Opsin

{{short description|Class of light-sensitive proteins}} {{About|animal opsins|microbial opsins|microbial rhodopsin}} [[Image:Rhodopsin 3D.jpeg|thumb|150px|Three-dimensional structure of cattle rhodopsin. The seven transmembrane domains are shown in varying colors. The chromophore is shown in red.]] thumb|right|400px|The retinal molecule inside an opsin protein absorbs a photon of light. Absorption of the photon causes retinal to change from its 11-cis-retinal isomer into its all-trans-retinal isomer. This change in shape of retinal pushes against the outer opsin protein to begin a signal cascade, which may eventually result in chemical signaling being sent to the brain as visual perception. The retinal is re-loaded by the body so that signaling can happen again. '''Animal opsins''' are G-protein-coupled receptors and a group of proteins made light-sensitive via a chromophore, typically retinal. When bound to retinal, opsins become retinylidene proteins, but are usually still called opsins regardless. Most prominently, they are found in photoreceptor cells of the retina. Five classical groups of opsins are involved in vision, mediating the conversion of a photon of light into an electrochemical signal, the first step in the visual transduction cascade. Another opsin found in the mammalian retina, melanopsin, is involved in circadian rhythms and pupillary reflex but not in vision. Humans have in total nine opsins. Beside vision and light perception, opsins may also sense temperature, sound, or chemicals.

== Structure and function == Animal opsins are molecules that absorb light from the environment, most of which allow for vision in animals. Opsins are G-protein-coupled receptors (GPCRs),<ref name=Casey1988>{{cite journal | vauthors = Casey PJ, Gilman AG | title = G protein involvement in receptor-effector coupling | journal = The Journal of Biological Chemistry | volume = 263 | issue = 6 | pages = 2577–2580 | date = February 1988 | pmid = 2830256 | doi = 10.1016/s0021-9258(18)69103-3 | s2cid = 38970721 | doi-access = free }}</ref><ref name=Attwood1994>{{cite journal | vauthors = Attwood TK, Findlay JB | title = Fingerprinting G-protein-coupled receptors | journal = Protein Engineering | volume = 7 | issue = 2 | pages = 195–203 | date = February 1994 | pmid = 8170923 | doi = 10.1093/protein/7.2.195 }}</ref> which are chemoreceptors and have seven transmembrane domains forming a binding pocket for a ligand.<ref>{{cite journal | vauthors = Dixon RA, Kobilka BK, Strader DJ, Benovic JL, Dohlman HG, Frielle T, Bolanowski MA, Bennett CD, Rands E, Diehl RE, Mumford RA, Slater EE, Sigal IS, Caron MG, Lefkowitz RJ, Strader CD | display-authors = 6 | title = Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin | journal = Nature | volume = 321 | issue = 6065 | pages = 75–79 | date = May 1986 | pmid = 3010132 | doi = 10.1038/321075a0 | s2cid = 4324074 | bibcode = 1986Natur.321...75D }}</ref><ref>{{cite journal | vauthors = Dixon RA, Sigal IS, Rands E, Register RB, Candelore MR, Blake AD, Strader CD | title = Ligand binding to the beta-adrenergic receptor involves its rhodopsin-like core | journal = Nature | volume = 326 | issue = 6108 | pages = 73–77 | date = March 1987 | pmid = 2881211 | doi = 10.1038/326073a0 | s2cid = 4352920 | bibcode = 1987Natur.326...73D }}</ref> The ligand for opsins is the vitamin A-based chromophore 11-''cis''-retinal,<ref>{{cite journal | vauthors = Wald G |title=Carotenoids and the Vitamin A Cycle in Vision |journal=Nature |date=July 1934 |volume=134 |issue=3376 |page=65 |doi=10.1038/134065a0|bibcode=1934Natur.134...65W |s2cid=4022911 |doi-access=free }}</ref><ref>{{cite journal | vauthors = Wald G, Brown PK, Hubbard R, Oroshnik W | title = Hindered Cis Isomers of Vitamin a and Retinene: The Structure of the Neo-B Isomer | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 41 | issue = 7 | pages = 438–451 | date = July 1955 | pmid = 16589696 | pmc = 528115 | doi = 10.1073/pnas.41.7.438 | doi-access = free | bibcode = 1955PNAS...41..438W }}</ref><ref>{{cite journal | vauthors = Brown PK, Wald G | title = The neo-b isomer of vitamin A and retinene | journal = The Journal of Biological Chemistry | volume = 222 | issue = 2 | pages = 865–877 | date = October 1956 | pmid = 13367054 | doi = 10.1016/S0021-9258(20)89944-X | doi-access = free }}</ref><ref>{{cite journal | vauthors = Oroshnik W |title = The Synthesis and Configuration of Neo-B Vitamin A and Neoretinine b | journal = Journal of the American Chemical Society | date = June 1956 | volume = 78 | issue = 11 | pages = 2651–2652 | doi = 10.1021/ja01592a095 |bibcode = 1956JAChS..78.2651O }}</ref><ref>{{cite journal | vauthors = Oroshnik W, Brown PK, Hubbard R, Wald G | title = HINDERED CIS ISOMERS OF VITAMIN A AND RETINENE: THE STRUCTURE OF THE NEO-b ISOMER | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 42 | issue = 9 | pages = 578–580 | date = September 1956 | pmid = 16589909 | pmc = 534254 | doi = 10.1073/pnas.42.9.578 | doi-access = free | bibcode = 1956PNAS...42..578O }}</ref> which is covalently bound to a lysine residue<ref>{{cite journal | vauthors = Bownds D | title = Site of attachment of retinal in rhodopsin | journal = Nature | volume = 216 | issue = 5121 | pages = 1178–1181 | date = December 1967 | pmid = 4294735 | doi = 10.1038/2161178a0 | s2cid = 1657759 | bibcode = 1967Natur.216.1178B }}</ref> in the seventh transmembrane domain<ref>{{cite journal | vauthors = Hargrave PA, McDowell JH, Curtis DR, Wang JK, Juszczak E, Fong SL, Rao JK, Argos P | display-authors = 6 | title = The structure of bovine rhodopsin | journal = Biophysics of Structure and Mechanism | volume = 9 | issue = 4 | pages = 235–244 | date = 1983 | pmid = 6342691 | doi = 10.1007/BF00535659 | s2cid = 20407577 }}</ref><ref name=Palczewski2000>{{cite journal | vauthors = Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M | display-authors = 6 | title = Crystal structure of rhodopsin: A G protein-coupled receptor | journal = Science | volume = 289 | issue = 5480 | pages = 739–745 | date = August 2000 | pmid = 10926528 | doi = 10.1126/science.289.5480.739 | citeseerx = 10.1.1.1012.2275 | bibcode = 2000Sci...289..739P }}</ref><ref name=Murakami2008>{{cite journal | vauthors = Murakami M, Kouyama T | title = Crystal structure of squid rhodopsin | journal = Nature | volume = 453 | issue = 7193 | pages = 363–367 | date = May 2008 | pmid = 18480818 | doi = 10.1038/nature06925 | s2cid = 4339970 | bibcode = 2008Natur.453..363M }}</ref> through a Schiff-base.<ref>{{cite journal | vauthors = Collins FD | title = Rhodopsin and indicator yellow | journal = Nature | volume = 171 | issue = 4350 | pages = 469–471 | date = March 1953 | pmid = 13046517 | doi = 10.1038/171469a0 | s2cid = 4152360 | bibcode = 1953Natur.171..469C }}</ref><ref>{{cite journal | vauthors = Pitt GA, Collins FD, Morton RA, Stok P | title = Studies on rhodopsin. VIII. Retinylidenemethylamine, an indicator yellow analogue | journal = The Biochemical Journal | volume = 59 | issue = 1 | pages = 122–128 | date = January 1955 | pmid = 14351151 | pmc = 1216098 | doi = 10.1042/bj0590122 }}</ref> When the 11-''cis''-retinal absorbs a photon of light and isomerizes to all-''trans''-retinal<ref>{{cite journal | vauthors = Hubbard R, Kropf A | title = The Action of Light on Rhodopsin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 44 | issue = 2 | pages = 130–139 | date = February 1958 | pmid = 16590155 | pmc = 335377 | doi = 10.1073/pnas.44.2.130 | doi-access = free | bibcode = 1958PNAS...44..130H }}</ref><ref>{{cite journal | vauthors = Kropf A, Hubbard R | title = The mechanism of bleaching rhodopsin | journal = Annals of the New York Academy of Sciences | volume = 74 | issue = 2 | pages = 266–280 | date = November 1959 | pmid = 13627857 | doi = 10.1111/j.1749-6632.1958.tb39550.x | bibcode = 1959NYASA..74..266K | s2cid = 45830716 }}</ref><ref name=Choe2011>{{cite journal | vauthors = Choe HW, Kim YJ, Park JH, Morizumi T, Pai EF, Krauss N, Hofmann KP, Scheerer P, Ernst OP | display-authors = 6 | title = Crystal structure of metarhodopsin II | journal = Nature | volume = 471 | issue = 7340 | pages = 651–655 | date = March 2011 | pmid = 21389988 | doi = 10.1038/nature09789 | s2cid = 4302421 | bibcode = 2011Natur.471..651C }}</ref><ref name=Wald1968>{{cite journal | vauthors = Wald G | title = Molecular basis of visual excitation | journal = Science | volume = 162 | issue = 3850 | pages = 230–239 | date = October 1968 | pmid = 4877437 | doi = 10.1126/science.162.3850.230 | bibcode = 1968Sci...162..230W }}</ref> this causes a conformal change in the opsin,<ref name=Choe2011 /> and activates a phototransduction cascade.<ref>{{cite journal | vauthors = Terakita A, Kawano-Yamashita E, Koyanagi M |title=Evolution and diversity of opsins |journal=Wiley Interdisciplinary Reviews: Membrane Transport and Signaling |date=January 2012 |volume=1 |issue=1 |pages=104–111 |doi=10.1002/wmts.6|doi-access=free }}</ref> Thus, a chemoreceptor is converted to a light or photo(n)receptor.<ref name=Guehmann2022>{{cite journal | vauthors = Gühmann M, Porter ML, Bok MJ | title = The Gluopsins: Opsins without the Retinal Binding Lysine | journal = Cells | volume = 11 | issue = 15 | page = 2441 | date = August 2022 | pmid = 35954284 | pmc = 9368030 | doi = 10.3390/cells11152441 | doi-access = free }} 50px Material was copied and adapted from this source, which is available under a [https://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International License].</ref>

In the vertebrate photoreceptor cells, all-''trans''-retinal is released and replaced by a newly synthesized 11-''cis''-retinal provided from the retinal epithelial cells. <!-- Expand this paragraph with A3 and A4 and citations. A2 is found in freshwater species. There are also retinas that contain both A1 and A2 --> Beside 11-''cis''-retinal (A1), 11-''cis''-3,4-didehydroretinal (A2) is also found as a ligand in some vertebrates, such as freshwater fishes.<ref name=Wald1968 /> A2-bound opsins have a shifted ''λ''_max and absorption spectrum compared to A1-bound opsins.<ref>{{cite journal | vauthors = Amora TL, Ramos LS, Galan JF, Birge RR | title = Spectral tuning of deep red cone pigments | journal = Biochemistry | volume = 47 | issue = 16 | pages = 4614–4620 | date = April 2008 | pmid = 18370404 | pmc = 2492582 | doi = 10.1021/bi702069d }}</ref>

