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42  structures 6565  species 0  interactions 91401  sequences 301  architectures

Family: Sigma70_r4_2 (PF08281)

Summary: Sigma-70, region 4

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This is the Wikipedia entry entitled "Sigma factor". More...

Sigma factor Edit Wikipedia article

A sigma factor (σ factor or specificity factor) is a protein needed for initiation of transcription in bacteria.[1][2] It is a bacterial transcription initiation factor that enables specific binding of RNA polymerase (RNAP) to gene promoters. It is homologous to archaeal transcription factor B and to eukaryotic factor TFIIB.[3] The specific sigma factor used to initiate transcription of a given gene will vary, depending on the gene and on the environmental signals needed to initiate transcription of that gene. Selection of promoters by RNA polymerase is dependent on the sigma factor that associates with it.[4] They are also found in plant chloroplasts as a part of the bacteria-like plastid-encoded polymerase (PEP).[5]

The sigma factor, together with RNA polymerase, is known as the RNA polymerase holoenzyme. Every molecule of RNA polymerase holoenzyme contains exactly one sigma factor subunit, which in the model bacterium Escherichia coli is one of those listed below. The number of sigma factors varies between bacterial species.[1][6] E. coli has seven sigma factors. Sigma factors are distinguished by their characteristic molecular weights. For example, σ70 is the sigma factor with a molecular weight of 70 kDa.

The sigma factor in the RNA polymerase holoenzyme complex is required for the initiation of transcription, although once that stage is finished, it is dissociated from the complex and the RNAP continues elongation on its own.

Specialized sigma factors

Different sigma factors are utilized under different environmental conditions. These specialized sigma factors bind the promoters of genes appropriate to the environmental conditions, increasing the transcription of those genes.

Sigma factors in E. coli:

  • σ70(RpoD) – σA – the "housekeeping" sigma factor or also called as primary sigma factor (Group 1), transcribes most genes in growing cells. Every cell has a "housekeeping" sigma factor that keeps essential genes and pathways operating.[1] In the case of E. coli and other gram-negative rod-shaped bacteria, the "housekeeping" sigma factor is σ70.[1] Genes recognized by σ70 all contain similar promoter consensus sequences consisting of two parts.[1] Relative to the DNA base corresponding to the start of the RNA transcript, the consensus promoter sequences are characteristically centered at 10 and 35 nucleotides before the start of transcription (−10 and −35).
  • σ19 (FecI) – the ferric citrate sigma factor, regulates the fec gene for iron transport and metabolism
  • σ24 (RpoE) – extreme heat stress response and the extracellular proteins sigma factor
  • σ28 (RpoF/FliA) – the flagellar synthesis and chemotaxis sigma factor
  • σ32 (RpoH) – the heat shock sigma factor, it is turned on when the bacteria are exposed to heat. Due to the higher expression, the factor will bind with a high probability to the polymerase-core-enzyme. Doing so, other heatshock proteins are expressed, which enable the cell to survive higher temperatures. Some of the enzymes that are expressed upon activation of σ32 are chaperones, proteases and DNA-repair enzymes.
  • σ38 (RpoS) – the starvation/stationary phase sigma factor
  • σ54 (RpoN) – the nitrogen-limitation sigma factor

There are also anti-sigma factors that inhibit the function of sigma factors and anti-anti-sigma factors that restore sigma factor function.


Domain organization, promoter recognition and structural organization of the σ70 family. (a) The domain organization of σ factors from Groups 1, 3 and 4 are illustrated above σ70 consensus E. coli promoter DNA. (b) Organization of E. coli σ70 in an RNA polymerase transcription initiation complex. (PDB 4YLN).

By sequence similarity, most sigma factors are σ70-like (InterPro: IPR000943). They have four main regions (domains) that are generally conserved:

N-terminus --------------------- C-terminus
             1.1    2    3    4

The regions are further subdivided. For example, region 2 includes 1.2 and 2.1 through 2.4.

