Q15306 (IRF4_HUMAN) 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
Multiple myeloma oncogene 1
NF-EM5

Gene names

Name:	IRF4
Synonyms:	MUM1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	451 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.
Subunit structure	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	Defects in IRF4 are a cause of multiple myeloma (MM) [MIM:254500]. MM is 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=A chromosomal aberration involving IRF4 is 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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	T cell activation Non-traceable author statement. Source: UniProtKB interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome positive regulation of interleukin-10 biosynthetic process Inferred from direct assay. Source: UniProtKB positive regulation of interleukin-13 biosynthetic process Inferred from direct assay. Source: UniProtKB positive regulation of interleukin-2 biosynthetic process Inferred from direct assay. Source: UniProtKB positive regulation of interleukin-4 biosynthetic process Inferred from direct assay. Source: UniProtKB regulation of T-helper cell differentiation Non-traceable author statement. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	regulatory region DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Non-traceable author statement. Source: UniProtKB transcription factor binding Non-traceable author statement. 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 451

451

Interferon regulatory factor 4

PRO_0000154556

Regions

DNA binding

21 – 129

109

IRF tryptophan pentad repeat

Amino acid modifications

Modified residue

447

1

Phosphoserine; by ROCK2 By similarity

Modified residue

448

1

Phosphoserine; by ROCK2 By similarity

Natural variations

Alternative sequence

165

1

Missing in isoform 2.

VSP_002755

Experimental info

Sequence conflict

300

1

Q → H in AAB37258. Ref.2

Sequence conflict

306

1

K → N in AAB37258. Ref.2

Sequence conflict

333

1

R → T in AAB37258. Ref.2

Secondary structure

1

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451

Helix Strand Turn

Details...

Helix

24 – 34

11

Beta strand

37 – 39

3

Beta strand

41 – 47

7

Beta strand

49 – 53

5

Beta strand

60 – 62

3

Helix

64 – 67

4

Helix

69 – 78

10

Helix

90 – 103

14

Beta strand

107 – 109

3

Turn

111 – 113

3

Beta strand

115 – 120

6

Beta strand

122 – 127

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 17CD1327C6F5BFFA	FASTA	451	51,772
	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
	Isoform 2 [UniParc]. Checksum: 85056FCEB84B0EBC	FASTA	450	51,644
	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 LPAQVHNYMM PPLDRSWRDY 190 200 210 220 230 240 VPDQPHPEIP YQCPMTFGPR GHHWQGPACE NGCQVTGTFY ACAPPESQAP GVPTEPSIRS 250 260 270 280 290 300 AEALAFSDCR LHICLYYREI LVKELTTSSP EGCRISHGHT YDASNLDQVL FPYPEDNGQR 310 320 330 340 350 360 KNIEKLLSHL ERGVVLWMAP DGLYAKRLCQ SRIYWDGPLA LCNDRPNKLE RDQTCKLFDT 370 380 390 400 410 420 QQFLSELQAF AHHGRSLPRF QVTLCFGEEF PDPQRQRKLI TAHVEPLLAR QLYYFAQQNS 430 440 450 GHFLRGYDLP EHISNPEDYH RSIRHSSIQE

References

	« Hide 'large scale' referencesShow '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: 8921401] [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: 9326949] [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. , 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: 14574404] [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: 15489334] [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: 10196196] [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: 12651066] [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: 21269460] [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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00215970.
IPI00289982.

RefSeq

NP_001182215.1. NM_001195286.1.
NP_002451.2. NM_002460.3.

UniGene

Hs.401013.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DLL	NMR	-	A	23-130	[»]

ProteinModelPortal

Q15306.

SMR

Q15306. Positions 18-130, 246-447.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q15306. 2 interactions.

STRING

Q15306.

PTM databases

PhosphoSite

Q15306.

Polymorphism databases

DMDM

2497445.

Proteomic databases

PRIDE

Q15306.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380956; ENSP00000370343; ENSG00000137265.

GeneID

3662.

KEGG

hsa:3662.

UCSC

uc003msz.2. human.
uc003mtb.2. human.

Organism-specific databases

CTD

3662.

GeneCards

GC06P000391.

H-InvDB

HIX0005514.

HGNC

HGNC:6119. IRF4.

HPA

CAB013508.
HPA002038.
HPA002698.

MIM

254500. phenotype.
601900. gene.

neXtProt

NX_Q15306.

PharmGKB

PA29918.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08016.

GeneTree

ENSGT00550000074205.

HOGENOM

HBG445888.

HOVERGEN

HBG003072.

InParanoid

Q15306.

OMA

NGCQVTG.

OrthoDB

EOG48GW3F.

PhylomeDB

Q15306.

Enzyme and pathway databases

Pathway_Interaction_DB

nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
il4_2pathway. IL4-mediated signaling events.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q15306.

Bgee

Q15306.

CleanEx

HS_IRF4.
HS_MUM1.

Genevestigator

Q15306.

GermOnline

ENSG00000137265. Homo sapiens.

Family and domain databases

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_trsnscrt_rep_DNA-bd.
[Graphical view]

Gene3D

G3DSA:2.60.200.10. MH2_Dwarfin-type. 1 hit.
G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.

KO

K09445.

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

14323.

SOURCE

Search...

Entry information

Entry name

IRF4_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 126 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.