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Q15306 (IRF4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interferon regulatory factor 4

Short name=IRF-4
Alternative name(s):
Lymphocyte-specific interferon regulatory factor
Short name=LSIRF
Multiple myeloma oncogene 1
NF-EM5
Gene names
Name:IRF4
Synonyms:MUM1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length451 AA.
Sequence statusComplete.
Protein existenceEvidence 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 By similarity.

Subunit structure

Interacts with the BATF-JUNB heterodimer. Interacts with BATF (via bZIP domain); the interaction is direct By similarity. Interacts with SPIB and DEF6. Ref.5 Ref.6

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 By similarity.

Involvement in disease

Multiple myeloma (MM) [MIM:254500]: A malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia.
Note: The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving IRF4 has been found in multiple myeloma. Translocation t(6;14)(p25;q32) with the IgH locus.

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
Chromosomal rearrangement
   LigandDNA-binding
   Molecular functionActivator
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell activation

Non-traceable author statement PubMed 12374808. Source: UniProtKB

T-helper 17 cell lineage commitment

Inferred from sequence or structural similarity. Source: UniProtKB

cytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

defense response to protozoan

Inferred from sequence or structural similarity. Source: UniProtKB

histone H3 acetylation

Inferred from electronic annotation. Source: Ensembl

histone H4 acetylation

Inferred from electronic annotation. Source: Ensembl

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

myeloid dendritic cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of toll-like receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of DNA binding

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-10 biosynthetic process

Inferred from direct assay PubMed 12374808. Source: UniProtKB

positive regulation of interleukin-13 biosynthetic process

Inferred from direct assay PubMed 12374808. Source: UniProtKB

positive regulation of interleukin-2 biosynthetic process

Inferred from direct assay PubMed 12374808. Source: UniProtKB

positive regulation of interleukin-4 biosynthetic process

Inferred from direct assay PubMed 12374808. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12374808. Source: UniProtKB

regulation of T-helper cell differentiation

Non-traceable author statement PubMed 12374808. 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

nuclear nucleosome

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred by curator PubMed 12374808. Source: UniProtKB

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 21903422. Source: IntAct

protein-lysine N-methyltransferase activity

Inferred from electronic annotation. Source: Ensembl

regulatory region DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

transcription factor binding

Non-traceable author statement PubMed 12374808. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q15306-1)

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: Q15306-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 451451Interferon regulatory factor 4
PRO_0000154556

Regions

DNA binding21 – 129109IRF tryptophan pentad repeat

Amino acid modifications

Modified residue4471Phosphoserine; by ROCK2 By similarity
Modified residue4481Phosphoserine; by ROCK2 By similarity

Natural variations

Alternative sequence1651Missing in isoform 2.
VSP_002755

Experimental info

Sequence conflict3001Q → H in AAB37258. Ref.2
Sequence conflict3061K → N in AAB37258. Ref.2
Sequence conflict3331R → T in AAB37258. Ref.2

Secondary structure

......................... 451
Helix Strand Turn

Details...

Sequences

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

Last modified November 1, 1997. Version 1.
Checksum: 17CD1327C6F5BFFA

FASTA45151,772
        10         20         30         40         50         60 
MNLEGGGRGG EFGMSAVSCG NGKLRQWLID QIDSGKYPGL VWENEEKSIF RIPWKHAGKQ 

        70         80         90        100        110        120 
DYNREEDAAL FKAWALFKGK FREGIDKPDP PTWKTRLRCA LNKSNDFEEL VERSQLDISD 

       130        140        150        160        170        180 
PYKVYRIVPE GAKKGAKQLT LEDPQMSMSH PYTMTTPYPS LPAQQVHNYM MPPLDRSWRD 

       190        200        210        220        230        240 
YVPDQPHPEI PYQCPMTFGP RGHHWQGPAC ENGCQVTGTF YACAPPESQA PGVPTEPSIR 

       250        260        270        280        290        300 
SAEALAFSDC RLHICLYYRE ILVKELTTSS PEGCRISHGH TYDASNLDQV LFPYPEDNGQ 

       310        320        330        340        350        360 
RKNIEKLLSH LERGVVLWMA PDGLYAKRLC QSRIYWDGPL ALCNDRPNKL ERDQTCKLFD 

       370        380        390        400        410        420 
TQQFLSELQA FAHHGRSLPR FQVTLCFGEE FPDPQRQRKL ITAHVEPLLA RQLYYFAQQN 

       430        440        450 
SGHFLRGYDL PEHISNPEDY HRSIRHSSIQ E 

« Hide

Isoform 2 [UniParc].

