Q8IXH7 (NELFD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Negative elongation factor C/D
Short name=NELF-C/D

Alternative name(s):
TH1-like protein

Gene names

Name:	TH1L
Synonyms:	NELFD, TH1
ORF Names:	HSPC130

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	590 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. Ref.6 Ref.8
Subunit structure	The NELF complex is composed of 4 subunits: WHSC2/NELF-A, COBRA1/NELF-B, TH1L (isoform NELF-C or isoform NELF-D) and RDBP/NELF-E. Interacts with ARAF1. Ref.7
Subcellular location	Nucleus Probable.
Tissue specificity	Widely expressed. Expressed in heart, brain, lung, placenta, liver, skeletal and cardiac muscle, adrenal, thyroid, kidney and pancreas. Ref.1 Ref.6
Sequence similarities	Belongs to the NELF-D family.
Sequence caution	The sequence AAF29094.1 differs from that shown. Reason: Frameshift at positions 462 and 464. The sequence BAA91618.1 differs from that shown. Reason: Erroneous initiation. The sequence BAB14519.1 differs from that shown. Reason: Erroneous initiation. The sequence CAB64339.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative initiation Alternative splicing
Molecular function	Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	negative regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro 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	nucleoplasm Traceable author statement. Source: Reactome
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARAF	P10398	5	EBI-536725,EBI-365961

Alternative products

This entry describes 3 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]

Isoform NELF-C (identifier: Q8IXH7-1)

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 3 (identifier: Q8IXH7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     178-201: LISDAGYQGEITSVSTACQQLEVF → VGRVLELRRKVFMNVYFWLLVCFL
     202-590: Missing.

Note: No experimental confirmation available.

Isoform NELF-D (identifier: Q8IXH7-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: Missing.

Note: Produced by alternative initiation at Met-10 of isoform NELF-C.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 590	590	Negative elongation factor C/D		PRO_0000019456
Amino acid modifications
	Modified residue	280	1	Phosphothreonine Ref.9
	Modified residue	285	1	Phosphothreonine Ref.9
	Modified residue	289	1	Phosphotyrosine Ref.9
	Modified residue	301	1	Phosphoserine Ref.9
Natural variations
	Alternative sequence	1 – 9	9	Missing in isoform NELF-D.		VSP_018769
	Alternative sequence	178 – 201	24	LISDA…QLEVF → VGRVLELRRKVFMNVYFWLL VCFL in isoform 3.		VSP_008950
	Alternative sequence	202 – 590	389	Missing in isoform 3.		VSP_008951
Experimental info
	Sequence conflict	117	1	N → D in BAA91618. Ref.3
	Sequence conflict	306	1	N → S in BAB14729. Ref.3
	Sequence conflict	430	1	W → R in BAA91618. Ref.3
	Sequence conflict	497	1	L → P in BAA91618. Ref.3
	Sequence conflict	573	1	D → V in BAA91618. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform NELF-C [UniParc]. Last modified November 14, 2003. Version 2. Checksum: 425437DC46DAF953	FASTA	590	66,247
	10 20 30 40 50 60 MAGAVPGAIM DEDYYGSAAE WGDEADGGQQ EDDSGEGEDD AEVQQECLHK FSTRDYIMEP 70 80 90 100 110 120 SIFNTLKRYF QAGGSPENVI QLLSENYTAV AQTVNLLAEW LIQTGVEPVQ VQETVENHLK 130 140 150 160 170 180 SLLIKHFDPR KADSIFTEEG ETPAWLEQMI AHTTWRDLFY KLAEAHPDCL MLNFTVKLIS 190 200 210 220 230 240 DAGYQGEITS VSTACQQLEV FSRVLRTSLA TILDGGEENL EKNLPEFAKM VCHGEHTYLF 250 260 270 280 290 300 AQAMMSVLAQ EEQGGSAVRR IAQEVQRFAQ EKGHDASQIT LALGTAASYP RACQALGAML 310 320 330 340 350 360 SKGALNPADI TVLFKMFTSM DPPPVELIRV PAFLDLFMQS LFKPGARINQ DHKHKYIHIL 370 380 390 400 410 420 AYAASVVETW KKNKRVSINK DELKSTSKAV ETVHNLCCNE NKGASELVAE LSTLYQCIRF 430 440 450 460 470 480 PVVAMGVLKW VDWTVSEPRY FQLQTDHTPV HLALLDEIST CHQLLHPQVL QLLVKLFETE 490 500 510 520 530 540 HSQLDVMEQL ELKKTLLDRM VHLLSRGYVL PVVSYIRKCL EKLDTDISLI RYFVTEVLDV 550 560 570 580 590 IAPPYTSDFV QLFLPILEND SIAGTIKTEG EHDPVTEFIA HCKSNFIMVN
	Isoform 3 [UniParc]. Checksum: 28EA9E5A52CD68FF	FASTA	201	22,903
	10 20 30 40 50 60 MAGAVPGAIM DEDYYGSAAE WGDEADGGQQ EDDSGEGEDD AEVQQECLHK FSTRDYIMEP 70 80 90 100 110 120 SIFNTLKRYF QAGGSPENVI QLLSENYTAV AQTVNLLAEW LIQTGVEPVQ VQETVENHLK 130 140 150 160 170 180 SLLIKHFDPR KADSIFTEEG ETPAWLEQMI AHTTWRDLFY KLAEAHPDCL MLNFTVKVGR 190 200 VLELRRKVFM NVYFWLLVCF L
	Isoform NELF-D [UniParc]. Checksum: DD20EFAF08DE67E8	FASTA	581	65,479
	10 20 30 40 50 60 MDEDYYGSAA EWGDEADGGQ QEDDSGEGED DAEVQQECLH KFSTRDYIME PSIFNTLKRY 70 80 90 100 110 120 FQAGGSPENV IQLLSENYTA VAQTVNLLAE WLIQTGVEPV QVQETVENHL KSLLIKHFDP 130 140 150 160 170 180 RKADSIFTEE GETPAWLEQM IAHTTWRDLF YKLAEAHPDC LMLNFTVKLI SDAGYQGEIT 190 200 210 220 230 240 SVSTACQQLE VFSRVLRTSL ATILDGGEEN LEKNLPEFAK MVCHGEHTYL FAQAMMSVLA 250 260 270 280 290 300 QEEQGGSAVR RIAQEVQRFA QEKGHDASQI TLALGTAASY PRACQALGAM LSKGALNPAD 310 320 330 340 350 360 ITVLFKMFTS MDPPPVELIR VPAFLDLFMQ SLFKPGARIN QDHKHKYIHI LAYAASVVET 370 380 390 400 410 420 WKKNKRVSIN KDELKSTSKA VETVHNLCCN ENKGASELVA ELSTLYQCIR FPVVAMGVLK 430 440 450 460 470 480 WVDWTVSEPR YFQLQTDHTP VHLALLDEIS TCHQLLHPQV LQLLVKLFET EHSQLDVMEQ 490 500 510 520 530 540 LELKKTLLDR MVHLLSRGYV LPVVSYIRKC LEKLDTDISL IRYFVTEVLD VIAPPYTSDF 550 560 570 580 VQLFLPILEN DSIAGTIKTE GEHDPVTEFI AHCKSNFIMV N

