IRF8

Protein identityUniProt · HPA

UniProt accession

Q02556

Gene

IRF8

Ensembl

ENSG00000140968

Chromosome

16

Canonical length

426 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm

OverviewNCBI Gene

Interferon consensus sequence-binding protein (ICSBP) is a transcription factor of the interferon (IFN) regulatory factor (IRF) family. Proteins of this family are composed of a conserved DNA-binding domain in the N-terminal region and a divergent C-terminal region that serves as the regulatory domain. The IRF family proteins bind to the IFN-stimulated response element (ISRE) and regulate expression of genes stimulated by type I IFNs, namely IFN-alpha and IFN-beta. IRF family proteins also control expression of IFN-alpha and IFN-beta-regulated genes that are induced by viral infection. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

426 residues, UniProt reviewed canonical sequence.

>Q02556|IRF8
     1  MCDRNGGRRL RQWLIEQIDS SMYPGLIWEN EEKSMFRIPW KHAGKQDYNQ EVDASIFKAW
    61  AVFKGKFKEG DKAEPATWKT RLRCALNKSP DFEEVTDRSQ LDISEPYKVY RIVPEEEQKC
   121  KLGVATAGCV NEVTEMECGR SEIDELIKEP SVDDYMGMIK RSPSPPEACR SQLLPDWWAQ
   181  QPSTGVPLVT GYTTYDAHHS AFSQMVISFY YGGKLVGQAT TTCPEGCRLS LSQPGLPGTK
   241  LYGPEGLELV RFPPADAIPS ERQRQVTRKL FGHLERGVLL HSSRQGVFVK RLCQGRVFCS
   301  GNAVVCKGRP NKLERDEVVQ VFDTSQFFRE LQQFYNSQGR LPDGRVVLCF GEEFPDMAPL
   361  RSKLILVQIE QLYVRQLAEE AGKSCGAGSV MQAPEEPPPD QVFRMFPDIC ASHQRSFFRE
   421  NQQITV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IRF8 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.39

Highest tissue expression

196 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IRF8.

Disease | AllUniProt

Conditions IRF8 is implicated in, by any mechanism.

• Immunodeficiency 32A (IMD32A) MIM:614893
• Immunodeficiency 32B (IMD32B) MIM:226990

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 439 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency
• Immunodeficiency 32B
• Esophageal atresia/tracheoesophageal fistula

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.34

gnomAD pLI

0.95

gnomAD missense Z

1.19

DepMap mean gene effect

0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• autophagy
• cellular response to lipopolysaccharide
• cellular response to type II interferon
• defense response to bacterium
• defense response to protozoan
• dendritic cell differentiation
• follicular B cell differentiation
• germinal center B cell differentiation
• immune response
• immune system process
• myeloid cell differentiation
• negative regulation of transcription by RNA polymerase II
• phagocytosis
• plasmacytoid dendritic cell differentiation
• positive regulation of apoptotic process
• positive regulation of interleukin-12 production
• positive regulation of transcription by RNA polymerase II
• positive regulation of type II interferon production
• regulation of transcription by RNA polymerase II
• regulation of type I interferon production

Molecular functions

• DNA-binding transcription factor activity, RNA polymerase II-specific
• DNA-binding transcription repressor activity, RNA polymerase II-specific
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• sequence-specific double-stranded DNA binding

Cellular components

• chromatin
• cytoplasm
• cytosol
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Interferon regulatory factor, DNA-binding domain
• SMAD/FHA domain superfamily
• SMAD-like domain superfamily
• Interferon regulatory factor-3
• Interferon regulatory factor, conserved site
• Winged helix-like DNA-binding domain superfamily
• Winged helix DNA-binding domain superfamily
• Interferon regulatory factor transcription factor
• Interferon-regulatory factor 3

KeywordsUniProt

• Activator
• Autophagy
• Cytoplasm
• DNA-binding
• Nucleus
• Repressor
• Transcription
• Transcription regulation
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of IRF8 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BATF
• COPS2
• SPI1
• IRF6