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), that share a common evolutionary origin. The designation is based on the currently best-characterized families present in this superfamily.
Contents
In addition to; (1) ion-translocating microbial rhodopsins (MR; TC# 3.E.1) and (2) G protein-coupled receptors (GPCRs; TC# 9.A.14), including visual rhodopsins (VRs), members of the following families share a common origin with microbial, invertebrate and vertebrate rhodopsins: (3) Sweet sugar transporters (Sweet; TC# 2.A.123), (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).
Origin
Visual rhodopsins are recognized members of the large and diverse family of G protein-coupled receptors (GPCRs). Shlykov characterized the 4-toluene sulfonate uptake permease (TSUP) family of transmembrane proteins, and showed that these 7-transmembrane segment (TMS) or 8-TMS proteins arose by intragenic duplication of a gene encoding a 4-TMS protein, sometimes followed by loss of an N-terminal TMS. Subsequently, the TSUP, GPCR and microbial rhodopsin families were shown to be related to each other and to six other recognized transport protein families. Despite their 8-TMS origins, the members of most constituent families exhibit 7-TMS topologies that are well conserved, and these arose by loss of either the N-terminal TMS (more frequent) or the C-terminal TMS (less frequent), depending on the family. Moreover, in rare instances, such as some prokaryotic members of the Sweet family, the complete transporter is encoded by two separate protein having only 3 TMSs each, where they can exist either as homo or hetero-dimeric complexes. Phylogenetic analyses have revealed familial relationships within the superfamily and protein relationships within each of the nine families. The results of statistical analyses leading to the conclusion of homology were confirmed using hidden Markov models, Pfam and 3D superimpositions. Proteins functioning by dissimilar mechanisms (channels, primary active transporters, secondary active transporters, group translocators and receptors) are interspersed on a phylogenetic tree of the TOG superfamily, suggesting that changes in the transport and energy-coupling mechanisms occurred multiple times during evolution of this superfamily.
Families
Currently recognized families within the TOG Superfamily (with TC numbers in blue) include:
Structures
A couple of the 3-D structures available for members of the following families include: