OPN3_HUMAN
ID OPN3_HUMAN Reviewed; 402 AA.
AC Q9H1Y3; Q8IX08; Q9Y344;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Opsin-3;
DE AltName: Full=Encephalopsin;
DE AltName: Full=Panopsin;
GN Name=OPN3; Synonyms=ECPN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10234000; DOI=10.1523/jneurosci.19-10-03681.1999;
RA Blackshaw S., Snyder S.H.;
RT "Encephalopsin: a novel mammalian extraretinal opsin discretely localized
RT in the brain.";
RL J. Neurosci. 19:3681-3690(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11401433; DOI=10.1006/geno.2001.6469;
RA Halford S., Freedman M.S., Bellingham J., Inglis S.L., Poopalasundaram S.,
RA Soni B.G., Foster R.G., Hunt D.M.;
RT "Characterization of a novel human opsin gene with wide tissue expression
RT and identification of embedded and flanking genes on chromosome 1q43.";
RL Genomics 72:203-208(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=12242008; DOI=10.1016/s0378-1119(02)00799-0;
RA Kasper G., Taudien S., Staub E., Mennerich D., Rieder M., Hinzmann B.,
RA Dahl E., Schwidetzky U., Rosenthal A., Rump A.;
RT "Different structural organization of the encephalopsin gene in man and
RT mouse.";
RL Gene 295:27-32(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28842328; DOI=10.1016/j.jid.2017.07.833;
RA Regazzetti C., Sormani L., Debayle D., Bernerd F., Tulic M.K.,
RA De Donatis G.M., Chignon-Sicard B., Rocchi S., Passeron T.;
RT "Melanocytes Sense Blue Light and Regulate Pigmentation through Opsin-3.";
RL J. Invest. Dermatol. 138:171-178(2018).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=30284927; DOI=10.1152/ajplung.00135.2018;
RA Yim P.D., Gallos G., Perez-Zoghbi J.F., Zhang Y., Xu D., Wu A.,
RA Berkowitz D.E., Emala C.W.;
RT "Airway smooth muscle photorelaxation via opsin receptor activation.";
RL Am. J. Physiol. 316:L82-L93(2019).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION BY BLUE
RP LIGHT.
RX PubMed=30168605; DOI=10.1002/lsm.23015;
RA Castellano-Pellicena I., Uzunbajakava N.E., Mignon C., Raafs B.,
RA Botchkarev V.A., Thornton M.J.;
RT "Does blue light restore human epidermal barrier function via activation of
RT Opsin during cutaneous wound healing?";
RL Lasers. Surg. Med. 51:370-382(2019).
RN [9]
RP FUNCTION, INTERACTION WITH MC1R, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND MUTAGENESIS OF LYS-299.
RX PubMed=31097585; DOI=10.1073/pnas.1902825116;
RA Ozdeslik R.N., Olinski L.E., Trieu M.M., Oprian D.D., Oancea E.;
RT "Human nonvisual opsin 3 regulates pigmentation of epidermal melanocytes
RT through functional interaction with melanocortin 1 receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:11508-11517(2019).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION BY
RP ULTRAVIOLET A LIGHT.
RX PubMed=31380578; DOI=10.1111/bjd.18410;
RA Lan Y., Wang Y., Lu H.;
RT "Opsin 3 is a key regulator of ultraviolet A-induced photoageing in human
RT dermal fibroblast cells.";
RL Br. J. Dermatol. 182:1228-1244(2020).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=31730232; DOI=10.1111/php.13178;
RA Wang Y., Lan Y., Lu H.;
RT "Opsin3 Downregulation Induces Apoptosis of Human Epidermal Melanocytes via
RT Mitochondrial Pathway.";
RL Photochem. Photobiol. 96:83-93(2020).
CC -!- FUNCTION: G-protein coupled receptor which selectively activates G
CC proteins via ultraviolet A (UVA) light-mediated activation in the skin
CC (PubMed:28842328, PubMed:31380578, PubMed:31097585). Binds both 11-cis
CC retinal and all-trans retinal (PubMed:31097585). Regulates
CC melanogenesis in melanocytes via inhibition of alpha-MSH-induced MC1R-
CC mediated cAMP signaling, modulation of calcium flux, regulation of
CC CAMK2 phosphorylation, and subsequently phosphorylation of CREB, p38,
CC ERK and MITF in response to blue light (PubMed:28842328,
CC PubMed:31097585). Plays a role in melanocyte survival through
CC regulation of intracellular calcium levels and subsequent BCL2/RAF1
CC signaling (PubMed:31730232). Additionally regulates apoptosis via
CC cytochrome c release and subsequent activation of the caspase cascade
CC (PubMed:31730232). Required for TYR and DCT blue light-induced complex
CC formation in melanocytes (PubMed:28842328). Involved in keratinocyte
CC differentiation in response to blue-light (PubMed:30168605). Required
CC for the UVA-mediated induction of calcium and mitogen-activated protein
CC kinase signaling resulting in the expression of MMP1, MMP2, MMP3, MMP9
CC and TIMP1 in dermal fibroblasts (PubMed:31380578). Plays a role in
CC light-mediated glucose uptake, mitochondrial respiration and fatty acid
CC metabolism in brown adipocyte tissues (By similarity). May be involved
CC in photorelaxation of airway smooth muscle cells, via blue-light
CC dependent GPCR signaling pathways (By similarity).