Domain 1.1 is found only in "primary sigma factors" (RpoD, RpoS in E.coli; "Group 1"). It is involved in ensuring the sigma factor will only bind the promoter when it is complexed with the RNA polymerase.[7] Domains 2-4 each interact with specific promoter elements and with RNAP. Region 2.4 recognizes and binds to the promoter −10 element (called the "Pribnow box"). Region 4.2 recognizes and binds to the promoter −35 element.[7]

Not every sigma factor of the σ70 family contains all the domains. Group 2, which includes RpoS, is very similar to Group 1 but lacks domain 1. Group 3 also lacks domain 1, and includes σ28. Group 4, also known as the Extracytoplasmic Function (ECF) group, lack both σ1.1 and σ3. RpoE is a member.[7]

Other known sigma factors are of the σ54/RpoN (InterPro: IPR000394) type. They are functional sigma factors, but they have significantly different primary amino acid sequences.[8]

Protein domain infoboxes
Sigma70 region 1.1
Sigma70 region 1.2
PDB 1ku2 EBI.jpg
Crystal structure of Thermus aquaticus RNA polymerase sigma subunit fragment containing regions 1.2 to 3.1
Sigma70 region 2
PDB 1sig EBI.jpg
Crystal structure of a sigma70 subunit fragment from Escherichia coli RNA polymerase
Pfam clanCL0123
Sigma70 region 3
PDB 1rp3 EBI.jpg
Solution structure of sigma70 region 3 from Thermotoga maritima
Pfam clanCL0123
Sigma70 region 4
PDB 1tty EBI.jpg
Solution structure of sigma70 region 4 from Thermotoga maritima
Pfam clanCL0123
Sigma70 region 4.2
PDB 2h27 EBI.jpg
Crystal structure of Escherichia coli sigma70 region 4 bound to its -35 element DNA
Pfam clanCL0123

Retention during transcription elongation

The core RNA polymerase (consisting of 2 alpha (α), 1 beta (β), 1 beta-prime (β'), and 1 omega (ω) subunits) binds a sigma factor to form a complex called the RNA polymerase holoenzyme. It was previously believed that the RNA polymerase holoenzyme initiates transcription, while the core RNA polymerase alone synthesizes RNA. Thus, the accepted view was that sigma factor must dissociate upon transition from transcription initiation to transcription elongation (this transition is called "promoter escape"). This view was based on analysis of purified complexes of RNA polymerase stalled at initiation and at elongation. Finally, structural models of RNA polymerase complexes predicted that, as the growing RNA product becomes longer than ~15 nucleotides, sigma must be "pushed out" of the holoenzyme, since there is a steric clash between RNA and a sigma domain. However, σ70 can remain attached in complex with the core RNA polymerase in early elongation[9] and sometimes throughout elongation.[10] Indeed, the phenomenon of promoter-proximal pausing indicates that sigma plays roles during early elongation. All studies are consistent with the assumption that promoter escape reduces the lifetime of the sigma-core interaction from very long at initiation (too long to be measured in a typical biochemical experiment) to a shorter, measurable lifetime upon transition to elongation.

Sigma cycle

It had long been thought that the sigma factor obligatorily leaves the core enzyme once it has initiated transcription, allowing it to link to another core enzyme and initiate transcription at another site. Thus, the sigma factor would cycle from one core to another. However, fluorescence resonance energy transfer was used to show that the sigma factor does not obligatorily leave the core.[9] Instead, it changes its binding with the core during initiation and elongation. Therefore, the sigma factor cycles between a strongly bound state during initiation and a weakly bound state during elongation.

