CNR2_HUMAN
ID CNR2_HUMAN Reviewed; 360 AA.
AC P34972; C6ES44; Q4VBK8; Q5JRH7; Q6B0G7; Q6NSY0;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Cannabinoid receptor 2;
DE Short=CB-2;
DE Short=CB2;
DE Short=hCB2;
DE AltName: Full=CX5;
GN Name=CNR2; Synonyms=CB2A, CB2B;
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].
RX PubMed=7689702; DOI=10.1038/365061a0;
RA Munro S., Thomas K.L., Abu-Shaar M.;
RT "Molecular characterization of a peripheral receptor for cannabinoids.";
RL Nature 365:61-65(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Spleen;
RX PubMed=19496827; DOI=10.1111/j.1601-183x.2009.00498.x;
RA Liu Q.-R., Pan C.H., Hishimoto A., Li C.Y., Xi Z.X., Llorente-Berzal A.,
RA Viveros M.P., Ishiguro H., Arinami T., Onaivi E.S., Uhl G.R.;
RT "Species differences in cannabinoid receptor 2 (CNR2 gene): identification
RT of novel human and rodent CB2 isoforms, differential tissue expression and
RT regulation by cannabinoid receptor ligands.";
RL Genes Brain Behav. 8:519-530(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Blood;
RA Bruess M., Boenisch H.;
RT "Cannabinoid receptors and their genes.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Warren C.N., Aronstam R.S., Sharma S.V.;
RT "Isolation of complete coding sequence for cannabinoid receptor 2 (CNR2).";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT TYR-316.
RC TISSUE=Blood;
RA Saravanan T., Chugh A., Kant R.;
RT "Amplification and cloning of human cannabinoid receptor 2 gene from
RT Asiatic origin.";
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-63 AND TYR-316.
RC TISSUE=Brain;
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 [9]
RP TISSUE SPECIFICITY.
RX PubMed=7556170; DOI=10.1111/j.1432-1033.1995.tb20780.x;
RA Galiegue S., Mary S., Marchand J., Dussossoy D., Carriere D., Carayon P.,
RA Bouaboula M., Shire D., Le Fur G., Casellas P.;
RT "Expression of central and peripheral cannabinoid receptors in human immune
RT tissues and leukocyte subpopulations.";
RL Eur. J. Biochem. 232:54-61(1995).
RN [10]
RP PHOSPHORYLATION AT SER-352, AND SUBCELLULAR LOCATION.
RX PubMed=10400664; DOI=10.1074/jbc.274.29.20397;
RA Bouaboula M., Dussossoy D., Casellas P.;
RT "Regulation of peripheral cannabinoid receptor CB2 phosphorylation by the
RT inverse agonist SR 144528. Implications for receptor biological
RT responses.";
RL J. Biol. Chem. 274:20397-20405(1999).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF LYS-109 AND SER-112.
RX PubMed=10051546;
RA Tao Q., McAllister S.D., Andreassi J., Nowell K.W., Cabral G.A.,
RA Hurst D.P., Bachtel K., Ekman M.C., Reggio P.H., Abood M.E.;
RT "Role of a conserved lysine residue in the peripheral cannabinoid receptor
RT (CB2): evidence for subtype specificity.";
RL Mol. Pharmacol. 55:605-613(1999).
RN [12]
RP IDENTIFICATION OF 2-ARACHIDONOYLGLYCEROL AS AN ENDOGENOUS LIGAND.
RX PubMed=10617657; DOI=10.1074/jbc.275.1.605;
RA Sugiura T., Kondo S., Kishimoto S., Miyashita T., Nakane S., Kodaka T.,
RA Suhara Y., Takayama H., Waku K.;
RT "Evidence that 2-arachidonoylglycerol but not N-palmitoylethanolamine or
RT anandamide is the physiological ligand for the cannabinoid CB2 receptor.
RT Comparison of the agonistic activities of various cannabinoid receptor
RT ligands in HL-60 cells.";
RL J. Biol. Chem. 275:605-612(2000).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=12153574; DOI=10.1046/j.1432-1033.2002.03078.x;
RA Matias I., Pochard P., Orlando P., Salzet M., Pestel J., Di Marzo V.;
RT "Presence and regulation of the endocannabinoid system in human dendritic
RT cells.";
RL Eur. J. Biochem. 269:3771-3778(2002).
RN [14]
RP MUTAGENESIS OF LEU-201 AND TYR-207.
RX PubMed=12417328; DOI=10.1016/s0014-5793(02)03537-8;
RA Song Z.H., Feng W.;
RT "Absence of a conserved proline and presence of a conserved tyrosine in the
RT CB2 cannabinoid receptor are crucial for its function.";
RL FEBS Lett. 531:290-294(2002).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-130; ARG-131 AND
RP ALA-244.
RX PubMed=12663043; DOI=10.1016/s0006-2952(03)00005-4;
RA Feng W., Song Z.H.;
RT "Effects of D3.49A, R3.50A, and A6.34E mutations on ligand binding and
RT activation of the cannabinoid-2 (CB2) receptor.";
RL Biochem. Pharmacol. 65:1077-1085(2003).
RN [16]
RP FUNCTION.
RX PubMed=12711605; DOI=10.1074/jbc.m301359200;
RA Kishimoto S., Gokoh M., Oka S., Muramatsu M., Kajiwara T., Waku K.,
RA Sugiura T.;
RT "2-arachidonoylglycerol induces the migration of HL-60 cells differentiated
RT into macrophage-like cells and human peripheral blood monocytes through the
RT cannabinoid CB2 receptor-dependent mechanism.";
RL J. Biol. Chem. 278:24469-24475(2003).
