TOG superfamily

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The transporter-opsin-G protein-coupled receptor (TOG) superfamily is a protein superfamily of integral membrane proteins, usually of 7 or 8 transmembrane alpha-helical segments (TMSs). It includes (1) ion-translocating microbial rhodopsins and (2) G protein-coupled receptors (GPCRs), (3) Sweet sugar transporters, (4) nicotinamide ribonucleoside uptake permeases (PnuC; TC# 4.B.1), (5) 4-toluene sulfonate uptake permeases (TSUP); TC# 2.A.102), (6) Ni2+–Co2+ transporters (NiCoT); TC# 2.A.52), (7) organic solute transporters (OST); TC# 2.A.82), (8) phosphate:Na+ symporters (PNaS); TC# 2.A.58) and (9) lysosomal cystine transporters (LCT); TC# 2.A.43). [1] [2]

A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred. Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if no sequence similarity is evident. Sequence homology can then be deduced even if not apparent. Superfamilies typically contain several protein families which show sequence similarity within each family. The term protein clan is commonly used for protease and glycosyl hydrolases superfamilies based on the MEROPS and CAZy classification systems.

Membrane protein class of proteins

Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane and can either penetrate the membrane (transmembrane) or associate with one or the other side of a membrane. Peripheral membrane proteins are transiently associated with the cell membrane.

The permeases are membrane transport proteins, a class of multipass transmembrane proteins that allow the diffusion of a specific molecule in or out of the cell in the direction of a concentration gradient, a form of facilitated diffusion.

Contents

Families

Currently recognized families within the TOG Superfamily (with TC numbers in blue) include: [3]

Protein family group of proteins that share a common evolutionary origin, reflected by similarity in their sequence

A protein family is a group of evolutionarily-related proteins. In many cases a protein family has a corresponding gene family, in which each gene encodes a corresponding protein with a 1:1 relationship. The term protein family should not be confused with family as it is used in taxonomy.

The testis-enhanced gene transfer (TEGT) family includes the testis-enhanced gene transfer proteins of mammals, which are expressed at high levels in the testis, the putative glutamate/aspartate binding proteins of plants and animals, the YccA protein of Escherichia coli and the YetJ protein of Bacillus subtilis. These proteins are about 200-250 residues in length and exhibit 7 TMSs.

Magnesium transporter E

Magnesium transporters E (MgtE) are a family of transmembrane eubacterial MgtE magnesium transporters. Related regions are found also in archaeal and eukaryotic proteins. They have sizes that vary considerably from 311 residues for the Methanococcus thermoautotrophicum protein, 463 residues for a Synechocystis homologue, and 513 residues for the human homologue, SLC41A1. These proteins are capable of transporting Mg2+ and Co2+ but not Ni2+. Multiple alignments contain two highly conserved aspartates that may be involved in cation binding.

The Magnesium Transporter1 (MagT1) Family (TC# 1.A.76) is a group of magnesium transporters that are part of the TOG superfamily. Goytain and Quamme identified a Mg2+ transporter encoded by an implantation-associated protein precursor, IAP, that is regulated by magnesium. They designated this protein, MagT1. MagT1 is of 335 amino acids and possesses five TMSs with an N-terminal cleavage site and a number of phosphorylation sites.

Structures

A couple of the 3-D structures available for members of the following families include:

See also

The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 65 families. Most members of the SLC group are located in the cell membrane. The SLC gene nomenclature system was originally proposed by the HUGO Gene Nomenclature Committee (HGNC) and is the basis for the official HGNC names of the genes that encode these transporters. A more general transmembrane transporter classification can be found in TCDB database.

The Transporter Classification Database is an International Union of Biochemistry and Molecular Biology (IUBMB)-approved classification system for membrane transport proteins, including ion channels.

Related Research Articles

A neurotransmitter sodium symporter (NSS) (TC# 2.A.22) is type of neurotransmitter transporter that catalyzes the uptake of a variety of neurotransmitters, amino acids, osmolytes and related nitrogenous substances by a solute:Na+ symport mechanism. The NSS family is a member of the APC superfamily. Its constituents have been found in bacteria, archaea and eukaryotes.

An amino acid transporter is a membrane transport protein that transports amino acids. They are mainly of the solute carrier family.

