P14316 (IRF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interferon regulatory factor 2
Short name=IRF-2

Gene names

Name:

IRF2

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

General annotation (Comments)

Function	Specifically binds to the upstream regulatory region of type I IFN and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)) and represses those genes. Also acts as an activator for several genes including H4 and IL7. Constitutively binds to the ISRE promoter to activate IL7. Involved in cell cycle regulation through binding the site II (HiNF-M) promoter region of H4 and activating transcription during cell growth. Antagonizes IRF1 transcriptional activation. Ref.9 Ref.12 Ref.14 Ref.15
Subunit structure	Interacts with BRD7, IRF2BP1 and IRF2BP2. Interacts with CREBBP in growing cells; the interaction acetylates IRF2 and regulates IRF2-dependent H4 promoter activity. Ref.10 Ref.12 Ref.13
Subcellular location	Nucleus.
Tissue specificity	Expressed throughout the epithelium of the colon. Also expressed in lamina propria. Ref.14
Induction	By viruses and IFN.
Post-translational modification	Acetylated by CBP/ p300 during cell-growth. Acetylation on Lys-75 is required for stimulation of H4 promoter activity. The major sites of sumoylation are Lys-137 and Lys-293. Sumoylation with SUMO1 increases its transcriptional repressor activity on IRF1 and diminishes its ability to activate ISRE and H4 promoter. Ref.15
Sequence similarities	Belongs to the IRF family. Contains 1 IRF tryptophan pentad repeat DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
Molecular function	Activator Repressor
PTM	Acetylation Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome cell proliferation Traceable author statement PubMed 8438157. Source: ProtInc interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome negative regulation of transcription from RNA polymerase II promoter Traceable author statement PubMed 7507207. Source: ProtInc transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome focal adhesion Inferred from direct assay. Source: HPA nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	DNA binding Inferred from direct assay Ref.9. Source: UniProtKB regulatory region DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from mutant phenotype Ref.9. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATG7	O95352	2	EBI-2866589,EBI-987834
FOXK1	P85037	2	EBI-2866589,EBI-2509974
FOXK2	Q01167	2	EBI-2866589,EBI-2509991
PPP3CB	P16298	2	EBI-2866589,EBI-1759540

Alternative products

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

Isoform 1 (identifier: P14316-1)

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: P14316-2)

Also known as: IRF-2s; IRF-2[S];

The sequence of this isoform differs from the canonical sequence as follows:
     177-178: Missing.

