UniProtKB - Q02556 (IRF8_HUMAN)
Interferon regulatory factor 8
IRF8
Functioni
Transcription factor that specifically binds to the upstream regulatory region of type I interferon (IFN) and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)) (PubMed:25122610).
Can both act as a transcriptional activator or repressor (By similarity).
Plays a negative regulatory role in cells of the immune system (By similarity).
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).
Required for the development of plasmacytoid dendritic cells (pDCs), which produce most of the type I IFN in response to viral infection (By similarity).
Positively regulates macroautophagy in dendritic cells (PubMed:29434592).
By similarity2 PublicationsRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 7 – 114 | IRF tryptophan pentad repeatPROSITE-ProRule annotationAdd BLAST | 108 |
GO - Molecular functioni
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: NTNU_SB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: NTNU_SB
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
GO - Biological processi
- autophagy Source: UniProtKB-KW
- cellular response to interferon-gamma Source: UniProtKB
- cellular response to lipopolysaccharide Source: Ensembl
- defense response to bacterium Source: Ensembl
- defense response to protozoan Source: Ensembl
- dendritic cell differentiation Source: UniProtKB
- follicular B cell differentiation Source: Ensembl
- germinal center B cell differentiation Source: Ensembl
- immune response Source: ProtInc
- immune system process Source: GO_Central
- myeloid cell differentiation Source: Ensembl
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- phagocytosis Source: Ensembl
- plasmacytoid dendritic cell differentiation Source: UniProtKB
- positive regulation of interferon-gamma production Source: Ensembl
- positive regulation of interleukin-12 production Source: Ensembl
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
- regulation of type I interferon production Source: UniProtKB
Keywordsi
Molecular function | Activator, DNA-binding, Repressor |
Biological process | Autophagy, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | Q02556 |
Reactomei | R-HSA-877300, Interferon gamma signaling R-HSA-909733, Interferon alpha/beta signaling |
SignaLinki | Q02556 |
SIGNORi | Q02556 |
Names & Taxonomyi
Protein namesi | Recommended name: Interferon regulatory factor 8CuratedShort name: IRF-8 Alternative name(s): Interferon consensus sequence-binding protein1 Publication Short name: H-ICSBP1 Publication Short name: ICSBP1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5358, IRF8 |
MIMi | 601565, gene |
neXtProti | NX_Q02556 |
VEuPathDBi | HostDB:ENSG00000140968 |
Subcellular locationi
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Immunodeficiency 32A (IMD32A)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_070084 | 80 | T → A in IMD32A; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA. 1 PublicationCorresponds to variant dbSNP:rs397514711EnsemblClinVar. | 1 |
Immunodeficiency 32B (IMD32B)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_070085 | 108 | K → E in IMD32B; in resting macrophages, no effect on cytoplasmic subcellular localization; loss of nuclear subcellular localization upon IFN-gamma induction; decreased protein abundance; increased proteasome-dependent degradation; increased ubiquitination and sumoylation; loss of transcriptional repressor activity; loss of IRF1-dependent transcriptional repressor activity; loss of IRF1-dependent transcriptional activator activity; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA. 2 PublicationsCorresponds to variant dbSNP:rs397514710EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 108 | K → H in resting macrophages, no effect on cytoplasmic subcellular localization. Decreased nuclear subcellular localization upon IFN-gamma induction. Partial loss of IRF1-dependent transcriptional activator activity. 1 Publication | 1 | |