== Functionally conserved residues and motifs == The seven transmembrane α-helical domains in opsins are connected by three extra-cellular and three cytoplasmic loops. Along the α-helices and the loops, many amino acid residues are highly conserved between all opsin groups, indicating that they serve important functions and thus are called ''functionally conserved residues''. Actually, insertions and deletions in the α-helices are very rare and should preferentially occur in the loops. Therefore, different G-protein-coupled receptors have different length and homologous residues may be in different positions. To make such positions comparable between different receptors, Ballesteros and Weinstein introduced a common numbering scheme for G-protein-coupled receptors.<ref>{{cite book | vauthors = Ballesteros JA, Weinstein H |chapter=Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors |title=Receptor Molecular Biology |series=Methods in Neurosciences |date=1995 |volume=25 |pages=366–428 |doi=10.1016/S1043-9471(05)80049-7|isbn=978-0-12-185295-5 }}</ref> The number before the period is the number of the transmembrane domain. The number after the period is set arbitrarily to 50 for the most conserved residue in that transmembrane domain among GPCRs known in 1995. For instance in the seventh transmembrane domain, the proline in the highly conserved NPxxY^7.53 motif is Pro^7.50, the asparagine before is then Asp^7.49, and the tyrosine three residues after is then Tyr^7.53.<ref name=Guehmann2022 /> Another numbering scheme is based on cattle rhodopsin. Cattle rhodopsin has 348 amino acids and is the first opsin whose amino acid sequence<ref name=Ovchinnikov1982>{{cite journal | title = Rhodopsin and bacteriorhodopsin: structure-function relationships | journal = FEBS Letters | volume = 148 | issue = 2 | pages = 179–191 | date = November 1982 | pmid = 6759163 | doi = 10.1016/0014-5793(82)80805-3 | s2cid = 85819100 | last1 = Ovchinnikov | first1 = Yu.A. | bibcode = 1982FEBSL.148..179O | doi-access = free }}</ref> and whose 3D-structure were determined.<ref name=Palczewski2000 /> The cattle rhodopsin numbering scheme is widespread in the opsin literature.<ref name=Guehmann2022 /> Therefore, it is useful to use both schemes.

=== The retinal binding lysine === Opsins without the retinal binding lysine are not light sensitive.<ref name=Katana2019>{{cite journal | vauthors = Katana R, Guan C, Zanini D, Larsen ME, Giraldo D, Geurten BR, Schmidt CF, Britt SG, Göpfert MC | display-authors = 6 | title = Chromophore-Independent Roles of Opsin Apoproteins in ''Drosophila'' Mechanoreceptors | journal = Current Biology | volume = 29 | issue = 17 | pages = 2961–2969.e4 | date = September 2019 | pmid = 31447373 | doi = 10.1016/j.cub.2019.07.036 | s2cid = 201420079 | doi-access = free | bibcode = 2019CBio...29E2961K }}</ref><ref name=Leung2020>{{cite journal | vauthors = Leung NY, Thakur DP, Gurav AS, Kim SH, Di Pizio A, Niv MY, Montell C | title = Functions of Opsins in ''Drosophila'' Taste | journal = Current Biology | volume = 30 | issue = 8 | pages = 1367–1379.e6 | date = April 2020 | pmid = 32243853 | pmc = 7252503 | doi = 10.1016/j.cub.2020.01.068 | bibcode = 2020CBio...30E1367L }}</ref> In cattle rhodopsin, this lysine is the 296th amino acid<ref name=Palczewski2000 /><ref name=Ovchinnikov1982 /> and thus according to both numbering schemes Lys296^7.43. It is well conserved among opsins, so well conserved that sequences without it were not even considered opsins and thus excluded from large scale phylogenetic reconstructions.<ref name="PorterBlasic2011">{{cite journal | vauthors = Porter ML, Blasic JR, Bok MJ, Cameron EG, Pringle T, Cronin TW, Robinson PR | title = Shedding new light on opsin evolution | journal = Proceedings. Biological Sciences | volume = 279 | issue = 1726 | pages = 3–14 | date = January 2012 | pmid = 22012981 | pmc = 3223661 | doi = 10.1098/rspb.2011.1819 | bibcode = 2012PBioS.279....3P }}</ref><ref name="Ramirez2016">{{cite journal | vauthors = Ramirez MD, Pairett AN, Pankey MS, Serb JM, Speiser DI, Swafford AJ, Oakley TH | title = The Last Common Ancestor of Most Bilaterian Animals Possessed at Least Nine Opsins | journal = Genome Biology and Evolution | volume = 8 | issue = 12 | pages = 3640–3652 | date = December 2016 | pmid = 28172965 | doi = 10.1093/gbe/evw248 | pmc = 5521729 }}</ref> Even so, most opsins have Lys296^7.43, some have lost it during evolution: In the nemopsins from nematodes, Lys296^7.43 is replaced by Arginine.<ref name=Troemmel>{{cite journal | vauthors = Troemel ER, Chou JH, Dwyer ND, Colbert HA, Bargmann CI | title = Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans | journal = Cell | volume = 83 | issue = 2 | pages = 207–218 | date = October 1995 | pmid = 7585938 | doi = 10.1016/0092-8674(95)90162-0 | bibcode = 1995Cell...83..207T | s2cid = 17819587 | doi-access = free }}</ref><ref name=Guehmann2022 /> In the astropsins from sea urchins<ref>{{cite journal | vauthors = D'Aniello S, Delroisse J, Valero-Gracia A, Lowe EK, Byrne M, Cannon JT, Halanych KM, Elphick MR, Mallefet J, Kaul-Strehlow S, Lowe CJ, Flammang P, Ullrich-Lüter E, Wanninger A, Arnone MI | display-authors = 6 | title = Opsin evolution in the Ambulacraria | journal = Marine Genomics | volume = 24 | issue = Pt 2 | pages = 177–183 | date = December 2015 | pmid = 26472700 | doi = 10.1016/j.margen.2015.10.001 | bibcode = 2015MarGn..24..177D | doi-access = free }}</ref><ref name=Guehmann2022 /> and in the gluopsins, Lys296^7.43 is replaced by glutamic acid.<ref name=Guehmann2022 /> A nemopsin is expressed in chemosensory cells in ''Caenorhabditis elegans''. Therefore, the nemopsins are thought to be chemoreceptors.<ref name=Troemmel /> The gluopsins are found in insects such as beetles, scorpionflies, dragonflies, and butterflies and moths including model organisms such as the silk moth and the tobacco hawk moth. However, the gluopsins have no known function.<ref name=Guehmann2022 />

Such function does not need to be light detection, as some opsins are also involved in thermosensation,<ref>{{cite journal | vauthors = Shen WL, Kwon Y, Adegbola AA, Luo J, Chess A, Montell C | title = Function of rhodopsin in temperature discrimination in ''Drosophila'' | journal = Science | volume = 331 | issue = 6022 | pages = 1333–1336 | date = March 2011 | pmid = 21393546 | doi = 10.1126/science.1198904 | s2cid = 206530389 | bibcode = 2011Sci...331.1333S }}</ref> mechanoreception such as hearing<ref>{{cite journal | vauthors = Senthilan PR, Piepenbrock D, Ovezmyradov G, Nadrowski B, Bechstedt S, Pauls S, Winkler M, Möbius W, Howard J, Göpfert MC | display-authors = 6 | title = ''Drosophila'' auditory organ genes and genetic hearing defects | journal = Cell | volume = 150 | issue = 5 | pages = 1042–1054 | date = August 2012 | pmid = 22939627 | doi = 10.1016/j.cell.2012.06.043 | s2cid = 1422764 | doi-access = free }}</ref> detecting phospholipids, chemosensation, and other functions.<ref name=Feuda2022>{{cite journal | vauthors = Feuda R, Menon AK, Göpfert MC | title = Rethinking Opsins | journal = Molecular Biology and Evolution | volume = 39 | issue = 3 | article-number = msac033 | date = March 2022 | pmid = 35143663 | pmc = 8892948 | doi = 10.1093/molbev/msac033 }}</ref><ref name=Leung2017>{{cite journal | vauthors = Leung NY, Montell C | title = Unconventional Roles of Opsins | journal = Annual Review of Cell and Developmental Biology | volume = 33 | issue = 1 | pages = 241–264 | date = October 2017 | pmid = 28598695 | pmc = 5963513 | doi = 10.1146/annurev-cellbio-100616-060432 }}</ref> In particular, the ''Drosophila'' rhabdomeric opsins (rhabopsins, r-opsins) Rh1, Rh4, and Rh7 function not only as photoreceptors, but also as chemoreceptors for aristolochic acid. These opsins still have Lys296^7.43 like other opsins. However, if this lysine is replaced by an arginine in Rh1, then Rh1 loses light sensitivity but still responds to aristolochic acid. Thus, Lys296^7.43 is not needed for Rh1 to function as chemoreceptor.<ref name=Leung2020 /> Also the ''Drosophila'' rhabopsins Rh1 and Rh6 are involved in mechanoreception, again for mechanoreception Lys296^7.43 is not needed, but needed for proper function in the photoreceptor cells.<ref name=Katana2019 />

Beside these functions, an opsin without Lys296^7.43, such as a gluopsin, could still be light sensitive, since in cattle rhodopsin, the retinal binding lysine can be shifted from position 296 to other positions, even into other transmembrane domains, without changing light sensitivity.<ref name="DevineOprian2013"/>

{{gallery |mode=packed |title=Opsins have the retinal binding lysine, except the nemopsins and gluopsins<ref name=Guehmann2022 /> |align=left |height=300 |width=300 |File:Opsin Phylogeny with the main Groups the Tetraopsins Highlighted.svg |Most known opsins have the retinal binding lysine except some among the tetraopins, The outgroup contains other G protein-coupled receptors. |File:Tetraopsin Phylogeny with the Chromopsins Highlighted.svg |Most tetraopsins have also the retinal binding lysine except some of the chromopsins, which are highlighted by the frame and expanded in the next image. The outgroup contains other G protein-coupled receptors including the other opsins. |File:Chromopsins with the Gluopsins Nemopsins and Astropsins Highlighted.svg |Most chromopsins have also the retinal binding lysine except the nemopsins, where it is replaced by argenine (R), and the gluopsins, where it is replaced by glutamic acid (E). The astropsins, the nemopsins and the gluopsins are highlighted by the frames. The outgroup contains other G protein-coupled receptors including the other opsins. }}

{{clear}} <!-- The next paragraph should be grouped with the gallery above --> In the phylogeny above, each clade contains sequences from opsins and other G protein-coupled receptors. The number of sequences and two pie charts are shown next to the clade. The first pie chart shows the percentage of a certain amino acid at the position in the sequences corresponding Lys296^7.43 in cattle rhodopsin. The amino acids are color-coded. The colors are red for lysine (K), purple for glutamic acid (E), orange for argenine (R), dark and mid-gray for other amino acids, and light gray for sequences that have no data at that position. The second pie chart gives the taxon composition for each clade, green stands for craniates, dark green for cephalochordates, mid green for echinoderms, brown for nematodes, pale pink for annelids, dark blue for arthropods, light blue for mollusks, and purple for cnidarians. The branches to the clades have pie charts, which give support values for the branches. The values are from right to left SH-aLRT/aBayes/UFBoot. The branches are considered supported when SH-aLRT ≥ 80%, aBayes ≥ 0.95, and UFBoot ≥ 95%. If a support value is above its threshold the pie chart is black otherwise gray.<ref name=Guehmann2022 />

=== The NPxxY motif === The NPxxY^7.53 motif is well-conserved among opsins and G-protein-coupled receptors. This motif is important for G-protein binding and receptor activation.<ref name=Guehmann2022 /> For instance, if it is mutated to DPxxY^7.53 (Asn^7.49 → Asp^7.49) in the human m3 muscarinic receptor, activation is not affected, but it is abolished if it is mutated to APxxY^7.53 (Asn^7.49 → Ala^7.49).<ref name=Borroto-Escuela2011>{{cite journal | vauthors = Borroto-Escuela DO, Romero-Fernandez W, García-Negredo G, Correia PA, Garriga P, Fuxe K, Ciruela F | title = Dissecting the conserved NPxxY motif of the M3 muscarinic acetylcholine receptor: critical role of Asp-7.49 for receptor signaling and multiprotein complex formation | journal = Cellular Physiology and Biochemistry | volume = 28 | issue = 5 | pages = 1009–1022 | date = 2011 | pmid = 22178951 | doi = 10.1159/000335788 | s2cid = 14008354 | hdl = 2445/126278 | hdl-access = free }}</ref> Such a mutation to APxxY^7.53 (Asn^7.49 → Ala^7.49) reduces the G-protein activation of cattle rhodopsin to 45% compared to wild type. Also in cattle rhodopsin, if the motif is mutated to NPxxA^7.53 (Tyr^7.53 → Ala^7.53), cattle rhodopsin does not activate the G-protein.<ref name=Fritze2003>{{cite journal | vauthors = Fritze O, Filipek S, Kuksa V, Palczewski K, Hofmann KP, Ernst OP | title = Role of the conserved NPxxY(x)5,6F motif in the rhodopsin ground state and during activation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 5 | pages = 2290–2295 | date = March 2003 | pmid = 12601165 | pmc = 151333 | doi = 10.1073/pnas.0435715100 | doi-access = free | bibcode = 2003PNAS..100.2290F }}</ref> Such a mutation also reduces the activation of the vasopressin V2 receptor. In fact in G-protein-coupled receptors, only loss of function disease mutations are known for Tyr^7.53⁠.<ref name=Zhou2019>{{cite journal | vauthors = Zhou Q, Yang D, Wu M, Guo Y, Guo W, Zhong L, Cai X, Dai A, Jang W, Shakhnovich EI, Liu ZJ, Stevens RC, Lambert NA, Babu MM, Wang MW, Zhao S | display-authors = 6 | title = Common activation mechanism of class A GPCRs | journal = eLife | volume = 8 | article-number = e50279 | date = December 2019 | pmid = 31855179 | pmc = 6954041 | doi = 10.7554/eLife.50279 | doi-access = free }}</ref>

Also mutations of Pro^7.50 influence G-protein activation, if the motif is mutated to NAxxY^7.53 (Pro^7.50 → Ala^7.50) in the rat m3 muscarinic receptor, the receptor can still be activated but less efficiently,<ref name=Wess1993>{{cite journal | vauthors = Wess J, Nanavati S, Vogel Z, Maggio R | title = Functional role of proline and tryptophan residues highly conserved among G protein-coupled receptors studied by mutational analysis of the m3 muscarinic receptor | journal = The EMBO Journal | volume = 12 | issue = 1 | pages = 331–338 | date = January 1993 | pmid = 7679072 | pmc = 413210 | doi = 10.1002/j.1460-2075.1993.tb05661.x }}</ref> this mutation even abolishes activation in the cholecystokinin B receptor completely.<ref name=Gales2000>{{cite journal | vauthors = Galés C, Kowalski-Chauvel A, Dufour MN, Seva C, Moroder L, Pradayrol L, Vaysse N, Fourmy D, Silvente-Poirot S | display-authors = 6 | title = Mutation of Asn-391 within the conserved NPXXY motif of the cholecystokinin B receptor abolishes Gq protein activation without affecting its association with the receptor | journal = The Journal of Biological Chemistry | volume = 275 | issue = 23 | pages = 17321–17327 | date = June 2000 | pmid = 10748160 | doi = 10.1074/jbc.M909801199 | doi-access = free }}</ref>⁠ In fact, the RGR-opsins have NAxxY^7.53 and retinochromes have VPxxY7.53 for annelids or YPxxY7.53 for mollusks, natively. Both RGR-opsins and retinochromes, belong to the chromopsins.<ref name=Guehmann2022 /> RGR-opsins<ref name="Hao1999">{{cite journal | vauthors = Hao W, Fong HK | title = The endogenous chromophore of retinal G protein-coupled receptor opsin from the pigment epithelium | journal = The Journal of Biological Chemistry | volume = 274 | issue = 10 | pages = 6085–6090 | date = March 1999 | pmid = 10037690 | doi = 10.1074/jbc.274.10.6085 | doi-access = free }}</ref> and retinochromes<ref>{{cite journal | vauthors = Hara T, Hara R | title = Rhodopsin and retinochrome in the squid retina | journal = Nature | volume = 214 | issue = 5088 | pages = 573–575 | date = May 1967 | pmid = 6036171 | doi = 10.1038/214573a0 | s2cid = 4184319 | bibcode = 1967Natur.214..573H }}</ref> also bind unlike most opsins all-''trans''-retinal in the dark and convert it to 11-''cis''-retinal when illuminated. Therefore, RGR-opsins and retinochromes are thought to neither signal nor activate a phototransduction cascade but to work as photoisomerases to produce 11-''cis''-retinal for other opsins.<ref name=Tsukamoto2010>{{cite journal | vauthors = Tsukamoto H, Terakita A | title = Diversity and functional properties of bistable pigments | journal = Photochemical & Photobiological Sciences | volume = 9 | issue = 11 | pages = 1435–1443 | date = November 2010 | pmid = 20852774 | doi = 10.1039/c0pp00168f | bibcode = 2010PhPhS...9.1435T | doi-access = free }}</ref><ref name=Terakita2005>{{cite journal | vauthors = Terakita A | title = The opsins | journal = Genome Biology | volume = 6 | issue = 3 | page = 213 | date = 1 March 2005 | pmid = 15774036 | pmc = 1088937 | doi = 10.1186/gb-2005-6-3-213 | doi-access = free }}</ref> This view is considered established in the opsin literature,<ref name=Leung2017 /><ref>{{cite journal | vauthors = Nagata T, Koyanagi M, Tsukamoto H, Terakita A | title = Identification and characterization of a protostome homologue of peropsin from a jumping spider | journal = Journal of Comparative Physiology A| volume = 196 | issue = 1 | pages = 51–59 | date = January 2010 | pmid = 19960196 | doi = 10.1007/s00359-009-0493-9 | s2cid = 22879394 }}</ref><ref name=Tsukamoto2010 /><ref>{{cite journal | vauthors = Gehring WJ | title = The evolution of vision | journal = Wiley Interdisciplinary Reviews. Developmental Biology | volume = 3 | issue = 1 | pages = 1–40 | date = January 2014 | pmid = 24902832 | doi = 10.1002/wdev.96 | s2cid = 36881435 }}</ref><ref name="Kato2016">{{cite journal | vauthors = Kato M, Sugiyama T, Sakai K, Yamashita T, Fujita H, Sato K, Tomonari S, Shichida Y, Ohuchi H | display-authors = 6 | title = Two Opsin 3-Related Proteins in the Chicken Retina and Brain: A TMT-Type Opsin 3 Is a Blue-Light Sensor in Retinal Horizontal Cells, Hypothalamus, and Cerebellum | journal = PLOS ONE | volume = 11 | issue = 11 | article-number = e0163925 | date = 18 November 2016 | pmid = 27861495 | pmc = 5115664 | doi = 10.1371/journal.pone.0163925 | doi-access = free | bibcode = 2016PLoSO..1163925K }}</ref> even so it has not been shown, conclusively.<ref name=Guehmann2022 /> In fact, the human MT2 melatonin receptor signals via a G-protein and has an NAxxY^7.53 motif natively. If this motif is mutated to NPxxY^7.53 (Ala^7.50 → Pro^7.50), the receptor cannot be activated, but can be rescued partially if the motif is mutated to NVxxY^7.53 (Ala^7.50 → Val^7.50).<ref name=Mazna2008>{{cite journal | vauthors = Mazna P, Grycova L, Balik A, Zemkova H, Friedlova E, Obsilova V, Obsil T, Teisinger J | display-authors = 6 | title = The role of proline residues in the structure and function of human MT2 melatonin receptor | journal = Journal of Pineal Research | volume = 45 | issue = 4 | pages = 361–372 | date = November 2008 | pmid = 18544139 | doi = 10.1111/j.1600-079X.2008.00598.x | s2cid = 6202186 }}</ref> Furthermore, when the motif is mutated to NAxxY^7.53 (Pro^7.50 → Ala^7.50) in cattle rhodopsin, the mutant has 141% of wild type activity.<ref name=Fritze2003 /> This evidence shows that a GPCR does not need a standard NPxxY^7.53 motif for signaling.<ref name=Guehmann2022 />

[[File:Chromopsin Consensus Sequence Logos.svg|left|frame|Consensus sequences of the different chromopsins: The first column contains a number for each chromopsin group for easy reference. The second column shows the names for each group. The third contains the number of sequences in each group. And the fourth column contains the sequence logo, the height of the letters indicates the percentage of that amino acid given at that position. The x-axis gives the position of the amino acid corresponding to cattle rhodopsin. Positions 292^7.39 and 314^7.64 are highlighted in gray. Lysine (K) 296^7.43 is highlighted with a gray background, which is replaced in the nemopsins by arginine (R) and in the gluopsins by glutamic acid (E). The NPxxY^7.53 motif is highlighted with a gray background. It is conserved in most opsins and G-protein-coupled receptors, however it is derived in the retinochromes, RGR-opsins, and Gluopsins.<ref name=Guehmann2022 />]] {{clear}}

=== Other residues and motifs === <!-- Expand this section to cover what is missing --> Cys138 and Cys110 form a highly conserved disulfide bridge. Glu113 serves as the counterion, stabilizing the protonation of the Schiff linkage between Lys296 and the ligand retinal. The Glu134-Arg135-Tyr136 is another highly conserved motif, involved in the propagation of the transduction signal once a photon has been absorbed.

== Spectral tuning sites == <!-- Expand this section. --> Certain amino acid residues, termed ''spectral tuning sites'', have a strong effect on ''λ''_max values. Using site-directed mutagenesis, it is possible to selectively mutate these residues and investigate the resulting changes in light absorption properties of the opsin. It is important to differentiate ''spectral tuning sites'', residues that affect the wavelength at which the opsin absorbs light, from ''functionally conserved sites'', residues important for the proper functioning of the opsin. They are not mutually exclusive, but, for practical reasons, it is easier to investigate spectral tuning sites that do not affect opsin functionality. For a comprehensive review of spectral tuning sites see Yokoyama<ref>{{cite journal | vauthors = Yokoyama S | title = Molecular evolution of vertebrate visual pigments | journal = Progress in Retinal and Eye Research | volume = 19 | issue = 4 | pages = 385–419 | date = July 2000 | pmid = 10785616 | doi = 10.1016/S1350-9462(00)00002-1 | s2cid = 28746630 }}</ref> and Deeb.<ref>{{cite journal | vauthors = Deeb SS | title = The molecular basis of variation in human color vision | journal = Clinical Genetics | volume = 67 | issue = 5 | pages = 369–377 | date = May 2005 | pmid = 15811001 | doi = 10.1111/j.1399-0004.2004.00343.x | s2cid = 24105079 }}</ref> The impact of spectral tuning sites on ''λ''_max differs between different opsin groups and between opsin groups of different species.