Note: Unable to bind to IRF2BP1 and IRF2BP2 corepressors and cannot mediate repression.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 349	349	Interferon regulatory factor 2		PRO_0000154549
Regions
	DNA binding	5 – 113	109	IRF tryptophan pentad repeat Ref.9
Amino acid modifications
	Modified residue	75	1	N6-acetyllysine Ref.12
	Modified residue	78	1	N6-acetyllysine Ref.12
	Cross-link	137		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.15
	Cross-link	166		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.15
	Cross-link	293		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.15
Natural variations
	Alternative sequence	177 – 178	2	Missing in isoform 2.		VSP_043965
Experimental info
	Mutagenesis	75	1	K → R: Diminished acetylation by both CREBBP/p300 and PCAF. Greatly reduced enhancement of H4 promoter activity. Ref.12
	Mutagenesis	78	1	K → R: Greatly diminished acetylation by PCAF. Lesser loss of acetylation by CREBBP/p300. Loss of DNA binding and no enhancement of H4 promoter activity. Ref.12
	Mutagenesis	137	1	K → R: Some loss of sumoylation. Increases IRF2-mediation activation of ISRE and H4 promoters. Increased inhibition of IRF1-mediated transcription. Additional small loss of sumoylation; when associated with R-166. Great loss of sumoylation; when associated with R-296. Abolishes sumoylation. Greatly increased activation of ISRE and H4 promoters and further increased ability to inhibit IRF1-mediated transcription; when associated with R-166 and R-293. Ref.15
	Mutagenesis	166	1	K → R: Little loss of sumoylation. Increases IRF2-mediation activation of ISRE and H4 promoters. Increased inhibition of IRF1-mediated transcription. Greater loss of sumoylation; when associated with R-137. Further loss of sumoylation; when associated with R-293. Abolishes sumoylation. Greatly increased activation of ISRE and H4 promoters and further increased ability to inhibit IRF1-mediated transcription; when associated with R-137 and R-293. Ref.15
	Mutagenesis	293	1	K → R: Some loss of sumoylation. Increases IRF2-mediation activation of ISRE and H4 promoters. Increased inhibition of IRF1-mediated transcription. Further small loss of sumoylation; when associated with R-166. Great loss of sumoylation; when associated with R-137. Abolishes sumoylation. Greatly increased activation of ISRE and H4 promoters and further increased ability to inhibit IRF1-mediated transcription; when associated with R-166 and R-293. Ref.15
	Sequence conflict	58	1	W → R in CAA34073. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 11, 2002. Version 2. Checksum: 6298341652466560	FASTA	349	39,354
	10 20 30 40 50 60 MPVERMRMRP WLEEQINSNT IPGLKWLNKE KKIFQIPWMH AARHGWDVEK DAPLFRNWAI 70 80 90 100 110 120 HTGKHQPGVD KPDPKTWKAN FRCAMNSLPD IEEVKDKSIK KGNNAFRVYR MLPLSERPSK 130 140 150 160 170 180 KGKKPKTEKE DKVKHIKQEP VESSLGLSNG VSDLSPEYAV LTSTIKNEVD STVNIIVVGQ 190 200 210 220 230 240 SHLDSNIENQ EIVTNPPDIC QVVEVTTESD EQPVSMSELY PLQISPVSSY AESETTDSVP 250 260 270 280 290 300 SDEESAEGRP HWRKRNIEGK QYLSNMGTRG SYLLPGMASF VTSNKPDLQV TIKEESNPVP 310 320 330 340 YNSSWPPFQD LPLSSSMTPA SSSSRPDRET RASVIKKTSD ITQARVKSC
	Isoform 2 (IRF-2s) (IRF-2[S]) [UniParc]. Checksum: EE67F41029BFD6BD	FASTA	347	39,156
	10 20 30 40 50 60 MPVERMRMRP WLEEQINSNT IPGLKWLNKE KKIFQIPWMH AARHGWDVEK DAPLFRNWAI 70 80 90 100 110 120 HTGKHQPGVD KPDPKTWKAN FRCAMNSLPD IEEVKDKSIK KGNNAFRVYR MLPLSERPSK 130 140 150 160 170 180 KGKKPKTEKE DKVKHIKQEP VESSLGLSNG VSDLSPEYAV LTSTIKNEVD STVNIIGQSH 190 200 210 220 230 240 LDSNIENQEI VTNPPDICQV VEVTTESDEQ PVSMSELYPL QISPVSSYAE SETTDSVPSD 250 260 270 280 290 300 EESAEGRPHW RKRNIEGKQY LSNMGTRGSY LLPGMASFVT SNKPDLQVTI KEESNPVPYN 310 320 330 340 SSWPPFQDLP LSSSMTPASS SSRPDRETRA SVIKKTSDIT QARVKSC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of a cDNA coding for human IRF-2." Itoh S., Harada H., Fujita T., Mimura T., Taniguchi T. Nucleic Acids Res. 17:8372-8372(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: T-cell.
[2]	"Human interferon regulatory factor 2 gene. Intron-exon organization and functional analysis of 5'-flanking region." Cha Y., Deisseroth A.B. J. Biol. Chem. 269:5279-5287(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[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: Trachea.
[5]	"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] (ISOFORM 1).
[6]	"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].
[7]	Mural R.J., Istrail S., Sutton 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].
[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] (ISOFORM 1). Tissue: Skin.