Mutagenesisi | 108 | K → Q in resting macrophages, no effect on cytoplasmic subcellular localization. Loss of nuclear subcellular localization upon IFN-gamma induction. Loss of IRF1-dependent transcriptional activator activity. 1 Publication | 1 | |
Mutagenesisi | 108 | K → R in resting macrophages, no effect on cytoplasmic subcellular localization. No effect on nuclear subcellular localization upon IFN-gamma induction. No effect on transcriptional activator activity. No effect on IRF1-dependent transcriptional activator activity. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 3394 |
MalaCardsi | IRF8 |
MIMi | 226990, phenotype 614893, phenotype |
OpenTargetsi | ENSG00000140968 |
Orphaneti | 319600, Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency |
PharmGKBi | PA29606 |
Miscellaneous databases
Pharosi | Q02556, Tbio |
Genetic variation databases
BioMutai | IRF8 |
DMDMi | 6016308 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000154564 | 1 – 426 | Interferon regulatory factor 8Add BLAST | 426 |
Post-translational modificationi
Keywords - PTMi
Ubl conjugationProteomic databases
jPOSTi | Q02556 |
MassIVEi | Q02556 |
MaxQBi | Q02556 |
PaxDbi | Q02556 |
PeptideAtlasi | Q02556 |
PRIDEi | Q02556 |
ProteomicsDBi | 58110 |
PTM databases
iPTMneti | Q02556 |
PhosphoSitePlusi | Q02556 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000140968, Expressed in lymph node and 227 other tissues |
ExpressionAtlasi | Q02556, baseline and differential |
Genevisiblei | Q02556, HS |
Organism-specific databases
HPAi | ENSG00000140968, Tissue enhanced (bone marrow, lymphoid tissue) |
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 PublicationBinary interactionsi
Protein-protein interaction databases
BioGRIDi | 109621, 25 interactors |
IntActi | Q02556, 12 interactors |
STRINGi | 9606.ENSP00000268638 |
Miscellaneous databases
RNActi | Q02556, protein |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502QT9P, Eukaryota |
GeneTreei | ENSGT00940000158140 |
InParanoidi | Q02556 |
OMAi | NNQGRFP |
OrthoDBi | 648909at2759 |
PhylomeDBi | Q02556 |
TreeFami | TF328512 |
Family and domain databases
CDDi | cd00103, IRF, 1 hit |
Gene3Di | 1.10.10.10, 1 hit 2.60.200.10, 1 hit |
InterProi | View protein in InterPro IPR019817, Interferon_reg_fac_CS IPR001346, Interferon_reg_fact_DNA-bd_dom IPR019471, Interferon_reg_factor-3 IPR044400, IRF8 IPR017855, SMAD-like_dom_sf IPR008984, SMAD_FHA_dom_sf IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR11949, PTHR11949, 1 hit PTHR11949:SF7, PTHR11949:SF7, 1 hit |
Pfami | View protein in Pfam PF00605, IRF, 1 hit PF10401, IRF-3, 1 hit |
PRINTSi | PR00267, INTFRNREGFCT |
SMARTi | View protein in SMART SM00348, IRF, 1 hit SM01243, IRF-3, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit SSF49879, SSF49879, 1 hit |
PROSITEi | View protein in PROSITE PS00601, IRF_1, 1 hit PS51507, IRF_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 8 potential isoforms that are computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH3BT31 | H3BT31_HUMAN | Interferon regulatory factor 8 | IRF8 | 328 | Annotation score: | ||
H3BPS5 | H3BPS5_HUMAN | Interferon regulatory factor 8 | IRF8 | 222 | Annotation score: | ||
H3BRT4 | H3BRT4_HUMAN | Interferon regulatory factor 8 | IRF8 | 220 | Annotation score: | ||
H3BQH6 | H3BQH6_HUMAN | Interferon regulatory factor 8 | IRF8 | 159 | Annotation score: | ||
H3BVC2 | H3BVC2_HUMAN | Interferon regulatory factor 8 | IRF8 | 126 | Annotation score: | ||
H3BNX4 | H3BNX4_HUMAN | Interferon regulatory factor 8 | IRF8 | 152 | Annotation score: | ||
H3BQK3 | H3BQK3_HUMAN | Interferon regulatory factor 8 | IRF8 | 47 | Annotation score: | ||
H3BQF9 | H3BQF9_HUMAN | Interferon regulatory factor 8 | IRF8 | 14 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_070084 | 80 | T → A in IMD32A; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA. 1 PublicationCorresponds to variant dbSNP:rs397514711EnsemblClinVar. | 1 | |
Natural variantiVAR_036490 | 81 | R → K in a breast cancer sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_070085 | 108 | K → E in IMD32B; in resting macrophages, no effect on cytoplasmic subcellular localization; loss of nuclear subcellular localization upon IFN-gamma induction; decreased protein abundance; increased proteasome-dependent degradation; increased ubiquitination and sumoylation; loss of transcriptional repressor activity; loss of IRF1-dependent transcriptional repressor activity; loss of IRF1-dependent transcriptional activator activity; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA. 2 PublicationsCorresponds to variant dbSNP:rs397514710EnsemblClinVar. | 1 | |
Natural variantiVAR_036491 | 197 | A → T in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1372132995Ensembl. | 1 |
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 |
Genome annotation databases
Ensembli | ENST00000268638; ENSP00000268638; ENSG00000140968 |
GeneIDi | 3394 |
KEGGi | hsa:3394 |
MANE-Selecti | ENST00000268638.10; ENSP00000268638.4; NM_002163.4; NP_002154.1 |
UCSCi | uc002fjh.4, human |
Similar proteinsi
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 |
3D structure databases
SMRi | Q02556 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 109621, 25 interactors |
IntActi | Q02556, 12 interactors |
STRINGi | 9606.ENSP00000268638 |
PTM databases
iPTMneti | Q02556 |
PhosphoSitePlusi | Q02556 |
Genetic variation databases
BioMutai | IRF8 |
DMDMi | 6016308 |
Proteomic databases
jPOSTi | Q02556 |
MassIVEi | Q02556 |
MaxQBi | Q02556 |
PaxDbi | Q02556 |
PeptideAtlasi | Q02556 |
PRIDEi | Q02556 |
ProteomicsDBi | 58110 |
Protocols and materials databases
Antibodypediai | 1058, 462 antibodies from 42 providers |
DNASUi | 3394 |
Genome annotation databases
Ensembli | ENST00000268638; ENSP00000268638; ENSG00000140968 |
GeneIDi | 3394 |
KEGGi | hsa:3394 |
MANE-Selecti | ENST00000268638.10; ENSP00000268638.4; NM_002163.4; NP_002154.1 |
UCSCi | uc002fjh.4, human |
Organism-specific databases
CTDi | 3394 |
DisGeNETi | 3394 |
GeneCardsi | IRF8 |
HGNCi | HGNC:5358, IRF8 |
HPAi | ENSG00000140968, Tissue enhanced (bone marrow, lymphoid tissue) |
MalaCardsi | IRF8 |
MIMi | 226990, phenotype 601565, gene 614893, phenotype |
neXtProti | NX_Q02556 |
OpenTargetsi | ENSG00000140968 |
Orphaneti | 319600, Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency |
PharmGKBi | PA29606 |
VEuPathDBi | HostDB:ENSG00000140968 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QT9P, Eukaryota |
GeneTreei | ENSGT00940000158140 |
InParanoidi | Q02556 |
OMAi | NNQGRFP |
OrthoDBi | 648909at2759 |
PhylomeDBi | Q02556 |
TreeFami | TF328512 |
Enzyme and pathway databases
PathwayCommonsi | Q02556 |
Reactomei | R-HSA-877300, Interferon gamma signaling R-HSA-909733, Interferon alpha/beta signaling |
SignaLinki | Q02556 |
SIGNORi | Q02556 |
Miscellaneous databases
BioGRID-ORCSi | 3394, 34 hits in 1066 CRISPR screens |
ChiTaRSi | IRF8, human |
GeneWikii | IRF8 |
GenomeRNAii | 3394 |
Pharosi | Q02556, Tbio |
PROi | PR:Q02556 |
RNActi | Q02556, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000140968, Expressed in lymph node and 227 other tissues |
ExpressionAtlasi | Q02556, baseline and differential |
Genevisiblei | Q02556, HS |
Family and domain databases
CDDi | cd00103, IRF, 1 hit |
Gene3Di | 1.10.10.10, 1 hit 2.60.200.10, 1 hit |
InterProi | View protein in InterPro IPR019817, Interferon_reg_fac_CS IPR001346, Interferon_reg_fact_DNA-bd_dom IPR019471, Interferon_reg_factor-3 IPR044400, IRF8 IPR017855, SMAD-like_dom_sf IPR008984, SMAD_FHA_dom_sf IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR11949, PTHR11949, 1 hit PTHR11949:SF7, PTHR11949:SF7, 1 hit |
Pfami | View protein in Pfam PF00605, IRF, 1 hit PF10401, IRF-3, 1 hit |
PRINTSi | PR00267, INTFRNREGFCT |
SMARTi | View protein in SMART SM00348, IRF, 1 hit SM01243, IRF-3, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit SSF49879, SSF49879, 1 hit |
PROSITEi | View protein in PROSITE PS00601, IRF_1, 1 hit PS51507, IRF_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | IRF8_HUMAN | |
Accessioni | Q02556Primary (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: | February 23, 2022 | |
This is version 187 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families