The Escherichia coli Ada protein repairs O6-methylguanine residues and methyl phosphotriesters in DNA by direct transfer of the methyl group to a cysteine residue. This domain contains four conserved cysteines that form a zinc binding site [, ]. One of these cysteines is a methyl group acceptor. The methylated domain can then specifically bind to the ada box on a DNA duplex. The zinc binding site is located in the N-terminal region and consists of four beta strands [].
Protein AHC1 is a component of the transcription regulatory histone acetylation (HAT) complex ADA and it required for its overall structural integrity [].The ADA complex is a transcription regulatory histone acetylation (HAT) complex. ADA preferentially acetylates nucleosomal histones H3 (at 'Lys-14' and 'Lys-18') and H2B. The complex consists of at least ADA2, ADA3, AHC1, and GCN5. AHC1 is required for the overall structural integrity of the ADA complex [].
The Escherichia coli Ada protein repairs O6-methylguanine residues and methyl phosphotriesters in DNA by direct transfer of the methyl group to a cysteine residue. This domain contains four conserved cysteines that form a zinc binding site [, ]. One of these cysteines is a methyl group acceptor. The methylated domain can then specifically bind to the ada box on a DNA duplex. The zinc binding site is located in the N-terminal region and consists of four beta strands [].The methylation of the N-terminal site of Ada induces a structural change, which is independent of the transferred methyl group but enhances the promoter affinity of a remodeled surface region, trigger of the transcriptional enhancement of the ada regulon [, ].This superfamily represents the N-terminal domain of the Ada domain as well as the C-terminal domain of some ribosomal proteins (L17 from Actinobacteria and S1 from Candidatus Peregrinibacteria).
This entry is found in Ada3 and homologous proteins which function as part of histone acetyltransferase complexes []. Ada3 is an essential component of the Ada transcriptional coactivator (alteration/deficiency in activation) complex. It plays a key role in linking histone acetyltransferase-containing complexes to p53 (tumour suppressor protein) thereby regulating p53 acetylation, stability and transcriptional activation following DNA damage [].
AidB is one of several genes involved in the SOS adaptive response to DNA alkylation damage, whose expression is activated by the Ada protein [, ]. Its function has not been entirely elucidated; however, it is similar in sequence and function to acyl-CoA dehydrogenases [, ]. It has been proposed that aidB directly destroys DNA alkylating agents such as nitrosoguanidines (nitrosated amides) or their reaction intermediates [, ].
Members of this family have been described as secreted proteins with growth factor activity and regions of adenosine deaminase homology in insects, molluscs, and vertebrates [].Adenosine deaminase-related growth factors (ADGF) are also known as CECR1 in vertebrates. They are a novel family of growth factors with sequence similarity to classical cellular adenosine deaminase. In Xenopus, it is essential for growth factor activity and is expressed in the somites, pronephros, eyes, cement gland, neural tube, and neural floor plate of the embryos []. It is also essential for insect development []. The mollusc derived growth factor (MDGF) is a member of the adenosine deaminase-related growth factor (ADGF) subfamily. ADGFs from vertebrates and invertebrates contain both an ADA domain and a novel N-terminal region of about 100 amino acids []. Adenosine deaminase (ADA) is an enzyme that catalyses the irreversible deamination of adenosine and deoxyadenosine to inosine and deoxyinosine []. Catalytic residues involved in ADA activity are conserved in ADGFs, and inhibitors of ADA can block ADGF activity [].
This entry includes histone acetyltransferases GCN5, KAT2A and KAT2B (all of which are included in ). GCN5 acetylates histones H2B, H3 and H4, providing a specific tag for epigenetic transcription activation. GCN5 is a component of the transcription regulatory histone acetylation (HAT) complexes SAGA [], SLIK [], SALSA []and ADA []. Mammals have two paralogues: KAT2A (also known as GCN5) and KAT2B. KAT2A acetylates core histones to provide a specific tag for epigenetic transcription activation, but not nucleosome core particles. It also acetylates proteins such as CEBPB []. KAT2A is a component of the ATAC complex, which has acetyltransferase activity on histones H3 and H4 []. KAT2B (also known as P300/calcium-binding protein (CBP)-associated factor or PCAF) can acetylate the core histones H3 and H4 as well as nucleosome core particles and non-histone proteins such as ACLY [].The transcription regulatory histone acetylation complex Spt-Ada-Gcn5 acetyltransferase (SAGA) is involved in RNA polymerase II-dependent transcriptional regulation of approximately 10% of yeast genes. SAGA preferentially acetylates histones H3 and H2B and deubiquitinates histone H2B []. SAGA is known as PCAF in vertebrates and PCAF acetylates nucleosomal histone H3 []. The SAGA complex consists of at least TRA1, CHD1, SPT7, TAF5, ADA3, SGF73, SPT20/ADA5, SPT8, TAF12, TAF6, HFI1/ADA1, UBP8, GCN5, ADA2, SPT3, SGF29, TAF10, TAF9, SGF11 and SUS1, and some of these components are present as two copies. The complex is built up from distinct modules, each of which has a separate function and crosslinks with either other proteins or other modules in the complex [].SLIK (SAGA-like) is a multi-subunit histone acetyltransferase complex that preferentially acetylates histones H3 and H2B and deubiquitinates histone H2B. It is an embellishment of the SAGA complex. The yeast SLIK complex consists of at least TRA1, CHD1, SPT7, CC TAF5, ADA3, SPT20, RTG2, TAF12, TAF6, HFI1, UBP8 (a deubiquitinase), GCN5, ADA2, SPT3, SGF29, TAF10 and TAF9 [, ].The yeast SALSA complex is an altered form of the SAGA complex and consists of at least TRA1, SPT7 (C-terminal truncated form), TAF5, ADA3, SPT20, TAF12, TAF6, HFI1, GCN5, ADA2 and SPT3 [].The ADA complex is a transcription regulatory histone acetylation (HAT) complex. ADA preferentially acetylates nucleosomal histones H3 (at 'Lys-14' and 'Lys-18') and H2B. The complex consists of at least ADA2, ADA3, AHC1, and GCN5. AHC1 is required for the overall structural integrity of the ADA complex [].
This family includes DUF34/metal-binding proteins from bacteria, NIF3 from budding yeasts and NIF3-like proteins from animals. This entry includes the DUF34/metal-binding protein/NIF3 proteins, which are widely distributed across superkingdoms. They were previously annotated as GTP cyclohydrolase 1 type 2 []and, recently, through a comprehensive literature review and integrative bioinformatic analyses it was revealed that annotations for these members are misleading as they were based on a single set of in vitro results examining the NIF3 homolog of Helicobacter pylori []. Actually, they have varied phenotypes with the unifying functional role as metal-binding proteins [].NIF3 interacts with the yeast transcriptional coactivator Ngg1p which is part of the ADA complex, the exact function of this interaction is unknown [, ].The structure of the Methanocaldococcus jannaschii MJ0927 NIF3 protein has been determined [, ]. It binds to both single-stranded and double-stranded DNA [].
This family represents DUF34/metal-binding proteins (previously known as GTP cyclohydrolase 1 type 2) from bacteria.This entry includes the DUF34/metal-binding protein/NIF3 proteins, which are widely distributed across superkingdoms. They were previously annotated as GTP cyclohydrolase 1 type 2 []and, recently, through a comprehensive literature review and integrative bioinformatic analyses it was revealed that annotations for these members are misleading as they were based on a single set of in vitro results examining the NIF3 homolog of Helicobacter pylori []. Actually, they have varied phenotypes with the unifying functional role as metal-binding proteins [].NIF3 interacts with the yeast transcriptional coactivator Ngg1p which is part of the ADA complex, the exact function of this interaction is unknown [, ].
This entry represents DUF34/metal-binding proteins (also referred to as NIF3-like protein 1) from animals. They share protein sequence similarity with budding yeast NIF3, which interacts with the yeast transcriptional coactivator Ngg1p that is part of the ADA complex [, ].This entry includes the DUF34/metal-binding protein/NIF3 proteins, which are widely distributed across superkingdoms. They were previously annotated as GTP cyclohydrolase 1 type 2 []and, recently, through a comprehensive literature review and integrative bioinformatic analyses it was revealed that annotations for these members are misleading as they were based on a single set of in vitro results examining the NIF3 homologue of Helicobacter pylori []. Actually, they have varied phenotypes with the unifying functional role as metal-binding proteins [].
This superfamily includes DUF34/metal-binding proteins (also known as GTP cyclohydrolase 1 type 2 proteins) from bacteria, NIF3 from budding yeasts and NIF3-like proteins from animals.This entry includes the DUF34/metal-binding protein/NIF3 proteins, which are widely distributed across superkingdoms. They were previously annotated as GTP cyclohydrolase 1 type 2 []and, recently, through a comprehensive literature review and integrative bioinformatic analyses it was revealed that annotations for these members are misleading as they were based on a single set of in vitro results examining the NIF3 homolog of Helicobacter pylori []. Actually, they have varied phenotypes with the unifying functional role as metal-binding proteins [].NIF3 interacts with the yeast transcriptional coactivator Ngg1p which is part of the ADA complex, the exact function of this interaction is unknown [, ].
