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P14316 (IRF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interferon regulatory factor 2

Short name=IRF-2
Gene names
Name:IRF2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length349 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Ref.12

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 processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   LigandDNA-binding
   Molecular functionActivator
Repressor
   PTMAcetylation
Isopeptide bond
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processblood coagulation

Traceable author statement. Source: Reactome

cell proliferation

Traceable author statement PubMed 8438157. Source: ProtInc

cytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

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

regulation of transcription, DNA-templated

Inferred from mutant phenotype Ref.9. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

type I interferon signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

   Molecular_functionDNA binding

Inferred from direct assay Ref.9. Source: UniProtKB

protein binding

Inferred from physical interaction 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...

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 349349Interferon regulatory factor 2
PRO_0000154549

Regions

DNA binding5 – 113109IRF tryptophan pentad repeat Ref.9

Amino acid modifications

Modified residue751N6-acetyllysine Ref.12
Modified residue781N6-acetyllysine Ref.12
Cross-link137Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.15
Cross-link166Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.15
Cross-link293Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.15

Natural variations

Alternative sequence177 – 1782Missing in isoform 2.
VSP_043965

Experimental info

Mutagenesis751K → R: Diminished acetylation by both CREBBP/p300 and PCAF. Greatly reduced enhancement of H4 promoter activity. Ref.12
Mutagenesis781K → 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
Mutagenesis1371K → 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
Mutagenesis1661K → 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
Mutagenesis2931K → 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 conflict581W → R in CAA34073. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 11, 2002. Version 2.
Checksum: 6298341652466560

FASTA34939,354
        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 

« Hide

Isoform 2 (IRF-2s) (IRF-2[S]) [UniParc].

Checksum: EE67F41029BFD6BD
Show »

FASTA34739,156

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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, IDENTIFICATION BY 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.
CCDSCCDS3835.1. [P14316-1]
PIRA53340.
RefSeqNP_002190.2. NM_002199.3. [P14316-1]
XP_005263041.1. XM_005262984.1. [P14316-2]
UniGeneHs.654566.

3D structure databases

ProteinModelPortalP14316.
SMRP14316. Positions 5-113.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109868. 26 interactions.
IntActP14316. 14 interactions.
STRING9606.ENSP00000377218.

PTM databases

PhosphoSiteP14316.

Polymorphism databases

DMDM20141499.

Proteomic databases

MaxQBP14316.
PaxDbP14316.
PRIDEP14316.

Protocols and materials databases

DNASU3660.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000393593; ENSP00000377218; ENSG00000168310. [P14316-1]
GeneID3660.
KEGGhsa:3660.
UCSCuc003iwf.4. human. [P14316-1]

Organism-specific databases

CTD3660.
GeneCardsGC04M185308.
H-InvDBHIX0004671.
HGNCHGNC:6117. IRF2.
HPACAB032306.
HPA030813.
MIM147576. gene.
neXtProtNX_P14316.
PharmGKBPA29916.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG41436.
HOGENOMHOG000037937.
HOVERGENHBG003455.
InParanoidP14316.
KOK10153.
OMASWPPFPD.
OrthoDBEOG72ZCFD.
PhylomeDBP14316.
TreeFamTF328512.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkP14316.

Gene expression databases

ArrayExpressP14316.
BgeeP14316.
CleanExHS_IRF2.
GenevestigatorP14316.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR017431. Interferon_reg_fac-1/2.
IPR019817. Interferon_reg_fac_CS.
IPR001346. Interferon_reg_fact_DNA-bd_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00605. IRF. 1 hit.
[Graphical view]
PIRSFPIRSF038196. IFN_RF1/2. 1 hit.
PRINTSPR00267. INTFRNREGFCT.
SMARTSM00348. IRF. 1 hit.
[Graphical view]
PROSITEPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiIRF2.
GenomeRNAi3660.
NextBio14315.
PROP14316.
SOURCESearch...

Entry information

Entry nameIRF2_HUMAN
AccessionPrimary (citable) accession number: P14316
Secondary accession number(s): D6RCK5 expand/collapse secondary AC list , H0Y8S3, Q6IAS7, Q96B99
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: February 11, 2002
Last modified: July 9, 2014
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM