| Putative Manganese Efflux Pump | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | MntP | ||||||||
| Pfam | PF02659 | ||||||||
| InterPro | IPR003810 | ||||||||
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The Manganese (Mn2+) Exporter (MntP) Family (TC# 2.A.107) is a member of the Lysine Exporter (LysE) Superfamily. [1] The MntP family is a small family whose members have been found in bacteria and archaea. MntP proteins are of about 200 amino acyl residues with 6 putative transmembrane segments (TMSs). The Conserved Domain Database (CDD) recognized two DUF204 repeats, each repeat having 3 TMSs. A representative list of proteins belonging to the MntP family can be found in the Transporter Classification Database.
At least one member (YebN of E. coli, TC# 2.A.107.1.1) has been shown to function as a putative manganese efflux pump. Manganese sensitivity and intracellular manganese levels significantly increased in bacteria when the mntP (formerly yebN) gene, which encodes the MntP efflux pump, was deleted. While manganese is a highly important trace nutrient for organisms from bacteria to humans, acting as an important element in the defense against oxidative stress and as an enzyme cofactor, it becomes toxic when present in excess. [2]
All microorganisms, with a few exceptions, have highly conserved DNA sequences in their genome that are transcribed and translated to efflux pumps. Efflux pumps are capable of moving a variety of different toxic compounds out of cells, such as antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals, bacterial metabolites and neurotransmitters via active efflux, which is vital part for xenobiotic metabolism. This active efflux mechanism is responsible for various types of resistance to bacterial pathogens within bacterial species - the most concerning being antibiotic resistance because microorganisms can have adapted efflux pumps to divert toxins out of the cytoplasm and into extracellular media.
The yybP-ykoY leader RNA element was originally discovered in E. coli during a large scale screen and was named SraF. This family was later found to exist upstream of related families of protein genes in many bacteria, including the yybP and ykoY genes in B. subtilis. The specific functions of these proteins are unknown, but this structured RNA element may be involved in their genetic regulation as a riboswitch. The yybP-ykoY element was later proposed to be manganese-responsive after another associated family of genes, YebN/MntP, was shown to encode Mn2+ efflux pumps in several bacteria. Genetic data and a crystal structure confirmed that yybp-ykoY is a manganese riboswitch that directly binds Mn2+
Multi-antimicrobial extrusion protein (MATE) also known as multidrug and toxin extrusion or multidrug and toxic compound extrusion is a family of proteins which function as drug/sodium or proton antiporters.
The Formate-Nitrite Transporter (FNT) Family belongs to the Major Intrinsic Protein (MIP) Superfamily. FNT family members have been sequenced from Gram-negative and Gram-positive bacteria, archaea, yeast, plants and lower eukaryotes. The prokaryotic proteins of the FNT family probably function in the transport of the structurally related compounds, formate and nitrite.
Cation diffusion facilitators (CDFs) are transmembrane proteins that provide tolerance of cells to divalent metal ions, such as cadmium, zinc, and cobalt. These proteins are considered to be efflux pumps that remove these divalent metal ions from cells. However, some members of the CDF superfamily are implicated in ion uptake. All members of the CDF family possess six putative transmembrane spanners with strongest conservation in the four N-terminal spanners. The Cation Diffusion Facilitator (CDF) Superfamily includes the following families:
The potassium (K+) uptake permease (KUP) family (TC# 2.A.72) is a member of the APC superfamily of secondary carriers. Proteins of the KUP/HAK/KT family include the KUP (TrkD) protein of E. coli and homologues in both Gram-positive and Gram-negative bacteria. High affinity (20 μM) K+ uptake systems (Hak1, TC# 2.A.72.2.1) of the yeast Debaryomyces occidentalis as well as the fungus, Neurospora crassa, and several homologues in plants have been characterized. Arabidopsis thaliana and other plants possess multiple KUP family paralogues. While many plant proteins cluster tightly together, the Hak1 proteins from yeast as well as the two Gram-positive and Gram-negative bacterial proteins are distantly related on the phylogenetic tree for the KUP family. All currently classified members of the KUP family can be found in the Transporter Classification Database.
The bacterial murein precursor exporter (MPE) family is a member of the cation diffusion facilitator (CDF) superfamily of membrane transporters. Members of the MPE family are found in a large variety of Gram-negative and Gram-positive bacteria and facilitate the translocation of lipid-linked murein precursors. A representative list of proteins belonging to the MPE family can be found in the Transporter Classification Database.
The multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) flippase superfamily is a group of integral membrane protein families. The MOP flippase superfamily includes twelve distantly related families, six for which functional data are available:
Lysine Exporters are a superfamily of transmembrane proteins which export amino acids, lipids and heavy metal ions. They provide ionic homeostasis, play a role in cell envelope assembly, and protect from excessive concentrations of heavy metals in cytoplasm. The superfamily was named based on the early discovery of the LysE carrier protein of Corynebacterium glutamicum.
