental cues; facilitates plasticity and cell fate commitment in
CC ESCs by establishing the appropriate expression level of signaling
CC molecules (PubMed:25773599). Supports the transcription of genes
CC involved in energy metabolism in cardiomyocytes; facilitates the
CC association of transcription initiation factors with the promoters of
CC the metabolism-related genes (PubMed:24656816).
CC {ECO:0000250|UniProtKB:Q8WX92, ECO:0000269|PubMed:19340312,
CC ECO:0000269|PubMed:24656816, ECO:0000269|PubMed:25773599}.
CC -!- SUBUNIT: The NELF complex is composed of NELFA, NELFB, NELFCD and
CC NELFE; the N-terminus of NELFB binds to the NELFA:NELFCD subcomplex (By
CC similarity). Binds RNA which may help to stabilize the NELF complex on
CC nucleic acid (By similarity) Interacts with the first BRCT repeat of
CC BRCA1 (By similarity). Interacts with KIAA1191 (By similarity). Isoform
CC 1 and isoform 2 interact with NELFA, NELFCD and NELFE
CC (PubMed:26010750). {ECO:0000250|UniProtKB:Q8WX92,
CC ECO:0000269|PubMed:26010750}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8WX92}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1;
CC IsoId=Q8C4Y3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C4Y3-3; Sequence=VSP_059999;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in the kidney, liver,
CC adipose and lung (PubMed:26010750). Isoform 2 is widely expressed
CC (PubMed:26010750). {ECO:0000269|PubMed:26010750}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit early embryonic lethality
CC (PubMed:25773599, PubMed:19340312). Knockdown in embryonic stem cells
CC (ESCs) leads to proliferation defects, increased differentiation,
CC increased expression of development-associated genes and the
CC dysregulation of genes involved in signaling and metabolic pathways
CC (PubMed:25773599, PubMed:19340312). Mice exhibit cardiomyopathy,
CC impaired response to cardiac stress and the reduced expression of
CC metabolism-related genes in cardiomyocytes (PubMed:24656816).
CC {ECO:0000269|PubMed:19340312, ECO:0000269|PubMed:24656816,
CC ECO:0000269|PubMed:25773599}.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative initiation at a CTG
CC start codon. {ECO:0000269|PubMed:26010750}.
CC -!- SIMILARITY: Belongs to the NELF-B family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH04762.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AK080419; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA95090.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL732309; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004762; AAH04762.1; ALT_INIT; mRNA.
DR EMBL; AK080419; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AB041607; BAA95090.1; ALT_INIT; mRNA.
DR EMBL; AK173124; BAD32402.1; -; mRNA.
DR RefSeq; NP_001297086.1; NM_001310157.1.
DR RefSeq; NP_067368.3; NM_021393.3.
DR AlphaFoldDB; Q8C4Y3; -.
DR SMR; Q8C4Y3; -.
DR BioGRID; 208386; 3.
DR STRING; 10090.ENSMUSP00000057731; -.
DR iPTMnet; Q8C4Y3; -.
DR PhosphoSitePlus; Q8C4Y3; -.
DR EPD; Q8C4Y3; -.
DR jPOST; Q8C4Y3; -.
DR MaxQB; Q8C4Y3; -.
DR PaxDb; Q8C4Y3; -.
DR PeptideAtlas; Q8C4Y3; -.
DR PRIDE; Q8C4Y3; -.
DR ProteomicsDB; 287369; -. [Q8C4Y3-1]
DR ProteomicsDB; 355156; -.
DR DNASU; 58202; -.
DR Ensembl; ENSMUST00000059849; ENSMUSP00000057731; ENSMUSG00000013465. [Q8C4Y3-3]
DR GeneID; 58202; -.
DR KEGG; mmu:58202; -.
DR UCSC; uc008iqm.2; mouse. [Q8C4Y3-1]
DR CTD; 25920; -.
DR MGI; MGI:1931035; Nelfb.
DR eggNOG; ENOG502QTMJ; Eukaryota.
DR GeneTree; ENSGT00390000012665; -.
DR HOGENOM; CLU_037919_0_0_1; -.
DR InParanoid; Q8C4Y3; -.
DR OMA; HINEMGQ; -.
DR OrthoDB; 1095614at2759; -.
DR PhylomeDB; Q8C4Y3; -.
DR TreeFam; TF324620; -.
DR Reactome; R-MMU-112382; Formation of RNA Pol II elongation complex.
DR Reactome; R-MMU-113418; Formation of the Early Elongation Complex.
DR Reactome; R-MMU-674695; RNA Polymerase II Pre-transcription Events.
DR Reactome; R-MMU-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-MMU-75955; RNA Polymerase II Transcription Elongation.
DR BioGRID-ORCS; 58202; 30 hits in 73 CRISPR screens.
DR ChiTaRS; Nelfb; mouse.
DR PRO; PR:Q8C4Y3; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8C4Y3; protein.
DR Bgee; ENSMUSG00000013465; Expressed in ear vesicle and 241 other tissues.
DR Genevisible; Q8C4Y3; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
DR GO; GO:0032021; C:NELF complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; IMP:UniProtKB.
DR GO; GO:2000737; P:negative regulation of stem cell differentiation; IMP:UniProtKB.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; IMP:UniProtKB.
DR GO; GO:0048863; P:stem cell differentiation; IMP:UniProtKB.
DR InterPro; IPR010405; COBRA1.
DR PANTHER; PTHR13503; PTHR13503; 1.
DR Pfam; PF06209; COBRA1; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative initiation; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; RNA-binding; Transcription;
KW Transcription regulation.
FT CHAIN 1..580
FT /note="Negative elongation factor B"
FT /id="PRO_0000219130"
FT REGION 552..580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 519
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8WX92"
FT MOD_RES 557
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WX92"
FT VAR_SEQ 1
FT /note="M -> MATLEAAGERGLGGPRGTVERASGAPSGSATAPAERGGDGVHSRASA
FT GASAM (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_059999"
FT CONFLICT 470
FT /note="V -> A (in Ref. 4; BAA95090)"
FT /evidence="ECO:0000305"
FT CONFLICT 547
FT /note="K -> R (in Ref. 4; BAA95090)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 580 AA; 65636 MW; 716FCC01C59D3F8A CRC64;
MFAGLQDLGV ANGEDLKETL TNCTEPLKAI EQFQTENGVL LPSLQSALPF LDLHGTPRLE
FHQSVFDELR DKLLERVSAI ASEGKAEERY KKLEDLLEKS FSLVKMPSLQ PVVMCVMKHL
PKVPEKKLKL VMADKELYRA CAVEVKRQIW QDNQALFGDE VSPLLKQYIL EKESALFSTE
LSVLHNFFSP SPKTRRQGEV VQKLTQMVGK NVKLYDMVLQ FLRTLFLRTR NVHYCTLRAE
LLMSLHDLDV SDICTVDPCH KFTWCLDACI RERFVDSKRA RELQGFLDGV KKGQEQVLGD
LSMILCDPFA INTLSLSTIR HLQELVSQET LPRDSPDLLL LLRLLALGQG AWDLIDSQVF
KEPKMEAELI TKFLPMLMSL VVDDFTFNVD QKLPAEEKAS VTYPNTLPES FTKFLQEQRM
ACEVGLYYVL HITKQRNKNA LLRLLPGLVE TFGDLAFSDI FLHLLTGSLV LLADEFALED
FCSSLFDGFF LTASPRKENV HRHVLRLLLH LHARVAPSKL EALQKALEPT GQSGEAVKEL
YSQLGEKLEQ LDHRKPSPTQ AAETPALDLP LPSVPAPATL