== Opsins in the human eye, brain, and skin == {| class="wikitable" |- ! {{abbr|Abbr.|Abbreviation}} ! Name ! λ{{sub|max}} ! Color ! Eye ! Brain ! Skin ! Chromosomal location<ref name=Terakita2005/> |- | OPN1LW | L-cone (red-cone) opsin | 557&nbsp;nm | Yellow | Cone | {{n/a}} | {{n/a}} | Xq28<ref name="Terakita2005" /> |- | OPN1MW | M-cone (green-cone) opsin | 527&nbsp;nm | Green | Cone | {{n/a}} | {{n/a}} | Xq28<ref name="Terakita2005"/> |- | OPN1SW | S-cone (blue-cone) opsin | 420&nbsp;nm | Violet | Cone | {{n/a}} | Melanocytes, keratinocytes<ref name="HaltaufderhydeOzdeslik2015"/> | 7q32.1<ref name="Terakita2005"/> |- | OPN2 (RHO) | Rhodopsin | 505&nbsp;nm | Blue–green | Rod | {{n/a}} | Melanocytes, keratinocytes<ref name="HaltaufderhydeOzdeslik2015"/> | 3q22.1<ref name="Terakita2005"/> |- | OPN3 | Encephalopsin, panopsin | S-M | Blue–green | Rod, cone, OPL, IPL, GCL<ref name="WhiteChiano2008">{{cite journal | vauthors = White JH, Chiano M, Wigglesworth M, Geske R, Riley J, White N, Hall S, Zhu G, Maurio F, Savage T, Anderson W, Cordy J, Ducceschi M, Vestbo J, Pillai SG | display-authors = 6 | title = Identification of a novel asthma susceptibility gene on chromosome 1qter and its functional evaluation | journal = Human Molecular Genetics | volume = 17 | issue = 13 | pages = 1890–1903 | date = July 2008 | pmid = 18344558 | doi = 10.1093/hmg/ddn087 | doi-access = free }}</ref> | Cerebral cortex, cerebellum, striatum, thalamus, hypothalamus<ref name="Blackshaw1999"/><ref>{{cite journal | vauthors = Nissilä J, Mänttäri S, Särkioja T, Tuominen H, Takala T, Timonen M, Saarela S | title = Encephalopsin (OPN3) protein abundance in the adult mouse brain | journal = Journal of Comparative Physiology A| volume = 198 | issue = 11 | pages = 833–839 | date = November 2012 | pmid = 22991144 | pmc = 3478508 | doi = 10.1007/s00359-012-0754-x }}</ref> | Melanocytes, keratinocytes<ref name="HaltaufderhydeOzdeslik2015"/> | 1q43<ref name="Terakita2005"/> |- | OPN4 | Melanopsin | 480&nbsp;nm<ref name="BailesLucas2013">{{cite journal | vauthors = Bailes HJ, Lucas RJ | title = Human melanopsin forms a pigment maximally sensitive to blue light (λmax ≈ 479 nm) supporting activation of G(q/11) and G(i/o) signalling cascades | journal = Proceedings. Biological Sciences | volume = 280 | issue = 1759 | article-number = 20122987 | date = May 2013 | pmid = 23554393 | pmc = 3619500 | doi = 10.1098/rspb.2012.2987 }}</ref> | Sky blue | ipRGC<ref name="BailesLucas2013"/> | {{n/a}} | {{n/a}} | 10q23.2<ref name="Terakita2005"/> |- | OPN5 | Neuropsin | 380&nbsp;nm<ref name="Kojima2011"/> | Ultraviolet<ref name="Kojima2011"/> | Neural retina, RPE<ref name="TarttelinBellingham2003">{{cite journal | vauthors = Tarttelin EE, Bellingham J, Hankins MW, Foster RG, Lucas RJ | title = Neuropsin (Opn5): a novel opsin identified in mammalian neural tissue | journal = FEBS Letters | volume = 554 | issue = 3 | pages = 410–416 | date = November 2003 | pmid = 14623103 | doi = 10.1016/S0014-5793(03)01212-2 | doi-access = free }}</ref> | Anterior hypothalamus<ref name="YamashitaOno2014">{{cite journal | vauthors = Yamashita T, Ono K, Ohuchi H, Yumoto A, Gotoh H, Tomonari S, Sakai K, Fujita H, Imamoto Y, Noji S, Nakamura K, Shichida Y | display-authors = 6 | title = Evolution of mammalian Opn5 as a specialized UV-absorbing pigment by a single amino acid mutation | journal = The Journal of Biological Chemistry | volume = 289 | issue = 7 | pages = 3991–4000 | date = February 2014 | pmid = 24403072 | pmc = 3924266 | doi = 10.1074/jbc.M113.514075 | doi-access = free }}</ref> | Melanocytes, keratinocytes<ref name="HaltaufderhydeOzdeslik2015"/> | 6p12.3<ref name="Terakita2005"/> |- | RRH | Peropsin | | | RPE cells – microvilli | {{n/a}} | {{n/a}} | 4q25<ref name="Terakita2005"/> |- | RGR | Retinal G protein coupled receptor | | | RPE cells | {{n/a}} | {{n/a}} | 10q23.1<ref name="Terakita2005"/> |}

RPE, retinal pigment epithelium; ipRGC, intrinsically photosensitive retinal ganglion cells; OPL, outer plexiform layer; IPL, inner plexiform layer; GCL, ganglion cell layer

== Cuttlefish == Cuttlefish and octopuses contain opsin in their skin as part of the chromophores. The opsin is part of the sensing network detecting the colour and shape of the cuttlefish's surroundings.<ref name="Mäthger2010">{{cite journal | vauthors = Mäthger LM, Roberts SB, Hanlon RT | title = Evidence for distributed light sensing in the skin of cuttlefish, Sepia officinalis | journal = Biology Letters | volume = 6 | issue = 5 | pages = 600–603 | date = October 2010 | pmid = 20392722 | pmc = 2936158 | doi = 10.1098/rsbl.2010.0223 }}</ref><ref name=Yong2015>{{cite news | vauthors = Yong E |title=Octopuses, and Maybe Squid, Can Sense Light With Their Skin |url=https://www.nationalgeographic.com/science/article/octopuses-and-maybe-squid-can-sense-light-with-their-skin |archive-url=https://web.archive.org/web/20210223230355/https://www.nationalgeographic.com/science/article/octopuses-and-maybe-squid-can-sense-light-with-their-skin |archive-date=February 23, 2021 |work=National Geographic |date=20 May 2015 }}</ref><ref name="Yu2014">{{cite journal | vauthors = Yu C, Li Y, Zhang X, Huang X, Malyarchuk V, Wang S, Shi Y, Gao L, Su Y, Zhang Y, Xu H, Hanlon RT, Huang Y, Rogers JA | display-authors = 6 | title = Adaptive optoelectronic camouflage systems with designs inspired by cephalopod skins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 36 | pages = 12998–13003 | date = September 2014 | pmid = 25136094 | pmc = 4246966 | doi = 10.1073/pnas.1410494111 | doi-access = free | bibcode = 2014PNAS..11112998Y }}</ref>

== Frogs (order Anura) == Frogs have evolved unique visual systems to adapt to their diverse habitats, from brightly lit forests to dimly lit ponds. Frogs are distinct among vertebrates because they lack the RH2 opsin, typically used for detecting middle wavelengths of light in other species. This loss likely reflects their evolutionary focus on low-light vision, with RH1, a rod-specific opsin, taking the lead in supporting nocturnal and crepuscular (dawn and dusk) activity.<ref name=":0">{{Cite journal |last1=Schott |first1=Ryan K. |last2=Perez |first2=Leah |last3=Kwiatkowski |first3=Matthew A. |last4=Imhoff |first4=Vance |last5=Gumm |first5=Jennifer M. |date=February 2022 |title=Evolutionary analyses of visual opsin genes in frogs and toads: Diversity, duplication, and positive selection |journal=Ecology and Evolution |language=en |volume=12 |issue=2 |article-number=e8595 |doi=10.1002/ece3.8595 |issn=2045-7758 |pmc=8820127 |pmid=35154658 |bibcode=2022EcoEv..12E8595S }}</ref><ref>{{Cite journal |last1=Hagen |first1=Joanna F. D. |last2=Roberts |first2=Natalie S. |last3=Johnston |first3=Robert J. |date=January 2023 |title=The evolutionary history and spectral tuning of vertebrate visual opsins |journal=Developmental Biology |volume=493 |pages=40–66 |doi=10.1016/j.ydbio.2022.10.014 |issn=1095-564X |pmc=9729497 |pmid=36370769}}</ref>

Despite the loss of RH2, frogs retain three cone opsins—SWS1, SWS2, and LWS—that allow for color vision during daylight. The SWS2 opsin, for instance, is tuned to detect blue and green light, which is especially useful in aquatic environments or shaded areas. This tuning is enhanced by specific mutations which increases sensitivity to low-light conditions and stabilizes the protein for better performance in dim environments.<ref name=":0" /> However, some frog species, such as poison dart frogs in the family Dendrobatidae, have lost the SWS2 opsin entirely. This change aligns with their reliance on longer wavelengths, like red and yellow, for tasks such as mate selection and predator deterrence, often linked to their vibrant aposematic (warning) coloration.<ref>{{Cite web |last=Howell |first=Kimberly |date=2023-01-25 |title=How does variation in a mating trait evolve? Insights from studies of color signals and their perception in a highly polymorphic poison frog |url=http://d-scholarship.pitt.edu/43966/ |access-date=2024-11-15 |website=d-scholarship.pitt.edu |language=en}}</ref>

== Phylogeny == Animal opsins (also known as type 2 opsins) are members of the seven-transmembrane-domain proteins <!--(35–55 kDa) You can put this back if you have a reference that actually shows this or summerizes it from a bunch of references. Terakita (2005) just claims 35–50 kDA. --> of the G protein-coupled receptor (GPCR) superfamily.<ref name=Casey1988 /><ref name=Attwood1994 />

Animal opsins fall phylogenetically into five groups: The ciliary opsins (cilopsins, c-opsins), the rhabdomeric opsins (r-opsins, rhabopsins), the xenopsins, the nessopsins, and the tetraopsins. Four of these subclades occur in Bilateria (all but the nessopsins).<ref name=Guehmann2022 /><ref name="Ramirez2016" /> However, the bilaterian clades constitute a paraphyletic taxon without the opsins from the cnidarians.<ref name=Guehmann2022 /><ref name="Ramirez2016" /><ref name="PorterBlasic2011" /><ref name="LiegertováPergner2015">{{cite journal | vauthors = Liegertová M, Pergner J, Kozmiková I, Fabian P, Pombinho AR, Strnad H, Pačes J, Vlček Č, Bartůněk P, Kozmik Z | display-authors = 6 | title = Cubozoan genome illuminates functional diversification of opsins and photoreceptor evolution | journal = Scientific Reports | volume = 5 | article-number = 11885 | date = July 2015 | pmid = 26154478 | pmc = 5155618 | doi = 10.1038/srep11885 | bibcode = 2015NatSR...511885L }}</ref> The nessopsins are also known as anthozoan opsins II<ref>{{cite journal | vauthors = Quiroga Artigas G, Lapébie P, Leclère L, Takeda N, Deguchi R, Jékely G, Momose T, Houliston E | display-authors = 6 | title = A gonad-expressed opsin mediates light-induced spawning in the jellyfish ''Clytia'' | journal = eLife | volume = 7 | article-number = e29555 | date = January 2018 | pmid = 29303477 | pmc = 5756024 | doi = 10.7554/eLife.29555 | doi-access = free }}</ref> or simply as the cnidarian opsins.<ref name=Rawlinson2019>{{cite journal | vauthors = Rawlinson KA, Lapraz F, Ballister ER, Terasaki M, Rodgers J, McDowell RJ, Girstmair J, Criswell KE, Boldogkoi M, Simpson F, Goulding D, Cormie C, Hall B, Lucas RJ, Telford MJ | display-authors = 6 | title = Extraocular, rod-like photoreceptors in a flatworm express xenopsin photopigment | journal = eLife | volume = 8 | article-number = e45465 | date = October 2019 | pmid = 31635694 | pmc = 6805122 | doi = 10.7554/eLife.45465 | doi-access = free }}</ref> The tetraopsins are also known as RGR/Go<ref name="FeudaHamilton2012">{{cite journal | vauthors = Feuda R, Hamilton SC, McInerney JO, Pisani D | title = Metazoan opsin evolution reveals a simple route to animal vision | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 46 | pages = 18868–18872 | date = November 2012 | pmid = 23112152 | pmc = 3503164 | doi = 10.1073/pnas.1204609109 | doi-access = free | bibcode = 2012PNAS..10918868F }}</ref> or Group 4 opsins<ref name="PorterBlasic2011" /> and contain three subgroups: the neuropsins, the Go-opsins, and the chromopsins.<ref name=Guehmann2022 /><ref name="Ramirez2016" /><ref name=Rawlinson2019 /> The chromopsins have seven subgroups: the RGR-opsins, the retinochromes, the peropsins, the varropsins, the astropsins, the nemopsins, and the gluopsins.<ref name=Guehmann2022 />

<!-- This is a bit odd. The work of Porter et al. (2011) should be checked for what they exactly mean. --> Animal visual opsins are traditionally classified as either ciliary or rhabdomeric. Ciliary opsins, found in vertebrates and cnidarians, attach to ciliary structures such as rods and cones. Rhabdomeric opsins are attached to light-gathering organelles called rhabdomeres. This classification cuts across phylogenetic categories (clades) so that both the terms "ciliary" and "rhabdomeric" can be ambiguous. Here, "C-opsins (ciliary)" refers to a clade found exclusively in Bilateria and excludes cnidarian ciliary opsins such as those found in the box jellyfish. Similarly, "R-opsin (rhabdomeric)" includes melanopsin even though it does not occur on rhabdomeres in vertebrates.<ref name="PorterBlasic2011"/>

== Ciliary opsins == Ciliary opsins (cilopsins, c-opsins) are expressed in ciliary photoreceptor cells, and include the vertebrate visual opsins and encephalopsins.<ref name=Shichida2009>{{cite journal | vauthors = Shichida Y, Matsuyama T | title = Evolution of opsins and phototransduction | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 364 | issue = 1531 | pages = 2881–2895 | date = October 2009 | pmid = 19720651 | pmc = 2781858 | doi = 10.1098/rstb.2009.0051 }}</ref> They convert light signals to nerve impulses via cyclic nucleotide gated ion channels, which work by increasing the charge differential across the cell membrane (i.e. hyperpolarization.<ref name=Plachetzki2009>{{cite journal | vauthors = Plachetzki DC, Fong CR, Oakley TH | title = The evolution of phototransduction from an ancestral cyclic nucleotide gated pathway | journal = Proceedings. Biological Sciences | volume = 277 | issue = 1690 | pages = 1963–1969 | date = July 2010 | pmid = 20219739 | pmc = 2880087 | doi = 10.1098/rspb.2009.1797 }}</ref>)

=== Vertebrate visual opsins === {{main|Vertebrate visual opsin}} Vertebrate visual opsins are a subclass of ciliary opsins that express in the vertebrate retina and mediate vision. They are further subdivided into: * Photopsins – those responsible for photopic vision (daylight), which are expressed in cone cells; hence also cone opsins. Photopsins are further subdivided according to their spectral sensitivity, namely the wavelength at which the highest light absorption is observed (''λ''_max). Vertebrates generally have four (SWS1, SWS2, RH2, LWS) classes of photopsins.<ref name="HuntCarvalho2009">{{cite journal | vauthors = Hunt DM, Carvalho LS, Cowing JA, Davies WL | title = Evolution and spectral tuning of visual pigments in birds and mammals | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 364 | issue = 1531 | pages = 2941–2955 | date = October 2009 | pmid = 19720655 | pmc = 2781856 | doi = 10.1098/rstb.2009.0044 }}</ref><ref name="TreziseCollin2005">{{cite journal | vauthors = Trezise AE, Collin SP | title = Opsins: evolution in waiting | journal = Current Biology | volume = 15 | issue = 19 | pages = R794–R796 | date = October 2005 | pmid = 16213808 | doi = 10.1016/j.cub.2005.09.025 | doi-access = free | bibcode = 2005CBio...15.R794T }}</ref> Mammals lost Rh2 and SWS2 classes during the nocturnal bottleneck, so are generally dichromatic. Primate ancestors later developed two distinct LWS opsins (LWS and MWS), leaving humans with 3 photopsins in 2 classes: SWS1 (OPN1SW) and two forms of LWS (OPN1LW, OPN1MW). * Scotopsins – those responsible for scotopic vision (dim light), which are expressed in rod cells; hence also rod opsins.<ref name=Shichida2009/> The most common form of scotopsin is rhodopsin, thus usually denoted Rh1.<ref name="pmid28289214">{{cite journal | vauthors = Gulati S, Jastrzebska B, Banerjee S, Placeres ÁL, Miszta P, Gao S, Gunderson K, Tochtrop GP, Filipek S, Katayama K, Kiser PD, Mogi M, Stewart PL, Palczewski K | display-authors = 6 | title = Photocyclic behavior of rhodopsin induced by an atypical isomerization mechanism | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 13 | pages = E2608–E2615 | date = March 2017 | pmid = 28289214 | pmc = 5380078 | doi = 10.1073/pnas.1617446114 | doi-access = free | bibcode = 2017PNAS..114E2608G }}</ref>

=== Extraretinal (or extra-ocular) Rhodopsin-Like Opsins (Exo-Rh) === These pineal opsins, found in the Actinopterygii (ray-finned fish) apparently arose as a result of gene duplication from Rh1 (rhodopsin). These opsins appear to serve functions similar to those of pinopsin found in birds and reptiles.<ref name="pmid10581404">{{cite journal | vauthors = Mano H, Kojima D, Fukada Y | title = Exo-rhodopsin: a novel rhodopsin expressed in the zebrafish pineal gland | journal = Brain Research. Molecular Brain Research | volume = 73 | issue = 1–2 | pages = 110–118 | date = November 1999 | pmid = 10581404 | doi = 10.1016/S0169-328X(99)00242-9 }}</ref> <ref name="TarttelinFransen2011">{{cite journal | vauthors = Tarttelin EE, Fransen MP, Edwards PC, Hankins MW, Schertler GF, Vogel R, Lucas RJ, Bellingham J | display-authors = 6 | title = Adaptation of pineal expressed teleost exo-rod opsin to non-image forming photoreception through enhanced Meta II decay | journal = Cellular and Molecular Life Sciences | volume = 68 | issue = 22 | pages = 3713–3723 | date = November 2011 | pmid = 21416149 | pmc = 3203999 | doi = 10.1007/s00018-011-0665-y }}</ref>

=== Pinopsins === The first Pineal Opsin (Pinopsin) was found in the chicken pineal gland. It is a blue sensitive opsin (''λ''_max = 470&nbsp;nm).<ref name="pmid7969427">{{cite journal | vauthors = Okano T, Yoshizawa T, Fukada Y | title = Pinopsin is a chicken pineal photoreceptive molecule | journal = Nature | volume = 372 | issue = 6501 | pages = 94–97 | date = November 1994 | pmid = 7969427 | doi = 10.1038/372094a0 | s2cid = 4301315 | bibcode = 1994Natur.372...94O }}</ref><ref name="Nakane-Yoshimura-2019">{{cite journal | vauthors = Nakane Y, Yoshimura T | title = Photoperiodic Regulation of Reproduction in Vertebrates | journal = Annual Review of Animal Biosciences | volume = 7 | issue = 1 | pages = 173–194 | date = February 2019 | pmid = 30332291 | doi = 10.1146/annurev-animal-020518-115216 | publisher = Annual Reviews | s2cid = 52984435 }}</ref>

Pineal opsins have a wide range of expression in the brain, most notably in the pineal region.

=== Vertebrate Ancient (VA) opsin === Vertebrate Ancient (VA) opsin has three isoforms VA short (VAS), VA medium (VAM), and VA long (VAL). It is expressed in the inner retina, within the horizontal and amacrine cells, as well as the pineal organ and habenular region of the brain.<ref name="pmid10821749">{{cite journal | vauthors = Philp AR, Garcia-Fernandez JM, Soni BG, Lucas RJ, Bellingham J, Foster RG | title = Vertebrate ancient (VA) opsin and extraretinal photoreception in the Atlantic salmon (Salmo salar) | journal = The Journal of Experimental Biology | volume = 203 | issue = Pt 12 | pages = 1925–1936 | date = June 2000 | pmid = 10821749 | doi = 10.1242/jeb.203.12.1925 | bibcode = 2000JExpB.203.1925P }}</ref> It is sensitive to approximately 500&nbsp;nm [14], found in most vertebrate classes, but not in mammals.<ref name="PoletiniRamos2015">{{cite journal | vauthors = Poletini MO, Ramos BC, Moraes MN, Castrucci AM | title = Nonvisual Opsins and the Regulation of Peripheral Clocks by Light and Hormones | journal = Photochemistry and Photobiology | volume = 91 | issue = 5 | pages = 1046–1055 | year = 2015 | pmid = 26174318 | doi = 10.1111/php.12494 | s2cid = 41895317 | doi-access = free }}</ref>

=== Parapinopsins === The first parapinopsin (PP) was found in the parapineal organ of the catfish.<ref name="pmid9334384">{{cite journal | vauthors = Blackshaw S, Snyder SH | title = Parapinopsin, a novel catfish opsin localized to the parapineal organ, defines a new gene family | journal = The Journal of Neuroscience | volume = 17 | issue = 21 | pages = 8083–8092 | date = November 1997 | pmid = 9334384 | pmc = 6573767 | doi = 10.1523/JNEUROSCI.17-21-08083.1997 | doi-access = free }}</ref> The parapinopsin of lamprey is a UV-sensitive opsin (''λ''_max = 370&nbsp;nm).<ref name=Koyanagi2004>{{cite journal | vauthors = Koyanagi M, Kawano E, Kinugawa Y, Oishi T, Shichida Y, Tamotsu S, Terakita A | title = Bistable UV pigment in the lamprey pineal | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 17 | pages = 6687–6691 | date = April 2004 | pmid = 15096614 | pmc = 404106 | doi = 10.1073/pnas.0400819101 | doi-access = free | bibcode = 2004PNAS..101.6687K }}</ref> The teleosts have two groups of parapinopsins, one is sensitive to UV (''λ''_max = 360-370&nbsp;nm), the other is sensitive to blue (''λ''_max = 460-480&nbsp;nm) light.<ref>{{cite journal | vauthors = Koyanagi M, Wada S, Kawano-Yamashita E, Hara Y, Kuraku S, Kosaka S, Kawakami K, Tamotsu S, Tsukamoto H, Shichida Y, Terakita A | display-authors = 6 | title = Diversification of non-visual photopigment parapinopsin in spectral sensitivity for diverse pineal functions | journal = BMC Biology | volume = 13 | issue = 1 | article-number = 73 | date = September 2015 | pmid = 26370232 | pmc = 4570685 | doi = 10.1186/s12915-015-0174-9 | doi-access = free }}</ref>

