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Q02556 (IRF8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interferon regulatory factor 8

Short name=IRF-8
Alternative name(s):
Interferon consensus sequence-binding protein
Short name=H-ICSBP
Short name=ICSBP
Gene names
Name:IRF8
Synonyms:ICSBP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length426 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Specifically binds to the upstream regulatory region of type I IFN and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)). Plays a negative regulatory role in cells of the immune system. 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 IRF8 and activation of genes By similarity.

Subunit structure

Interacts (via C-terminus) with TRIM21 (via C-terminus). Interacts with the BATF-JUNB heterodimer. Interacts with BATF (via bZIP domain); the interaction is direct By similarity. Interacts with COPS2. Ref.4

Subcellular location

Nucleus Ref.5.

Tissue specificity

Predominantly expressed in lymphoid tissues. Ref.1 Ref.5

Induction

By IFNG/IFN-gamma. Negatively regulated by microRNA-155 (miR155). Ref.1 Ref.5

Post-translational modification

Ubiquitinated. Ubiquitination by TRIM21 in macrophages, a process that is strongly increased upon interferon gamma stimulation, leds to the enhanced transcriptional activity of target cytokine genes By similarity.

Involvement in disease

IRF8 deficiency, autosomal dominant (IRF8DD) [MIM:614893]: An immunologic disorder characterized by abnormal peripheral blood myeloid phenotype with a marked loss of CD11C-positive/CD1C dendritic cells, resulting in selective susceptibility to mycobacterial infections.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

IRF8 deficiency, autosomal recessive (IRF8DR) [MIM:614894]: A life-threatening pediatric disease characterized by monocyte and dendritic cell deficiency, myeloproliferation, and susceptibility to severe opportunistic infections, including disseminated BCG infection and oral candidiasis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

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 diversityPolymorphism
   DiseaseDisease mutation
   LigandDNA-binding
   PTMUbl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

cytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

defense response to bacterium

Inferred from electronic annotation. Source: Ensembl

defense response to protozoan

Inferred from electronic annotation. Source: Ensembl

immune response

Traceable author statement PubMed 8861914. Source: ProtInc

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

myeloid cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of growth of symbiont in host

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Traceable author statement Ref.1. Source: ProtInc

phagocytosis

Inferred from electronic annotation. Source: Ensembl

positive regulation of interferon-gamma production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-12 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription initiation from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

transcription from RNA polymerase II promoter

Traceable author statement Ref.1. Source: GOC

type I interferon signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionRNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.1. Source: ProtInc

protein binding

Inferred from physical interaction PubMed 21903422. Source: IntAct

regulatory region DNA binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

IRF6O148963EBI-2866563,EBI-6115643

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 426426Interferon regulatory factor 8
PRO_0000154564

Regions

DNA binding7 – 114108IRF tryptophan pentad repeat

Natural variations

Natural variant801T → A in IRF8DD; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA. Ref.7
VAR_070084
Natural variant811R → K in a breast cancer sample; somatic mutation. Ref.6
VAR_036490
Natural variant1081K → E in IRF8DR; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA. Ref.7
VAR_070085
Natural variant1971A → T in a breast cancer sample; somatic mutation. Ref.6
VAR_036491

Sequences

Sequence LengthMass (Da)Tools
Q02556 [UniParc].

Last modified July 15, 1999. Version 2.
Checksum: 1535D1B7C83E0355

FASTA42648,356
        10         20         30         40         50         60 
MCDRNGGRRL RQWLIEQIDS SMYPGLIWEN EEKSMFRIPW KHAGKQDYNQ EVDASIFKAW 

        70         80         90        100        110        120 
AVFKGKFKEG DKAEPATWKT RLRCALNKSP DFEEVTDRSQ LDISEPYKVY RIVPEEEQKC 

       130        140        150        160        170        180 
KLGVATAGCV NEVTEMECGR SEIDELIKEP SVDDYMGMIK RSPSPPEACR SQLLPDWWAQ 

       190        200        210        220        230        240 
QPSTGVPLVT GYTTYDAHHS AFSQMVISFY YGGKLVGQAT TTCPEGCRLS LSQPGLPGTK 

       250        260        270        280        290        300 
LYGPEGLELV RFPPADAIPS ERQRQVTRKL FGHLERGVLL HSSRQGVFVK RLCQGRVFCS 