CC {ECO:0000250|UniProtKB:Q9WUK7, ECO:0000269|PubMed:28842328,
CC ECO:0000269|PubMed:30168605, ECO:0000269|PubMed:31097585,
CC ECO:0000269|PubMed:31380578, ECO:0000269|PubMed:31730232}.
CC -!- SUBUNIT: Interacts with MC1R; the interaction results in a decrease in
CC MC1R-mediated cAMP signaling and ultimately a decrease in melanin
CC production in melanocytes. {ECO:0000269|PubMed:31097585}.
CC -!- INTERACTION:
CC Q9H1Y3; Q01726: MC1R; NbExp=5; IntAct=EBI-21871627, EBI-9538513;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:30168605,
CC ECO:0000269|PubMed:31097585, ECO:0000269|PubMed:31380578,
CC ECO:0000269|PubMed:31730232}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasm {ECO:0000269|PubMed:30168605}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=1-4b-5-6;
CC IsoId=Q9H1Y3-1; Sequence=Displayed;
CC Name=2; Synonyms=1-2-5-6;
CC IsoId=Q9H1Y3-2; Sequence=VSP_010209;
CC -!- TISSUE SPECIFICITY: Expressed in tracheal airway smooth muscle (at
CC protein level) (PubMed:30284927). Expressed throughout the epidermis
CC and dermis, predominantly in the basal layer on the facial and
CC abdominal skin (at protein level) (PubMed:30168605). Expressed in
CC dermal fibroblasts (at protein level) (PubMed:31380578). Expressed in
CC melanocytes (at protein level) (PubMed:28842328, PubMed:31097585,
CC PubMed:31730232). Expressed in keratinocytes (PubMed:28842328).
CC Expressed in the retina (PubMed:30284927).
CC {ECO:0000269|PubMed:28842328, ECO:0000269|PubMed:30168605,
CC ECO:0000269|PubMed:30284927, ECO:0000269|PubMed:31097585,
CC ECO:0000269|PubMed:31380578, ECO:0000269|PubMed:31730232}.
CC -!- INDUCTION: Induced by low-level blue light (453nm) during epithelial
CC wound healing (PubMed:30168605). Induced by ultraviolet A light in
CC dermal fibroblasts (PubMed:31380578). {ECO:0000269|PubMed:30168605,
CC ECO:0000269|PubMed:31380578}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. Opsin
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF140242; AAD32671.1; -; mRNA.
DR EMBL; AF303588; AAK37447.1; -; mRNA.
DR EMBL; AF482426; AAO15715.1; -; Genomic_DNA.
DR EMBL; AF482426; AAO15717.1; -; Genomic_DNA.
DR EMBL; AL133390; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036773; AAH36773.1; -; mRNA.
DR CCDS; CCDS31072.1; -. [Q9H1Y3-1]
DR RefSeq; NP_055137.2; NM_014322.2. [Q9H1Y3-1]
DR AlphaFoldDB; Q9H1Y3; -.
DR SMR; Q9H1Y3; -.
DR BioGRID; 117131; 8.
DR IntAct; Q9H1Y3; 9.
DR STRING; 9606.ENSP00000355512; -.
DR ChEMBL; CHEMBL4523919; -.
DR GlyGen; Q9H1Y3; 2 sites.
DR iPTMnet; Q9H1Y3; -.
DR PhosphoSitePlus; Q9H1Y3; -.
DR BioMuta; OPN3; -.
DR DMDM; 17380172; -.
DR jPOST; Q9H1Y3; -.
DR MassIVE; Q9H1Y3; -.
DR MaxQB; Q9H1Y3; -.
DR PaxDb; Q9H1Y3; -.
DR PeptideAtlas; Q9H1Y3; -.
DR PRIDE; Q9H1Y3; -.
DR ProteomicsDB; 80458; -. [Q9H1Y3-1]
DR Antibodypedia; 34703; 247 antibodies from 29 providers.
DR DNASU; 23596; -.
DR Ensembl; ENST00000366554.3; ENSP00000355512.2; ENSG00000054277.14. [Q9H1Y3-1]
DR GeneID; 23596; -.
DR KEGG; hsa:23596; -.
DR MANE-Select; ENST00000366554.3; ENSP00000355512.2; NM_014322.3; NP_055137.2.
DR UCSC; uc001hza.4; human. [Q9H1Y3-1]
DR CTD; 23596; -.
DR DisGeNET; 23596; -.
DR GeneCards; OPN3; -.
DR HGNC; HGNC:14007; OPN3.
DR HPA; ENSG00000054277; Tissue enhanced (placenta).
DR MIM; 606695; gene.
DR neXtProt; NX_Q9H1Y3; -.
DR OpenTargets; ENSG00000054277; -.
DR PharmGKB; PA31939; -.
