Reviewed, UniProtKB/Swiss-Prot P10914 (IRF1_HUMAN)

Names and origin

Protein names

Recommended name:
    Interferon regulatory factor 1
      Short name=IRF-1

Gene names

Name:

IRF1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	325 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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)) and activates those genes. Acts as a tumor suppressor. Ref.7 Ref.8
Subcellular location	Nucleus.
Induction	By viruses and IFN.
Post-translational modification	Sumoylation represses the transcriptional activity and displays enhanced resistance to protein degradation. Inactivates the tumor suppressor activity. Elevated levels in tumor cells. Major site is Lys-275. Sumoylation is enhanced by PIAS3 By similarity. Desumoylated by SENP1 in tumor cells and appears to compete with ubiquitination on C-terminal sites. Ubiquitinated. Appears to compete with sumoylation on C-terminal sites. Ref.7
Involvement in disease	Deletion or rearrangement of IRF1 are a cause of preleukemic myelodysplastic syndrome (MDS) and of acute myelogenous leukemia (AML).
Sequence similarities	Belongs to the IRF family. Contains 1 tryptophan pentad repeat DNA-binding domain.

Ontologies

Keywords
Biological process	Cell cycle Transcription Transcription regulation
Cellular component	Nucleus
Ligand	DNA-binding
Molecular function	Activator Anti-oncogene
PTM	Isopeptide bond Ubl conjugation
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell cycle Inferred from electronic annotation. Source: UniProtKB-KW transcription from RNA polymerase II promoter Traceable author statement. Source: ProtInc
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 325	325	Interferon regulatory factor 1		PRO_0000154545
Regions
	DNA binding	7 – 109	103	Tryptophan pentad repeat
Amino acid modifications
	Cross-link	275		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.7
	Cross-link	299		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.7
Experimental info
	Mutagenesis	275	1	K → R: Some loss of sumoylation. Abolishes sumoylation, diminished ubiquitination, higher resistance to degradation, and increased apoptopic activity; when associated with R-299. Ref.7
	Mutagenesis	299	1	K → R: Large loss of sumoylation. Abolishes sumoylation, diminished ubiquitination, higher resistance to degradation, and increased apoptopic activity; when associated with R-275. Ref.7
	Sequence conflict	5	1	R → W Ref.1
	Sequence conflict	5	1	R → W Ref.2
	Sequence conflict	34 – 35	2	FQ → LE Ref.1
	Sequence conflict	34 – 35	2	FQ → LE Ref.2
	Sequence conflict	220	1	T → I Ref.1
	Sequence conflict	220	1	T → I Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P10914-1 [UniParc]. Last modified April 16, 2002. Version 2. Checksum: 2E06245A212D1541	FASTA	325	36,502
	10 20 30 40 50 60 MPITRMRMRP WLEMQINSNQ IPGLIWINKE EMIFQIPWKH AAKHGWDINK DACLFRSWAI 70 80 90 100 110 120 HTGRYKAGEK EPDPKTWKAN FRCAMNSLPD IEEVKDQSRN KGSSAVRVYR MLPPLTKNQR 130 140 150 160 170 180 KERKSKSSRD AKSKAKRKSC GDSSPDTFSD GLSSSTLPDD HSSYTVPGYM QDLEVEQALT 190 200 210 220 230 240 PALSPCAVSS TLPDWHIPVE VVPDSTSDLY NFQVSPMPST SEATTDEDEE GKLPEDIMKL 250 260 270 280 290 300 LEQSEWQPTN VDGKGYLLNE PGVQPTSVYG DFSCKEEPEI DSPGGDIGLS LQRVFTDLKN 310 320 MDATWLDSLL TPVRLPSIQA IPCAP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of a cDNA coding for human IRF-1." Maruyama M., Fujita T., Taniguchi T. Nucleic Acids Res. 17:3292-3292(1989) [PubMed: 2726461] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements." Miyamoto M., Fujita T., Kimura Y., Maruyama M., Harada H., Sudo Y., Miyata T., Taniguchi T. Cell 54:903-913(1988) [PubMed: 3409321] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Human interferon regulatory factor 1: intron-exon organization." Cha Y., Sims S.H., Romine M.F., Kaufmann M., Deisseroth A.B. DNA Cell Biol. 11:605-611(1992) [PubMed: 1382447] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[6]	"Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia." Willman C.L., Sever C.E., Pallavicini M.G., Harada H., Tanaka N., Slovak M.L., Yamamoto H., Harada K., Meeker T.C., List A.F., Taniguchi T. Science 259:968-971(1993) [PubMed: 8438156] [Abstract] Cited for: INVOLVEMENT IN LEUKEMIAS.
[7]	"Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis." Park J., Kim K., Lee E.-J., Seo Y.-J., Lim S.-N., Park K., Rho S.B., Lee S.-H., Lee J.-H. Proc. Natl. Acad. Sci. U.S.A. 104:17028-17033(2007) [PubMed: 17942705] [Abstract] Cited for: SUMOYLATION AT LYS-275 AND LYS-299, UBIQUITINATION AT LYS-275 AND LYS-299, FUNCTION, MUTAGENESIS OF LYS-275 AND LYS-299.
[8]	"IRF-1 promotes apoptosis in p53-damaged basal-type human mammary epithelial cells: a model for early basal-type mammary carcinogenesis." Bowie M.L., Ibarra C., Seewalt V.L. Adv. Exp. Med. Biol. 617:367-374(2008) [PubMed: 18497060] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	X14454 mRNA. Translation: CAA32624.1. L05072 Genomic DNA. Translation: AAA36043.1. BT019756 mRNA. Translation: AAV38561.1. BC009483 mRNA. Translation: AAH09483.1.
IPI	IPI00023600.
PIR	B31595. I52998.
RefSeq	NP_002189.1.
UniGene	Hs.436061
3D structure databases
HSSP	HSSP built from PDB template 1IF1 based on UniProtKB P15314.
SMR	P10914. Positions 7-111.
ModBase	Search...
Protein-protein interaction databases
IntAct	P10914. 2 interactions.
PTM databases
PhosphoSite	P10914.
Proteomic databases
PRIDE	P10914.
Genome annotation databases
Ensembl	ENSG00000125347. Homo sapiens. [Contig view]
GeneID	3659.
KEGG	hsa:3659.
Organism-specific databases
GeneCards	GC05M131846.
H-InvDB	HIX0005159.
HGNC	HGNC:6116. IRF1.
HPA	CAB011662.
MIM	147575. gene. 153550. phenotype.
PharmGKB	PA29915.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P10914.
HOVERGEN	P10914.
OMA	P10914. CKEEPEV.
Enzyme and pathway databases
Pathway_Interaction_DB	ifngpathway. IFN-gamma pathway. il12_stat4pathway. IL12 signaling mediated by STAT4. il6_7pathway. IL6-mediated signaling events. telomerasepathway. Regulation of Telomerase.
Gene expression databases
ArrayExpress	P10914.
Bgee	P10914.
CleanEx	HS_IRF1.
GermOnline	ENSG00000125347. Homo sapiens.
Family and domain databases
InterPro	IPR017431. Interferon_regulatory_fac-1/2. IPR019817. Interferon_regulatory_fac_CS. IPR001346. Interferon_regulatory_factor. IPR011991. Wing_hlx_DNA_bd. [Graphical view]
Gene3D	G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
Pfam	PF00605. IRF. 1 hit. [Graphical view]
PIRSF	PIRSF038196. IFN_RF1/2. 1 hit.
PRINTS	PR00267. INTFRNREGFCT.
ProDom	PD002355. IRF. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00348. IRF. 1 hit. [Graphical view]
PROSITE	PS00601. IRF. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	14311.
SOURCE	Search...

Entry information

Entry name

IRF1_HUMAN

Accession

Primary (citable) accession number: P10914
Secondary accession number(s): Q96GG7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	April 16, 2002
Last modified:	June 16, 2009
This is version 88 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)