       310        320        330        340        350        360 
GNAVVCKGRP NKLERDEVVQ VFDTSQFFRE LQQFYNSQGR LPDGRVVLCF GEEFPDMAPL 

       370        380        390        400        410        420 
RSKLILVQIE QLYVRQLAEE AGKSCGAGSV MQAPEEPPPD QVFRMFPDIC ASHQRSFFRE 


NQQITV 

« Hide

References

« Hide 'large scale' references
[1]"Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes."
Weisz A., Marx P., Sharf R., Appella E., Driggers P.H., Ozato K., Levi B.-Z.
J. Biol. Chem. 267:25589-25596(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION BY IFNG.
Tissue: Lung and Monocyte.
[2]Schmidt M.
Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"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].
Tissue: Brain.
[4]"Interaction between interferon consensus sequence-binding protein and COP9/signalosome subunit CSN2 (Trip15). A possible link between interferon regulatory factor signaling and the COP9/signalosome."
Cohen H., Azriel A., Cohen T., Meraro D., Hashmueli S., Bech-Otschir D., Kraft R., Dubiel W., Levi B.Z.
J. Biol. Chem. 275:39081-39089(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH COPS2.
[5]"BCL6 positively regulates AID and germinal center gene expression via repression of miR-155."
Basso K., Schneider C., Shen Q., Holmes A.B., Setty M., Leslie C., Dalla-Favera R.
J. Exp. Med. 209:2455-2465(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LYS-81 AND THR-197.
[7]"IRF8 mutations and human dendritic-cell immunodeficiency."
Hambleton S., Salem S., Bustamante J., Bigley V., Boisson-Dupuis S., Azevedo J., Fortin A., Haniffa M., Ceron-Gutierrez L., Bacon C.M., Menon G., Trouillet C., McDonald D., Carey P., Ginhoux F., Alsina L., Zumwalt T.J., Kong X.F. expand/collapse author list , Kumararatne D., Butler K., Hubeau M., Feinberg J., Al-Muhsen S., Cant A., Abel L., Chaussabel D., Doffinger R., Talesnik E., Grumach A., Duarte A., Abarca K., Moraes-Vasconcelos D., Burk D., Berghuis A., Geissmann F., Collin M., Casanova J.L., Gros P.
N. Engl. J. Med. 365:127-138(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT IRF8DD ALA-80, VARIANT IRF8DR GLU-108, CHARACTERIZATION OF VARIANT IRF8DD ALA-80, CHARACTERIZATION OF VARIANT IRF8DR GLU-108.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M91196 mRNA. Translation: AAB63813.1.
BC126247 mRNA. Translation: AAI26248.1.
CCDSCCDS10956.1.
PIRA45064.
RefSeqNP_002154.1. NM_002163.2.
UniGeneHs.137427.

3D structure databases

ProteinModelPortalQ02556.
SMRQ02556. Positions 9-115, 198-379.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109621. 24 interactions.
IntActQ02556. 10 interactions.
STRING9606.ENSP00000268638.

PTM databases

PhosphoSiteQ02556.

Polymorphism databases

DMDM6016308.

Proteomic databases

MaxQBQ02556.
PaxDbQ02556.
PRIDEQ02556.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000268638; ENSP00000268638; ENSG00000140968.
GeneID3394.
KEGGhsa:3394.
UCSCuc002fjh.3. human.

Organism-specific databases

CTD3394.
GeneCardsGC16P085932.
HGNCHGNC:5358. IRF8.
HPACAB013480.
HPA002267.
HPA002531.
MIM601565. gene.
614893. phenotype.
614894. phenotype.
neXtProtNX_Q02556.
Orphanet319600. Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency.
PharmGKBPA29606.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42878.
HOGENOMHOG000010107.
HOVERGENHBG003072.
InParanoidQ02556.
KOK10155.
OMARELQQFY.
OrthoDBEOG7CCBR1.
PhylomeDBQ02556.
TreeFamTF328512.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkQ02556.

Gene expression databases

ArrayExpressQ02556.
BgeeQ02556.
CleanExHS_IRF8.
GenevestigatorQ02556.

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

GeneWikiIRF8.
GenomeRNAi3394.
NextBio13414.
PROQ02556.
SOURCESearch...

Entry information

Entry nameIRF8_HUMAN
AccessionPrimary (citable) accession number: Q02556
Secondary accession number(s): A0AV82
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 15, 1999
Last modified: July 9, 2014
This is version 131 of the entry and version 2 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

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM