P70434 (IRF7_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interferon regulatory factor 7
Short name=IRF-7

Gene names

Name:

Irf7

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	457 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages. Ref.3 Ref.4 Ref.5 Ref.9
Enzyme regulation	In the absence of viral infection, maintained as a monomer in an autoinhibited state and phosphorylation disrupts this autoinhibition leading to the liberation of the DNA-binding and dimerization activities and its nuclear localization where it can activate type I IFN and ISG genes.
Subunit structure	Monomer. Homodimer; phosphorylation-induced. Heterodimer with IRF3. Interacts with TICAM1 and TICAM2. Interacts with rotavirus A NSP1; this interaction leads to the proteasome-dependent degradation of IRF7. Interacts with Epstein-Barr virus LF2. Interacts with MYD88 AND TRAF6. Ref.4
Subcellular location	Nucleus. Cytoplasm. Note: The phosphorylated and active form accumulates selectively in the nucleus. Ref.4
Induction	By type I interferon (IFN) and viruses.
Post-translational modification	Acetylation inhibits its DNA-binding ability and activity By similarity. In response to a viral infection, phosphorylated by TBK1 and IKBKE1. Phosphorylation, and subsequent activation is inhibited by vaccinia virus protein E3. In TLR7- and TLR9-mediated signaling pathway, phosphorylated by IRAK1 By similarity. Ref.3 Ref.4 TRAF6-mediated ubiquitination is required for IRF7 activation. Sumoylated by TRIM28, which inhibits its transactivation activity By similarity.
Sequence similarities	Belongs to the IRF family. Contains 1 IRF tryptophan pentad repeat DNA-binding domain.

Ontologies

Keywords
Biological process	Immunity Innate immunity Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Ligand	DNA-binding
Molecular function	Activator
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	immunoglobulin mediated immune response Inferred from mutant phenotype Ref.5. Source: MGI innate immune response Inferred from electronic annotation. Source: UniProtKB-KW interferon-alpha production Inferred from mutant phenotype Ref.5. Source: UniProtKB interferon-beta production Inferred from mutant phenotype Ref.5. Source: UniProtKB positive regulation of interferon-alpha production Traceable author statement Ref.7. Source: UniProtKB positive regulation of interferon-beta production Traceable author statement Ref.7. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of type I interferon-mediated signaling pathway Inferred from mutant phenotype PubMed 17618271. Source: MGI protein acetylation Inferred from electronic annotation. Source: Compara protein phosphorylation Inferred from electronic annotation. Source: Compara regulation of MyD88-dependent toll-like receptor signaling pathway Inferred from mutant phenotype Ref.5. Source: UniProtKB regulation of MyD88-independent toll-like receptor signaling pathway Inferred from mutant phenotype Ref.5. Source: UniProtKB regulation of adaptive immune response Inferred from sequence or structural similarity. Source: UniProtKB type I interferon biosynthetic process Inferred from mutant phenotype Ref.5. Source: MGI
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Inferred from sequence or structural similarity. Source: UniProtKB RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara RNA polymerase II core promoter sequence-specific DNA binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Chuk	Q60680	3	EBI-997907,EBI-646245

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 457

457

Interferon regulatory factor 7

PRO_0000154563

Regions

DNA binding

9 – 126

118

IRF tryptophan pentad repeat

Amino acid modifications

Modified residue

92

1

N6-acetyllysine; by KAT2A and KAT2B By similarity

Modified residue

425

1

Phosphoserine Probable

Modified residue

426

1

Phosphoserine Probable

Modified residue

429

1

Phosphoserine Probable

Modified residue

431

1

Phosphoserine; by TBK1 and IKKE By similarity

Modified residue

437

1

Phosphoserine Probable

Modified residue

438

1

Phosphoserine Probable

Cross-link

398

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Cross-link

400

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Experimental info

Mutagenesis

425

1

S → A: Strongly decreased transcriptional activation in response to viral infection; when associated with A-426. Ref.3

