P10914 (IRF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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.
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. Ref.7 Ubiquitinated. Appears to compete with sumoylation on C-terminal sites. Ref.7
Involvement in disease	Defects in IRF1 are a cause of gastric cancer (GASC) [MIM:613659]; also called gastric cancer intestinal or stomach cancer. Gastric cancer is a malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. Ref.9 Ref.10
Miscellaneous	Deletion or rearrangement of IRF1 are found in preleukemic myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML).
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
Disease	Disease mutation Tumor suppressor
Ligand	DNA-binding
Molecular function	Activator
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	blood coagulation Traceable author statement. Source: Reactome cellular response to mechanical stimulus Inferred from expression pattern. Source: UniProtKB interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome transcription from RNA polymerase II promoter Traceable author statement. Source: ProtInc type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular function	regulatory region DNA binding Inferred from electronic annotation. Source: InterPro
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	5 – 113	109	IRF 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
Natural variations
	Natural variant	8	1	M → L in GASC; somatic mutation; produces a protein with markedly reduced transcriptional activity but unaltered DNA-binding activity. Ref.9		VAR_065134
	Natural variant	11	1	W → R in GASC; the mutation abolishes DNA binding and transactivating activities. Ref.10		VAR_065135
Experimental info
	Mutagenesis	275	1	K → R: Some loss of sumoylation. Abolishes sumoylation, diminished ubiquitination, higher resistance to degradation, and increased apoptotic 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 apoptotic activity; when associated with R-275. Ref.7
	Sequence conflict	5	1	R → W no nucleotide entry Ref.1
	Sequence conflict	5	1	R → W no nucleotide entry Ref.2
	Sequence conflict	34 – 35	2	FQ → LE no nucleotide entry Ref.1
	Sequence conflict	34 – 35	2	FQ → LE no nucleotide entry Ref.2
	Sequence conflict	220	1	T → I no nucleotide entry Ref.1
	Sequence conflict	220	1	T → I no nucleotide entry Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P10914 [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.
[9]	"Functionally inactivating point mutation in the tumor-suppressor IRF-1 gene identified in human gastric cancer." Nozawa H., Oda E., Ueda S., Tamura G., Maesawa C., Muto T., Taniguchi T., Tanaka N. Int. J. Cancer 77:522-527(1998) [PubMed: 9679752] [Abstract] Cited for: VARIANT GASC LEU-8, CHARACTERIZATION OF VARIANT GASC LEU-8.
[10]	"Interferon regulatory factor 1 tryptophan 11 to arginine point mutation abolishes DNA binding." Eason D.D., Shepherd A.T., Blanck G. Biochim. Biophys. Acta 1446:140-144(1999) [PubMed: 10395927] [Abstract] Cited for: VARIANT GASC ARG-11.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. NM_002198.2.
UniGene	Hs.436061.
3D structure databases
ProteinModelPortal	P10914.
SMR	P10914. Positions 7-111.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-40988N.
IntAct	P10914. 2 interactions.
MINT	MINT-123145.
STRING	P10914.
PTM databases
PhosphoSite	P10914.
Polymorphism databases
DMDM	20178295.
Proteomic databases
PRIDE	P10914.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000245414; ENSP00000245414; ENSG00000125347. ENST00000405885; ENSP00000384406; ENSG00000125347.
GeneID	3659.
KEGG	hsa:3659.
UCSC	uc003kxa.1. human.
Organism-specific databases
CTD	3659.
GeneCards	GC05M131846.
H-InvDB	HIX0005159. HIX0200727.
HGNC	HGNC:6116. IRF1.
HPA	CAB011662.
MIM	147575. gene. 613659. phenotype.
neXtProt	NX_P10914.
PharmGKB	PA29915.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17305.
HOGENOM	HBG443977.
HOVERGEN	HBG003455.
InParanoid	P10914.
OMA	CKEEPEV.
OrthoDB	EOG4JWVDV.
PhylomeDB	P10914.
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.
Reactome	REACT_604. Hemostasis. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P10914.
Bgee	P10914.
CleanEx	HS_IRF1.
Genevestigator	P10914.
GermOnline	ENSG00000125347. Homo sapiens.
Family and domain databases
InterPro	IPR017431. Interferon_reg_fac-1/2. IPR019817. Interferon_reg_fac_CS. IPR001346. Interferon_reg_fact_DNA-bd_dom. IPR011991. WHTH_trsnscrt_rep_DNA-bd. [Graphical view]
Gene3D	G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
KO	K09444.
Pfam	PF00605. IRF. 1 hit. [Graphical view]
PIRSF	PIRSF038196. IFN_RF1/2. 1 hit.
PRINTS	PR00267. INTFRNREGFCT.
SMART	SM00348. IRF. 1 hit. [Graphical view]
PROSITE	PS00601. IRF_1. 1 hit. PS51507. IRF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
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:	January 25, 2012
This is version 115 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.