DR VEuPathDB; HostDB:ENSG00000054277; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01030000234631; -.
DR HOGENOM; CLU_009579_3_0_1; -.
DR InParanoid; Q9H1Y3; -.
DR OMA; KMCFLMV; -.
DR OrthoDB; 940057at2759; -.
DR PhylomeDB; Q9H1Y3; -.
DR TreeFam; TF324998; -.
DR PathwayCommons; Q9H1Y3; -.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-419771; Opsins.
DR SignaLink; Q9H1Y3; -.
DR BioGRID-ORCS; 23596; 20 hits in 1076 CRISPR screens.
DR ChiTaRS; OPN3; human.
DR GeneWiki; OPN3; -.
DR GenomeRNAi; 23596; -.
DR Pharos; Q9H1Y3; Tbio.
DR PRO; PR:Q9H1Y3; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9H1Y3; protein.
DR Bgee; ENSG00000054277; Expressed in middle temporal gyrus and 191 other tissues.
DR ExpressionAtlas; Q9H1Y3; baseline and differential.
DR Genevisible; Q9H1Y3; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0001750; C:photoreceptor outer segment; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005502; F:11-cis retinal binding; IDA:UniProtKB.
DR GO; GO:0005503; F:all-trans retinal binding; IDA:UniProtKB.
DR GO; GO:0008020; F:G protein-coupled photoreceptor activity; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; TAS:ProtInc.
DR GO; GO:0009881; F:photoreceptor activity; NAS:UniProtKB.
DR GO; GO:0071482; P:cellular response to light stimulus; IBA:GO_Central.
DR GO; GO:0071492; P:cellular response to UV-A; IDA:UniProtKB.
DR GO; GO:0009583; P:detection of light stimulus; NAS:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0030216; P:keratinocyte differentiation; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0048022; P:negative regulation of melanin biosynthetic process; IMP:UniProtKB.
DR GO; GO:0007602; P:phototransduction; IBA:GO_Central.
DR GO; GO:1901857; P:positive regulation of cellular respiration; IEA:Ensembl.
DR GO; GO:0046326; P:positive regulation of glucose import; IEA:Ensembl.
DR GO; GO:0048023; P:positive regulation of melanin biosynthetic process; IMP:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; NAS:UniProtKB.
DR GO; GO:0009637; P:response to blue light; IDA:UniProtKB.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR027430; Retinal_BS.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR PROSITE; PS00238; OPSIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Chromophore; Cytoplasm;
KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Lipoprotein;
KW Membrane; Palmitate; Photoreceptor protein; Receptor; Reference proteome;
KW Retinal protein; Sensory transduction; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..402
FT /note="Opsin-3"
FT /id="PRO_0000197813"
FT TOPO_DOM 1..40
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 41..65
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 66..77
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 78..102
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 103..117
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 118..137
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 138..153
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 154..177
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 178..201
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..229
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..255
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 256..279
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 280..287
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 288..312
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 313..402
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 299
FT /note="N6-(retinylidene)lysine"
FT LIPID 325
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 5
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 198
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 114..188
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 126..231
FT /note="IVSIATLTVLAYERYIRVVHARVINFSWAWRAITYIWLYSLAWAGAPLLGWN
FT RYILDVHGLGCTVDWKSKDANDSSFVLFLFLGCLVVPLGVIAHCYGHILYSIRM -> W
FT ISQLQAATREARASMGPVQQGTICMQ (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_010209"
FT VARIANT 167
FT /note="A -> V (in dbSNP:rs12072790)"
FT /id="VAR_050613"
FT VARIANT 183
FT /note="V -> I (in dbSNP:rs2273712)"
FT /id="VAR_050614"
FT MUTAGEN 299
FT /note="K->G: Abolishes binding of 11-cis retinal and all-
FT trans retinal. No effect on G-alpha (i) protein signaling."
FT /evidence="ECO:0000269|PubMed:31097585"
FT CONFLICT 390..396
FT /note="NGSKVDV -> IGVQSLML (in Ref. 1; AAD32671)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 402 AA; 44873 MW; 370F64C19F834A71 CRC64;
MYSGNRSGGH GYWDGGGAAG AEGPAPAGTL SPAPLFSPGT YERLALLLGS IGLLGVGNNL
LVLVLYYKFQ RLRTPTHLLL VNISLSDLLV SLFGVTFTFV SCLRNGWVWD TVGCVWDGFS
GSLFGIVSIA TLTVLAYERY IRVVHARVIN FSWAWRAITY IWLYSLAWAG APLLGWNRYI
LDVHGLGCTV DWKSKDANDS SFVLFLFLGC LVVPLGVIAH CYGHILYSIR MLRCVEDLQT
IQVIKILKYE KKLAKMCFLM IFTFLVCWMP YIVICFLVVN GHGHLVTPTI SIVSYLFAKS
NTVYNPVIYV FMIRKFRRSL LQLLCLRLLR CQRPAKDLPA AGSEMQIRPI VMSQKDGDRP
KKKVTFNSSS IIFIITSDES LSVDDSDKTN GSKVDVIQVR PL