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of TH1 and CTSZ, two non-imprinted genes downstream of GNAS1 in chromosome 20q13." Bonthron D.T., Hayward B.E., Moran V., Strain L. Hum. Genet. 107:165-175(2000) [PubMed: 11030415] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM NELF-C), TISSUE SPECIFICITY.
[2]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed: 11042152] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM NELF-C). Tissue: Umbilical cord blood.
[3]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS NELF-C AND 3). Tissue: Ovarian carcinoma, Teratocarcinoma and Thyroid.
[4]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM NELF-C). Tissue: Skin.
[6]	"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: 12612062] [Abstract] Cited for: PROTEIN SEQUENCE OF 126-139; 223-230; 303-315 AND 476-491, IDENTIFICATION IN A NELF COMPLEX, ALTERNATIVE INITIATION, FUNCTION, TISSUE SPECIFICITY.
[7]	"Identification of TH1 as an interaction partner of A-Raf kinase." Yin X.L., Chen S., Gu J.X. Mol. Cell. Biochem. 231:69-74(2002) [PubMed: 11952167] [Abstract] Cited for: INTERACTION WITH ARAF1.
[8]	"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: 10199401] [Abstract] Cited for: FUNCTION OF THE NELF COMPLEX.
[9]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-280; THR-285; TYR-289 AND SER-301, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[10]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ238374 mRNA. Translation: CAB64337.1. AJ238375 mRNA. Translation: CAB64373.1. AJ238379 mRNA. Translation: CAB64339.1. Different initiation. AF161479 mRNA. Translation: AAF29094.1. Frameshift. AK001316 mRNA. Translation: BAA91618.1. Different initiation. AK023310 mRNA. Translation: BAB14519.1. Different initiation. AK023927 mRNA. Translation: BAB14729.1. AK293410 mRNA. Translation: BAG56917.1. AL109840 Genomic DNA. Translation: CAC09368.1. BC014952 mRNA. Translation: AAH14952.1.
IPI	IPI00164949. IPI00387090. IPI00759539.
RefSeq	NP_945327.1. NM_198976.1.
UniGene	Hs.517148.
3D structure databases
ProteinModelPortal	Q8IXH7.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-34061N.
IntAct	Q8IXH7. 14 interactions.
MINT	MINT-260753.
STRING	Q8IXH7.
Polymorphism databases
DMDM	38372376.
Proteomic databases
PRIDE	Q8IXH7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000344018; ENSP00000342300; ENSG00000101158.
GeneID	51497.
KEGG	hsa:51497.
UCSC	uc002yag.1. human.
Organism-specific databases
CTD	51497.
GeneCards	GC20P057556.
H-InvDB	HIX0015956. HIX0138057.
HGNC	HGNC:15934. TH1L.
MIM	605297. gene.
neXtProt	NX_Q8IXH7.
PharmGKB	PA38055.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13799.
GeneTree	ENSGT00390000001799.
HOVERGEN	HBG052597.
InParanoid	Q8IXH7.
OMA	PDYIMEP.
OrthoDB	EOG4V170G.
PhylomeDB	Q8IXH7.
Enzyme and pathway databases
Reactome	REACT_1788. Transcription. REACT_1892. Elongation arrest and recovery. REACT_6185. HIV Infection. REACT_71. Gene Expression. REACT_769. Pausing and recovery of elongation.
Gene expression databases
ArrayExpress	Q8IXH7.
Bgee	Q8IXH7.
Genevestigator	Q8IXH7.
GermOnline	ENSG00000101158. Homo sapiens.
Family and domain databases
InterPro	IPR006942. TH1. [Graphical view]
KO	K15181.
PANTHER	PTHR12144. TH1. 1 hit.
Pfam	PF04858. TH1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	55171.
SOURCE	Search...

Entry information

Entry name

NELFD_HUMAN

Accession

Primary (citable) accession number: Q8IXH7
Secondary accession number(s): B4DE06 , Q9BYL2, Q9H405, Q9H888, Q9H8T3, Q9NVX5, Q9P029, Q9UGN1, Q9UGN2, Q9UGN3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 14, 2003
Last sequence update:	November 14, 2003
Last modified:	January 25, 2012
This is version 93 of the entry and version 2 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.