Q64287 (IRF4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interferon regulatory factor 4
Short name=IRF-4

Alternative name(s):
Lymphocyte-specific interferon regulatory factor
Short name=LSIRF
NF-EM5
PU.1 interaction partner
Transcriptional activator PIP

Gene names

Name:	Irf4
Synonyms:	Spip

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	450 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional activator. Binds to the interferon-stimulated response element (ISRE) of the MHC class I promoter. Binds the immunoglobulin lambda light chain enhancer, together with PU.1. Probably plays a role in ISRE-targeted signal transduction mechanisms specific to lymphoid cells. Involved in CD8+ dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF4 and activation of genes. Ref.5 Ref.6 Ref.7
Subunit structure	Interacts with SPIB and DEF6 By similarity. Interacts with the BATF-JUNB heterodimer. Interacts with BATF (via bZIP domain); the interaction is direct. Ref.5 Ref.6 Ref.7
Subcellular location	Nucleus.
Tissue specificity	Lymphoid cells.
Induction	Not induced by interferons.
Post-translational modification	Phosphorylation by ROCK2 regulates IL-17 and IL-21 production.
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
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	T-helper 17 cell lineage commitment Inferred from mutant phenotype Ref.7. Source: UniProtKB defense response to protozoan Inferred from mutant phenotype Ref.5. Source: UniProtKB histone H3 acetylation Inferred from mutant phenotype PubMed 16428437. Source: MGI histone H4 acetylation Inferred from mutant phenotype PubMed 16428437. Source: MGI myeloid dendritic cell differentiation Inferred from mutant phenotype Ref.5. Source: UniProtKB negative regulation of toll-like receptor signaling pathway Inferred from mutant phenotype PubMed 16236719. Source: MGI peptidyl-lysine methylation Inferred from direct assay PubMed 22948820. Source: GOC positive regulation of DNA binding Inferred from mutant phenotype PubMed 16428437. Source: MGI positive regulation of interleukin-10 biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-13 biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-2 biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-4 biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 16428437. Source: MGI positive regulation of transcription, DNA-templated Inferred from sequence or structural similarity. Source: UniProtKB protein methylation Inferred from direct assay PubMed 22948820. Source: UniProtKB transcription, DNA-templated Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Ensembl nuclear nucleosome Inferred from direct assay PubMed 16428437. Source: MGI
Molecular_function	protein binding Inferred from physical interaction Ref.7Ref.6Ref.5. Source: UniProtKB protein-lysine N-methyltransferase activity Inferred from direct assay PubMed 22948820. Source: UniProtKB regulatory region DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding Inferred from direct assay Ref.7Ref.6Ref.5. Source: UniProtKB sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.7Ref.6Ref.5. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Batf	O35284	7	EBI-6398485,EBI-6398523

Alternative products

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

Isoform 1 (identifier: Q64287-1)

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: Q64287-2)

The sequence of this isoform differs from the canonical sequence as follows:
     165-165: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 450	450	Interferon regulatory factor 4		PRO_0000154557
Regions
	DNA binding	21 – 129	109	IRF tryptophan pentad repeat
Amino acid modifications
	Modified residue	446	1	Phosphoserine; by ROCK2 Ref.4
	Modified residue	447	1	Phosphoserine; by ROCK2 Ref.4
Natural variations
	Alternative sequence	165	1	Missing in isoform 2.		VSP_002756

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 5FD94CA6C453869C	FASTA	450	51,577
	10 20 30 40 50 60 MNLETGSRGS EFGMSAVSCG NGKLRQWLID QIDSGKYPGL VWENEEKSVF RIPWKHAGKQ 70 80 90 100 110 120 DYNREEDAAL FKAWALFKGK FREGIDKPDP PTWKTRLRCA LNKSNDFEEL VERSQLDISD 130 140 150 160 170 180 PYKVYRIVPE GAKKGAKQLT LDDTQMAMGH PYPMTAPYGS LPAQQVHNYM MPPHDRSWRD 190 200 210 220 230 240 YAPDQSHPEI PYQCPVTFGP RGHHWQGPSC ENGCQVTGTF YACAPPESQA PGIPIEPSIR 250 260 270 280 290 300 SAEALALSDC RLHICLYYRD ILVKELTTTS PEGCRISHGH TYDVSNLDQV LFPYPDDNGQ 310 320 330 340 350 360 RKNIEKLLSH LERGLVLWMA PDGLYAKRLC QSRIYWDGPL ALCSDRPNKL ERDQTCKLFD 370 380 390 400 410 420 TQQFLSELQV FAHHGRPAPR FQVTLCFGEE FPDPQRQRKL ITAHVEPLLA RQLYYFAQQN 430 440 450 TGHFLRGYEL PEHVTTPDYH RSLRHSSIQE
	Isoform 2 [UniParc]. Checksum: C4E4A0DC04AA8A52	FASTA	449	51,449
	10 20 30 40 50 60 MNLETGSRGS EFGMSAVSCG NGKLRQWLID QIDSGKYPGL VWENEEKSVF RIPWKHAGKQ 70 80 90 100 110 120 DYNREEDAAL FKAWALFKGK FREGIDKPDP PTWKTRLRCA LNKSNDFEEL VERSQLDISD 130 140 150 160 170 180 PYKVYRIVPE GAKKGAKQLT LDDTQMAMGH PYPMTAPYGS LPAQVHNYMM PPHDRSWRDY 190 200 210 220 230 240 APDQSHPEIP YQCPVTFGPR GHHWQGPSCE NGCQVTGTFY ACAPPESQAP GIPIEPSIRS 250 260 270 280 290 300 AEALALSDCR LHICLYYRDI LVKELTTTSP EGCRISHGHT YDVSNLDQVL FPYPDDNGQR 310 320 330 340 350 360 KNIEKLLSHL ERGLVLWMAP DGLYAKRLCQ SRIYWDGPLA LCSDRPNKLE RDQTCKLFDT 370 380 390 400 410 420 QQFLSELQVF AHHGRPAPRF QVTLCFGEEF PDPQRQRKLI TAHVEPLLAR QLYYFAQQNT 430 440 GHFLRGYELP EHVTTPDYHR SLRHSSIQE

