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35  structures 133  species 3  interactions 1034  sequences 13  architectures

Family: IRF (PF00605)

Summary: Interferon regulatory factor transcription factor

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This is the Wikipedia entry entitled "Interferon regulatory factors". More...

Interferon regulatory factors Edit Wikipedia article

Interferon regulatory factor transcription factor
PDB 1irf EBI.jpg
interferon regulatory factor-2 dna binding domain, nmr, minimized average structure
Symbol IRF
Pfam PF00605
InterPro IPR001346
SCOP 1if1

Interferon regulatory factors are proteins which regulate transcription of interferons (see regulation of gene expression).[1]

They are used in the JAK-STAT signaling pathway.[2]

Interferon regulatory factors contain a conserved N-terminal region of about 120 amino acids, which folds into a structure that binds specifically to the interferon consensus sequence (ICS), which is located upstream of the interferon genes.[3] The remaining parts of the interferon regulatory factor sequence vary depending on the precise function of the protein.[3]


See also


  1. ^ Paun A, Pitha PM (2007). "The IRF family, revisited". Biochimie. 89 (6–7): 744–53. doi:10.1016/j.biochi.2007.01.014. PMC 2139905Freely accessible. PMID 17399883. 
  2. ^ Tsuneya Ikezu; Howard E. Gendelman (2008). Neuroimmune Pharmacology. Springer. pp. 213–. ISBN 978-0-387-72572-7. Retrieved 28 November 2010. 
  3. ^ a b Weisz A, Marx P, Sharf R, Appella E, Driggers PH, Ozato K, Levi BZ (December 1992). "Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes". J. Biol. Chem. 267 (35): 25589–96. PMID 1460054. 

External links

This article incorporates text from the public domain Pfam and InterPro IPR001346

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Interferon regulatory factor transcription factor Provide feedback

This family of transcription factors are important in the regulation of interferons in response to infection by virus and in the regulation of interferon-inducible genes. Three of the five conserved tryptophan residues bind to DNA.

Literature references

  1. Escalante CR, Yie J, Thanos D, Aggarwal AK; , Nature 1998;1:103-106.: Structure of IRF-1 with bound DNA reveals determinants of interfereon regulation. PUBMED:9422515 EPMC:9422515

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001346

Viral infections induce the expression of type I interferons (IFN-alpha and IFN-beta) genes. The induction is due to the transcriptional activation of the IFN genes. Interferon regulatory factor I (IRF-1) is one of the transcription factors responsible for that activation. IRF-1 binds to an upstream regulatory cis element, known as the interferon consensus sequence (ICS), which is found in the promoters of type I IFN and IFN-inducible MHC class I genes. Interferon regulatory factor 2 (IRF-2) is a protein that also interacts with the ICS, but that does not function as an activator; rather, it suppresses the function of IRF-1 under certain circumstances [PUBMED:2691585].

These proteins share a highly conserved N-terminal domain of about 100 amino acid residues which is involved in DNA-binding and which contain five conserved tryptophans. This domain is known as a 'tryptophan pentad repeat' or a 'tryptophan cluster' and is also present in:

  • Interferon consensus sequence binding protein (ICSBP) [PUBMED:2111015], a transcription factor expressed predominantly in lymphoid tissues and induced by IFN-gamma that also binds to the ICS.
  • Transcriptional regulator ISGF3 gamma subunit [PUBMED:1630447]. ISGF3 is responsible for the initial stimulation of interferon-alpha-responsive genes. It recognises and binds to the interferon-stimulated response element (ISRE) within the regulatory sequences of target genes.
  • Interferon regulatory factor 3 (IRF-3).
  • Interferon regulatory factor 4 (IRF-4) which binds to the interferon- stimulated response element (ISRE) of the MHC class I promoter.
  • Interferon regulatory factor 5 (IRF-5).
  • Interferon regulatory factor 6 (IRF-6).
  • Interferon regulatory factor 7 (IRF-7).
  • Gamma Herpesviruses vIRF-1, -2 and -3, proteins with homology to the cellular transcription factors of the IRF family [PUBMED:10933732]. Neither vIRF-1 nor vIRF-2 bind to DNA with the same specificity as cellular IRFs, indicating that if vIRFs are DNA-binding proteins, their binding has a pattern distinct from that of the cellular IRFs. Whether vIRF-3 can bind DNA with the same specificity as cellular IRFs is not known.

The IRF tryptophan pentad repeat DNA-binding domain has an alpha/beta architecture comprising a cluster of three alpha-helices (alpha1-alpha3) flanked on one side by a mixed four-stranded beta-sheet (beta1-beta4). It forms a helix-turn-helix motif that binds to ISRE consensus sequences found in target promoters. Three of the tryptophan residues contact DNA by recognising a GAAA sequence [PUBMED:9422515].

This entry represents the IRF tryptophan pentad repeat DNA-binding domain.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan HTH (CL0123), which has the following description:

This family contains a diverse range of mostly DNA-binding domains that contain a helix-turn-helix motif.