The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. The Mediator complex is composed of at least 31 subunits: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The subunits form at least three structurally distinct submodules. The head and the middle modules interact directly with RNA polymerase II, whereas the elongated tail module interacts with gene-specific regulatory proteins. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation.The head module contains: MED6, MED8, MED11, SRB4/MED17, SRB5/MED18, ROX3/MED19, SRB2/MED20 and SRB6/MED22. The middle module contains: MED1, MED4, NUT1/MED5, MED7, CSE2/MED9, NUT2/MED10, SRB7/MED21 and SOH1/MED31. CSE2/MED9 interacts directly with MED4. The tail module contains: MED2, PGD1/MED3, RGR1/MED14, GAL11/MED15 and SIN4/MED16. The CDK8 module contains: MED12, MED13, CCNC and CDK8. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.Regulation of mRNA synthesis requires intermediary proteins that transduce regulatory signals from upstream transcriptional activator proteins to basal transcription machinery at the core promoter. Three types of intermediary factors that enable the basal transcription machinery to respond to transcriptional activator proteins bound to regulatory DNA sequences have been identified: (i) TAFIIs, which associate with TATA-binding protein (TBP) to form TFIID; (ii) mediator, which associates with RNA polymerase II to form a holo-polymerase; and (iii) coactivators such as human upstream stimulatory activity (USA), mammalian CBP/P300, yeast ADA complex, and HMG proteins. The interaction of these multiprotein complexes with activators and general transcription factors is essential for transcriptional regulation. This family of proteins represent the transcriptional mediator protein that is required for activation of many RNA polymerase II promoters and which are conserved from yeast to humans [].This entry represents the Med6 subunit of the Mediator complex in fungi.
The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. The Mediator complex is composed of at least 31 subunits: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The subunits form at least three structurally distinct submodules. The head and the middle modules interact directly with RNA polymerase II, whereas the elongated tail module interacts with gene-specific regulatory proteins. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation.The head module contains: MED6, MED8, MED11, SRB4/MED17, SRB5/MED18, ROX3/MED19, SRB2/MED20 and SRB6/MED22. The middle module contains: MED1, MED4, NUT1/MED5, MED7, CSE2/MED9, NUT2/MED10, SRB7/MED21 and SOH1/MED31. CSE2/MED9 interacts directly with MED4. The tail module contains: MED2, PGD1/MED3, RGR1/MED14, GAL11/MED15 and SIN4/MED16. The CDK8 module contains: MED12, MED13, CCNC and CDK8. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.Regulation of mRNA synthesis requires intermediary proteins that transduce regulatory signals from upstream transcriptional activator proteins to basal transcription machinery at the core promoter. Three types of intermediary factors that enable the basal transcription machinery to respond to transcriptional activator proteins bound to regulatory DNA sequences have been identified: (i) TAFIIs, which associate with TATA-binding protein (TBP) to form TFIID; (ii) mediator, which associates with RNA polymerase II to form a holo-polymerase; and (iii) coactivators such as human upstream stimulatory activity (USA), mammalian CBP/P300, yeast ADA complex, and HMG proteins. The interaction of these multiprotein complexes with activators and general transcription factors is essential for transcriptional regulation.This family of proteins represent the transcriptional mediator protein subunit 6 that is required for activation of many RNA polymerase II promoters and which are conserved from yeast to humans [].
The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. The Mediator complex is composed of at least 31 subunits: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The subunits form at least three structurally distinct submodules. The head and the middle modules interact directly with RNA polymerase II, whereas the elongated tail module interacts with gene-specific regulatory proteins. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation.The head module contains: MED6, MED8, MED11, SRB4/MED17, SRB5/MED18, ROX3/MED19, SRB2/MED20 and SRB6/MED22. The middle module contains: MED1, MED4, NUT1/MED5, MED7, CSE2/MED9, NUT2/MED10, SRB7/MED21 and SOH1/MED31. CSE2/MED9 interacts directly with MED4. The tail module contains: MED2, PGD1/MED3, RGR1/MED14, GAL11/MED15 and SIN4/MED16. The CDK8 module contains: MED12, MED13, CCNC and CDK8. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.Regulation of mRNA synthesis requires intermediary proteins that transduce regulatory signals from upstream transcriptional activator proteins to basal transcription machinery at the core promoter. Three types of intermediary factors that enable the basal transcription machinery to respond to transcriptional activator proteins bound to regulatory DNA sequences have been identified: (i) TAFIIs, which associate with TATA-binding protein (TBP) to form TFIID; (ii) mediator, which associates with RNA polymerase II to form a holo-polymerase; and (iii) coactivators such as human upstream stimulatory activity (USA), mammalian CBP/P300, yeast ADA complex, and HMG proteins. The interaction of these multiprotein complexes with activators and general transcription factors is essential for transcriptional regulation. This family of proteins represent the transcriptional mediator protein that is required for activation of many RNA polymerase II promoters and which are conserved from yeast to humans [].This group represents a RNA polymerase II mediator complex, subunit 6, metazoa/plant types.
