NELFA_MOUSE
ID NELFA_MOUSE Reviewed; 530 AA.
AC Q8BG30; Q8BVE4; Q8VEI7; Q9CSJ9; Q9Z1V9;
DT 14-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Negative elongation factor A;
DE Short=NELF-A;
DE AltName: Full=Wolf-Hirschhorn syndrome candidate 2 homolog;
DE Short=mWHSC2;
GN Name=Nelfa; Synonyms=Whsc2, Whsc2h;
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 MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Embryo, and Thymus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor, and Salivary gland;
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 [MRNA] OF 8-530, AND TISSUE SPECIFICITY.
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [5]
RP INTERACTION WITH NELFB.
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 (By similarity). 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 (By similarity).
CC {ECO:0000250|UniProtKB:Q9H3P2}.
CC -!- SUBUNIT: The NELF complex is composed of NELFA, NELFB, NELFCD and
CC NELFE; NELFA and NELFCD form a stable subcomplex that binds to the N-
CC terminus of NELFB (By similarity). In vitro, the NELFA:NELFCD
CC subcomplex binds to ssDNA and ssRNA in a sequence- and structure-
CC dependent manner (By similarity). Interacts with the RNA polymerase II
CC complex when it is not phosphorylated by P-TEFb (By similarity).
CC Interacts with NELFB (PubMed:26010750). {ECO:0000250|UniProtKB:Q9H3P2,
CC ECO:0000269|PubMed:26010750}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9H3P2}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in brain, heart, spleen,
CC lung, liver, muscle, kidney and testis. Already expressed in 7 dpc
CC embryos. {ECO:0000269|PubMed:10409432}.
CC -!- DOMAIN: The HDAg-like domain is essential for transcriptional
CC repression, and mediates the interaction with the RNA polymerase II
CC complex. {ECO:0000250|UniProtKB:Q9H3P2}.
CC -!- SIMILARITY: Belongs to the NELF-A family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC37379.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK012673; BAB28399.1; -; mRNA.
DR EMBL; AK078760; BAC37379.1; ALT_INIT; mRNA.
DR EMBL; AK088384; BAC40319.1; -; mRNA.
DR EMBL; BC018423; AAH18423.1; -; mRNA.
DR EMBL; BC038003; AAH38003.1; -; mRNA.
DR EMBL; AF101435; AAC72983.1; -; mRNA.
DR CCDS; CCDS19208.1; -.
DR RefSeq; NP_036044.1; NM_011914.2.
DR AlphaFoldDB; Q8BG30; -.
DR SMR; Q8BG30; -.
DR BioGRID; 204907; 8.
DR IntAct; Q8BG30; 5.
DR STRING; 10090.ENSMUSP00000030993; -.
DR iPTMnet; Q8BG30; -.
DR PhosphoSitePlus; Q8BG30; -.
DR EPD; Q8BG30; -.
DR jPOST; Q8BG30; -.
DR MaxQB; Q8BG30; -.
DR PaxDb; Q8BG30; -.
DR PRIDE; Q8BG30; -.
DR ProteomicsDB; 252805; -.
DR Antibodypedia; 4097; 197 antibodies from 26 providers.
DR DNASU; 24116; -.
DR Ensembl; ENSMUST00000030993; ENSMUSP00000030993; ENSMUSG00000029111.
DR GeneID; 24116; -.
DR KEGG; mmu:24116; -.
DR UCSC; uc008xbn.1; mouse.
DR CTD; 7469; -.
DR MGI; MGI:1346098; Nelfa.
DR VEuPathDB; HostDB:ENSMUSG00000029111; -.
DR eggNOG; ENOG502QTCD; Eukaryota.
DR GeneTree; ENSGT00390000005342; -.
DR HOGENOM; CLU_039060_1_0_1; -.
DR InParanoid; Q8BG30; -.
DR OMA; RNIKDCF; -.
DR OrthoDB; 1011916at2759; -.
DR PhylomeDB; Q8BG30; -.
DR TreeFam; TF324956; -.
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; 24116; 20 hits in 75 CRISPR screens.
DR ChiTaRS; Nelfa; mouse.
DR PRO; PR:Q8BG30; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8BG30; protein.
DR Bgee; ENSMUSG00000029111; Expressed in secondary oocyte and 76 other tissues.
DR Genevisible; Q8BG30; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0032021; C:NELF complex; ISS:UniProtKB.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; IMP:MGI.
DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR InterPro; IPR037517; HDAG_dom.
DR PROSITE; PS51838; HDAG; 1.
PE 1: Evidence at protein level;
KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..530
FT /note="Negative elongation factor A"
FT /id="PRO_0000219127"
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 213..248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 266..296
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 312..409
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 223..244
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 267..292
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 312..339
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 340..363
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 364..379
FT /note="Polar 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:0000250|UniProtKB:Q9H3P2"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H3P2"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H3P2"
FT MOD_RES 277
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9H3P2"
FT MOD_RES 363
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H3P2"
FT CONFLICT 64
FT /note="P -> Q (in Ref. 1; BAC37379)"
FT /evidence="ECO:0000305"
FT CONFLICT 72
FT /note="K -> N (in Ref. 3; AAC72983)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="D -> E (in Ref. 3; AAC72983)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="K -> I (in Ref. 3; AAC72983)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="P -> T (in Ref. 3; AAC72983)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="L -> V (in Ref. 3; AAC72983)"
FT /evidence="ECO:0000305"
FT CONFLICT 386..387
FT /note="Missing (in Ref. 3; AAC72983)"
FT /evidence="ECO:0000305"
FT CONFLICT 395..397
FT /note="LTP -> RTH (in Ref. 3; AAC72983)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="Q -> R (in Ref. 1; BAC37379)"
FT /evidence="ECO:0000305"
FT CONFLICT 435
FT /note="L -> F (in Ref. 3; AAC72983)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 530 AA; 57585 MW; CEC4938A6E071BA9 CRC64;
MASMRESDTG LWLHNKLGAT DELWAPPSIA SLLTAAVIDN IRLCFHRLSS AVKLKLLLGT
LHLPRRTVDE MKAALMDIIQ LATLDSDPWV LMVADILKSF PDTGSLNLDL EEQNPNVQDI
LGELREKVSE CEASAMLPLE CQYLNKNALT TLAGPLTPPV KHFQLKRKPK SATLRAELLQ
KSTETAQQLK RSAGVPFHAK GRGLLRKMDT TTPLKGIPKQ APFRSPTTPS VFSPSGNRTP
IPPSRTPLQK ERGVKLLDIS ELNTVGAGRE AKRRRKTLDT EVVEKPTKEE TVVENATPDY
AAGLVSTQKL GSLNSEPTLP STSYLPSTPS VVPASSYIPS SETPPAPPSR EASRPPEEPS
APSPTLPTQF KQRAPMYNSG LSPATPAPAA PTSPLTPTTP PAVTPTAQTP PVAMVAPQTQ
APAPVQQQPK KNLSLTREQM FAAQEMFKTA NKVTRPEKAL ILGFMAGSRE NPCPEQGDVI
QIKLSEHTED LPKADGQGST TMLVDTVFEM NYATGQWTRF KKYKPMTNVS
