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OPN4

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Target id: 2758

Nomenclature: OPN4

Family: Opsin receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 478 10q23.2 OPN4 opsin 4 4
Mouse 7 521 14 B Opn4 opsin 4 (melanopsin) 4
Rat 7 474 16p15 Opn4 opsin 4 2
Gene and Protein Information Comments
Two receptor isoforms have been identified for the human and mouse opsin 4 proteins. The shorter isoforms are listed in the table above. So far only one rat isoform has been identified.
Previous and Unofficial Names Click here for help
melanopsin | MOP
Database Links Click here for help
Specialist databases
GPCRdb OPN4_HUMAN (Hs), OPN4_MOUSE (Mm), OPN4_RAT (Rn)
Other databases
Alphafold Q9UHM6 (Hs), Q9QXZ9 (Mm), Q8R456 (Rn)
Ensembl Gene ENSG00000122375 (Hs), ENSMUSG00000021799 (Mm), ENSRNOG00000053893 (Rn)
Entrez Gene 94233 (Hs), 30044 (Mm), 192223 (Rn)
Human Protein Atlas ENSG00000122375 (Hs)
KEGG Gene hsa:94233 (Hs), mmu:30044 (Mm), rno:192223 (Rn)
OMIM 606665 (Hs)
Pharos Q9UHM6 (Hs)
RefSeq Nucleotide NM_001030015 (Hs), NM_033282 (Hs), NM_001128599 (Mm), NM_013887 (Mm), NM_138860 (Rn)
RefSeq Protein NP_150598 (Hs), NP_001025186 (Hs), NP_038915 (Mm), NP_001122071 (Mm), NP_620215 (Rn)
UniProtKB Q9UHM6 (Hs), Q9QXZ9 (Mm), Q8R456 (Rn)
Wikipedia OPN4 (Hs)
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family
Gq/G11 family 		Adenylyl cyclase inhibition
Phospholipase C stimulation
Comments:  G protein coupling was assessed using heterologous expression in HEK293 cells and luminescent reporters for second messenger systems [1].
References:  1
Tissue Distribution Click here for help
Inner retina (retinal glial cells)
Species:  Mouse
Technique:  In situ hybridization histochemistry
References:  4
Retinal glial cells
Species:  Rat
Technique:  Confocal immunocytochemistry
References:  2
Tissue Distribution Comments
OPN4 is also expressed in inner retina cells in the monkey [4].
Physiological Consequences of Altering Gene Expression Click here for help
At high irradiances the pupillary reflex is incomplete in Opn4 knockout mice.
Species:  Mouse
Tissue:  Retinal ganglion cells
Technique:  Knockout (homologous recombination) including insertion of tau-lacZ into the target gene locus to allow visualisation of expression pattern in knockout animals.
References:  2-3
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cnga3tm1Biel|Gnat1tm1Clma|Opn4tm1Yau Cnga3tm1Biel/Cnga3tm1Biel,Gnat1tm1Clma/Gnat1tm1Clma,Opn4tm1Yau/Opn4tm1Yau
involves: 129 * C57BL/6		 MGI:1341818  MGI:1353425  MGI:95778  MP:0001502 abnormal circadian rhythm PMID: 12808468 
Cnga3tm1Biel|Gnat1tm1Clma|Opn4tm1Yau Cnga3tm1Biel/Cnga3tm1Biel,Gnat1tm1Clma/Gnat1tm1Clma,Opn4tm1Yau/Opn4tm1Yau
involves: 129 * C57BL/6		 MGI:1341818  MGI:1353425  MGI:95778  MP:0002638 abnormal pupillary reflex PMID: 12808468 
Cnga3tm1Biel|Gnat1tm1Clma|Opn4tm1Yau Cnga3tm1Biel/Cnga3tm1Biel,Gnat1tm1Clma/Gnat1tm1Clma,Opn4tm1Yau/Opn4tm1Yau
involves: 129 * C57BL/6		 MGI:1341818  MGI:1353425  MGI:95778  MP:0002003 miotic pupils PMID: 12808468 
Cnga3tm1Biel|Gnat1tm1Clma|Opn4tm1Yau Cnga3tm1Biel/Cnga3tm1Biel,Gnat1tm1Clma/Gnat1tm1Clma,Opn4tm1Yau/Opn4tm1Yau
involves: 129 * C57BL/6		 MGI:1341818  MGI:1353425  MGI:95778  MP:0002563 shortened circadian period PMID: 12808468 
Gene Expression and Pathophysiology Comments
Polymorphisms in the OPN4 gene have been found to be associated with seasonal affective disorder in humans [5].
Biologically Significant Variants Click here for help
Type:  Missense mutation
Species:  Human
Description:  Missense variant (P10L) in melanopsin (OPN4) resulting from a C/T nucleotide polymorphism identified in genes of patients with seasonal affective disorder.
Amino acid change:  P10L
Nucleotide change:  29C>T
Global MAF (%):  9.5
SNP accession:  rs2675703
Validation:  1000 Genomes, Frequency, Cluster & HapMap
References:  5
General Comments
Opsin 4 appears to be a component of occular, non-image forming light detection [6,8], and may be involved in sleep modulation and regulation of the circadian clock [7].

References

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1. Bailes HJ, Lucas RJ. (2013) 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. Proc Biol Sci, 280 (1759): 20122987. [PMID:23554393]

2. Hattar S, Liao HW, Takao M, Berson DM, Yau KW. (2002) Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science, 295 (5557): 1065-70. [PMID:11834834]

3. Lucas RJ, Hattar S, Takao M, Berson DM, Foster RG, Yau KW. (2003) Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice. Science, 299 (5604): 245-7. [PMID:12522249]

4. Provencio I, Rodriguez IR, Jiang G, Hayes WP, Moreira EF, Rollag MD. (2000) A novel human opsin in the inner retina. J Neurosci, 20 (2): 600-5. [PMID:10632589]

5. Roecklein KA, Rohan KJ, Duncan WC, Rollag MD, Rosenthal NE, Lipsky RH, Provencio I. (2009) A missense variant (P10L) of the melanopsin (OPN4) gene in seasonal affective disorder. J Affect Disord, 114 (1-3): 279-85. [PMID:18804284]

6. Sexton T, Buhr E, Van Gelder RN. (2012) Melanopsin and mechanisms of non-visual ocular photoreception. J Biol Chem, 287 (3): 1649-56. [PMID:22074930]

7. Tsai JW, Hannibal J, Hagiwara G, Colas D, Ruppert E, Ruby NF, Heller HC, Franken P, Bourgin P. (2009) Melanopsin as a sleep modulator: circadian gating of the direct effects of light on sleep and altered sleep homeostasis in Opn4(-/-) mice. PLoS Biol, 7 (6): e1000125. [PMID:19513122]

8. van Oosterhout F, Fisher SP, van Diepen HC, Watson TS, Houben T, VanderLeest HT, Thompson S, Peirson SN, Foster RG, Meijer JH. (2012) Ultraviolet light provides a major input to non-image-forming light detection in mice. Curr Biol, 22 (15): 1397-402. [PMID:22771039]

How to cite this page

Opsin receptors: OPN4. Last modified on 15/07/2019. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2758.