=== Parietopsins === The first parietopsin was found in the photoreceptor cells of the lizard parietal eye. The lizard parietopsin is green-sensitive (''λ''_max = 522&nbsp;nm), and despite it is a c-opsin, like the vertebrate visual opsins, it does not induce hyperpolarization via a Gt-protein, but induces depolarization via a Go-protein.<ref>{{cite journal | vauthors = Su CY, Luo DG, Terakita A, Shichida Y, Liao HW, Kazmi MA, Sakmar TP, Yau KW | display-authors = 6 | title = Parietal-eye phototransduction components and their potential evolutionary implications | journal = Science | volume = 311 | issue = 5767 | pages = 1617–1621 | date = March 2006 | pmid = 16543463 | doi = 10.1126/science.1123802 | s2cid = 28604455 | bibcode = 2006Sci...311.1617S }}</ref><ref name="KoyanagiTerakita2014">{{cite journal | vauthors = Koyanagi M, Terakita A | title = Diversity of animal opsin-based pigments and their optogenetic potential | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1837 | issue = 5 | pages = 710–716 | date = May 2014 | pmid = 24041647 | doi = 10.1016/j.bbabio.2013.09.003 | doi-access = free }}</ref>

=== Encephalopsin or Panopsin === The panopsins are found in many tissues (skin,<ref name="HaltaufderhydeOzdeslik2015">{{cite journal | vauthors = Haltaufderhyde K, Ozdeslik RN, Wicks NL, Najera JA, Oancea E | title = Opsin expression in human epidermal skin | journal = Photochemistry and Photobiology | volume = 91 | issue = 1 | pages = 117–123 | year = 2015 | pmid = 25267311 | pmc = 4303996 | doi = 10.1111/php.12354 }}</ref> brain,<ref name="Blackshaw1999">{{cite journal | vauthors = Blackshaw S, Snyder SH | title = Encephalopsin: a novel mammalian extraretinal opsin discretely localized in the brain | journal = The Journal of Neuroscience | volume = 19 | issue = 10 | pages = 3681–3690 | date = May 1999 | pmid = 10234000 | pmc = 6782724 | doi = 10.1523/JNEUROSCI.19-10-03681.1999 | doi-access = free }}</ref><ref name="Halford2001">{{cite journal | vauthors = Halford S, Freedman MS, Bellingham J, Inglis SL, Poopalasundaram S, Soni BG, Foster RG, Hunt DM | display-authors = 6 | title = Characterization of a novel human opsin gene with wide tissue expression and identification of embedded and flanking genes on chromosome 1q43 | journal = Genomics | volume = 72 | issue = 2 | pages = 203–208 | date = March 2001 | pmid = 11401433 | doi = 10.1006/geno.2001.6469 }}</ref> testes,<ref name="Blackshaw1999" /> heart, liver,<ref name="Halford2001" /> kidney, skeletal muscle, lung, pancreas and retina<ref name="Halford2001" />). They were originally found in the human and mouse brain and thus called encephalopsin.<ref name="Blackshaw1999" />

The first invertebrate panopsin was found in the ciliary photoreceptor cells of the annelid ''Platynereis dumerilii'' and is called c(iliary)-opsin.<ref name=Arendt2004>{{cite journal | vauthors = Arendt D, Tessmar-Raible K, Snyman H, Dorresteijn AW, Wittbrodt J | title = Ciliary photoreceptors with a vertebrate-type opsin in an invertebrate brain | journal = Science | volume = 306 | issue = 5697 | pages = 869–871 | date = October 2004 | pmid = 15514158 | doi = 10.1126/science.1099955 | s2cid = 2583520 | bibcode = 2004Sci...306..869A }}</ref> This c-opsin is UV-sensitive (''λ''_max = 383&nbsp;nm) and can be tuned by 125&nbsp;nm at a single amino-acid (range ''λ''_max = 377–502&nbsp;nm).<ref name="Tsukamoto2017">{{cite journal | vauthors = Tsukamoto H, Chen IS, Kubo Y, Furutani Y | title = A ciliary opsin in the brain of a marine annelid zooplankton is ultraviolet-sensitive, and the sensitivity is tuned by a single amino acid residue | journal = The Journal of Biological Chemistry | volume = 292 | issue = 31 | pages = 12971–12980 | date = August 2017 | pmid = 28623234 | pmc = 5546036 | doi = 10.1074/jbc.M117.793539 | doi-access = free }}</ref> Thus, not unsurprisingly, a second but cyan sensitive c-opsin (''λ''_max = 490&nbsp;nm) exists in ''Platynereis dumerilii''.<ref name="Ayers2018">{{cite journal | vauthors = Ayers T, Tsukamoto H, Gühmann M, Veedin Rajan VB, Tessmar-Raible K | title = A G_o-type opsin mediates the shadow reflex in the annelid Platynereis dumerilii | journal = BMC Biology | volume = 16 | issue = 1 | article-number = 41 | date = April 2018 | pmid = 29669554 | pmc = 5904973 | doi = 10.1186/s12915-018-0505-8 | doi-access = free }}</ref> The first c-opsin mediates in the larva UV induced gravitaxis. The gravitaxis forms with phototaxis a ratio-chromatic depth-gauge.<ref name="Veraszto2018">{{cite journal | vauthors = Verasztó C, Gühmann M, Jia H, Rajan VB, Bezares-Calderón LA, Piñeiro-Lopez C, Randel N, Shahidi R, Michiels NK, Yokoyama S, Tessmar-Raible K, Jékely G | display-authors = 6 | title = Ciliary and rhabdomeric photoreceptor-cell circuits form a spectral depth gauge in marine zooplankton | journal = eLife | volume = 7 | date = May 2018 | article-number = e36440 | pmid = 29809157 | pmc = 6019069 | doi = 10.7554/eLife.36440 | doi-access = free }}</ref> In different depths, the light in water is composed of different wavelengths: First the red (> 600&nbsp;nm) and the UV and violet (< 420&nbsp;nm) wavelengths disappear. The higher the depth the narrower the spectrum so that only cyan light (480&nbsp;nm) is left.<ref name=Guehmann2015>{{cite journal | vauthors = Gühmann M, Jia H, Randel N, Verasztó C, Bezares-Calderón LA, Michiels NK, Yokoyama S, Jékely G | display-authors = 6 | title = Spectral Tuning of Phototaxis by a Go-Opsin in the Rhabdomeric Eyes of Platynereis | journal = Current Biology | volume = 25 | issue = 17 | pages = 2265–2271 | date = August 2015 | pmid = 26255845 | doi = 10.1016/j.cub.2015.07.017 | doi-access = free | bibcode = 2015CBio...25.2265G }}</ref> Thus, the larvae can determine their depth by color. The color unlike brightness stays almost constant independent of time of day or the weather, for instance if it is cloudy.<ref name="Nilsson2009">{{cite journal | vauthors = Nilsson DE | title = The evolution of eyes and visually guided behaviour | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 364 | issue = 1531 | pages = 2833–2847 | date = October 2009 | pmid = 19720648 | pmc = 2781862 | doi = 10.1098/rstb.2009.0083 }}</ref><ref name="Nilsson2013">{{cite journal | vauthors = Nilsson DE | title = Eye evolution and its functional basis | journal = Visual Neuroscience | volume = 30 | issue = 1–2 | pages = 5–20 | date = March 2013 | pmid = 23578808 | pmc = 3632888 | doi = 10.1017/S0952523813000035 }}</ref>

Panopsins are also expressed in the brains of some insects.<ref name=Shichida2009/> The panopsins of mosquito and pufferfish absorb maximally at 500&nbsp;nm and 460&nbsp;nm, respectively. Both activate in vitro Gi and Go proteins.<ref>{{cite journal | vauthors = Koyanagi M, Takada E, Nagata T, Tsukamoto H, Terakita A | title = Homologs of vertebrate Opn3 potentially serve as a light sensor in nonphotoreceptive tissue | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 13 | pages = 4998–5003 | date = March 2013 | pmid = 23479626 | pmc = 3612648 | doi = 10.1073/pnas.1219416110 | doi-access = free | bibcode = 2013PNAS..110.4998K }}</ref> The panopsins are sister to the TMT-opsins.<ref name="Ramirez2016" /><ref name=Sakai2015>{{cite journal | vauthors = Sakai K, Yamashita T, Imamoto Y, Shichida Y | title = Diversity of Active States in TMT Opsins | journal = PLOS ONE | volume = 10 | issue = 10 | article-number = e0141238 | date = 22 October 2015 | pmid = 26491964 | pmc = 4619619 | doi = 10.1371/journal.pone.0141238 | doi-access = free | bibcode = 2015PLoSO..1041238S }}</ref><ref name="Kato2016" /><ref name="Fischer2013">{{cite journal | vauthors = Fischer RM, Fontinha BM, Kirchmaier S, Steger J, Bloch S, Inoue D, Panda S, Rumpel S, Tessmar-Raible K | display-authors = 6 | title = Co-expression of VAL- and TMT-opsins uncovers ancient photosensory interneurons and motorneurons in the vertebrate brain | journal = PLOS Biology | volume = 11 | issue = 6 | article-number = e1001585 | date = 11 June 2013 | pmid = 23776409 | pmc = 3679003 | doi = 10.1371/journal.pbio.1001585 | doi-access = free }}</ref>

=== Teleost Multiple Tissue (TMT) Opsin === The first TMT-opsin was found in many tissues in Teleost fish and therefore they are called Teleost Multiple Tissue (TMT) opsins.<ref name="Moutsaki2003">{{cite journal | vauthors = Moutsaki P, Whitmore D, Bellingham J, Sakamoto K, David-Gray ZK, Foster RG | title = Teleost multiple tissue (tmt) opsin: a candidate photopigment regulating the peripheral clocks of zebrafish? | journal = Brain Research. Molecular Brain Research | volume = 112 | issue = 1–2 | pages = 135–145 | date = April 2003 | pmid = 12670711 | doi = 10.1016/S0169-328X(03)00059-7 }}</ref> TMT-opsins form three groups which are most closely related to a fourth group the panopsins, which thus are paralogous to the TMT-opsins.<ref name="Ramirez2016" /><ref name="Kato2016" /><ref name=Sakai2015 /><ref name="Fischer2013"/> TMT-opsins and panopsins also share the same introns, which confirms that they belong together.<ref name="Moutsaki2003" />

