Q02556 (IRF8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	IRF8
Synonyms:	ICSBP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	426 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
Tissue specificity	Predominantly expressed in lymphoid tissues. Ref.1
Induction	By IFNG/IFN-gamma. Ref.1
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.
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	Polymorphism
Ligand	DNA-binding
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to lipopolysaccharide Inferred from electronic annotation. Source: Compara defense response to bacterium Inferred from electronic annotation. Source: Compara defense response to protozoan Inferred from electronic annotation. Source: Compara interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome myeloid cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of growth of symbiont in host Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Traceable author statement Ref.1. Source: ProtInc phagocytosis Inferred from electronic annotation. Source: Compara positive regulation of interferon-gamma production Inferred from electronic annotation. Source: Compara positive regulation of interleukin-12 production Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Traceable author statement Ref.1. Source: ProtInc regulatory region DNA binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IRF6	O14896	3	EBI-2866563,EBI-6115643

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 426	426	Interferon regulatory factor 8		PRO_0000154564
Regions
	DNA binding	7 – 114	108	IRF tryptophan pentad repeat
Natural variations
	Natural variant	81	1	R → K in a breast cancer sample; somatic mutation. Ref.5		VAR_036490
	Natural variant	197	1	A → T in a breast cancer sample; somatic mutation. Ref.5		VAR_036491

Sequences

	Sequence		Length	Mass (Da)
	Q02556 [UniParc]. Last modified July 15, 1999. Version 2. Checksum: 1535D1B7C83E0355	FASTA	426	48,356
	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

References

	« Hide 'large scale' referencesShow '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]	"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. , 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M91196 mRNA. Translation: AAB63813.1. BC126247 mRNA. Translation: AAI26248.1.
IPI	IPI00026224.
PIR	A45064.
RefSeq	NP_002154.1. NM_002163.2.
UniGene	Hs.137427.
3D structure databases
ProteinModelPortal	Q02556.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q02556. 10 interactions.
STRING	9606.ENSP00000268638.
PTM databases
PhosphoSite	Q02556.
Polymorphism databases
DMDM	6016308.
Proteomic databases
PaxDb	Q02556.
PRIDE	Q02556.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000268638; ENSP00000268638; ENSG00000140968.
GeneID	3394.
KEGG	hsa:3394.
UCSC	uc002fjh.3. human.
Organism-specific databases
CTD	3394.
GeneCards	GC16P085932.
HGNC	HGNC:5358. IRF8.
HPA	CAB013480. HPA002267. HPA002531.
MIM	601565. gene.
neXtProt	NX_Q02556.
PharmGKB	PA29606.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG42878.
HOGENOM	HOG000010107.
HOVERGEN	HBG003072.
InParanoid	Q02556.
KO	K10155.
OMA	RELQQFY.
OrthoDB	EOG434W5Z.
PhylomeDB	Q02556.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q02556.
Bgee	Q02556.
CleanEx	HS_IRF8.
Genevestigator	Q02556.
GermOnline	ENSG00000140968. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.10. 1 hit. 2.60.200.10. 1 hit.
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_DNA-bd_dom. [Graphical view]
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
GenomeRNAi	3394.
NextBio	13414.
SOURCE	Search...

Entry information

Entry name

IRF8_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 119 of the entry and version 2 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.