Checksum: 85056FCEB84B0EBC
Show »

FASTA45051,644

References

« Hide 'large scale' references
[1]"Cloning of human lymphocyte-specific interferon regulatory factor (hLSIRF/hIRF4) and mapping of the gene to 6p23-p25."
Grossman A., Mittrucker H.W., Nicholl J., Suzuki A., Chung S., Antonio L., Sugga S., Sutherland G.R., Siderovski D.P., Mak T.W.
Genomics 37:229-233(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Spleen.
[2]"Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma."
Iida S., Rao P.H., Butler M., Corradini P., Boccadoro M., Klein B., Chaganti R.S.K., Dalla-Favera R.
Nat. Genet. 17:226-230(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN MULTIPLE MYELOMA.
Tissue: Spleen.
[3]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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.
[5]"SPI-B activates transcription via a unique proline, serine, and threonine domain and exhibits DNA binding affinity differences from PU.1."
Rao S., Matsumura A., Yoon J., Simon M.C.
J. Biol. Chem. 274:11115-11124(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SPIB.
[6]"Molecular cloning of IBP, a SWAP-70 homologous GEF, which is highly expressed in the immune system."
Gupta S., Lee A.E., Hu C., Fanzo J.C., Goldberg I., Cattoretti G., Pernis A.B.
Hum. Immunol. 64:389-401(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DEF6.
Tissue: Lymph node.
[7]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Solution structure of the IRF domain of human interferon regulator factor 4."
RIKEN structural genomics initiative (RSGI)
Submitted (OCT-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 22-130.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U52682 mRNA. Translation: AAC50779.1.
U63738 mRNA. Translation: AAB37258.1.
AL589962, AL365272 Genomic DNA. Translation: CAH71554.1.
AL365272, AL589962 Genomic DNA. Translation: CAH72537.1.
BC015752 mRNA. Translation: AAH15752.1.
CCDSCCDS4469.1. [Q15306-1]
RefSeqNP_001182215.1. NM_001195286.1. [Q15306-2]
NP_002451.2. NM_002460.3. [Q15306-1]
UniGeneHs.401013.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2DLLNMR-A23-130[»]
ProteinModelPortalQ15306.
SMRQ15306. Positions 18-130, 252-446.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109870. 22 interactions.
IntActQ15306. 10 interactions.
STRING9606.ENSP00000370343.

PTM databases

PhosphoSiteQ15306.

Polymorphism databases

DMDM2497445.

Proteomic databases

MaxQBQ15306.
PaxDbQ15306.
PRIDEQ15306.

Protocols and materials databases

DNASU3662.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000380956; ENSP00000370343; ENSG00000137265. [Q15306-1]
GeneID3662.
KEGGhsa:3662.
UCSCuc003msz.4. human. [Q15306-1]
uc003mtb.4. human. [Q15306-2]

Organism-specific databases

CTD3662.
GeneCardsGC06P000391.
HGNCHGNC:6119. IRF4.
HPACAB013508.
HPA002038.
HPA002698.
MIM254500. phenotype.
601900. gene.
neXtProtNX_Q15306.
PharmGKBPA29918.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39558.
HOGENOMHOG000010107.
HOVERGENHBG003072.
InParanoidQ15306.
KOK09445.
OMADNGQRKN.
OrthoDBEOG7CCBR1.
PhylomeDBQ15306.
TreeFamTF328512.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressQ15306.
BgeeQ15306.
CleanExHS_IRF4.
HS_MUM1.
GenevestigatorQ15306.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProIPR019817. 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]
PfamPF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
[Graphical view]
PRINTSPR00267. INTFRNREGFCT.
SMARTSM00348. IRF. 1 hit.
[Graphical view]
SUPFAMSSF49879. SSF49879. 1 hit.
PROSITEPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ15306.
GeneWikiIRF4.
GenomeRNAi3662.
NextBio14323.
PROQ15306.
SOURCESearch...

Entry information

Entry nameIRF4_HUMAN
AccessionPrimary (citable) accession number: Q15306
Secondary accession number(s): Q5VUI7, Q99660
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: July 9, 2014
This is version 150 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM