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P10914 (IRF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interferon regulatory factor 1

Short name=IRF-1
Gene names
Name:IRF1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length325 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 325325Interferon regulatory factor 1
PRO_0000154545

Regions

DNA binding5 – 113109IRF tryptophan pentad repeat

Amino acid modifications

Cross-link275Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.7
Cross-link299Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.7

Natural variations

Natural variant81M → L in GASC; somatic mutation; produces a protein with markedly reduced transcriptional activity but unaltered DNA-binding activity. Ref.9
VAR_065134
Natural variant111W → R in GASC; the mutation abolishes DNA binding and transactivating activities. Ref.10
VAR_065135

Experimental info

Mutagenesis2751K → R: Some loss of sumoylation. Abolishes sumoylation, diminished ubiquitination, higher resistance to degradation, and increased apoptotic activity; when associated with R-299. Ref.7
Mutagenesis2991K → 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 conflict51R → W no nucleotide entry Ref.1
Sequence conflict51R → W no nucleotide entry Ref.2
Sequence conflict34 – 352FQ → LE no nucleotide entry Ref.1
Sequence conflict34 – 352FQ → LE no nucleotide entry Ref.2
Sequence conflict2201T → I no nucleotide entry Ref.1
Sequence conflict2201T → I no nucleotide entry Ref.2

Sequences

Sequence LengthMass (Da)Tools
P10914 [UniParc].

Last modified April 16, 2002. Version 2.
Checksum: 2E06245A212D1541

FASTA32536,502
        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 

« Hide

References

« Hide '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.

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.
IPIIPI00023600.
PIRB31595.
I52998.
RefSeqNP_002189.1. NM_002198.2.
UniGeneHs.436061.

3D structure databases

ProteinModelPortalP10914.
SMRP10914. Positions 7-111.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-40988N.
IntActP10914. 2 interactions.
MINTMINT-123145.
STRINGP10914.

PTM databases

PhosphoSiteP10914.

Polymorphism databases

DMDM20178295.

Proteomic databases

PRIDEP10914.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000245414; ENSP00000245414; ENSG00000125347.
ENST00000405885; ENSP00000384406; ENSG00000125347.
GeneID3659.
KEGGhsa:3659.
UCSCuc003kxa.1. human.

Organism-specific databases

CTD3659.
GeneCardsGC05M131846.
H-InvDBHIX0005159.
HIX0200727.
HGNCHGNC:6116. IRF1.
HPACAB011662.
MIM147575. gene.
613659. phenotype.
neXtProtNX_P10914.
PharmGKBPA29915.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG17305.
HOGENOMHBG443977.
HOVERGENHBG003455.
InParanoidP10914.
OMACKEEPEV.
OrthoDBEOG4JWVDV.
PhylomeDBP10914.

Enzyme and pathway databases

Pathway_Interaction_DBifngpathway. IFN-gamma pathway.
il12_stat4pathway. IL12 signaling mediated by STAT4.
il6_7pathway. IL6-mediated signaling events.
telomerasepathway. Regulation of Telomerase.
ReactomeREACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP10914.
BgeeP10914.
CleanExHS_IRF1.
GenevestigatorP10914.
GermOnlineENSG00000125347. Homo sapiens.

Family and domain databases

InterProIPR017431. 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]
Gene3DG3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
KOK09444.
PfamPF00605. IRF. 1 hit.
[Graphical view]
PIRSFPIRSF038196. IFN_RF1/2. 1 hit.
PRINTSPR00267. INTFRNREGFCT.
SMARTSM00348. IRF. 1 hit.
[Graphical view]
PROSITEPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio14311.
SOURCESearch...

Entry information

Entry nameIRF1_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families