[9]	"The integrated activities of IRF-2 (HiNF-M), CDP/cut (HiNF-D) and H4TF-2 (HiNF-P) regulate transcription of a cell cycle controlled human histone H4 gene: mechanistic differences between distinct H4 genes." Aziz F., van Wijnen A.J., Vaughan P.S., Wu S., Shakoori A.R., Lian J.B., Soprano K.J., Stein J.L., Stein G.S. Mol. Biol. Rep. 25:1-12(1998) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING, FUNCTION AS AN ACTIVATOR.
[10]	"Molecular characterization of celtix-1, a bromodomain protein interacting with the transcription factor interferon regulatory factor 2." Staal A., Enserink J.M., Stein J.L., Stein G.S., van Wijnen A.J. J. Cell. Physiol. 185:269-279(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BRD7.
[11]	"Cloning of an interferon regulatory factor 2 isoform with different regulatory ability." Koenig Merediz S.A., Schmidt M., Hoppe G.J., Alfken J., Meraro D., Levi B.Z., Neubauer A., Wittig B. Nucleic Acids Res. 28:4219-4224(2000) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING.
[12]	"Interferon regulatory factor-2 regulates cell growth through its acetylation." Masumi A., Yamakawa Y., Fukazawa H., Ozato K., Komuro K. J. Biol. Chem. 278:25401-25407(2003) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT LYS-75 AND LYS-78, INTERACTION WITH CREBBP, FUNCTION, MASS SPECTROMETRY, MUTAGENESIS OF LYS-75 AND LYS-78.
[13]	"Identification of novel co-repressor molecules for interferon regulatory factor-2." Childs K.S., Goodbourn S. Nucleic Acids Res. 31:3016-3026(2003) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING, INTERACTION WITH IRF2BP1 AND IRF2BP2.
[14]	"Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells." Oshima S., Nakamura T., Namiki S., Okada E., Tsuchiya K., Okamoto R., Yamazaki M., Yokota T., Aida M., Yamaguchi Y., Kanai T., Handa H., Watanabe M. Mol. Cell. Biol. 24:6298-6310(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[15]	"Regulation of IRF2 transcriptional activity by its sumoylation." Han K.-J., Jiang L., Shu H.-B. Biochem. Biophys. Res. Commun. 372:772-778(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-137; LYS-166 AND LYS-293, FUNCTION, MUTAGENESIS OF LYS-137; LYS-166 AND LYS-293.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X15949 mRNA. Translation: CAA34073.1. BT007264 mRNA. Translation: AAP35928.1. AK312953 mRNA. Translation: BAG35793.1. CR457077 mRNA. Translation: CAG33358.1. AC099343 Genomic DNA. No translation available. CH471056 Genomic DNA. Translation: EAX04677.1. CH471056 Genomic DNA. Translation: EAX04678.1. CH471056 Genomic DNA. Translation: EAX04680.1. BC015803 mRNA. Translation: AAH15803.1.
IPI	IPI00293657.
PIR	A53340.
RefSeq	NP_002190.2. NM_002199.3.
UniGene	Hs.654566.
3D structure databases
ProteinModelPortal	P14316.
ModBase	Search...
Protein-protein interaction databases
IntAct	P14316. 14 interactions.
STRING	9606.ENSP00000377218.
PTM databases
PhosphoSite	P14316.
Polymorphism databases
DMDM	20141499.
Proteomic databases
PaxDb	P14316.
PRIDE	P14316.
Protocols and materials databases
DNASU	3660.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000393593; ENSP00000377218; ENSG00000168310.
GeneID	3660.
KEGG	hsa:3660.
UCSC	uc003iwf.4. human.
Organism-specific databases
CTD	3660.
GeneCards	GC04M185308.
H-InvDB	HIX0004671.
HGNC	HGNC:6117. IRF2.
HPA	CAB032306. HPA030813.
MIM	147576. gene.
neXtProt	NX_P14316.
PharmGKB	PA29916.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG41436.
HOGENOM	HOG000037937.
HOVERGEN	HBG003455.
InParanoid	P14316.
KO	K10153.
OMA	SWPPFPD.
OrthoDB	EOG4VT5Z4.
PhylomeDB	P14316.
Enzyme and pathway databases
Reactome	REACT_604. Hemostasis. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P14316.
Bgee	P14316.
CleanEx	HS_IRF2.
Genevestigator	P14316.
GermOnline	ENSG00000168310. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR017431. Interferon_reg_fac-1/2. IPR019817. Interferon_reg_fac_CS. IPR001346. Interferon_reg_fact_DNA-bd_dom. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF00605. IRF. 1 hit. [Graphical view]
PIRSF	PIRSF038196. IFN_RF1/2. 1 hit.
PRINTS	PR00267. INTFRNREGFCT.
SMART	SM00348. IRF. 1 hit. [Graphical view]
PROSITE	PS00601. IRF_1. 1 hit. PS51507. IRF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	3660.
NextBio	14315.
SOURCE	Search...

Entry information

Entry name

IRF2_HUMAN

Accession

Primary (citable) accession number: P14316
Secondary accession number(s): D6RCK5 , H0Y8S3, Q6IAS7, Q96B99

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	February 11, 2002
Last modified:	May 1, 2013
This is version 128 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.