Q16649 (NFIL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nuclear factor interleukin-3-regulated protein

Alternative name(s):
E4 promoter-binding protein 4
Interleukin-3 promoter transcriptional activator
Interleukin-3-binding protein 1
Transcriptional activator NF-IL3A

Gene names

Name:	NFIL3
Synonyms:	E4BP4, IL3BP1

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	462 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a transcriptional regulator that recognizes and binds to the sequence 5'-[GA]TTA[CT]GTAA[CT]-3', a sequence present in many cellular and viral promoters. Represses transcription from promoters with activating transcription factor (ATF) sites. Represses promoter activity in osteoblasts By similarity. Represses transcriptional activity of PER1 By similarity. Represses transcriptional activity of PER2 via the B-site on the promoter By similarity. Activates transcription from the interleukin-3 promoter in T-cells. Competes for the same consensus-binding site with PAR DNA-binding factors (DBP, HLF and TEF) By similarity. Component of the circadian clock that acts as a negative regulator for the circadian expression of PER2 oscillation in the cell-autonomous core clock By similarity. Protects pro-B cells from programmed cell death By similarity. Ref.1 Ref.2 Ref.9
Subunit structure	Homodimer. Binds DNA as a dimer. Interacts with DR1. Interacts with PER2 and CRY2 By similarity. Ref.1 Ref.9
Subcellular location	Nucleus By similarity.
Tissue specificity	Expressed in bladder stomach, thyroid, spinal cord, lymph node, trachea, adrenal gland, bone marrow and muscle. Ref.10
Induction	Up-regulated by PHA or TPA. Ref.2
Sequence similarities	Belongs to the bZIP family. NFIL3 subfamily. Contains 1 bZIP (basic-leucine zipper) domain.

