Transcriptional regulators RcnR and FrmR, and related domains; this domain family was previously known as part of DUF156
This domain family includes various transcriptional regulators that respond to different stressors. It includes Escherichia coli RncR (formally known as YohL, nickel and cobalt-sensitive), and E. coli FrmR (formally known as YaiN, formaldehyde sensitive). Escherichia coli RncR represses expression of the gene encoding the nickel and cobalt-efflux protein RcnA; RcnA may act through modulating NikR, to repress the NIkABCDE nickel transporter. In vitro, purified RncR binds to the rncA promoter DNA fragment in the absence of Ni2+ or Co2+, and the affinity of RncR for this promoter is reduced in the presence of excess nickel. Escherichia coli FrmR regulates the formaldehyde degradation frmRAB operon. This family belongs to a larger superfamily that includes CsoRs (copper-sensitive operon repressors). CsoRs form homotetramers (dimer of dimers). In Mycobacterium tuberculosis CsoR, within each dimer, two Cys residues on opposite subunits, along with a His residue, bind the Cu(I) ion (forming a triagonal S2N coordination complex, C-H-C). These residues are conserved in the majority of members of this superfamily. In this family, however, not all these residues are conserved; in E.coli RcnR and FrmR there is a His or a Thr instead of the second Cys (C-H-H or C-H-T) respectively. For E. coli FrmR, an N-terminal His residue, not conserved in all members of this family, is also involved in metal binding (H-C-H-H). A conserved Tyr and a Glu residue that facilitate allosteric regulation of DNA binding for CsoRs are poorly conserved in this family.
Feature 1:putative metal binding site [ion binding site]
Evidence:
Comment:based on other superfamily members with structure: Thermus thermophilus CsoR/TthCsoR, and on Mycobacterium tuberculosis CsoR/MtCsoR, bound to Cu(I)
Comment:not all members of this family may be responsive to metal ions, FrmR is a regulator of an operon induced by formaldehyde
Comment:MtCsoR forms a homotetramer (dimer of dimers); each CsoR homodimer contains two symmetry-related subunit-bridging Cu(I) binding sites, one on either end. Each Cu(I) is coordinated by a Cys residue from one monomer, and a His and Cys residue from its partner monomer. In this family, not all these residues are conserved: for example, nickel/cobalt-sensitive RncR (C-H-H) and formaldehyde-sensitive FrmR (C-H-T); for RcnR, the most N-terminal His residue may also be involved in metal-ion binding.
Jiyao W et al.(2023). "The conserved domain database in 2023.",