The resistance to homoserine/threonine (RhtB) family belongs to the lysine exporter (LysE) superfamily of transporters. Hundreds of sequenced proteins, derived from Gram-negative and Gram-positive bacteria as well as archaea, comprise the RhtB family, but few of these proteins are functionally characterized.
The Tellurium Ion Resistance (TerC) Family is part of the Lysine Exporter (LysE) Superfamily. A representative list of proteins belonging to the TerC family can be found in the Transporter Classification Database.
The iron/lead transporter (ILT) family is a family of transmembrane proteins within the lysine exporter (LysE) superfamily. The ILT family includes two subfamilies, the iron-transporting (OFeT) family and the lead-transporting (PbrT) family. A representative list of the proteins belonging to these subfamilies of the ILT family can be found in the Transporter Classification Database.
The Nickel/Cobalt Transporter (NicO) Family is a member of the Lysine Exporter (LysE) Superfamily. A representative list of proteins belonging to the NicO family can be found in the Transporter Classification Database.
The Disulfide bond oxidoreductase D (DsbD) family is a member of the Lysine Exporter (LysE) Superfamily. A representative list of proteins belonging to the DsbD family can be found in the Transporter Classification Base.
The p-aminobenzoyl-glutamate transporter(AbgT) family is a family of transporter proteins belonging to the ion transporter (IT) superfamily. The AbgT family consists of the AbgT protein of E. coli and the MtrF drug exporter of Neisseria gonorrhoeae. The former protein is apparently cryptic in wild-type cells, but when expressed on a high copy number plasmid, or when expressed at higher levels due to mutation, it appeared to allow uptake and subsequent utilization of p-aminobenzoyl-glutamate as a source of p-aminobenzoate for p-aminobenzoate auxotrophs. p-Aminobenzoate is a constituent of and a precursor for the biosynthesis of folic acid. MtrF was annotated as a putative drug efflux pump.
The C4-dicarboxylate uptake family or Dcu family is a family of transmembrane ion transporters found in bacteria. Their function is to exchange dicarboxylates such as aspartate, malate, fumarate and succinate.
Arsenite resistance (Ars) efflux pumps of bacteria may consist of two proteins, ArsB and ArsA, or of one protein. ArsA proteins have two ATP binding domains and probably arose by a tandem gene duplication event. ArsB proteins all possess twelve transmembrane spanners and may also have arisen by a tandem gene duplication event. Structurally, the Ars pumps resemble ABC-type efflux pumps, but there is no significant sequence similarity between the Ars and ABC pumps. When only ArsB is present, the system operates by a pmf-dependent mechanism, and consequently belongs in TC subclass 2.A. When ArsA is also present, ATP hydrolysis drives efflux, and consequently the system belongs in TC subclass 3.A. ArsB therefore appears twice in the TC system but ArsA appears only once. These pumps actively expel both arsenite and antimonite.
The 6TMS Neutral Amino Acid Transporter (NAAT) Family is a family of transporters belonging to the Lysine Exporter (LysE) Superfamily. Homologues are found in numerous Gram-negative and Gram-positive bacteria including many human pathogens. Several archaea also encode MarC homologues. Some of these organisms have 2 or more paralogues. Most of these proteins are of about the same size although a few are larger. They exhibit 6 putative TMSs. A representative list of members belonging to the NAAT family can be found in the Transporter Classification Database.
The Monovalent Cation:Proton Antiporter-2 (CPA2) Family is a moderately large family of transporters belonging to the CPA superfamily. Members of the CPA2 family have been found in bacteria, archaea and eukaryotes. The proteins of the CPA2 family consist of between 333 and 900 amino acyl residues and exhibit 10-14 transmembrane α-helical spanners (TMSs).
Resistance-nodulation-division (RND) family transporters are a category of bacterial efflux pumps, especially identified in Gram-negative bacteria and located in the cytoplasmic membrane, that actively transport substrates. The RND superfamily includes seven families: the heavy metal efflux (HME), the hydrophobe/amphiphile efflux-1, the nodulation factor exporter family (NFE), the SecDF protein-secretion accessory protein family, the hydrophobe/amphiphile efflux-2 family, the eukaryotic sterol homeostasis family, and the hydrophobe/amphiphile efflux-3 family. These RND systems are involved in maintaining homeostasis of the cell, removal of toxic compounds, and export of virulence determinants. They have a broad substrate spectrum and can lead to the diminished activity of unrelated drug classes if over-expressed. The first reports of drug resistant bacterial infections were reported in the 1940s after the first mass production of antibiotics. Most of the RND superfamily transport systems are made of large polypeptide chains. RND proteins exist primarily in gram-negative bacteria but can also be found in gram-positive bacteria, archaea, and eukaryotes.
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