The clan contains the following 256 members:

AbiEi_3_N AbiEi_4 ANAPC2 AphA_like Arg_repressor ARID B-block_TFIIIC Bac_DnaA_C BetR Bot1p BrkDBD C_LFY_FLO Cdc6_C CENP-B_N Cro Crp CSN8_PSD8_EIF3K Cullin_Nedd8 CUT DDRGK DEP Dimerisation Dimerisation2 DsrD DUF1133 DUF1153 DUF1323 DUF134 DUF1441 DUF1492 DUF1495 DUF1670 DUF1804 DUF1836 DUF1870 DUF2089 DUF2250 DUF2316 DUF2582 DUF3116 DUF3253 DUF3853 DUF3860 DUF3908 DUF433 DUF4364 DUF4447 DUF480 DUF722 DUF739 DUF742 DUF977 E2F_TDP EAP30 ELL ESCRT-II Ets Exc F-112 FaeA Fe_dep_repr_C Fe_dep_repress FeoC FokI_C FokI_N Forkhead Ftsk_gamma FUR GcrA GerE GntR HARE-HTH HemN_C HNF-1_N Homeobox Homeobox_KN Homez HPD HrcA_DNA-bdg HSF_DNA-bind HTH_1 HTH_10 HTH_11 HTH_12 HTH_13 HTH_15 HTH_16 HTH_17 HTH_18 HTH_19 HTH_20 HTH_21 HTH_22 HTH_23 HTH_24 HTH_25 HTH_26 HTH_27 HTH_28 HTH_29 HTH_3 HTH_30 HTH_31 HTH_32 HTH_33 HTH_34 HTH_35 HTH_36 HTH_37 HTH_38 HTH_39 HTH_40 HTH_41 HTH_42 HTH_43 HTH_45 HTH_46 HTH_47 HTH_5 HTH_6 HTH_7 HTH_8 HTH_9 HTH_AraC HTH_AsnC-type HTH_CodY HTH_Crp_2 HTH_DeoR HTH_IclR HTH_Mga HTH_micro HTH_OrfB_IS605 HTH_psq HTH_Tnp_1 HTH_Tnp_1_2 HTH_Tnp_4 HTH_Tnp_IS1 HTH_Tnp_IS630 HTH_Tnp_ISL3 HTH_Tnp_Mu_1 HTH_Tnp_Mu_2 HTH_Tnp_Tc3_1 HTH_Tnp_Tc3_2 HTH_Tnp_Tc5 HTH_WhiA HxlR IBD IF2_N IRF KicB KORA KorB La LacI LexA_DNA_bind Linker_histone LZ_Tnp_IS481 MADF_DNA_bdg MarR MarR_2 MerR MerR-DNA-bind MerR_1 MerR_2 Mga Mnd1 Mor MotA_activ MqsA_antitoxin MRP-L20 Myb_DNA-bind_2 Myb_DNA-bind_3 Myb_DNA-bind_4 Myb_DNA-bind_5 Myb_DNA-bind_6 Myb_DNA-bind_7 Myb_DNA-binding Neugrin NUMOD1 OST-HTH P22_Cro PaaX PadR PAX PCI Penicillinase_R Phage_AlpA Phage_antitermQ Phage_CI_repr Phage_CII Phage_rep_org_N Phage_terminase Pou Pox_D5 PuR_N Put_DNA-bind_N Rap1-DNA-bind Rep_3 RepA_C RepA_N RepC RepL Replic_Relax RFX_DNA_binding Ribosomal_S19e Ribosomal_S25 Rio2_N RNA_pol_Rpc34 RP-C RPA RPA_C RQC Rrf2 RTP RuvB_C SAC3_GANP SANT_DAMP1_like SatD SelB-wing_1 SelB-wing_2 SelB-wing_3 SgrR_N Sigma54_CBD Sigma54_DBD Sigma70_ECF Sigma70_ner Sigma70_r2 Sigma70_r3 Sigma70_r4 Sigma70_r4_2 SLIDE SMC_ScpB SpoIIID STN1_2 Sulfolobus_pRN SWIRM TBPIP Terminase_5 TetR_N TFIIE_alpha TFIIE_beta TFIIF_alpha TFIIF_beta Tn7_Tnp_TnsA_C Tn916-Xis TraI_2_C Trans_reg_C TrfA TrmB Trp_repressor UPF0122 Vir_act_alpha_C YdaS_antitoxin YjcQ YokU z-alpha


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Curation and family details

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Curation View help on the curation process

Seed source: [1]
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 90
Number in full: 1034
Average length of the domain: 101.80 aa
Average identity of full alignment: 47 %
Average coverage of the sequence by the domain: 25.96 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.0 21.0
Trusted cut-off 21.5 23.1
Noise cut-off 20.4 20.9
Model length: 105
Family (HMM) version: 16
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Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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There are 3 interactions for this family. More...



For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the IRF domain has been found. There are 35 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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