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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487634942  3 STPEEKKKVLTRVRRIRGQIDALERSLEGDAECRAILQQIAAVRGAANGLMAEGLESHIRETFDRNDCYSREVSQSVDDT 82
Cdd:cd10153   1 HTPKEKKKLLARVRRIRGQVEALERALEAEADCAAVLQQIAAVRGAVNGLMAEVLESHLREHVADPELSDAERAQAAEEL 80

                ....*...
gi 487634942 83 IELVRAYL 90
Cdd:cd10153  81 IEVLRSYL 88

Metal-sensitive transcriptional repressor; This is a family of metal-sensitive repressors, involved in resistance to metal ions. Members of this family bind copper, nickel or cobalt ions via conserved cysteine and histidine residues. In the absence of metal ions, these proteins bind to promoter regions and repress transcription. When bound to metal ions they are unable to bind DNA, leading to transcriptional derepression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487634942   7 EKKKVLTRVRRIRGQIDALERSLEGDAECRAILQQIAAVRGAANGLMAEGLESHIRETFDRNDCYSREvsQSVDDTIELV 86
Cdd:pfam02583  1 EKKKLLNRLKRIEGQVRGIERMIEEDRYCIDILTQLAAVRSALNGVGKEILEDHLRHCVVEAIEEGRE--EKIEELIELL 78

                 .
gi 487634942  87 R 87
Cdd:pfam02583 79 K 79

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487634942  3 STPEEKKKVLTRVRRIRGQIDALERSLEGDAECRAILQQIAAVRGAANGLMAEGLESHIRETFDRNDCYSREVSQSVDDT 82
Cdd:cd10153   1 HTPKEKKKLLARVRRIRGQVEALERALEAEADCAAVLQQIAAVRGAVNGLMAEVLESHLREHVADPELSDAERAQAAEEL 80

                ....*...
gi 487634942 83 IELVRAYL 90
Cdd:cd10153  81 IEVLRSYL 88

Metal-sensitive transcriptional repressor; This is a family of metal-sensitive repressors, involved in resistance to metal ions. Members of this family bind copper, nickel or cobalt ions via conserved cysteine and histidine residues. In the absence of metal ions, these proteins bind to promoter regions and repress transcription. When bound to metal ions they are unable to bind DNA, leading to transcriptional derepression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487634942   7 EKKKVLTRVRRIRGQIDALERSLEGDAECRAILQQIAAVRGAANGLMAEGLESHIRETFDRNDCYSREvsQSVDDTIELV 86
Cdd:pfam02583  1 EKKKLLNRLKRIEGQVRGIERMIEEDRYCIDILTQLAAVRSALNGVGKEILEDHLRHCVVEAIEEGRE--EKIEELIELL 78

                 .
gi 487634942  87 R 87
Cdd:pfam02583 79 K 79

Transcriptional regulators CsoR (copper-sensitive operon repressor), RcnR, and FrmR, and related domains; this domain superfamily was previously known as DUF156; This superfamily includes various transcriptional regulators that respond to stressors including Cu(I), Ni(I), sulfite, and formaldehyde. It includes CsoR (copper-sensitive operon repressor) from Mycobacterium tuberculosis (MtCsoR), Bacillus subtilis (BsCsoR), Thermus thermophilus (TthCsoR), and Staphylococcus aureus (SaCsoR), Mycobacterium tuberculosis RicR (regulated in copper repressor, MtRicR), Escherichia coli RncR (formally known as YohL, nickel and cobalt-sensitive), Alcaligenes xylosoxidans NreA (nickel-sensitive), E. coli FrmR (formally known as YaiN, formaldehyde sensitive), and Staphylococcus aureus CstR (CsoR-like sulfur transferase repressor, NWMN_0026.5, SaCstR). CsoR is Cu(I)-inducible, and regulates the expression of genes involved in copper homeostasis. For example, TthCsoR binds the promoter region of the copZ-csoR-copA operon, and represses expression of these genes, which encode the copper chaperone CopZ, CsoR, and the copper efflux P-type ATPase CopA, respectively. In the presence of excess Cu(I), TthCsoR binds this ion, and is released from the DNA, allowing expression of the downstream genes. TthCsoR also senses other metal ions such as Cu(II), Zn(II), Ag(I), Cd(II) and Ni(II). CsoRs form a homotetramer (dimer of dimers). In the case of MtCsoR, two Cys residues on opposite subunits within each dimer, along with a His residue, bind the Cu(I) ion. These residues are conserved in the majority of members of this superfamily. Exceptions include the functionally uncharacterized Bacillus subtilis YrkD where there is an Asn instead of His (C-N-C), E.coli RcnR where there is a Thr instead of the second Cys (C-H-T), or TthCsoR and E.coli FrmR where there is a His instead of the second Cys and which have an additional N-terminal His (not found in those family members having C-H-C) that may also be involved in metal binding (H-C-H-H). A conserved Tyr and a Glu residue facilitate allosteric regulation of DNA binding. SaCstR regulates genes predicted to function in sulfur metabolism; it is thought that oxidation of the intersubunit Cys pair to a mixture of disulphide and trisulphide linkages by sulfite, results in a reduced affinity of SaCstR for the operator DNA. SaCstR exists as a mixture of oligomeric states, including dimers, tetramers and octamers. The sequence of SaCstR was not available at the time this hierarchy was curated and therefore was not included. Escherichia coli RncR represses expression of the gene encoding the nickel and cobalt-efflux protein RcnA. The gene encoding Alcaligenes xylosoxidans NreA is part of the nre nickel resistance locus located on the pTOM9 plasmid from thisbacteria. Escherichia coli FrmR regulates the formaldehyde degradation frmRAB operon.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487634942  8 KKKVLTRVRRIRGQIDALERSLEGDAECRAILQQIAAVRGAANGLMAEGLESHIRETFDRNDCySREVSQSVDDTIELVR 87
Cdd:cd10148   1 KKDLLKRLRRIEGQVRGIQRMIEEDRYCVDILTQLAAVRSALDKVGLLILEDHLKHCVAEAIE-SGEAEEKIEELLKLLK 79

