RegulonDB RegulonDB 10.9: Regulon form help
Regulon form help

Synonyms: Alternative names for the TF, in which could specified the functional conformation of the TF when known (for instance NtrC-Phosphorylated).

Summary: A brief statement of current knowledge of the TF.

Transcription Factor
TF conformation(s): The functional conformation of the TF when known. Most dedicated TFs usually have two conformations, one with a noncovalently bound allosteric metabolite, or covalent phosphorylation (holo conformation), and one that is a free protein or multimer (the apo conformation). We consider the functional conformation the one that is capable of binding to its specific transcription factor binding sites (TFBSs) and exerts its effect on the regulated promoter.
Conformation Name. It is the name of the conformation of the TF, depending on whether it is bound or not to its effector.
Conformation type. The genetic switch implies that one of the conformations (apo or holo) for a TF binds with stronger affinity to its TF binding sites (TFBSs). We call "functional" the conformation that best binds, and "non´functional" the one that does not exert a specific binding to the TFBS.
TF-effector interaction. This can be either non-covalent (mostly by allosteric effectors) or covalent (i.e. phosphorylation).
It is important to distinguish covalent vs non-covalent as different from allosteric or not allosteric. For instance phosphorylation of a two-component TF can occur in an allosteric site, that is to say, a site that is different from the one for the DNA binding.
Apo/Holo conformation. Following the holo and apo description for RNAPolymerase, we call holo the conformation of a TF when bound to its effector, and apo when the TF it is free, unbound.
Evidence (Confirmed, Strong, Weak). Evidence types associated to the conformations, following the RegulonDB evidence classification scheme.
References. Those associated to the conformations.
Sensing class: The class is based in the type of the effector as external, internally synthesized or both (dual). This classification is based on the origin of the effector metabolites that usually bind allosterically to the TFs.
Connectivity class: Local or global regulator. The connectivity of TFs is based in the number of regulated genes, as either local or global (Martínez-Antonio et al., 2003).
Gene name: Name of gene producing the TF or a subunit of the TF.
        Genome position: Start and end absolute positions of the gene in the chromosome.
        Length: The length of the gene and gene product, in base pairs and amino acids (bp/aa), respectively. In case of RNA genes, it is the length of the processed transcript.
Operon name: Name of the operon containing the gene for the TF (or a subunit of the TF).
TU(s) encoding the TF: One or more TU encoding the TF (or a subunit of the TF).

Regulon: The original concept of a regulon is a set of genes regulated by one and only one transcription factor. It was defined by Werner Mass (1964) when studying the arginine ArgR regulon. For the sake of conceptual clarity we expanded this definition to distinguish simple regulons (genes regulated by one and only one TF), from complex regulons (genes regulated by several and exactly the same set of TFs), as well as strict regulons with the effect of TFs on all regulated genes (activation or repression) is the same (Gutiérrez-Ríos et al., 2003).
Regulated gene(s): Name of the genes under regulation by the TF.
Multifun term(s) of regulated gene(s): Multifunctional classification scheme for Escherichia coli K-12 gene products (Multifun). It is a classification system for cellular functions of gene products of E. coli K-12, developed based on the initial classification by Monica Riley (Riley et al., 2006). Cellular functions are divided into 10 major categories: Metabolism, Information Transfer, Regulation, Transport, Cell Processes, Cell Structure, Location, Extra-chromosomal Origin, DNA Site, and Cryptic Gene.
Regulated first gene(s): Name of the first transcribed gene of a regulated TU(s).
Regulated operon(s): List of operon(s) regulated by the TF.
Simple and complex regulons: List of simple and complex regulons where the queried TF participates.
Simple and complex regulatory phrases: Simple phrases are collection of TFBSs, usually for the same TF, that participate in a single mechanism of regulation. Complex phrases involve at least two TFs where at least one of them requires the other TF to exert its function. The phrase page will contain all instantiations of such arrangements in different promoters.
The TFBSs within a phrase are classified as proximal or remote based on their relative distance to the regulated TSS. Proximal sites are those within the interval from -93 to +30; from where the TF can in principle directly interact with RNA polymerase. All other sites are considered remote, either upstream or downstream.

Transcription factor binding sites (TFBSs) arrangements
Functional conformation(s): TF alone if apo; TF-metabolite if holo. See above ?functional conformations?.
Function: Activation, repression, both (dual) or unknown; it is the effect on regulated promoter.
Promoter: Name of the regulated promoter.
Sigma Factor: Sigma Factor used by the RNA polymerase to recognize the regulated promoter.
Central Rel-Pos: Central relative position. Distance from the transcription start site (+1) of the regulated promoter to the central position of a TFBS. Sites upstream from the promoter are negative, whereas sites downstream from the promoter have positive relative distances. Note that the same physical site can regulate different promoters with different relative distances.
Distance to first Gene: Distance from the first transcribed gene of a regulated TU to the central position of the TFBS. Negative distances indicate sites upstream from the gene and positive distances indicate downstream sites.
Genes: Names of the regulated genes.
Sequence: DNA sequence of the TFBS in colored uppercases, with additional 10 bp on each side.
LeftPos:Absolute left position in the genome of a TFBS. Left positions are always smaller than right positions.
RightPos:Absolute right position in the genome of a TFBS.
Evidence: Evidence code of the source of information supporting the regulatory interaction of the TF binding to the TFBS. Bold indicate strong or confirmed evidence. For a full list and explanation of all evidence codes see: Evidence Classification.
References: Original and subsequent literature supporting the evidence behind the regulatory interaction (TF, promoter, TFBS).

DNA binding site length: The length of the TFBS.
DNA binding site symmetry: Symmetric or asymmetric; it is the internal symmetry of the TFBS.
Non-redundant binding site(s): All the unique TFBSs for the TF. When TFBSs participate in more than one regulatory interaction, they are displayed for each interaction as shown in the TFBSs arrangement section. In that section these repetitions are eliminated.

Alignment and PSSM for TF TFBSs
Aligned TFBS of TF: DNA sequence alignment of experimentally identified TFBSs for a TF.
Position weight matrix (PWM): A position weight matrix (PWM), also called position-specific weight matrix (PSWM) or position-specific scoring matrix (PSSM), is a commonly used representation of motifs (patterns) in biological sequences. A PWM is an M x 4 matrix of score values for M rows of the length of the site, and 4 columns for each nucleotide. Each (i,j) position gives the frequency of in the ith position of the jth nucleotide. It gives a weighted match to any given substring of fixed length.
PWM logo: The Logo represents at each position the frequency of each nucleotide with letters of variable size in a vertical scale of information content per position.

Evolutionary conservation of regulatory elements
TF-target gene evolutionary conservation: A regulatory interaction (RI) is defined by a TF-target gene pair irrespective of the number of TFBSs in the upstream region of the target gene. Its evolutionary conservation is inferred from the overrepresentation of TFBSs in a set of orthologous regulatory regions for the target gene.
Promoter-target gene evolutionary conservation: The evolutionary conservation of a promoter-target gene pair is defined by the p-value of the conserved promoter motifs in the set of upstream regions of the orthologous genes.

Evidence: Evidence supporting the TU; bold indicate strong or confirmed evidence. For a full list of all evidence codes see: Evidence Classification.

Reference(s): Literature source supporting the identification of the TU.