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| <SX load='6ddf' size='340' side='right' viewer='molstar' caption='[[6ddf]], [[Resolution|resolution]] 3.50Å' scene=''> | | <SX load='6ddf' size='340' side='right' viewer='molstar' caption='[[6ddf]], [[Resolution|resolution]] 3.50Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6ddf]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DDF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6DDF FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6ddf]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DDF FirstGlance]. <br> |
| </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=ETA:ETHANOLAMINE'>ETA</scene>, <scene name='pdbligand=MEA:N-METHYLPHENYLALANINE'>MEA</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.5Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6dde|6dde]]</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=ETA:ETHANOLAMINE'>ETA</scene>, <scene name='pdbligand=MEA:N-METHYLPHENYLALANINE'>MEA</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GNAI1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GNB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GNG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Oprm1, Mor, Oprm ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ddf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ddf OCA], [https://pdbe.org/6ddf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ddf RCSB], [https://www.ebi.ac.uk/pdbsum/6ddf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ddf ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ddf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ddf OCA], [http://pdbe.org/6ddf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ddf RCSB], [http://www.ebi.ac.uk/pdbsum/6ddf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ddf ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/OPRM_MOUSE OPRM_MOUSE]] Receptor for endogenous opioids such as beta-endorphin and endomorphin. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 9 is involved in morphine-induced scratching and seems to cross-activate GRPR in response to morphine.<ref>PMID:10842167</ref> <ref>PMID:16682964</ref> <ref>PMID:21422164</ref> <ref>PMID:22437502</ref> <ref>PMID:7797593</ref> <ref>PMID:9037090</ref> [[http://www.uniprot.org/uniprot/GNAI1_HUMAN GNAI1_HUMAN]] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:17635935</ref> <ref>PMID:17264214</ref> [[http://www.uniprot.org/uniprot/GBG2_HUMAN GBG2_HUMAN]] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction (By similarity). [[http://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_HUMAN]] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.<ref>PMID:18611381</ref> | | [https://www.uniprot.org/uniprot/GNAI1_HUMAN GNAI1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:17635935</ref> <ref>PMID:17264214</ref> |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| ==See Also== | | ==See Also== |
| | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] |
| | *[[Opioid receptor|Opioid receptor]] |
| *[[Transducin 3D structures|Transducin 3D structures]] | | *[[Transducin 3D structures|Transducin 3D structures]] |
| == References == | | == References == |
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| __TOC__ | | __TOC__ |
| </SX> | | </SX> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Lk3 transgenic mice]] | | [[Category: Mus musculus]] |
| [[Category: Hu, H]] | | [[Category: Hu H]] |
| [[Category: Kobilka, B K]] | | [[Category: Kobilka BK]] |
| [[Category: Koehl, A]] | | [[Category: Koehl A]] |
| [[Category: Maeda, S]] | | [[Category: Maeda S]] |
| [[Category: Manglik, A]] | | [[Category: Manglik A]] |
| [[Category: Skiniotis, G]] | | [[Category: Skiniotis G]] |
| [[Category: Weis, W I]] | | [[Category: Weis WI]] |
| [[Category: Complex]]
| |
| [[Category: Membrane protein]]
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| [[Category: Transmembrane]]
| |