TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*3.E.1.1.1









Bacteriorhodopsin. Proton efflux occurs via a transient linear water-molecule chain in a hydrophobic section of the Brho channel between Asp96 and Asp85 (Freier et al., 2011).  It can be converted to a chloride uptake pump by a single amino acid substitution at position 85.  However, halorhodopsin (3.E.1.2.1), which pumps chloride ions (Cl-) into the cell, apparently does not use hydrogen-bonded water molecules for Cl- transport (Muroda et al. 2012).  Nango et al. 2016 used time-resolved serial femtosecond crystallography and an x-ray free electron laser to visualize conformational changes in bRho from nanoseconds to milliseconds following photoactivation. An initially twisted retinal chromophore displaces a conserved tryptophan residue of transmembrane helix F on the cytoplasmic side of the protein while dislodging a key water molecule on the extracellular side. The resulting cascade of structural changes throughout the protein shows how motions are choreographed as bRho transports protons uphill against a transmembrane concentration gradient. Nango et al. 2016 have created a 3-d movie of structural changes in the protein showing that an initially twisted retinal chromophore displaces a conserved tryptophan residue of transmembrane helix F on the cytoplasmic side of the protein while dislodging a key water molecule on the extracellular side. Brho has light-independent lipid scramblase activity (Verchère et al. 2017). This activity occurs  at a rate >10,000 per trimer per second, comparable to that of other scramblases including bovine rhodopsin and fungal TMEM16 proteins. BR scrambles fluorescent analogues of common phospholipids but does not transport a glycosylated diphosphate isoprenoid lipid. In silico analyses suggested that membrane-exposed polar residues in transmembrane helices 1 and 2 of BR may provide the molecular basis for lipid translocation by coordinating the polar head-groups of transiting phospholipids. Consistent with this possibility, extensive coarse-grained molecular dynamics simulations of a BR trimer in a phospholipid membrane revealed water penetration along transmembrane helix 1 with the cooperation of a polar residue (Y147 in transmembrane helix 5) in the adjacent protomer. These findings suggest that the lipid translocation pathway may lie at or near the interface of the protomers of the BR trimer (Verchère et al. 2017). Retinal isomerization has been observed in the using a femtosecond x-ray laser (Nogly et al. 2018).

Archaea
Euryarchaeota
Bacteriorhodopsin of Halobacterium salinarum
*3.E.1.1.2









Archaerhodopsin-2 (aR2) (a retinal protein-carotenoid complex) (Yoshimura and Kouyama, 2007).
Archaea
Euryarchaeota
aR2 of Halorubrum sp. aus-2 (P29563)
*3.E.1.1.3









"Middle" rhodopsin or Brhol; has 11-cis-retinal and shows intermediate properties between Brho and sensory rhodopsin II (Sudo et al., 2011). Its structure is known to 2.0 Å resolution following crystalization using polymer-bounded lipid nanodiscs (Broecker et al. 2017).

Archaea
Euryarchaeota
Middle rhodopsin of Haloquadratum walsbyi (G0LFX8)
*3.E.1.1.4









Archaerhodopsin 3, AR3.  Pumps protons in response to light absorption (Saint Clair et al. 2012). 86% identical to 3.E.1.1.2.

Archaea
Euryarchaeota
AR3 of Halorubrum sodomense
*3.E.1.1.5









Bacteriorhodopsin I (HmBRI) of 250 aas and 7 TMSs. The structure is known to 2.5 Å resolution, revealing the usual BRI fold but with several modifications (Shevchenko et al. 2014). Expression in E. coli membranes does not affect the overall structure.

Archaea
Euryarchaeota
Bacteriorhodopsin I of Haloarcula marismortui
*3.E.1.1.6









Sensory rhodopsin (green-light-activated photoreceptor; does not transport ions) (Jung et al., 2003). Has all-trans-retinal when dark adapted, but 11-cis-retinal when light adapted due to reversible interconversion (Sineshchekov et al., 2005).  Anabaena sensory rhodopsin, a photochromic sensor that interacts with a soluble 14-kDa cytoplasmic transducer that is encoded on the same operon, interconverts between all-trans-15-anti and 13-cis-15-syn retinal forms depending on the wavelength of illumination, although only the former participates in a photocycle with a signaling M intermediate (Dong et al. 2016). A mutation in the cytoplasmic half-channel of the protein, replacing Asp217 with Glu (D217E), results in the creation of a light-driven, single- photon, inward proton transporter. Dong et al. 2016 presented the 2.3 A structure of dark-adapted D217E ASR, which reveals changes in the water network surrounding Glu217, as well as a shift in the carbon backbone near retinal-binding Lys210, illustrating a possible pathway leading to the protonation of Glu217 in the cytoplasmic half-channel, located 15 A from the Schiff base.

 

Bacteria
Cyanobacteria
Sensory rhodopsin of Anabaena (Nostoc) sp. PCC7120
*3.E.1.1.7









H+-pumping electrogenic bacteriorhodopsin of 250 aas and 7 TMSs (Kamo et al. 2006).

Archaea
Euryarchaeota
Brho of Haloterrigena turkmenica
*3.E.1.1.8









Inward H+ pumping xenorhodopsin (bacteriorhodopsin) of 228 aas and 7 TMSs.

Archaea
Candidatus Nanohaloarchaeota
Xenorhodopsin of Nanosalina sp. (strain J07AB43)
*3.E.1.2.1









Halorhodopsin Cl- uptake pump; homologous to bacteriorhodopsin (3.E.1.1.1) which can be converted from a proton pump with outwardly directed polarity into a chloride pump with inwardly directed polarity via a single amino acid substitution at position 85.  Cl- transport does not depend on water hydrogen bonded to the chromophore as in the case of bacteriorhodopsin (Muroda et al. 2012).  However, inter-helical hydrogen bonds, mediated by a key arginine residue, largely govern the dynamics of the protein and water groups coordinating the chloride ion (Jardón-Valadez et al. 2014).  Helices E and F probably move considerable during chloride binding and ion transport (Schreiner et al. 2016).

Archaea
Euryarchaeota
Halorhodopsin of Halobacterium salinarum
*3.E.1.2.2









Halorhodopsin (a trimer with the carotenoid, bacterioruberin, binding to crevices between adjacent protein subunits in the trimeric assembly; Sasaki et al., 2012). Structure known to 2.0 Å resolution (Kouyama et al., 2010) (PDB# 3A7K)).

Archaea
Euryarchaeota
Halorhodopsin of Natronomonas pharaonis (P15647)
*3.E.1.3.1









Sensory rhodopsin I
Archaea
Euryarchaeota
Sensory rhodopsin I of Halobacterium salinarum
*3.E.1.3.2









Sensory rhodopsin II or photoreceptor phoborhodopsin (ppR).  The 3-d structure has been solved by NMR (Gautier and Nietlispach 2012). The dynamics of light induced conformational changes have been studied (Taniguchi et al. 2007).

Archaea
Euryarchaeota
Sensory rhodopsin II (phoborhodopsin) of Halobacterium salinarum
*3.E.1.3.3









Sensory rhodopsin II, SR2 (Sop2), also called phoborhodopsin. The NMR solution structure of the detergent solubilized protein is in good agreement with the x-ray structure (Gautier et al. 2010).

Archaea
Euryarchaeota
SRII of Natronomonas pharaonis (P42196)
*3.E.1.3.4









Sensory rhodopsin III, SRIII, of 232 aas and 7 TMSs (Fu et al. 2010).

Archaea
Euryarchaeota
SRIII of Haloarcula marismortui
*3.E.1.3.5









Phoborhodopsin (sensory rhodopsin II) of 249 aas and 7 TMSs.  The photochemistry and proton transport have been reviewed (Kamo et al. 2001) and the crystal structure is known (Kandori and Kamo 2002).

Archaea
Euryarchaeota
Phoborhodopsin of Halorubrum chaoviator
*3.E.1.4.1









Heat shock protein HSP30
Eukaryota
Fungi
HSP30 of Saccharomyces cerevisiae
*3.E.1.4.2









Retinal binding protein, Neurospora Opsin-1, NOP-1 (Bieszke et al. 1999; Bieszke et al. 2007).