The Nucleobase:Cation Symporter-1 (NCS1) Family (TC# 2.A.39) consists of over 1000 currently sequenced proteins derived from Gram-negative and Gram-positive bacteria, archaea, fungi and plants. These proteins function as transporters for nucleobases including purines and pyrimidines. Members of this family possess twelve transmembrane α-helical spanners (TMSs). At least some of them have been shown to function in uptake by substrate:H+ symport mechanism.

Sodium-solute symporter

Members of the Solute:Sodium Symporter (SSS) Family (TC# 2.A.21) catalyze solute:Na+ symport. The SSS family is within the APC Superfamily. The solutes transported may be sugars, amino acids, organo cations such as choline, nucleosides, inositols, vitamins, urea or anions, depending on the system. Members of the SSS family have been identified in bacteria, archaea and eukaryotes. Almost all functionally well-characterized members normally catalyze solute uptake via Na+ symport.

The Nucleobase:Cation Symporter-2(NCS2) Family, also called the Nucleobase/Ascorbate Transporter(NAT) Family, consists of over 1000 sequenced proteins derived from gram-negative and gram-positive bacteria, archaea, fungi, plants and animals. The NCS2/NAT family is a member of the APC Superfamily of secondary carriers. Of the five known families of transporters that act on nucleobases, NCS2/NAT is the only one that is most widespread. Many functionally characterized members are specific for nucleobases including both purines and pyrimidines, but others are purine-specific. However, two closely related rat/human members of the family, SVCT1 and SVCT2, localized to different tissues of the body, co-transport L-ascorbate (vitamin C) and Na+ with a high degree of specificity and high affinity for the vitamin. Clustering of NCS2/NAT family members on the phylogenetic tree is complex, with bacterial proteins and eukaryotic proteins each falling into at least three distinct clusters. The plant and animal proteins cluster loosely together, but the fungal proteins branch from one of the three bacterial clusters forming a tighter grouping. E. coli possesses four distantly related paralogous members of the NCS2 family.

The 4-Toluene Sulfonate Uptake Permease (TSUP) family is also referred to as the TauE/SafE/YfcA/DUF81 Family. Although its members have not been rigorously characterized, evidence is available that at least some members function in the transport of sulfur containing organic compounds. These include 4-toluene sulfonate which may be transported by the TsaS of Cupriavidus necator, sulfolactate which may be exported by the TauE protein of Cupriavidus necator and sulfoacetate which may be exported by the SafE1 protein of Neptuniibacter caesariensis. Another member of the TSUP family, TsaS of Comamonas testosteroni, has been reported to function in the uptake of 4-toluene sulfonate. None of these functional assignments can be considered to be certain.

The amino acid-polyamine-organocation (APC) superfamily is the second largest superfamily of secondary carrier proteins currently known, and it contain several Solute carriers. Originally, the APC superfamily consisted of subfamilies under the transporter classification number 2.A.3. This superfamily has since been expanded to include eighteen different families.

The Amino Acid-Polyamine-Organocation (APC) Family of transport proteins includes members that function as solute:cation symporters and solute:solute antiporters. They occur in bacteria, archaea, fungi, unicellular eukaryotic protists, slime molds, plants and animals. They vary in length, being as small as 350 residues and as large as 850 residues. The smaller proteins are generally of prokaryotic origin while the larger ones are of eukaryotic origin. Most of them possess twelve transmembrane α-helical spanners but have a re-entrant loop involving TMSs 2 and 3. The APC Superfamily was established to encompass a wider range of homologues.

The Hydroxy/Aromatic Amino Acid Permease (HAAAP) Family is a member of the large Amino Acid-Polyamine-OrganoCation (APC) Superfamily of secondary carriers. Members of the HAAAP family all function in amino acid uptake. Homologues are present in a large number of Gram-negative and Gram-positive bacteria, with at least one member classified from archaea .

The benzoate:H symporter (BenE) family is a member of the APC Superfamily. The BenE family contains only two functionally characterized and sequenced members, the benzoate permeases of Acinetobacter calcoaceticus and E. coli. These proteins are about 400 residues in length and probably span the membrane 12 times. Some members of the BenE family can have as little as 7 TMSs, or as many as 14 TMSs. BenE family members exhibit about 30% identity to each other and limited sequence similarity to members of the Aromatic Acid:H Symporter (AAHS) family of the Major Facilitator Superfamily (MFS). The degree of similarity with the latter proteins is insufficient to establish homology. As of early 2016, no crystal structural data is available for members of the BenE family.

The putative amino acid permease (PAAP) family belongs to the APC superfamily. The PAAP family consists of many proteins, all of a uniform topology with a 5 + 5 TMS repeat in a 2 + 3 + 2 + 3 arrangement. These proteins show similarity to members of the LIVCS family in the APC Superfamily. A representative list of recognized members of the PAAP family is available in the Transporter Classification Database.

The sulfate permease (SulP) family is a member of the large APC superfamily of secondary carriers. The SulP family is a large and ubiquitous family of proteins derived from archaea, bacteria, fungi, plants and animals. Many organisms including Bacillus subtilis, Synechocystis sp, Saccharomyces cerevisiae, Arabidopsis thaliana and Caenorhabditis elegans possess multiple SulP family paralogues. Many of these proteins are functionally characterized, and most are inorganic anion uptake transporters or anion:anion exchange transporters. Some transport their substrate(s) with high affinities, while others transport it or them with relatively low affinities. Others may catalyze SO2−
4
:HCO
3
exchange, or more generally, anion:anion antiport. For example, the mouse homologue, SLC26A6, can transport sulfate, formate, oxalate, chloride and bicarbonate, exchanging any one of these anions for another. A cyanobacterial homologue can transport nitrate. Some members can function as channels. SLC26A3 and SLC26A6 can function as carriers or channels, depending on the transported anion. In these porters, mutating a glutamate, also involved in transport in the CIC family, created a channel out of the carrier. It also changed the stoichiometry from 2Cl/HCO
3
to 1Cl/HCO
3
.

The SWEET family, also known as the PQ-loop, Saliva or MtN3 family, is a family of sugar transporters and a member of the TOG superfamily. The proteins of the SWEET family have been found in plants, animals, protozoans, and bacteria. Eukaryotic family members have 7 transmembrane segments (TMSs) in a 3+1+3 repeat arrangement.

The Nicotinamide Ribonucleoside (NR) Uptake Permease (PnuC) Family is a family of transmembrane transporters that is part of the TOG superfamily. Close PnuC homologues are found in a wide range of Gram-negative and Gram-positive bacteria, archaea and eukaryotes.

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 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 gluconate:H+ symporter (GntP) family (TC# 2.A.8) is a family of transport proteins belonging to the ion transporter (IT) superfamily. Members of the GntP family include known gluconate permeases of E. coli and Bacillus species such as the D-Gluconate:H+ symporter of Bacillus subtillus (GntP; TC# 2.A.8.1.1) and the D-fructuronate/D-gluconate:H+ symporter of E. coli (GntP; TC# 2.A.8.1.3). A representative list of proteins belonging to the GntP family can be found in the Transporter Classification Database.

The ion transporter (IT) superfamily is a superfamily of secondary carriers that transport charged substrates.

The Pho1 phosphate permease family is a family of phosphate transporters belonging to the ion transporter (IT) superfamily. Representative members of the Pho1 family include the putative phosphate transporter PHO1 of Arabidopsis thaliana, and the xenotropic and polytropic murine-leukemia virus receptor Xpr1 of Culex pipiens.

References

  1. Maksim A. Shlykov; Wei Hao Zheng; Jonathan S. Chen & Milton H. Saier, Jr.. (March 2012). "Bioinformatic Characterization of the 4-Toluene Sulfonate Uptake Permease (TSUP) Family of Transmembrane Proteins". Biochimica et Biophysica Acta. 1818 (3): 703–717. doi:10.1016/j.bbamem.2011.12.005. PMC   3917603 . PMID   22192777.
  2. Yee DC1, Shlykov MA, Västermark A, Reddy VS, Arora S, Sun EI, Saier MH Jr.. (September 2013). "The transporter-opsin-G protein-coupled receptor (TOG) superfamily". The FEBS Journal. 280 (22): 5780–5800. doi:10.1111/febs.12499. PMC   3832197 . PMID   23981446.CS1 maint: multiple names: authors list (link)
  3. Saier, Milton. "Transporter-Opsin-G protein-coupled receptor (TOG) Superfamily". tcdb.org. Retrieved 28 December 2015.

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