OPN4

Target id: 2758

Nomenclature: OPN4

Family: Opsin receptors

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for OPN4 in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 478 10q22 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
melanopsin | MOP
Database Links
Specialist databases
GPCRDB OPN4_HUMAN (Hs), OPN4_MOUSE (Mm), OPN4_RAT (Rn)
Other databases
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
Gq/G11 family
Adenylate 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
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
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 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
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: 
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. Science295 (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. Science299 (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 Disord114 (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 30/10/2017. Accessed on 26/04/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2758.