Q9H3P2 (NELFA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Negative elongation factor A
Short name=NELF-A

Alternative name(s):
Wolf-Hirschhorn syndrome candidate 2 protein

Gene names

Name:	NELFA
Synonyms:	WHSC2
ORF Names:	P/OKcl.15

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	528 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II. The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex. Probably required to interact with the RNA polymerase II complex. Ref.9 Ref.11 Ref.12
Subunit structure	The NELF complex is composed of NELFA, NELFB, NELFCD (isoform NELF-C or isoform NELF-D) and NELFE. Interacts with the RNA polymerase II complex when it is not phosphorylated by P-TEFb. Ref.8
Subcellular location	Nucleus Ref.10.
Tissue specificity	Ubiquitous. Expressed in heart, brain, placenta, liver, skeletal muscle, kidney and pancreas. Expressed at lower level in adult lung. Expressed in fetal brain, lung, liver and kidney. Ref.1 Ref.10 Ref.12
Domain	The HDAg-like domain is essential for transcriptional repression, and mediates the interaction with the RNA polymerase II complex. Ref.12
Sequence similarities	Belongs to the NELF-A family. Contains 1 HDAg-like domain.
Caution	Ref.12 has shown that it is not involved in Wolf-Hirschhorn syndrome.
Sequence caution	The sequence AAC72982.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAG54283.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAM15219.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence EAW82546.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	multicellular organismal development Traceable author statement Ref.1. Source: ProtInc negative regulation of transcription elongation from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of viral transcription Traceable author statement. Source: Reactome transcription elongation from RNA polymerase II promoter Traceable author statement. Source: Reactome viral reproduction Traceable author statement. Source: Reactome
Cellular_component	NELF complex Inferred from direct assay Ref.12. Source: UniProtKB
Molecular_function	chromatin binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TH1L	Q8IXH7-4	3	EBI-5461341,EBI-6109710