Mutagenesis

425

1

S → D: Strongly decreased transcriptional activation in response to viral infection; when associated with D-426. Ref.3

Mutagenesis

426

1

S → A: Strongly decreased transcriptional activation in response to viral infection; when associated with A-425. Ref.3

Mutagenesis

426

1

S → D: Strongly decreased transcriptional activation in response to viral infection; when associated with D-425. Ref.3

Mutagenesis

427

1

L → A: Strongly decreased transcriptional activation in response to viral infection. Ref.3

Mutagenesis

427

1

L → D: No effect on transcriptional activation in response to viral infection. Ref.3

Mutagenesis

429

1

S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-430 and A-431. Ref.3

Mutagenesis

429

1

S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-430 and A-431. Ref.3

Mutagenesis

430

1

S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-429 and A-431.

Mutagenesis

430

1

S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-429 and A-431.

Mutagenesis

431

1

S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-429 and A-430. Ref.3

Mutagenesis

431

1

S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-429 and A-430. Ref.3

Mutagenesis

437

1

S → A: Almost complete loss of transcriptional activation; when associated with A-438. Ref.3

Mutagenesis

437

1

S → D: Increased transcriptional activation; when associated with D-438. Ref.3

Mutagenesis

438

1

S → A: Almost complete loss of transcriptional activation; when associated with A-437. Ref.3

Mutagenesis

438

1

S → D: Increased transcriptional activation; when associated with D-437. Ref.3

Mutagenesis

441

1

S → A: Almost no effect on transcriptional activation in response to viral infection. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

457

Helix Strand Turn

Details...

Helix

12 – 22

11

Beta strand

29 – 32

4

Beta strand

37 – 41

5

Helix

52 – 55

4

Helix

56 – 64

9

Helix

77 – 85

9

Helix

88 – 100

13

Beta strand

105 – 111

7

Beta strand

119 – 124

6

Sequences

	Sequence		Length	Mass (Da)
	P70434 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: 30B102C668F56142	FASTA	457	51,222
	10 20 30 40 50 60 MAEVRGVQRV LFGDWLLGEV SSGQYEGLQW LNEARTVFRV PWKHFGRRDL DEEDAQIFKA 70 80 90 100 110 120 WAVARGRWPP SGVNLPPPEA EAAERRERRG WKTNFRCALH STGRFILRQD NSGDPVDPHK 130 140 150 160 170 180 VYELSRELGS TVGPATENRE EVSLSNALPT QGVSPGSFLA RENAGLQTPS PLLSSDAGDL 190 200 210 220 230 240 LLQVLQYSHI LESESGADPV PPQAPGQEQD RVYEEPYAAW QVEAVPSPRP QQPALTERSL 250 260 270 280 290 300 GFLDVTIMYK GRTVLQAVVG HPRCVFLYSP MAPAVRTSEP QPVIFPSPAE LPDQKQLHYT 310 320 330 340 350 360 ETLLQHVSPG LQLELRGPSL WALRMGKCKV YWEVGSPMGT TGPSTPPQLL ERNRHTPIFD 370 380 390 400 410 420 FSTFFRELEE FRARRRQGSP HYTIYLGFGQ DLSAGRPKEK TLILVKLEPW VCKAYLEGVQ 430 440 450 REGVSSLDSS SLGLCLSSTN SLYEDIEHFL MDLGQWP