Eukaryota
Fungi
NOP-1 of Neurospora crassa
*3.E.1.4.3









Eukaryota
Fungi
Rhodopsin of Leptosphaeria maculans (AAG01180)
*3.E.1.4.4









Acetaularia rhodopsin I, ARI or c102333 of 246 aas.  It exhibits outward H+ pumping activity, and D89 and D100 are essential for pumping activity (Lee et al. 2015). Blue-light causes a shunt of the photocycle under H+ reuptake from the extracellular side (Tsunoda et al. 2006). Similarities and differences of AR with BR have been revealed by detailed electrophysiological studies, revealing among other things, the voltage dependencies of the pump (Tsunoda et al. 2006).

Eukaryota
Viridiplantae
c102333 of Acetabularia acetabulum (Q1AJZ3)
*3.E.1.4.5









Opsin 1, Bacteriorhodopsin-like protein

Eukaryota
Cryptophyta
Opsin 1 of Guillardia theta (Q2QCJ4)
*3.E.1.4.6









Possible chaperone membrane protein related to Hsp30, Mrh1 (320 aas; 33% identical to Hsp30p). This protein and its two paralogues, Hsp30 and YR02, are induced by heat shock and are present primarily in the plasma membrane (Wu et al. 2000).  It plays a role in acetic acid tolerance and may be an acetic acid exporter (Takabatake et al. 2015).

Eukaryota
Fungi
Mrh1p of Saccharomyces cerevisiae (Q12117)
*3.E.1.4.7









Cyanorhodopsin of 334 aas and 7 TMSs, Ops1 (Frassanito et al. 2010).

Eukaryota
Glaucocystophyceae
Cyanorhodopsin of Cyanophora paradoxa
*3.E.1.4.8









Yro2 of 344 aas and 7 TMSs.  Plays a role in acetic acid tolereance and is induced by acetic acid stress and by entry into the stationary phase.  It is 72% identical to Mrh1 (TC# 3.E.1.4.6) which is also believed to be involved in the acetic acid stress response (Takabatake et al. 2015).

Eukaryota
Fungi
Yro2 of Saccharomyces cerevisiae
*3.E.1.4.9









Pentachlorophenone-induced protein, FDD123
Eukaryota
Fungi
FDD123 of Coriolus versicolor
*3.E.1.5.1









Bacterio-rhodopsin/guanylyl cyclase 1 fusion protein of 626 aas; light-activated enzyme, RhCG, Gc1 or Cyc1Op. The central bacteriorhodopsin domain with 7 TMSs is linked via an additional TMS to the C-terminal adenylate/guanylate cyclase catalytic domain. CyclOp enables precise and rapid optogenetic manipulation of cGMP levels in cells and animals (Gao et al. 2015).

Eukaryota
Metazoa
Gc1 of Blastocladiella emersonii (Aquatic fungus)
*3.E.1.6.1









Proteorhopdopsin (exhibits variable vectorality: H+ is pumped out at basic pH but not at acidic pH; see Friedrich et al., 2002). Proteorhodopsin has been used to measure membrane potentials and electrical spiking in E. coli (Kralj et al., 2011; Ward et al., 2011).  3-d structures of three proteorhodopsins show that they can exist as pentamers or hexamers, depending on the protein (Ran et al. 2013).  Protonation states of several carboxylic acids, the boundaries and distortions of transmembrane α-helices, and secondary structural elements in the loops have been identified (Shi et al. 2009). Proteorhodopsin molecules incorporated into mesostructured silica films exhibit native-like function, as well as enhanced thermal stability compared to surfactant or lipid environments (Jahnke et al. 2018).

Bacteria
Proteobacteria
Proteorhodopsin from an uncultured γ-proteobacterium EOAC 31A08
*3.E.1.6.2









Xanthorhodopsin, a proton pump with a carotenoid antenna, salinixanthin (Lanyi and Balashov 2008). A crystal structure (1.9 Å resolution) is available (Luecke et al., 2008).

Bacteria
Bacteroidetes/Chlorobi group
Xanthorhodopsin with a salinixanthin chromophore of Salinibacter ruber (Q2S2F8)
*3.E.1.6.3









Rhodopsin of 298 aas and 7 TMSs (associates with salinixanthin, the light-harvesting carotenoid antenna of xanthorhodopsin) (Imasheva et al., 2009Hashimoto et al., 2010).  Expression in a chemotrophic E. coli enabled light-driven phototrophic energy generation (Kim et al. 2017).

Bacteria
Cyanobacteria
Rhodopsin of Gloeobacter violaceus (Q7NP59)
*3.E.1.6.4









Bacteriorhodopsin-like circadian clock related protein (Okamoto and Hastings, 2003)

Eukaryota
Dinophyceae
BacRhodopsin of Pyrocystis lunula (Q8GZE7)
*3.E.1.6.5









H+-pumping bacteriorhodopsin, Brho or ESR (Petrovskaya et al. 2010). Photoelectric potential generation correlates with the ESR structure and proposed mechanism of proton transfer (Siletsky et al. 2016).

Bacteria
Firmicutes
Brho of Exiguobacterium sibiricum (B1YFV8)
*3.E.1.6.6









Proton pumping proteorhodopsin of 253 aas (Kimura et al. 2011).

Bacteria
Bacteroidetes/Chlorobi group
Proteorhodopsin of Nonlabens dokdonensis (Donghaeana dokdonensis)
*3.E.1.6.7









Na+ or H+ pumping bacteriorhodopsin, NaR, Kr2 or KR2.  It uses light to pump protons or sodium ions from the cell depending on the ionic composition of the medium. In cells suspended in a KCl solution, NaR functions as a light-driven proton pump, whereas in a NaCl solution, it exhibits light-driven sodium ion pumping, a novel activity within the rhodopsin family (da Silva et al. 2015).  A cation switch controls its conformations, and specific interactions of Na+ with the half-channels open an appropriate path for ion translocation (da Silva et al. 2015). Several high resolution x-ray structures have been solved (4XTO, Kato et al. 2015). Putative Na+ binding sites have been identified, and it was shown how protonation and conformational changes gate the ion through these sites toward the extracellular side (Suomivuori et al. 2017). Evidence for homology of this and other microbial rhodopsin with GPCR receptors including mamalian rhodopsins has been presented (Yee et al. 2013; Shalaeva et al. 2015).

Bacteria
Bacteroidetes/Chlorobi group
NaR of Dokdonia eikasta (Krokinobacter eikastus)
*3.E.1.6.8









Proteorhodopsin of 246 aas and 7 TMSs, Pro.  A light-driven Na+ pump (Bertsova et al. 2015).

Bacteria
Bacteroidetes
Proteorhodopsin of Dokdonia sp. PRO95
*3.E.1.6.9









Bacteriorhodopsin (thermophilic rhodopsin; TR) of 260 aas and 7 TMSs.  53% identical to xanthorhodopsin (TC# 3.E.1.6.2).  It is a photoreceptor protein with extremely high thermal stability and a light-driven electrogenic proton pump. The x-ray crystal structure revealed the presence of a putative binding site for a carotenoid antenna and a larger number of hydrophobic residues and aromatic-aromatic interactions than in most microbial rhodopsins (Tsukamoto et al. 2016). The structural changes upon thermal stimulation involved a thermally induced structure in which an increase of hydrophobic interactions in the extracellular domain, the movement of extracellular domains, the formation of a hydrogen bond, and the tilting of transmembrane helices were observed. An extracellular LPGG motif between helices F and G may play an important role in thermal stability, acting as a "thermal sensor" (Tsukamoto et al. 2016).

Bacteria
Deinococcus-Thermus
Bacteriorhodopsin of Thermus thermophilus
*3.E.1.6.10









Uncharaacterized bacteriorhodopsin of 289 aas and 7 TMSs.

Bacteria
Proteobacteria
UP of Parvularcula oceani
*3.E.1.6.11









Uncharacterized bacteriorhodopsin of 321 aas and 7 TMSs.

Bacteria
Proteobacteria
UP of Parvularcula oceani
*3.E.1.7.1









Channelrhodopsin-1 (chlamyrhodopsin-3) (ChR1; Cop3; CSOA) (light-gated proton channel) (Nagel et al., 2003). TMSs 1 and 2 are the main structures involved in desensitization involving the stabilization of the protein's conformation and the alteration of the charge distribution around the retinal-Schiff base (Zamani et al. 2017).

