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Q02556

- IRF8_HUMAN

UniProt

Q02556 - IRF8_HUMAN

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Protein

Interferon regulatory factor 8

Gene

IRF8

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi7 – 114108IRF tryptophan pentad repeatPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. regulatory region DNA binding Source: InterPro
  2. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: ProtInc

GO - Biological processi

  1. cellular response to lipopolysaccharide Source: Ensembl
  2. cytokine-mediated signaling pathway Source: Reactome
  3. defense response to bacterium Source: Ensembl
  4. defense response to protozoan Source: Ensembl
  5. immune response Source: ProtInc
  6. interferon-gamma-mediated signaling pathway Source: Reactome
  7. myeloid cell differentiation Source: Ensembl
  8. negative regulation of growth of symbiont in host Source: Ensembl
  9. negative regulation of transcription from RNA polymerase II promoter Source: ProtInc
  10. phagocytosis Source: Ensembl
  11. positive regulation of interferon-gamma production Source: Ensembl
  12. positive regulation of interleukin-12 production Source: Ensembl
  13. positive regulation of transcription initiation from RNA polymerase II promoter Source: Ensembl
  14. transcription from RNA polymerase II promoter Source: GOC
  15. type I interferon signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_25078. Interferon gamma signaling.
REACT_25162. Interferon alpha/beta signaling.
SignaLinkiQ02556.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:IRF8
Synonyms:ICSBP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:5358. IRF8.

Subcellular locationi

Nucleus 1 Publication

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 32A (IMD32A) [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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti80 – 801T → A in IMD32A; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA. 1 Publication
VAR_070084
Immunodeficiency 32B (IMD32B) [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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti108 – 1081K → E in IMD32B; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA. 1 Publication
VAR_070085

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi614893. phenotype.
614894. phenotype.
Orphaneti319600. Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency.
PharmGKBiPA29606.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 426426Interferon regulatory factor 8PRO_0000154564Add
BLAST

Post-translational modificationi

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).By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ02556.
PaxDbiQ02556.
PRIDEiQ02556.

PTM databases

PhosphoSiteiQ02556.

Expressioni

Tissue specificityi

Predominantly expressed in lymphoid tissues.2 Publications

Inductioni

By IFNG/IFN-gamma. Negatively regulated by microRNA-155 (miR155).2 Publications

Gene expression databases

BgeeiQ02556.
CleanExiHS_IRF8.
ExpressionAtlasiQ02556. baseline and differential.
GenevestigatoriQ02556.

Organism-specific databases

HPAiCAB013480.
HPA002267.
HPA002531.

Interactioni

Subunit structurei

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.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
IRF6O148963EBI-2866563,EBI-6115643

Protein-protein interaction databases

BioGridi109621. 24 interactions.
IntActiQ02556. 10 interactions.
STRINGi9606.ENSP00000268638.

Structurei

3D structure databases

ProteinModelPortaliQ02556.
SMRiQ02556. Positions 9-115, 198-379.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IRF family.PROSITE-ProRule annotation
Contains 1 IRF tryptophan pentad repeat DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG42878.
GeneTreeiENSGT00760000119093.
HOGENOMiHOG000010107.
HOVERGENiHBG003072.
InParanoidiQ02556.
KOiK10155.
OMAiRELQQFY.
OrthoDBiEOG7CCBR1.
PhylomeDBiQ02556.
TreeFamiTF328512.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProiIPR019817. 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]
PfamiPF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
[Graphical view]
PRINTSiPR00267. INTFRNREGFCT.
SMARTiSM00348. IRF. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
PROSITEiPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q02556-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MCDRNGGRRL RQWLIEQIDS SMYPGLIWEN EEKSMFRIPW KHAGKQDYNQ
60 70 80 90 100
EVDASIFKAW AVFKGKFKEG DKAEPATWKT RLRCALNKSP DFEEVTDRSQ
110 120 130 140 150
LDISEPYKVY RIVPEEEQKC KLGVATAGCV NEVTEMECGR SEIDELIKEP
160 170 180 190 200
SVDDYMGMIK RSPSPPEACR SQLLPDWWAQ QPSTGVPLVT GYTTYDAHHS
210 220 230 240 250
AFSQMVISFY YGGKLVGQAT TTCPEGCRLS LSQPGLPGTK LYGPEGLELV
260 270 280 290 300
RFPPADAIPS ERQRQVTRKL FGHLERGVLL HSSRQGVFVK RLCQGRVFCS
310 320 330 340 350
GNAVVCKGRP NKLERDEVVQ VFDTSQFFRE LQQFYNSQGR LPDGRVVLCF
360 370 380 390 400
GEEFPDMAPL RSKLILVQIE QLYVRQLAEE AGKSCGAGSV MQAPEEPPPD
410 420
QVFRMFPDIC ASHQRSFFRE NQQITV
Length:426
Mass (Da):48,356
Last modified:July 15, 1999 - v2
Checksum:i1535D1B7C83E0355
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti80 – 801T → A in IMD32A; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA. 1 Publication
VAR_070084
Natural varianti81 – 811R → K in a breast cancer sample; somatic mutation. 1 Publication
VAR_036490
Natural varianti108 – 1081K → E in IMD32B; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA. 1 Publication
VAR_070085
Natural varianti197 – 1971A → T in a breast cancer sample; somatic mutation. 1 Publication
VAR_036491

