Recombinant Human Opsin-3 (OPN3) Protein

Function

G protein-coupled photoreceptor that selectively activates G(i/o) proteins in response to light, thereby decreasing intracellular cAMP levels (PubMed:28842328, PubMed:30168605, PubMed:31380578, PubMed:36869204). Activation occurs when the opsin-bound cis-retinal chromophore absorbs a photon and isomerizes to all-trans-retinal, inducing a conformational change in the opsin that triggers a G protein-mediated phototransduction cascade (PubMed:36869204). Mediates blue light-induced pigmentation in melanocytes by activating calcium/CAMK2 signaling, followed by phosphorylation of CREB, p38, ERK and MITF. Required for TYR and DCT blue light-induced complex formation in melanocytes (PubMed:28842328). Involved in keratinocyte differentiation in response to blue-light (PubMed:30168605). Plays a role in melanocyte survival through regulation of intracellular calcium levels and subsequent BCL2/RAF1 signaling. Additionally, regulates apoptosis via cytochrome c release and subsequent activation of the caspase cascade (PubMed:31730232). Responsible for ultraviolet A (UVA)-induced keratinocytes supranuclear melanin cap formation via activating calcium/CAMK2, CREB, and Akt signal transduction, and ultimately increasing DYNC1I1 and DCTN1 expression levels, thereby playing a role in the skin response to UV radiation (PubMed:36869204). Required for the UVA-mediated induction of calcium and MAPK signaling resulting in the expression of MMP1, MMP2, MMP3, MMP9 and TIMP1 in dermal fibroblasts (PubMed:31380578). Also plays a role in light-mediated glucose uptake, mitochondrial respiration and fatty acid metabolism in brown adipocyte tissues. May be involved in photorelaxation of airway smooth muscle cells, via blue light-dependent GPCR signaling pathways (By similarity). Also inhibits melanogenesis in melanocytes by specifically inhibiting MC1R-evoked cAMP signaling in a constitutive, light-independent manner (PubMed:31097585). In the paraventricular nucleus of the hypothalamus, inhibits MC4R-mediated cAMP signaling and activates KCNJ13 channel opening in a constitutive manner, thereby promoting food intake and modulating spontaneous firing of neurons (PubMed:39951488)

Subcellular Location

Cell membrane (Multi-pass membrane protein); Cytoplasm

Tissue Specificity

Expressed throughout the epidermis and dermis, predominantly in the basal layer on the facial and abdominal skin (at protein level) (PubMed:30168605). Expressed in dermal fibroblasts (at protein level) (PubMed:31380578). Expressed in melanocytes (at protein level) (PubMed:28842328, PubMed:31097585, PubMed:31730232). Expressed in keratinocytes (PubMed:28842328). Expressed in the retina (PubMed:30284927). Expressed in tracheal airway smooth muscle (at protein level) (PubMed:30284927)

Subunit

Interacts with MC1R; the interaction results in a decrease in MC1R-mediated cAMP signaling and ultimately a decrease in melanin production in melanocytes (PubMed:31097585). Forms a complex with KCNJ13 and MC4R; OPN3 inhibits MC4R signaling and potentiates KCNJ13 (PubMed:39951488)

• Blackshaw S. et al. Encephalopsin: a novel mammalian extraretinal opsin discretely localized in the brain. — J. Neurosci. (1999)
• Halford S. et al. Characterization of a novel human opsin gene with wide tissue expression and identification of embedded and flanking genes on chromosome 1q43. — Genomics (2001)
• Kasper G. et al. Different structural organization of the encephalopsin gene in man and mouse. — Gene (2002)
• Gregory S.G. et al. The DNA sequence and biological annotation of human chromosome 1. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Regazzetti C. et al. Melanocytes Sense Blue Light and Regulate Pigmentation through Opsin-3. — J. Invest. Dermatol. (2018)
• Yim P.D. et al. Airway smooth muscle photorelaxation via opsin receptor activation. — Am. J. Physiol. (2019)
• Castellano-Pellicena I. et al. Does blue light restore human epidermal barrier function via activation of Opsin during cutaneous wound healing? — Lasers. Surg. Med. (2019)