References

[1]	"Pip, a novel IRF family member, is a lymphoid-specific, PU.1-dependent transcriptional activator." Eisenbeis C.F., Singh H., Storb U. Genes Dev. 9:1377-1387(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c.
[2]	"Molecular cloning of LSIRF, a lymphoid-specific member of the interferon regulatory factor family that binds the interferon-stimulated response element (ISRE)." Matsuyama T., Grossman A., Mittruecker H.-W., Siderovski D.P., Kiefer F., Kawakami T., Richardson C.D., Taniguchi T., Yoshinaga S.K., Mak T.W. Nucleic Acids Res. 23:2127-2136(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Strain: 129/SvJ and C57BL/6. Tissue: Spleen.
[3]	Lubec G., Sunyer B., Chen W.-Q. Submitted (JAN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 65-72, IDENTIFICATION BY MASS SPECTROMETRY. Strain: OF1. Tissue: Hippocampus.
[4]	"Phosphorylation of IRF4 by ROCK2 regulates IL-17 and IL-21 production and the development of autoimmunity in mice." Biswas P.S., Gupta S., Chang E., Song L., Stirzaker R.A., Liao J.K., Bhagat G., Pernis A.B. J. Clin. Invest. 120:3280-3295(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-446 AND SER-447.
[5]	"Compensatory dendritic cell development mediated by BATF-IRF interactions." Tussiwand R., Lee W.L., Murphy T.L., Mashayekhi M., Kc W., Albring J.C., Satpathy A.T., Rotondo J.A., Edelson B.T., Kretzer N.M., Wu X., Weiss L.A., Glasmacher E., Li P., Liao W., Behnke M., Lam S.S., Aurthur C.T. , Leonard W.J., Singh H., Stallings C.L., Sibley L.D., Schreiber R.D., Murphy K.M. Nature 490:502-507(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH BATF.
[6]	"BATF-JUN is critical for IRF4-mediated transcription in T cells." Li P., Spolski R., Liao W., Wang L., Murphy T.L., Murphy K.M., Leonard W.J. Nature 490:543-546(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH BATF.
[7]	"A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes." Glasmacher E., Agrawal S., Chang A.B., Murphy T.L., Zeng W., Vander Lugt B., Khan A.A., Ciofani M., Spooner C., Rutz S., Hackney J., Nurieva R., Escalante C.R., Ouyang W., Littman D.R., Murphy K.M., Singh H. Science 338:975-980(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH BATF.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U34307 mRNA. Translation: AAA75283.1. U11692 mRNA. Translation: AAA75309.1. U20949 Genomic DNA. Translation: AAA75316.1. U20949 Genomic DNA. Translation: AAA75317.1.
CCDS	CCDS26419.1. [Q64287-1]
PIR	S57837.
RefSeq	NP_038702.1. NM_013674.1. [Q64287-1] XP_006516623.1. XM_006516560.1. [Q64287-2]
UniGene	Mm.4677.
3D structure databases
ProteinModelPortal	Q64287.
SMR	Q64287. Positions 18-130, 252-418.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	200786. 3 interactions.
DIP	DIP-59740N.
IntAct	Q64287. 1 interaction.
PTM databases
PhosphoSite	Q64287.
Proteomic databases
PRIDE	Q64287.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000021784; ENSMUSP00000021784; ENSMUSG00000021356. [Q64287-1] ENSMUST00000110307; ENSMUSP00000105936; ENSMUSG00000021356. [Q64287-2]
GeneID	16364.
KEGG	mmu:16364.
UCSC	uc007pyz.1. mouse. [Q64287-1]
Organism-specific databases
CTD	3662.
MGI	MGI:1096873. Irf4.
Phylogenomic databases
eggNOG	NOG39558.
GeneTree	ENSGT00740000114956.
HOGENOM	HOG000010107.
HOVERGEN	HBG003072.
InParanoid	Q64287.
KO	K09445.
OMA	DNGQRKN.
OrthoDB	EOG7CCBR1.
PhylomeDB	Q64287.
TreeFam	TF328512.
Gene expression databases
ArrayExpress	Q64287.
Bgee	Q64287.
CleanEx	MM_IRF4.
Genevestigator	Q64287.
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. SSF49879. 1 hit.
PROSITE	PS00601. IRF_1. 1 hit. PS51507. IRF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	289474.
PRO	Q64287.
SOURCE	Search...

Entry information

Entry name

IRF4_MOUSE

Accession

Primary (citable) accession number: Q64287
Secondary accession number(s): Q60802

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	July 9, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program