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M91196 mRNA. Translation: AAB63813.1.
BC126247 mRNA. Translation: AAI26248.1.
CCDSiCCDS10956.1.
PIRiA45064.
RefSeqiNP_002154.1. NM_002163.2.
UniGeneiHs.137427.

Genome annotation databases

EnsembliENST00000268638; ENSP00000268638; ENSG00000140968.
GeneIDi3394.
KEGGihsa:3394.
UCSCiuc002fjh.3. human.

Polymorphism databases

DMDMi6016308.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M91196 mRNA. Translation: AAB63813.1 .
BC126247 mRNA. Translation: AAI26248.1 .
CCDSi CCDS10956.1.
PIRi A45064.
RefSeqi NP_002154.1. NM_002163.2.
UniGenei Hs.137427.

3D structure databases

ProteinModelPortali Q02556.
SMRi Q02556. Positions 9-115, 198-379.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109621. 24 interactions.
IntActi Q02556. 10 interactions.
STRINGi 9606.ENSP00000268638.

PTM databases

PhosphoSitei Q02556.

Polymorphism databases

DMDMi 6016308.

Proteomic databases

MaxQBi Q02556.
PaxDbi Q02556.
PRIDEi Q02556.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000268638 ; ENSP00000268638 ; ENSG00000140968 .
GeneIDi 3394.
KEGGi hsa:3394.
UCSCi uc002fjh.3. human.

Organism-specific databases

CTDi 3394.
GeneCardsi GC16P085932.
HGNCi HGNC:5358. IRF8.
HPAi CAB013480.
HPA002267.
HPA002531.
MIMi 601565. gene.
614893. phenotype.
614894. phenotype.
neXtProti NX_Q02556.
Orphaneti 319600. Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency.
PharmGKBi PA29606.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG42878.
GeneTreei ENSGT00760000119093.
HOGENOMi HOG000010107.
HOVERGENi HBG003072.
InParanoidi Q02556.
KOi K10155.
OMAi RELQQFY.
OrthoDBi EOG7CCBR1.
PhylomeDBi Q02556.
TreeFami TF328512.

Enzyme and pathway databases

Reactomei REACT_25078. Interferon gamma signaling.
REACT_25162. Interferon alpha/beta signaling.
SignaLinki Q02556.

Miscellaneous databases

ChiTaRSi IRF8. human.
GeneWikii IRF8.
GenomeRNAii 3394.
NextBioi 13414.
PROi Q02556.
SOURCEi Search...

Gene expression databases

Bgeei Q02556.
CleanExi HS_IRF8.
ExpressionAtlasi Q02556. baseline and differential.
Genevestigatori Q02556.

Family and domain databases

Gene3Di 1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProi 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 ]
Pfami PF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
[Graphical view ]
PRINTSi PR00267. INTFRNREGFCT.
SMARTi SM00348. IRF. 1 hit.
[Graphical view ]
SUPFAMi SSF49879. SSF49879. 1 hit.
PROSITEi PS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: VARIANTS [LARGE SCALE ANALYSIS] LYS-81 AND THR-197.
  7. Cited for: VARIANT IMD32A ALA-80, VARIANT IMD32B GLU-108, CHARACTERIZATION OF VARIANT IMD32A ALA-80, CHARACTERIZATION OF VARIANT IMD32B GLU-108.

Entry informationi

Entry nameiIRF8_HUMAN
AccessioniPrimary (citable) accession number: Q02556
Secondary accession number(s): A0AV82
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 15, 1999
Last modified: November 26, 2014
This is version 135 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3