Staphylococcus aureus copper-sensitive operon repressor (CsoR), and related domains; this family was previously known as part of DUF156; This domain family includes Staphylococcus aureus CsoR (SaCsoR). SaCsoR is Cu(I)-inducible, and regulates the expression of genes involved in copper homeostasis; it represses a genetically unlinked copA-copZ operon. copA encodes a copper efflux P-type ATPase, and copZ, a copper chaperone. This family belongs to a larger superfamily that contains various transcriptional regulators that respond to different stressors such as Cu(I), Ni(I), sulfite, and formaldehyde, and includes Mycobacterium tuberculosis CsoR (MtCsoR), Bacillus subtilis CsoR, and Thermus thermophilus CsoR. The latter three proteins do not belong to this family. CsoRs form homotetramers (dimer of dimers). In MtCsoR, 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, including this family, and a conserved Tyr and a Glu residue that facilitate allosteric regulation of DNA binding for CsoRs are also well conserved.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 487634942  8 KKKVLTRVRRIRGQIDALERSLEGDAECRAILQQIAAVRGAANGLMAEGLESHIRetfdrnDCYSREVSQSVDDTIE 84
Cdd:cd10152   1 KKNLINRLNRIEGQIRGIKGMIENDVYCDDVLNQIASVKSALDGVSKLLLESHIK------SCVVEQIKEGEEEVVE 71

Thermus thermophilus CsoR, a Cu(I)-sensing transcriptional regulator, and related domains; this domain family was previously known as part of DUF156; This domain family contains various Cu(I)-inducible transcriptional regulators including CsoR (copper-sensitive operon repressor) from Mycobacterium tuberculosis (MtCsoR), and Thermus thermophilus (TthCsoR). CsoR regulates the expression of genes involved in copper homeostasis. For example, TthCsoR binds the promoter region of the copZ-csoR-copA operon, and represses expression of these genes, which encode the copper chaperone CopZ, CsoR, and the copper efflux P-type ATPase CopA, respectively. In the presence of excess Cu(I), TthCsoR binds this ion, and is released from the DNA, allowing expression of the downstream genes. TthCsoR also senses other metal ions such as Cu(II), Zn(II), Ag(I), Cd(II) and Ni(II). MtCsoR regulates an operon that includes CsoR and a putative copper transporter gene, ctpV (cation transporter P-type ATPase). CsoRs form a homotetramer (dimer of dimers). In MtCsoR, 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 some but not all members of this family; for example, for TthCsoR, there is a His instead of the second Cys as well as an N-terminal His (not found in those family members having C-H-C) which may also be involved in metal binding (H-C-H-H). A conserved Tyr and a Glu residue facilitate allosteric regulation of DNA binding.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 487634942  6 EEKKKVLTRVRRIRGQIDALERSLEGDAECRAILQQIAAVRGA---ANGLMAEG-LESHIRETFDRND 69
Cdd:cd10151   1 AKKEDALRRLKIIEGHLEGIQKMLEEDKYCVDVLRQIKAVQSAlekVSDLILEGhLESCVTTAIERGE 68

Uncharacterized protein YrkD from Bacillus subtilis and related domains; this domain superfamily was previously known as part of DUF156; This domain family contains an uncharacterized protein YrkD from Bacillus subtilis and related proteins. This family is part of a larger superfamily that contains various transcriptional regulators that respond to different stressors such as Cu(I), Ni(I), sulfite, and formaldehyde, and 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, there is an Asn instead of the His (C-N-C); also a conserved Tyr and a Glu residue that facilitates allosteric regulation of DNA binding for CsoRs are very poorly conserved.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 487634942  8 KKKVLTRVRRIRGQIDALERSLEGDAECRAILQQIAAVRGAANGLMAEGLESHIRETFDRNDCYSREVSQSVDDTIELV 86
Cdd:cd10155   1 DKKIKNRLKRAEGQLRGILKMMEEGKECKDVVTQLSAVRSSVDRAIGLIVAENLEECVREEEEDGEDQEEKIQEAINLL 79

Uncharacterized family 4; belongs to a superfamily containing the transcriptional regulators CsoR (copper-sensitive operon repressor), RcnR, and FrmR, and related domains; this family was previously known as part of DUF156; Uncharacterized family 4, belonging to a larger superfamily that contains various transcriptional regulators that respond to different stressors such as Cu(I), Ni(I), sulfite, and formaldehyde, and 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, only one of these residues is conserved (the first Cys); and a conserved Tyr and a Glu residue that facilitate allosteric regulation of DNA binding for CsoRs are also not conserved.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 487634942  8 KKKVLTRVRRIRGQIDALERSLEGDAECRAILQQIAAVRGAANGLMAEGLESHIRETFDRNDCYSREVSQSVDDTIELVR 87
Cdd:cd10161   1 RTGLLNRLARVEGQIRGIQRMIEEGEDCESIAQQMSASRKALDKAYCEMLACFIEQEIQEEGQLNDAVQTMLSDVTTLLT 80

                ..
gi 487634942 88 AY 89
Cdd:cd10161  81 KY 82