References

[1]	Grossman A., Nicholl J., Antonio L., Luethy R., Suggs S., Sutherland G.R., Mak T.W. Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c. Tissue: Spleen.
[2]	"Structure and function of IRF-7." Zhang L., Pagano J.S. J. Interferon Cytokine Res. 22:95-101(2002) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[3]	"Regulatory serine residues mediate phosphorylation-dependent and phosphorylation-independent activation of interferon regulatory factor 7." Caillaud A., Hovanessian A.G., Levy D.E., Marie I.J. J. Biol. Chem. 280:17671-17677(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-429; SER-431; SER-437; SER-438 AND SER-441, MUTAGENESIS OF SER-425; SER-426; LEU-427; SER-429; SER-431; SER-437; SER-438 AND SER-441.
[4]	"Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6." Kawai T., Sato S., Ishii K.J., Coban C., Hemmi H., Yamamoto M., Terai K., Matsuda M., Inoue J., Uematsu S., Takeuchi O., Akira S. Nat. Immunol. 5:1061-1068(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, UBIQUITINATION, INTERACTION WITH MYD88 AND TRAF6.
[5]	"IRF-7 is the master regulator of type-I interferon-dependent immune responses." Honda K., Yanai H., Negishi H., Asagiri M., Sato M., Mizutani T., Shimada N., Ohba Y., Takaoka A., Yoshida N., Taniguchi T. Nature 434:772-777(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and control of anti-tumor activity in primary macrophages." Solis M., Goubau D., Romieu-Mourez R., Genin P., Civas A., Hiscott J. Biochem. Pharmacol. 72:1469-1476(2006) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[7]	"Type I interferon gene induction by the interferon regulatory factor family of transcription factors." Honda K., Takaoka A., Taniguchi T. Immunity 25:349-360(2006) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[8]	Erratum Honda K., Takaoka A., Taniguchi T. Immunity 25:849-849(2006)
[9]	"Interferon regulatory factor IRF-7 induces the antiviral alpha interferon response and protects against lethal West Nile virus infection." Daffis S., Samuel M.A., Suthar M.S., Keller B.C., Gale M. Jr., Diamond M.S. J. Virol. 82:8465-8475(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Regulation of immunity and oncogenesis by the IRF transcription factor family." Savitsky D., Tamura T., Yanai H., Taniguchi T. Cancer Immunol. Immunother. 59:489-510(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[11]	"IRF7: activation, regulation, modification and function." Ning S., Pagano J.S., Barber G.N. Genes Immun. 12:399-414(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U73037 mRNA. Translation: AAB18626.1.

IPI

IPI00109286.

RefSeq

NP_058546.1. NM_016850.3.

UniGene

Mm.3233.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3QU3	X-ray	1.30	A/B/C	1-134	[»]

ProteinModelPortal

P70434.

SMR

P70434. Positions 9-130, 243-417.

ModBase

Search...

Protein-protein interaction databases

IntAct

P70434. 3 interactions.

PTM databases

PhosphoSite

P70434.

Proteomic databases

PaxDb

P70434.

PRIDE

P70434.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000026571; ENSMUSP00000026571; ENSMUSG00000025498.

GeneID

54123.

KEGG

mmu:54123.

Organism-specific databases

CTD

3665.

MGI

MGI:1859212. Irf7.

Phylogenomic databases

eggNOG

NOG39245.

HOGENOM

HOG000111812.

HOVERGEN

HBG105600.

InParanoid

P70434.

KO

K09447.

OMA

ELPDQKQ.

OrthoDB

EOG4Z8XWR.

Gene expression databases

ArrayExpress

P70434.

Bgee

P70434.

CleanEx

MM_IRF7.

Genevestigator

P70434.

GermOnline

ENSMUSG00000025498. Mus musculus.

Family and domain databases

Gene3D

1.10.10.10. 1 hit.
2.60.200.10. 1 hit.

InterPro

IPR019817. Interferon_reg_fac_CS.
IPR001346. Interferon_reg_fact_DNA-bd_dom.
IPR019471. Interferon_reg_factor-3.
IPR017855. SMAD_dom-like.
IPR008984. SMAD_FHA_domain.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

Pfam

PF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
[Graphical view]

PRINTS

PR00267. INTFRNREGFCT.

SMART

SM00348. IRF. 1 hit.
[Graphical view]

SUPFAM

SSF49879. SMAD_FHA. 1 hit.

PROSITE

PS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

310909.

SOURCE

Search...

Entry information

Entry name

IRF7_MOUSE

Accession

Primary (citable) accession number: P70434

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	February 1, 1997
Last modified:	May 1, 2013
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program