Ontologies

Keywords
Biological process	Biological rhythms Transcription Transcription regulation
Cellular component	Nucleus
Ligand	DNA-binding
Molecular function	Activator Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	circadian rhythm Inferred from electronic annotation. Source: InterPro immune response Traceable author statement Ref.2. Source: ProtInc positive regulation of gene expression Inferred from electronic annotation. Source: Compara
Cellular_component	nucleus Inferred from direct assay. Source: HPA
Molecular_function	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Inferred from direct assay PubMed 20093779. Source: BHF-UCL RNA polymerase II core promoter sequence-specific DNA binding Inferred from electronic annotation. Source: Compara RNA polymerase II regulatory region sequence-specific DNA binding Inferred from direct assay PubMed 20093779. Source: BHF-UCL transcription corepressor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 462	462	Nuclear factor interleukin-3-regulated protein		PRO_0000292667
Regions
	Domain	73 – 136	64	bZIP
	Region	79 – 95	17	Basic motif By similarity
	Region	99 – 106	8	Leucine-zipper By similarity
	Region	299 – 363	65	Necessary for transcriptional repression and sufficient for interaction with DR1
	Compositional bias	155 – 210	56	Ser-rich
Amino acid modifications
	Modified residue	286	1	Phosphoserine By similarity
	Modified residue	301	1	Phosphoserine Ref.11 Ref.14
	Modified residue	353	1	Phosphoserine Ref.14
Experimental info
	Mutagenesis	330	1	K → A: Interacts with DR1 and partially affects transcriptional repression; when associated with E-332. Ref.9
	Mutagenesis	330	1	K → E: Does not interact with DR1 and drastically affects transcriptional repression; when associated with E-332. Ref.9
	Mutagenesis	332	1	K → A: Interacts with DR1 and partially affects transcriptional repression; when associated with E-330. Ref.9
	Mutagenesis	332	1	K → E: Does not interact with DR1 and drastically affects transcriptional repression; when associated with E-330. Ref.9
	Sequence conflict	44 – 45	2	EL → DV in AAA93067. Ref.1
	Sequence conflict	44 – 45	2	EL → DV in CAA45597. Ref.1
	Sequence conflict	44 – 45	2	EL → DV in AAB35410. Ref.2
	Sequence conflict	149	1	F → S in CAG46846. Ref.4
	Sequence conflict	273	1	R → G in AAA93067. Ref.1
	Sequence conflict	273	1	R → G in CAA45597. Ref.1
	Sequence conflict	273	1	R → G in AAB35410. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q16649 [UniParc]. Last modified June 26, 2007. Version 2. Checksum: D19946AAC774C3E7	FASTA	462	51,472
	10 20 30 40 50 60 MQLRKMQTVK KEQASLDASS NVDKMMVLNS ALTEVSEDST TGEELLLSEG SVGKNKSSAC 70 80 90 100 110 120 RRKREFIPDE KKDAMYWEKR RKNNEAAKRS REKRRLNDLV LENKLIALGE ENATLKAELL 130 140 150 160 170 180 SLKLKFGLIS STAYAQEIQK LSNSTAVYFQ DYQTSKSNVS SFVDEHEPSM VSSSCISVIK 190 200 210 220 230 240 HSPQSSLSDV SEVSSVEHTQ ESSVQGSCRS PENKFQIIKQ EPMELESYTR EPRDDRGSYT 250 260 270 280 290 300 ASIYQNYMGN SFSGYSHSPP LLQVNRSSSN SPRTSETDDG VVGKSSDGED EQQVPKGPIH 310 320 330 340 350 360 SPVELKHVHA TVVKVPEVNS SALPHKLRIK AKAMQIKVEA FDNEFEATQK LSSPIDMTSK 370 380 390 400 410 420 RHFELEKHSA PSMVHSSLTP FSVQVTNIQD WSLKSEHWHQ KELSGKTQNS FKTGVVEMKD 430 440 450 460 SGYKVSDPEN LYLKQGIANL SAEVVSLKRL IATQPISASD SG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Transcriptional repression by a novel member of the bZIP family of transcription factors." Cowell I.G., Skinner A., Hurst H.C. Mol. Cell. Biol. 12:3070-3077(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, DNA-BINDING. Tissue: Placenta.
[2]	"Molecular cloning and characterization of NF-IL3A, a transcriptional activator of the human interleukin-3 promoter." Zhang W., Zhang J., Kornuc M., Kwan K., Frank R., Nimer S.D. Mol. Cell. Biol. 15:6055-6063(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION, DNA-BINDING. Tissue: T-cell.
[3]	NHLBI resequencing and genotyping service (RS&G) Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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]. Tissue: Liver.
[6]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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]. Tissue: Placenta.
[9]	"Protein-protein interaction between the transcriptional repressor E4BP4 and the TBP-binding protein Dr1." Cowell I.G., Hurst H.C. Nucleic Acids Res. 24:3607-3613(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DR1, MUTAGENESIS OF LYS-330 AND LYS-332.
[10]	"Exclusion of NFIL3 as the gene causing hereditary sensory neuropathy type I by mutation analysis." Hulme D.J., Blair I.P., Dawkins J.L., Nicholson G.A. Hum. Genet. 106:594-596(2000) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[11]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[13]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[14]	"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 SER-301 AND SER-353, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U26173 mRNA. Translation: AAA93067.1. X64318 mRNA. Translation: CAA45597.1. S79880 mRNA. Translation: AAB35410.1. EF028070 Genomic DNA. Translation: ABK15691.1. CR542049 mRNA. Translation: CAG46846.1. AK313970 mRNA. Translation: BAG36685.1. AL353764 Genomic DNA. Translation: CAH73854.1. CH471089 Genomic DNA. Translation: EAW62796.1. BC008197 mRNA. Translation: AAH08197.1.
IPI	IPI00290562.
PIR	G01804.
RefSeq	NP_005375.2. NM_005384.2.
UniGene	Hs.79334.
3D structure databases
ProteinModelPortal	Q16649.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q16649. 4 interactions.
MINT	MINT-268122.
STRING	9606.ENSP00000297689.
PTM databases
PhosphoSite	Q16649.
Polymorphism databases
DMDM	150385077.
Proteomic databases
PaxDb	Q16649.
PRIDE	Q16649.
Protocols and materials databases
DNASU	4783.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000297689; ENSP00000297689; ENSG00000165030. ENST00000375724; ENSP00000364876; ENSG00000165030.
GeneID	4783.
KEGG	hsa:4783.
UCSC	uc004arh.3. human.
Organism-specific databases
CTD	4783.
GeneCards	GC09M094171.
H-InvDB	HIX0169355.
HGNC	HGNC:7787. NFIL3.
HPA	HPA003261.
MIM	605327. gene.
neXtProt	NX_Q16649.
PharmGKB	PA31593.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG260819.
HOGENOM	HOG000059596.
HOVERGEN	HBG105717.
InParanoid	Q16649.
KO	K09059.
OMA	QTIKKEQ.
OrthoDB	EOG43N7CJ.
PhylomeDB	Q16649.
Enzyme and pathway databases
SignaLink	Q16649.
Gene expression databases
Bgee	Q16649.
CleanEx	HS_NFIL3.
Genevestigator	Q16649.
Family and domain databases
InterPro	IPR004827. bZIP. IPR016743. TF_bZIP_E4BP4. IPR010533. Vert_IL3-reg_TF. [Graphical view]
Pfam	PF07716. bZIP_2. 1 hit. PF06529. Vert_IL3-reg_TF. 1 hit. [Graphical view]
PIRSF	PIRSF019029. bZIP_E4BP4. 1 hit.
SMART	SM00338. BRLZ. 1 hit. [Graphical view]
PROSITE	PS50217. BZIP. 1 hit. PS00036. BZIP_BASIC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NFIL3. human.
GenomeRNAi	4783.
NextBio	18446.
SOURCE	Search...

Entry information

Entry name

NFIL3_HUMAN

Accession

Primary (citable) accession number: Q16649
Secondary accession number(s): B2R9Y8 , Q14211, Q6FGQ8, Q96HS0

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 26, 2007
Last sequence update:	June 26, 2007
Last modified:	May 29, 2013
This is version 99 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.