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Protein

Interferon regulatory factor 4

Gene

IRF4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi21 – 129IRF tryptophan pentad repeatPROSITE-ProRule annotationAdd BLAST109

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-877300 Interferon gamma signaling
R-HSA-909733 Interferon alpha/beta signaling
SIGNORiQ15306

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:IRF4
Synonyms:MUM1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000137265.14
HGNCiHGNC:6119 IRF4
MIMi601900 gene
neXtProtiNX_Q15306

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Multiple myeloma (MM)1 Publication
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.
Disease descriptionA 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.
See also OMIM:254500

Organism-specific databases

DisGeNETi3662
MalaCardsiIRF4
MIMi254500 phenotype
611724 phenotype
OpenTargetsiENSG00000137265
PharmGKBiPA29918

Polymorphism and mutation databases

BioMutaiIRF4
DMDMi2497445

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001545561 – 451Interferon regulatory factor 4Add BLAST451

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei447Phosphoserine; by ROCK2By similarity1
Modified residuei448Phosphoserine; by ROCK2By similarity1

Post-translational modificationi

Phosphorylation by ROCK2 regulates IL-17 and IL-21 production.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ15306
PaxDbiQ15306
PeptideAtlasiQ15306
PRIDEiQ15306

PTM databases

iPTMnetiQ15306
PhosphoSitePlusiQ15306

Expressioni

Tissue specificityi

Lymphoid cells.

Inductioni

Not induced by interferons.

Gene expression databases

BgeeiENSG00000137265
CleanExiHS_IRF4
HS_MUM1
ExpressionAtlasiQ15306 baseline and differential
GenevisibleiQ15306 HS

Organism-specific databases

HPAiCAB013508
HPA002038
HPA002698

Interactioni

Subunit structurei

Interacts with the BATF-JUNB heterodimer. Interacts with BATF (via bZIP domain); the interaction is direct (By similarity). Interacts with SPIB and DEF6. Directly interacts with NLRP3 in the nucleus of Th2 cells; this interaction enhances IRF4 ability to bind to the IL4 promoter and is required for optimal IRF4-dependent IL4 transcription (By similarity).By similarity2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109870, 24 interactors
IntActiQ15306, 11 interactors
STRINGi9606.ENSP00000370343

Structurei

Secondary structure

1451
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi24 – 34Combined sources11
Beta strandi37 – 39Combined sources3
Beta strandi41 – 47Combined sources7
Beta strandi49 – 53Combined sources5
Beta strandi60 – 62Combined sources3
Helixi64 – 67Combined sources4
Helixi69 – 78Combined sources10
Helixi90 – 103Combined sources14
Beta strandi107 – 109Combined sources3
Turni111 – 113Combined sources3
Beta strandi115 – 120Combined sources6
Beta strandi122 – 127Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DLLNMR-A23-130[»]
ProteinModelPortaliQ15306
SMRiQ15306
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15306

Family & Domainsi

Sequence similaritiesi

Belongs to the IRF family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IES5 Eukaryota
ENOG411023V LUCA
GeneTreeiENSGT00760000119093
HOGENOMiHOG000010107
HOVERGENiHBG003072
InParanoidiQ15306
KOiK09445
OMAiDCRLHIC
OrthoDBiEOG091G067P
PhylomeDBiQ15306
TreeFamiTF328512

Family and domain databases

CDDicd00103 IRF, 1 hit
Gene3Di1.10.10.10, 1 hit
2.60.200.10, 1 hit
InterProiView protein in InterPro
IPR019817 Interferon_reg_fac_CS
IPR001346 Interferon_reg_fact_DNA-bd_dom
IPR019471 Interferon_reg_factor-3
IPR017855 SMAD-like_dom_sf
IPR008984 SMAD_FHA_dom_sf
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PANTHERiPTHR11949 PTHR11949, 1 hit
PfamiView protein in Pfam
PF00605 IRF, 1 hit
PF10401 IRF-3, 1 hit
PRINTSiPR00267 INTFRNREGFCT
SMARTiView protein in SMART
SM00348 IRF, 1 hit
SM01243 IRF-3, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
SSF49879 SSF49879, 1 hit
PROSITEiView protein in PROSITE
PS00601 IRF_1, 1 hit
PS51507 IRF_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15306-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MNLEGGGRGG EFGMSAVSCG NGKLRQWLID QIDSGKYPGL VWENEEKSIF
60 70 80 90 100
RIPWKHAGKQ DYNREEDAAL FKAWALFKGK FREGIDKPDP PTWKTRLRCA
110 120 130 140 150
LNKSNDFEEL VERSQLDISD PYKVYRIVPE GAKKGAKQLT LEDPQMSMSH
160 170 180 190 200
PYTMTTPYPS LPAQQVHNYM MPPLDRSWRD YVPDQPHPEI PYQCPMTFGP
210 220 230 240 250
RGHHWQGPAC ENGCQVTGTF YACAPPESQA PGVPTEPSIR SAEALAFSDC
260 270 280 290 300
RLHICLYYRE ILVKELTTSS PEGCRISHGH TYDASNLDQV LFPYPEDNGQ
310 320 330 340 350
RKNIEKLLSH LERGVVLWMA PDGLYAKRLC QSRIYWDGPL ALCNDRPNKL
360 370 380 390 400
ERDQTCKLFD TQQFLSELQA FAHHGRSLPR FQVTLCFGEE FPDPQRQRKL
410 420 430 440 450
ITAHVEPLLA RQLYYFAQQN SGHFLRGYDL PEHISNPEDY HRSIRHSSIQ

E
Length:451
Mass (Da):51,772
Last modified:November 1, 1997 - v1
Checksum:i17CD1327C6F5BFFA
GO
Isoform 2 (identifier: Q15306-2) [UniParc]FASTAAdd to basket

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

Show »
Length:450
Mass (Da):51,644
Checksum:i85056FCEB84B0EBC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti300Q → H in AAB37258 (PubMed:9326949).Curated1
Sequence conflicti306K → N in AAB37258 (PubMed:9326949).Curated1
Sequence conflicti333R → T in AAB37258 (PubMed:9326949).Curated1

Polymorphismi

Genetic variants in IRF4 define the skin/hair/eye pigmentation variation locus 8 (SHEP8) [MIMi:611724]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair.2 Publications

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002755165Missing in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U52682 mRNA Translation: AAC50779.1
U63738 mRNA Translation: AAB37258.1
AL365272 Genomic DNA No translation available.
AL589962 Genomic DNA No translation available.
BC015752 mRNA Translation: AAH15752.1
CCDSiCCDS4469.1 [Q15306-1]
RefSeqiNP_001182215.1, NM_001195286.1 [Q15306-2]
NP_002451.2, NM_002460.3 [Q15306-1]
UniGeneiHs.401013

Genome annotation databases

EnsembliENST00000380956; ENSP00000370343; ENSG00000137265 [Q15306-1]
GeneIDi3662
KEGGihsa:3662
UCSCiuc003msz.5 human [Q15306-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement

Similar proteinsi

Entry informationi

Entry nameiIRF4_HUMAN
AccessioniPrimary (citable) accession number: Q15306
Secondary accession number(s): Q5VUI7, Q99660
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: May 23, 2018
This is version 184 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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