Eukaryota
Viridiplantae
Channelrhodopsin-1 of Chlamydomonas reinhardtii
*3.E.1.7.2









Channelrhodopsin-2 (chlamyrhodopsin-4; ChR2; CR2; Cop4; CSOB) (light-gated cation-selective ion channel (both monovalent and divalent cations are transported)) (Nagel et al., 2003). Berndt et al. (2010) showed that ChR2 has two open states with differing ion selectivities. The channel is fairly nonspecific at the beginning of a light pulse, and becomes more specific for protons during longer periods of light exposure. Residues involved in channel closure have been identified (Bamann et al. 2010).  ChR2 is 712 aas long; the MR domain is N-terminal (Lee et al. 2015). The free energy profiles computed for proton transfer to the counterion, either via a direct jump or mediated by a water molecule, demonstrate that, when retinal is all-trans, water and protein electrostatic interactions largely favour the protonated retinal Schiff base state (Adam and Bondar 2018).
   Blue light illumination of ChR2 activates an intrinsic leak channel conductive for cations. Sequence comparison of ChR2 with the related ChR1 protein revealed a cluster of charged amino acids within the predicted transmembrane domain 2 (TM2), which includes glutamates E90, E97 and E101. Charge inversion substitutions altered ChR2 function, replacement of E90 by lysine or alanine resulted in differential effects on H+- and Na+-mediated currents. These results are consistent with this glutamate side chain within TMS2 contributing to ion flux through and the cation selectivity of ChR2 (Ruffert et al., 2011). Glutamate residue-97 lies in the outer pore where it interacts with a cation to facilitate dehydration. This residue is also the primary binding target of Gd3+(Tanimoto et al., 2012).  Channelrhodopsin has been converted into a light-gated chloride channel (Wietek et al. 2014).  TMSs 2, 6 and 7 reorient or rearrange during the photocycle with no major differences near TMSs 3 and 4 at the dimer interface. TMS2 plays a key role in light-induced channel opening and closing in ChR2 (Müller et al. 2015).  Negative charges at the extracellular side of transmembrane domain 7 funnel cations into the pore (Richards and Dempski 2015).  CrChR2, is the most widely used optogenetic tool in neuroscience.  Water efflux and the cessation of the ion conductance are synchronized (Lórenz-Fonfría et al. 2015).  light and pH induce changes in the structure and accessibility of TMSB (Volz et al. 2016). Residues V86, K93 and N258 form a putative barrier to ion translocation. These residues contribute to cation selectivity (V86 and N258), the transition between the two open states (V86), open channel stability, and the hydrogen-bonding network (K93I and K93N) (Richards and Dempski 2017). The x-ray structure is available and reveals much about the mechanism of channel regulation (Gerwert 2017; Volkov et al. 2017).

Eukaryota
Viridiplantae
Channelrhodopsin-2, CR2, of Chlamydomonas reinhardtii (Q8RUT8)
*3.E.1.7.3









Channelrhodopsin-2 light-gated ion channel. A 6Å projection map is available (Müller et al., 2011). Glutamate residue-97 lies in the outer pore where it interacts with a cation to facilitate dehydration. This residue is also the primary binding target of Gd3+ (Tanimoto et al., 2012).

Eukaryota
Viridiplantae
Channelrhodopsin-2 of Volvox carteri (B4Y105)
*3.E.1.7.4









Channelopsin, MChR1 (Govorunova et al., 2011). In another channelrhodopsin (CrChR2) of this family, an E97A mutation in TMS 2 prevents high affiinity binding of the inhibitor, Gd3+ and interfers with photocurrent, but this ChR1 with an alanine at this position, has low affininty for Gd3+ but normal photocurrent (Watanabe et al. 2016).

Eukaryota
Viridiplantae
MChR1 of Mesostigma viride (F8UVI5)
*3.E.1.8.1









Anion-specific light-gated channel rhodopsin of 438 aas, Acr1, lacking measurable cation transport capability (Govorunova et al. 2015).

Eukaryota
Cryptophyta
Arc1 of Guillardia theta
*3.E.1.8.2









Anion-specific light-gated channel rhodopsin of 438 aas, Acr2, lacking measurable cation transport capability (Govorunova et al. 2015).

Eukaryota
Cryptophyta
Acr2 of Guillardia theta
*3.E.1.8.3









Homologue of anion-specific light-gated channel rhodopsin of 461 aas and 7 putative TMSs, lacking apparent channel activity  (Govorunova et al. 2015).

Eukaryota
Cryptophyta
Acr homologue of Guillardia theta