== Opsins in cnidarians == Cnidaria, which include jellyfish, corals, and sea anemones, are the most basal animals to possess complex eyes. Jellyfish opsins in the rhopalia couple to Gs-proteins raising the intracellular cAMP level.<ref name="Koyanagi2008">{{cite journal | vauthors = Koyanagi M, Takano K, Tsukamoto H, Ohtsu K, Tokunaga F, Terakita A | title = Jellyfish vision starts with cAMP signaling mediated by opsin-G(s) cascade | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 40 | pages = 15576–15580 | date = October 2008 | pmid = 18832159 | pmc = 2563118 | doi = 10.1073/pnas.0806215105 | doi-access = free | bibcode = 2008PNAS..10515576K }}</ref><ref name="LiegertováPergner2015"/> Coral opsins can couple to Gq-proteins and Gc-proteins. Gc-proteins are a subtype of G-proteins specific to cnidarians.<ref name="Mason2012">{{cite journal | vauthors = Mason B, Schmale M, Gibbs P, Miller MW, Wang Q, Levay K, Shestopalov V, Slepak VZ | display-authors = 6 | title = Evidence for multiple phototransduction pathways in a reef-building coral | journal = PLOS ONE | volume = 7 | issue = 12 | article-number = e50371 | date = 5 December 2012 | pmid = 23227169 | pmc = 3515558 | doi = 10.1371/journal.pone.0050371 | doi-access = free | bibcode = 2012PLoSO...750371M }}</ref> The cnidarian opsins belong to two groups the xenopsins and the nessopsins. The xenopsins contain also bilaterian opsins, while the nessopsins are restricted to the cnidarians.<ref name=Guehmann2022 /><ref name="Ramirez2016" /> However, earlier studies have found that some cnidarian opsins belong to the cilopsins, rhabopsins, and the tetraopsins of the bilaterians.<ref name="FeudaHamilton2012" /><ref name="Suga2008">{{cite journal | vauthors = Suga H, Schmid V, Gehring WJ | title = Evolution and functional diversity of jellyfish opsins | journal = Current Biology | volume = 18 | issue = 1 | pages = 51–55 | date = January 2008 | pmid = 18160295 | doi = 10.1016/j.cub.2007.11.059 | doi-access = free | bibcode = 2008CBio...18...51S }}</ref><ref name="Feuda2014">{{cite journal | vauthors = Feuda R, Rota-Stabelli O, Oakley TH, Pisani D | title = The comb jelly opsins and the origins of animal phototransduction | journal = Genome Biology and Evolution | volume = 6 | issue = 8 | pages = 1964–1971 | date = July 2014 | pmid = 25062921 | pmc = 4159004 | doi = 10.1093/gbe/evu154 }}</ref>

== Rhabdomeric opsins == Rhabdomeric opsins (rhabopsins, r-opsins) are also known as Gq-opsins, because they couple to a Gq-protein. Rhabopsins are used by molluscs and arthropods. Arthropods appear to attain colour vision in a similar fashion to the vertebrates, by using three (or more) distinct groups of opsins, distinct both in terms of phylogeny and spectral sensitivity.<ref name=Shichida2009/> The rhabopsin melanopsin is also expressed in vertebrates, where it regulates circadian rhythms and mediates the pupillary reflex.<ref name=Shichida2009/>

Unlike cilopsins, rhabopsins are associated with canonical transient receptor potential ion channels; these lead to the electric potential difference across a cell membrane being eradicated (i.e. depolarization).<ref name=Plachetzki2009 />

The identification of the crystal structure of squid rhodopsin<ref name=Murakami2008 /> is likely to further our understanding of its function in this group.

Arthropods use different opsins in their different eye types, but at least in ''Limulus'' the opsins expressed in the lateral and the compound eyes are 99% identical and presumably diverged recently.<ref>{{cite journal | vauthors = Smith WC, Price DA, Greenberg RM, Battelle BA | title = Opsins from the lateral eyes and ocelli of the horseshoe crab, Limulus polyphemus | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 13 | pages = 6150–6154 | date = July 1993 | pmid = 8327495 | pmc = 46885 | doi = 10.1073/pnas.90.13.6150 | doi-access = free | bibcode = 1993PNAS...90.6150S }}</ref>

=== Melanopsin === Melanopsin (OPN4) is involved in circadian rhythms, the pupillary reflex, and color correction in high-brightness situations. Phylogenetically, it is a member of the rhabdomeric opsins (rhabopsins, r-opsins) and functionally and structurally a rhabopsin, but does not occur in rhabdomeres.

== Tetraopsins == The tetraopsins include the neuropsins, the Go-opsins, and the chromopsins.<ref name=Guehmann2022 /><ref name="Ramirez2016" /><ref name=Rawlinson2019 /> The chromopsins consist of seven subgroups: the RGR-opsins, the retinochromes, the peropsins, the varropsins, the astropsins, the nemopsins, and the gluopsins.<ref name=Guehmann2022 />

=== Neuropsins === Neuropsins are sensitive to UVA, typically at 380&nbsp;nm. They are found in the brain, testes, skin, and retina of humans and rodents, as well as in the brain and retina of birds. In birds and rodents they mediate ultraviolet vision.<ref name="HaltaufderhydeOzdeslik2015" /><ref name="Kojima2011">{{cite journal | vauthors = Kojima D, Mori S, Torii M, Wada A, Morishita R, Fukada Y | title = UV-sensitive photoreceptor protein OPN5 in humans and mice | journal = PLOS ONE | volume = 6 | issue = 10 | article-number = e26388 | date = 17 October 2011 | pmid = 22043319 | pmc = 3197025 | doi = 10.1371/journal.pone.0026388 | doi-access = free | bibcode = 2011PLoSO...626388K }}</ref><ref name="Yamashita2010">{{cite journal | vauthors = Yamashita T, Ohuchi H, Tomonari S, Ikeda K, Sakai K, Shichida Y | title = Opn5 is a UV-sensitive bistable pigment that couples with Gi and Gq subtype of G protein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 51 | pages = 22084–22089 | date = December 2010 | pmid = 21135214 | pmc = 3009823 | doi = 10.1073/pnas.1012498107 | doi-access = free | bibcode = 2010PNAS..10722084Y }}</ref> They couple to Gi-proteins.<ref name="Kojima2011" /><ref name="Yamashita2010" /> In humans, Neuropsin is encoded by the OPN5 gene. In the human retina, its function is unknown. In the mouse, it photo-entrains the retina and cornea at least ex vivo.<ref name="Buhr2015">{{cite journal | vauthors = Buhr ED, Yue WW, Ren X, Jiang Z, Liao HW, Mei X, Vemaraju S, Nguyen MT, Reed RR, Lang RA, Yau KW, Van Gelder RN | display-authors = 6 | title = Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 42 | pages = 13093–13098 | date = October 2015 | pmid = 26392540 | pmc = 4620855 | doi = 10.1073/pnas.1516259112 | doi-access = free | bibcode = 2015PNAS..11213093B }}</ref>

=== Go-opsins === Go-opsins are absent from higher vertebrates<ref name="PorterBlasic2011"/> and ecdysozoans.<ref name=HeringMayer2014>{{cite journal | vauthors = Hering L, Mayer G | title = Analysis of the opsin repertoire in the tardigrade Hypsibius dujardini provides insights into the evolution of opsin genes in panarthropoda | journal = Genome Biology and Evolution | volume = 6 | issue = 9 | pages = 2380–2391 | date = September 2014 | pmid = 25193307 | pmc = 4202329 | doi = 10.1093/gbe/evu193 }}</ref> They are found in the ciliary photoreceptor cells of the scallop eye<ref name=Kojima1997>{{cite journal | vauthors = Kojima D, Terakita A, Ishikawa T, Tsukahara Y, Maeda A, Shichida Y | title = A novel Go-mediated phototransduction cascade in scallop visual cells | journal = The Journal of Biological Chemistry | volume = 272 | issue = 37 | pages = 22979–22982 | date = September 1997 | pmid = 9287291 | doi = 10.1074/jbc.272.37.22979 | bibcode = 1997JBiCh.27222979K | doi-access = free }}</ref> and the basal chordate amphioxus.<ref>{{cite journal | vauthors = Koyanagi M, Terakita A, Kubokawa K, Shichida Y | title = Amphioxus homologs of Go-coupled rhodopsin and peropsin having 11-cis- and all-trans-retinals as their chromophores | journal = FEBS Letters | volume = 531 | issue = 3 | pages = 525–528 | date = November 2002 | pmid = 12435605 | doi = 10.1016/s0014-5793(02)03616-5 | bibcode = 2002FEBSL.531..525K | s2cid = 11669142 | doi-access = free }}</ref> In ''Platynereis dumerilii'' however, a Go-opsin is expressed in the rhabdomeric photoreceptor cells of the eyes.<ref name=Guehmann2015 />

=== RGR-opsins === RGR-opsins, also known as Retinal G protein coupled receptors are expressed in the retinal pigment epithelium (RPE) and Müller cells.<ref name="Jiang1993">{{cite journal | vauthors = Jiang M, Pandey S, Fong HK | title = An opsin homologue in the retina and pigment epithelium | journal = Investigative Ophthalmology & Visual Science | volume = 34 | issue = 13 | pages = 3669–3678 | date = December 1993 | pmid = 8258527 }}</ref> They preferentially bind all-trans-retinal in the dark instead of 11-cis-retinal.<ref name="Hao1999" /> RGR-opsins were thought to be photoisomerases<ref name=Terakita2005 /> but instead, they regulate retinoid traffic and production.<ref name=Shichida2009 /><ref name="Nagata2010">{{cite web| vauthors = Nagata T, Koyanagi M, Terakita A |title=Molecular Evolution and Functional Diversity of Opsin-Based Photopigments|date=20 October 2010|url=http://photobiology.info/Terakita.html|access-date=7 May 2018}}</ref> In particular, they speed up light-independently the production of 11-cis-retinol (a precursor of 11-cis-retinal) from all-trans-retinyl-esters.<ref name="Wenzel2005">{{cite journal | vauthors = Wenzel A, Oberhauser V, Pugh EN, Lamb TD, Grimm C, Samardzija M, Fahl E, Seeliger MW, Remé CE, von Lintig J | display-authors = 6 | title = The retinal G protein-coupled receptor (RGR) enhances isomerohydrolase activity independent of light | journal = The Journal of Biological Chemistry | volume = 280 | issue = 33 | pages = 29874–29884 | date = August 2005 | pmid = 15961402 | doi = 10.1074/jbc.M503603200 | doi-access = free }}</ref> However, the all-trans-retinyl-esters are made available light-dependently by RGR-opsins. Whether RGR-opsins regulate this via a G-protein or another signaling mechanism is unknown.<ref name=Radu2008>{{cite journal | vauthors = Radu RA, Hu J, Peng J, Bok D, Mata NL, Travis GH | title = Retinal pigment epithelium-retinal G protein receptor-opsin mediates light-dependent translocation of all-trans-retinyl esters for synthesis of visual chromophore in retinal pigment epithelial cells | journal = The Journal of Biological Chemistry | volume = 283 | issue = 28 | pages = 19730–19738 | date = July 2008 | pmid = 18474598 | pmc = 2443657 | doi = 10.1074/jbc.M801288200 | doi-access = free }}</ref> The cattle RGR-opsin absorbs maximally at different wavelengths depending on the pH-value. At high pH it absorbs maximally blue (469&nbsp;nm) light and at low pH it absorbs maximally UV (370&nbsp;nm) light.<ref name="Hao1996">{{cite journal | vauthors = Hao W, Fong HK | title = Blue and ultraviolet light-absorbing opsin from the retinal pigment epithelium | journal = Biochemistry | volume = 35 | issue = 20 | pages = 6251–6256 | date = May 1996 | pmid = 8639565 | doi = 10.1021/bi952420k }}</ref>

=== Peropsin === Peropsin, a visual pigment-like receptor, is a protein that in humans is encoded by the ''RRH'' gene.<ref name="pmid9275222">{{cite journal | vauthors = Sun H, Gilbert DJ, Copeland NG, Jenkins NA, Nathans J | title = Peropsin, a novel visual pigment-like protein located in the apical microvilli of the retinal pigment epithelium | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 18 | pages = 9893–9898 | date = September 1997 | pmid = 9275222 | pmc = 23288 | doi = 10.1073/pnas.94.18.9893 | doi-access = free | bibcode = 1997PNAS...94.9893S }}</ref>

== Other proteins called opsins == {{main|Microbial rhodopsin}} Photoreceptors can be classified several ways, including function (vision, phototaxis, photoperiodism, etc.), type of chromophore (retinal, flavine, bilin), molecular structure (tertiary, quaternary), signal output (phosphorylation, reduction, oxidation), etc.<ref name="Björn2015">{{cite book| vauthors = Björn LO |title=Photobiology: The Science of Light and Life|url=https://books.google.com/books?id=VDgLBgAAQBAJ&pg=PA169|access-date=3 September 2015|date=2 January 2015|publisher=Springer|isbn=978-1-4939-1468-5|page=169}}</ref>

Beside animal opsins, which are G protein-coupled receptors, there is another group of photoreceptor proteins called opsins.<ref name=Plachetzki2009/><ref name=Fernald2006>{{cite journal | vauthors = Fernald RD | title = Casting a genetic light on the evolution of eyes | journal = Science | volume = 313 | issue = 5795 | pages = 1914–1918 | date = September 2006 | pmid = 17008522 | doi = 10.1126/science.1127889 | s2cid = 84439732 | bibcode = 2006Sci...313.1914F }}</ref> These are the microbial opsin, they are used by prokaryotes and by some algae (as a component of channelrhodopsins) and fungi,<ref name=Waschuk2005>{{cite journal | vauthors = Waschuk SA, Bezerra AG, Shi L, Brown LS | title = Leptosphaeria rhodopsin: bacteriorhodopsin-like proton pump from a eukaryote | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 19 | pages = 6879–6883 | date = May 2005 | pmid = 15860584 | pmc = 1100770 | doi = 10.1073/pnas.0409659102 | doi-access = free | bibcode = 2005PNAS..102.6879W }}</ref> whereas animals use animal opsins, exclusively. No opsins have been found outside these groups (for instance in plants, or placozoans).<ref name=Plachetzki2009/>

Microbial and animal opsins are also called type 1 and type 2 opsins respectively. Both types are called opsins, because at one time it was thought that they were related: Both are seven-transmembrane receptors and bind covalently retinal as chromophore, which turns them into photoreceptors sensing light. However, both types are not related on the sequence level.<ref>{{cite journal | vauthors = Findlay JB, Pappin DJ | title = The opsin family of proteins | journal = The Biochemical Journal | volume = 238 | issue = 3 | pages = 625–642 | date = September 1986 | pmid = 2948499 | pmc = 1147185 | doi = 10.1042/bj2380625 }}</ref>

In fact, the sequence identity between animal and mirobial opsins is no greater than could be accounted for by random chance. However, in recent years new methods have been developed specific to ''deep phylogeny''. As a result, several studies have found evidence of a possible phylogenetic relationship between the two.<ref name="ShenChen2013">{{cite journal | vauthors = Shen L, Chen C, Zheng H, Jin L | title = The evolutionary relationship between microbial rhodopsins and metazoan rhodopsins | journal = TheScientificWorldJournal | volume = 2013 | article-number = 435651 | year = 2013 | pmid = 23476135 | pmc = 3583139 | doi = 10.1155/2013/435651 | doi-access = free }}</ref><ref name="DevineOprian2013">{{cite journal | vauthors = Devine EL, Oprian DD, Theobald DL | title = Relocating the active-site lysine in rhodopsin and implications for evolution of retinylidene proteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 33 | pages = 13351–13355 | date = August 2013 | pmid = 23904486 | pmc = 3746867 | doi = 10.1073/pnas.1306826110 | doi-access = free | bibcode = 2013PNAS..11013351D }}</ref><ref name="ZhangWu2014">{{cite journal | vauthors = Zhang Z, Jin Z, Zhao Y, Zhang Z, Li R, Xiao J, Wu J | title = Systematic study on G-protein couple receptor prototypes: did they really evolve from prokaryotic genes? | journal = IET Systems Biology | volume = 8 | issue = 4 | pages = 154–161 | date = August 2014 | pmid = 25075528 | pmc = 8687355 | doi = 10.1049/iet-syb.2013.0037 | doi-access = free }}</ref> However, this does not necessarily mean that the last common ancestor of microbial and animal opsins was itself light sensitive: All animal opsins arose (by gene duplication and divergence) late in the history of the large G-protein coupled receptor (GPCR) gene family, which itself arose after the divergence of plants, fungi, choanflagellates and sponges from the earliest animals. The retinal chromophore is found solely in the opsin branch of this large gene family, meaning its occurrence elsewhere represents convergent evolution, not homology. Microbial rhodopsins are, by sequence, very different from any of the GPCR families.<ref name=pmid21402729>{{cite journal | vauthors = Nordström KJ, Sällman Almén M, Edstam MM, Fredriksson R, Schiöth HB | title = Independent HHsearch, Needleman--Wunsch-based, and motif analyses reveal the overall hierarchy for most of the G protein-coupled receptor families | journal = Molecular Biology and Evolution | volume = 28 | issue = 9 | pages = 2471–2480 | date = September 2011 | pmid = 21402729 | doi = 10.1093/molbev/msr061 | doi-access = free }}</ref> According to one hypothesis, both microbial and animal opsins belong to the ''transporter-opsin-G protein-coupled receptor (TOG) superfamily'', a proposed clade that includes G protein-coupled receptor (GPCR), Ion-translocating microbial rhodopsin (MR), and seven others.<ref name="YeeShlykov2013">{{cite journal | vauthors = Yee DC, Shlykov MA, Västermark A, Reddy VS, Arora S, Sun EI, Saier MH | title = The transporter-opsin-G protein-coupled receptor (TOG) superfamily | journal = The FEBS Journal | volume = 280 | issue = 22 | pages = 5780–5800 | date = November 2013 | pmid = 23981446 | pmc = 3832197 | doi = 10.1111/febs.12499 }}</ref>

Most microbial opsins are ion channels or pumps instead of proper receptors and do not bind to a G protein. Microbial opsins are found in all three domains of life: Archaea, Bacteria, and Eukaryota. In Eukaryota, microbial opsins are found mainly in unicellular organisms such as green algae, and in fungi. In most complex multicellular eukaryotes, microbial opsins have been replaced with other light-sensitive molecules such as cryptochrome and phytochrome in plants, and animal opsins in animals.<ref name="YoshizawaKumagai2014">{{cite journal | vauthors = Yoshizawa S, Kumagai Y, Kim H, Ogura Y, Hayashi T, Iwasaki W, DeLong EF, Kogure K | display-authors = 6 | title = Functional characterization of flavobacteria rhodopsins reveals a unique class of light-driven chloride pump in bacteria | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 18 | pages = 6732–6737 | date = May 2014 | pmid = 24706784 | pmc = 4020065 | doi = 10.1073/pnas.1403051111 | doi-access = free | bibcode = 2014PNAS..111.6732Y }}</ref>

Microbial opsins are often known by the rhodopsin form of the molecule, i.e., rhodopsin (in the broad sense) = opsin + chromophore. Among the many kinds of microbial opsins are the proton pumps bacteriorhodopsin (BR) and xanthorhodopsin (xR), the chloride pump halorhodopsin (HR), the photosensors sensory rhodopsin I (SRI) and sensory rhodopsin II (SRII), as well as proteorhodopsin (PR), Neurospora opsin I (NOPI), Chlamydomonas sensory rhodopsins A (CSRA), Chlamydomonas sensory rhodopsins B (CSRB), channelrhodopsin (ChR), and archaerhodopsin (Arch).<ref name="GroteEngelhard2014">{{cite journal | vauthors = Grote M, Engelhard M, Hegemann P | title = Of ion pumps, sensors and channels – perspectives on microbial rhodopsins between science and history | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1837 | issue = 5 | pages = 533–545 | date = May 2014 | pmid = 23994288 | doi = 10.1016/j.bbabio.2013.08.006 | doi-access = free }}</ref>

Several microbal opsins, such as proteo- and bacteriorhodopsin, are used by various bacterial groups to harvest energy from light to carry out metabolic processes using a non-chlorophyll-based pathway. Beside that, halorhodopsins of Halobacteria and channelrhodopsins of some algae, e.g. Volvox, serve them as light-gated ion channels, amongst others also for phototactic purposes. Sensory rhodopsins exist in Halobacteria that induce a phototactic response by interacting with transducer membrane-embedded proteins that have no relation to G proteins.<ref name="RomplerStaubert2007">{{cite journal | vauthors = Römpler H, Stäubert C, Thor D, Schulz A, Hofreiter M, Schöneberg T | title = G protein-coupled time travel: evolutionary aspects of GPCR research | journal = Molecular Interventions | volume = 7 | issue = 1 | pages = 17–25 | date = February 2007 | pmid = 17339603 | doi = 10.1124/mi.7.1.5 }}</ref>

Microbal opsins (like channelrhodopsin, halorhodopsin, and archaerhodopsin) are used in optogenetics to switch on or off neuronal and cardiac activity<ref>{{Cite journal |last1=Hsueh |first1=Brian |last2=Chen |first2=Ritchie |last3=Jo |first3=YoungJu |last4=Tang |first4=Daniel |last5=Raffiee |first5=Misha |last6=Kim |first6=Yoon Seok |last7=Inoue |first7=Masatoshi |last8=Randles |first8=Sawyer |last9=Ramakrishnan |first9=Charu |last10=Patel |first10=Sneha |last11=Kim |first11=Doo Kyung |last12=Liu |first12=Tony X. |last13=Kim |first13=Soo Hyun |last14=Tan |first14=Longzhi |last15=Mortazavi |first15=Leili |date=March 2023 |title=Cardiogenic control of affective behavioural state |journal=Nature |language=en |volume=615 |issue=7951 |pages=292–299 |doi=10.1038/s41586-023-05748-8 |pmid=36859543 |pmc=9995271 |bibcode=2023Natur.615..292H |issn=1476-4687}}</ref>. Microbal opsins are preferred if the neuronal activity should be modulated at higher frequency, because they respond faster than animal opsins. This is because microbal opsins are ion channels or proton/ion pumps and thus are activated by light directly, while animal opsins activate G-proteins, which then activate effector enzymes that produce metabolites to open ion channels.<ref>{{cite journal | vauthors = Zhang F, Vierock J, Yizhar O, Fenno LE, Tsunoda S, Kianianmomeni A, Prigge M, Berndt A, Cushman J, Polle J, Magnuson J, Hegemann P, Deisseroth K | display-authors = 6 | title = The microbial opsin family of optogenetic tools | journal = Cell | volume = 147 | issue = 7 | pages = 1446–1457 | date = December 2011 | pmid = 22196724 | pmc = 4166436 | doi = 10.1016/j.cell.2011.12.004 }}</ref>

== See also == * Retinylidene protein * Visual cycle * Visual phototransduction * Microbial rhodopsin * Channelrhodopsins

== External links == * [http://homepages.bw.edu/~mbumbuli/cell/fig/opsin/ Illustration] {{Webarchive|url=https://web.archive.org/web/20200109152958/http://homepages.bw.edu/~mbumbuli/cell/fig/opsin/ |date=2020-01-09 }} at Baldwin-Wallace College * {{MeshName|Opsin}}

== References == {{Reflist|2}}

{{Eye proteins}} {{G protein-coupled receptors}}

Category:G protein-coupled receptors Category:Vision