See also


  1. ^ a b c d e Gruber TM, Gross CA (2003). "Multiple sigma subunits and the partitioning of bacterial transcription space". Annual Review of Microbiology. 57: 441–66. doi:10.1146/annurev.micro.57.030502.090913. PMID 14527287.
  2. ^ Kang JG, Hahn MY, Ishihama A, Roe JH (July 1997). "Identification of sigma factors for growth phase-related promoter selectivity of RNA polymerases from Streptomyces coelicolor A3(2)". Nucleic Acids Research. 25 (13): 2566–73. doi:10.1093/nar/25.13.2566. PMC 146787. PMID 9185565.
  3. ^ Burton SP, Burton ZF (6 November 2014). "The σ enigma: bacterial σ factors, archaeal TFB and eukaryotic TFIIB are homologs". Transcription. 5 (4): e967599. doi:10.4161/21541264.2014.967599. PMC 4581349. PMID 25483602.
  4. ^ Ho TD, Ellermeier CD (April 2012). "Extra cytoplasmic function σ factor activation". Current Opinion in Microbiology. 15 (2): 182–8. doi:10.1016/j.mib.2012.01.001. PMC 3320685. PMID 22381678.
  5. ^ Schweer J, Türkeri H, Kolpack A, Link G (December 2010). "Role and regulation of plastid sigma factors and their functional interactors during chloroplast transcription - recent lessons from Arabidopsis thaliana". European Journal of Cell Biology. 89 (12): 940–6. doi:10.1016/j.ejcb.2010.06.016. PMID 20701995.
  6. ^ Sharma UK, Chatterji D (September 2010). "Transcriptional switching in Escherichia coli during stress and starvation by modulation of sigma activity". FEMS Microbiology Reviews. 34 (5): 646–57. doi:10.1111/j.1574-6976.2010.00223.x. PMID 20491934.
  7. ^ a b c Paget MS (June 2015). "Bacterial Sigma Factors and Anti-Sigma Factors: Structure, Function and Distribution". Biomolecules. 5 (3): 1245–65. doi:10.3390/biom5031245. PMC 4598750. PMID 26131973.
  8. ^ Merrick MJ (December 1993). "In a class of its own--the RNA polymerase sigma factor sigma 54 (sigma N)". Molecular Microbiology. 10 (5): 903–9. doi:10.1111/j.1365-2958.1993.tb00961.x. PMID 7934866. S2CID 84789281.
  9. ^ a b Kapanidis AN, Margeat E, Laurence TA, Doose S, Ho SO, Mukhopadhyay J, Kortkhonjia E, Mekler V, Ebright RH, Weiss S (November 2005). "Retention of transcription initiation factor sigma70 in transcription elongation: single-molecule analysis". Molecular Cell. 20 (3): 347–56. doi:10.1016/j.molcel.2005.10.012. PMID 16285917.
  10. ^ Harden TT, Wells CD, Friedman LJ, Landick R, Hochschild A, Kondev J, Gelles J (January 2016). "Bacterial RNA polymerase can retain σ70 throughout transcription". Proc Natl Acad Sci U S A. 113 (3): 602–7. Bibcode:2016PNAS..113..602H. doi:10.1073/pnas.1513899113. PMC 4725480. PMID 26733675.

External links

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.

Sigma-70, region 4 Provide feedback

Region 4 of sigma-70 like sigma-factors are involved in binding to the -35 promoter element via a helix-turn-helix motif [1].

Literature references

  1. Campbell EA, Muzzin O, Chlenov M, Sun JL, Olson CA, Weinman O, Trester-Zedlitz ML, Darst SA; , Mol Cell 2002;9:527-539.: Structure of the bacterial RNA polymerase promoter specificity sigma subunit. PUBMED:11931761 EPMC:11931761

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR013249

The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [ PUBMED:3052291 ]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.

With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [ PUBMED:3092189 , PUBMED:1597408 ].

The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [ PUBMED:25596450 ].

Region 4 of sigma-70 like sigma-factors are involved in binding to the -35 promoter element via a helix-turn-helix motif [ PUBMED:11931761 ].

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 381 members:

AbiEi_3_N AbiEi_4 ANAPC2 AphA_like AraR_C Arg_repressor ARID ArsR B-block_TFIIIC B5 Bac_DnaA_C Baculo_PEP_N BetR BHD_3 BLACT_WH Bot1p BrkDBD BrxA BsuBI_PstI_RE_N C_LFY_FLO CaiF_GrlA CarD_CdnL_TRCF CDC27 Cdc6_C Cdh1_DBD_1 CDT1 CDT1_C CENP-B_N Costars CPSase_L_D3 Cro Crp CSN4_RPN5_eIF3a CSN8_PSD8_EIF3K CtsR Cullin_Nedd8 CUT CUTL CvfB_WH DBD_HTH DDRGK DEP Dimerisation Dimerisation2 DNA_binding_1 DNA_meth_N DpnI_C DprA_WH DsrC DsrD DUF1016_N DUF1133 DUF1153 DUF1323 DUF134 DUF1376 DUF1441 DUF1492 DUF1495 DUF1670 DUF1804 DUF1836 DUF1870 DUF2089 DUF2250 DUF2316 DUF2513 DUF2551 DUF2582 DUF3116 DUF3161 DUF3253 DUF3489 DUF3853 DUF3860 DUF3895 DUF3908 DUF433 DUF434 DUF4364 DUF4373 DUF4423 DUF4447 DUF4777 DUF480 DUF4817 DUF5635 DUF573 DUF5805 DUF6088 DUF6262 DUF6362 DUF6432 DUF6462 DUF6471 DUF722 DUF739 DUF742 DUF937 DUF977 E2F_TDP EAP30 eIF-5_eIF-2B ELL ESCRT-II Ets EutK_C Exc F-112 FaeA Fe_dep_repr_C Fe_dep_repress FeoC FokI_D1 FokI_dom_2 Forkhead FtsK_gamma FUR GcrA GerE GntR GP3_package HARE-HTH HemN_C HNF-1_N Homeobox_KN Homeodomain 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_48 HTH_49 HTH_5 HTH_50 HTH_51 HTH_52 HTH_53 HTH_54 HTH_55 HTH_56 HTH_57 HTH_58 HTH_59 HTH_6 HTH_60 HTH_61 HTH_7 HTH_8 HTH_9 HTH_ABP1_N HTH_AraC HTH_AsnC-type HTH_CodY HTH_Crp_2 HTH_DeoR HTH_IclR HTH_Mga HTH_micro HTH_OrfB_IS605 HTH_PafC HTH_ParB HTH_psq HTH_SUN2 HTH_Tnp_1 HTH_Tnp_1_2 HTH_Tnp_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 KilA-N Kin17_mid KORA KorB La LacI LexA_DNA_bind Linker_histone LZ_Tnp_IS481 MADF_DNA_bdg MAGE MARF1_LOTUS MarR MarR_2 MC6 MC7 MC8 MerR MerR-DNA-bind MerR_1 MerR_2 Mga Mnd1 MogR_DNAbind Mor MotA_activ MqsA_antitoxin MRP-L20 Mrr_N MukE 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 NFRKB_winged NOD2_WH NUMOD1 ORC_WH_C OST-HTH P22_Cro PaaX PadR PapB PAX PCI Penicillinase_R Phage_AlpA Phage_antitermQ Phage_CI_repr Phage_CII Phage_NinH Phage_Nu1 Phage_rep_O Phage_rep_org_N Phage_terminase PheRS_DBD1 PheRS_DBD2 PheRS_DBD3 PhetRS_B1 Pou Pox_D5 PqqD PRC2_HTH_1 PUFD PuR_N Put_DNA-bind_N pXO2-72 Raf1_HTH Rap1-DNA-bind Rep_3 RepA_C RepA_N RepB RepC RepL Replic_Relax RFX_DNA_binding Ribosomal_S18 Ribosomal_S19e Ribosomal_S25 Rio2_N RNA_pol_Rpc34 RNA_pol_Rpc82 RNase_H2-Ydr279 ROQ_II ROXA-like_wH RP-C RPA RPA_C RPN6_C_helix RQC Rrf2 RTP RuvB_C S10_plectin 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 SinI SKA1 Ski_Sno SLIDE Slx4 SMC_Nse1 SMC_ScpB SoPB_HTH SpoIIID SRP19 SRP_SPB STN1_2 Stn1_C Stork_head Sulfolobus_pRN Suv3_N Swi6_N SWIRM Tau95 TBPIP TEA Terminase_5 TetR_N TFA2_Winged_2 TFIIE_alpha TFIIE_beta TFIIF_alpha TFIIF_beta Tn7_Tnp_TnsA_C Tn916-Xis TraI_2_C Trans_reg_C TrfA TrmB tRNA_bind_2 tRNA_bind_3 Trp_repressor UPF0122 UPF0175 Vir_act_alpha_C XPA_C Xre-like-HTH YdaS_antitoxin YidB 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: Pfam-B_125 (Release 17.0)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 141
Number in full: 91401
Average length of the domain: 53.40 aa
Average identity of full alignment: 25 %
Average coverage of the sequence by the domain: 24.26 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.7 25.7
Trusted cut-off 25.7 25.7
Noise cut-off 25.6 25.6
Model length: 54
Family (HMM) version: 15
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Species distribution

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


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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 Sigma70_r4_2 domain has been found. There are 42 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 sequence.

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