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9H3P2-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9H3P2-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-263: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 528	528	Negative elongation factor A		PRO_0000219126
Regions
	Domain	189 – 248	60	HDAg-like
Amino acid modifications
	Modified residue	157	1	Phosphothreonine Ref.13 Ref.15 Ref.16
	Modified residue	277	1	Phosphothreonine Ref.16
	Modified residue	363	1	Phosphoserine Ref.14 Ref.16
Natural variations
	Alternative sequence	1 – 263	263	Missing in isoform 2.		VSP_035589
	Natural variant	335	1	S → A. Corresponds to variant rs2234569 [ dbSNP | Ensembl ].		VAR_059459
Experimental info
	Sequence conflict	37	1	V → I in BAB18651. Ref.2
	Sequence conflict	40	1	N → NIRLCFHGLSSASLLTAAVI DN in BAB18651. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 4, 2008. Version 3. Checksum: 4F33C3BC68BDC798	FASTA	528	57,277
	10 20 30 40 50 60 MASMRESDTG LWLHNKLGAT DELWAPPSIA SLLTAAVIDN IRLCFHGLSS AVKLKLLLGT 70 80 90 100 110 120 LHLPRRTVDE MKGALMEIIQ LASLDSDPWV LMVADILKSF PDTGSLNLEL EEQNPNVQDI 130 140 150 160 170 180 LGELREKVGE CEASAMLPLE CQYLNKNALT TLAGPLTPPV KHFQLKRKPK SATLRAELLQ 190 200 210 220 230 240 KSTETAQQLK RSAGVPFHAK GRGLLRKMDT TTPLKGIPKQ APFRSPTAPS VFSPTGNRTP 250 260 270 280 290 300 IPPSRTLLRK ERGVKLLDIS ELDMVGAGRE AKRRRKTLDA EVVEKPAKEE TVVENATPDY 310 320 330 340 350 360 AAGLVSTQKL GSLNNEPALP STSYLPSTPS VVPASSYIPS SETPPAPSSR EASRPPEEPS 370 380 390 400 410 420 APSPTLPAQF KQRAPMYNSG LSPATPTPAA PTSPLTPTTP PAVAPTTQTP PVAMVAPQTQ 430 440 450 460 470 480 APAQQQPKKN LSLTREQMFA AQEMFKTANK VTRPEKALIL GFMAGSRENP CQEQGDVIQI 490 500 510 520 KLSEHTEDLP KADGQGSTTM LVDTVFEMNY ATGQWTRFKK YKPMTNVS
	Isoform 2 [UniParc]. Checksum: 66F97A90BF7F1C62	FASTA	265	28,416
	10 20 30 40 50 60 MVGAGREAKR RRKTLDAEVV EKPAKEETVV ENATPDYAAG LVSTQKLGSL NNEPALPSTS 70 80 90 100 110 120 YLPSTPSVVP ASSYIPSSET PPAPSSREAS RPPEEPSAPS PTLPAQFKQR APMYNSGLSP 130 140 150 160 170 180 ATPTPAAPTS PLTPTTPPAV APTTQTPPVA MVAPQTQAPA QQQPKKNLSL TREQMFAAQE 190 200 210 220 230 240 MFKTANKVTR PEKALILGFM AGSRENPCQE QGDVIQIKLS EHTEDLPKAD GQGSTTMLVD 250 260 TVFEMNYATG QWTRFKKYKP MTNVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Comparative analysis of a novel gene from the Wolf-Hirschhorn/Pitt-Rogers-Danks syndrome critical region." Wright T.J., Costa J.L., Naranjo C., Francis-West P., Altherr M.R. Genomics 59:203-212(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Brain.
[2]	"Molecular basis of T cell-mediated recognition of pancreatic cancer cells." Ito M., Shichijo S., Tsuda N., Ochi M., Harashima N., Saito N., Itoh K. Cancer Res. 61:2038-2046(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Pancreatic cancer.
[3]	Mei G., Yu W., Gibbs R.A. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[8]	"Stimulation of RNA polymerase II elongation by hepatitis delta antigen." Yamaguchi Y., Filipovska J., Yano K., Furuya A., Inukai N., Narita T., Wada T., Sugimoto S., Konarska M.M., Handa H. Science 293:124-127(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 212-221; 309-321 AND 503-513, IDENTIFICATION IN THE NELF COMPLEX.
[9]	"NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation." Yamaguchi Y., Takagi T., Wada T., Yano K., Furuya A., Sugimoto S., Hasegawa J., Handa H. Cell 97:41-51(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE NELF COMPLEX.
[10]	"Modulation of WHSC2 expression in human endothelial cells." Mariotti M., Manganini M., Maier J.A.M. FEBS Lett. 487:166-170(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[11]	"Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2." Zollino M., Lecce R., Fischetto R., Murdolo M., Faravelli F., Selicorni A., Butte C., Memo L., Capovilla G., Neri G. Am. J. Hum. Genet. 72:590-597(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex." Narita T., Yamaguchi Y., Yano K., Sugimoto S., Chanarat S., Wada T., Kim D.-K., Hasegawa J., Omori M., Inukai N., Endoh M., Yamada T., Handa H. Mol. Cell. Biol. 23:1863-1873(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DOMAIN.
[13]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-157, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-157, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[16]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-157; THR-277 AND SER-363, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF101434 mRNA. Translation: AAC72982.1. Different initiation. AB044549 mRNA. Translation: BAB18651.1. AF131751 mRNA. Translation: AAD20034.1. AK126056 mRNA. Translation: BAG54283.1. Different initiation. AL132868 Genomic DNA. Translation: CAM15219.1. Different initiation. CH471131 Genomic DNA. Translation: EAW82546.1. Different initiation. BC002764 mRNA. Translation: AAH02764.2.
IPI	IPI00643383. IPI01011851.
RefSeq	NP_005654.3. NM_005663.4.
UniGene	Hs.21771.
3D structure databases
ProteinModelPortal	Q9H3P2.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48478N.
IntAct	Q9H3P2. 5 interactions.
STRING	9606.ENSP00000372335.
PTM databases
PhosphoSite	Q9H3P2.
Polymorphism databases
DMDM	212276499.
Proteomic databases
PaxDb	Q9H3P2.
PRIDE	Q9H3P2.
Protocols and materials databases
DNASU	7469.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000382882; ENSP00000372335; ENSG00000185049. ENST00000411638; ENSP00000399165; ENSG00000185049.
GeneID	7469.
KEGG	hsa:7469.
UCSC	uc003gek.3. human.
Organism-specific databases
CTD	7469.
GeneCards	GC04M001984.
HGNC	HGNC:12768. NELFA.
HPA	CAB009960.
MIM	606026. gene.
neXtProt	NX_Q9H3P2.
Orphanet	280. Wolf-Hirschhorn syndrome.
PharmGKB	PA37371.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG10551.
HOGENOM	HOG000113765.
HOVERGEN	HBG052595.
InParanoid	Q9H3P2.
KO	K15179.
OrthoDB	EOG4PC9S3.
PhylomeDB	Q9H3P2.
Enzyme and pathway databases
Reactome	REACT_116125. Disease. REACT_1788. Transcription. REACT_1892. Elongation arrest and recovery. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q9H3P2.
Bgee	Q9H3P2.
CleanEx	HS_WHSC2.
Genevestigator	Q9H3P2.
GermOnline	ENSG00000185049. Homo sapiens.
Family and domain databases
InterPro	IPR026305. NELF-A. [Graphical view]
PANTHER	PTHR13328. PTHR13328. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	7469.
NextBio	29260.
SOURCE	Search...

Entry information

Entry name

NELFA_HUMAN

Accession

Primary (citable) accession number: Q9H3P2
Secondary accession number(s): A2A2T1, O95392

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 14, 2003
Last sequence update:	November 4, 2008
Last modified:	April 3, 2013
This is version 107 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.