RN [17]
RP TISSUE SPECIFICITY.
RX PubMed=12511587; DOI=10.1172/jci200316116;
RA Casanova M.L., Blazquez C., Martinez-Palacio J., Villanueva C.,
RA Fernandez-Acenero M.J., Huffman J.W., Jorcano J.L., Guzman M.;
RT "Inhibition of skin tumor growth and angiogenesis in vivo by activation of
RT cannabinoid receptors.";
RL J. Clin. Invest. 111:43-50(2003).
RN [18]
RP TISSUE SPECIFICITY.
RX PubMed=14657172; DOI=10.1523/jneurosci.23-35-11136.2003;
RA Benito C., Nunez E., Tolon R.M., Carrier E.J., Rabano A., Hillard C.J.,
RA Romero J.;
RT "Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively
RT overexpressed in neuritic plaque-associated glia in Alzheimer's disease
RT brains.";
RL J. Neurosci. 23:11136-11141(2003).
RN [19]
RP TISSUE SPECIFICITY.
RX PubMed=15266552; DOI=10.1002/syn.20050;
RA Nunez E., Benito C., Pazos M.R., Barbachano A., Fajardo O., Gonzalez S.,
RA Tolon R.M., Romero J.;
RT "Cannabinoid CB2 receptors are expressed by perivascular microglial cells
RT in the human brain: an immunohistochemical study.";
RL Synapse 53:208-213(2004).
RN [20]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18692962; DOI=10.1016/j.pain.2008.06.007;
RA Anand U., Otto W.R., Sanchez-Herrera D., Facer P., Yiangou Y., Korchev Y.,
RA Birch R., Benham C., Bountra C., Chessell I.P., Anand P.;
RT "Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of
RT capsaicin responses in human sensory neurons.";
RL Pain 138:667-680(2008).
RN [21]
RP INDUCTION BY ENDOCANNABINOID ANANDAMIDE.
RX PubMed=23955712; DOI=10.1038/nm.3265;
RA Jourdan T., Godlewski G., Cinar R., Bertola A., Szanda G., Liu J., Tam J.,
RA Han T., Mukhopadhyay B., Skarulis M.C., Ju C., Aouadi M., Czech M.P.,
RA Kunos G.;
RT "Activation of the Nlrp3 inflammasome in infiltrating macrophages by
RT endocannabinoids mediates beta cell loss in type 2 diabetes.";
RL Nat. Med. 19:1132-1140(2013).
RN [22]
RP STRUCTURE BY NMR OF 240-272.
RX PubMed=19397896; DOI=10.1016/j.bbrc.2009.04.099;
RA Tiburu E.K., Tyukhtenko S., Deshmukh L., Vinogradova O., Janero D.R.,
RA Makriyannis A.;
RT "Structural biology of human cannabinoid receptor-2 helix 6 in membrane-
RT mimetic environments.";
RL Biochem. Biophys. Res. Commun. 384:243-248(2009).
RN [23]
RP VARIANTS ARG-63 AND TYR-316.
RX PubMed=18286196; DOI=10.1371/journal.pone.0001640;
RA Onaivi E.S., Ishiguro H., Gong J.-P., Patel S., Meozzi P.A., Myers L.,
RA Perchuk A., Mora Z., Tagliaferro P.A., Gardner E., Brusco A.,
RA Akinshola B.E., Hope B., Lujilde J., Inada T., Iwasaki S., Macharia D.,
RA Teasenfitz L., Arinami T., Uhl G.R.;
RT "Brain neuronal CB2 cannabinoid receptors in drug abuse and depression:
RT from mice to human subjects.";
RL PLoS ONE 3:E1640-E1640(2008).
CC -!- FUNCTION: Heterotrimeric G protein-coupled receptor for endocannabinoid
CC 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May
CC function in inflammatory response, nociceptive transmission and bone
CC homeostasis. {ECO:0000269|PubMed:10051546, ECO:0000269|PubMed:12663043,
CC ECO:0000269|PubMed:12711605, ECO:0000269|PubMed:18692962}.
CC -!- INTERACTION:
CC P34972; Q9UKJ8: ADAM21; NbExp=3; IntAct=EBI-2835940, EBI-12046857;
CC P34972; Q15848: ADIPOQ; NbExp=3; IntAct=EBI-2835940, EBI-10827839;
CC P34972; Q9NRZ5: AGPAT4; NbExp=3; IntAct=EBI-2835940, EBI-1754287;
CC P34972; P13236: CCL4; NbExp=3; IntAct=EBI-2835940, EBI-2873970;
CC P34972; P21964: COMT; NbExp=3; IntAct=EBI-2835940, EBI-372265;
CC P34972; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-2835940, EBI-12175685;
CC P34972; Q8N387: MUC15; NbExp=3; IntAct=EBI-2835940, EBI-17937277;
CC P34972; Q8IXM6: NRM; NbExp=3; IntAct=EBI-2835940, EBI-10262547;
CC P34972; I3L0A0: PEDS1-UBE2V1; NbExp=3; IntAct=EBI-2835940, EBI-12213001;
CC P34972; Q96AA3: RFT1; NbExp=3; IntAct=EBI-2835940, EBI-6269616;
CC P34972; Q9Y6D0: SELENOK; NbExp=3; IntAct=EBI-2835940, EBI-9679163;
CC P34972; Q6ICL7: SLC35E4; NbExp=3; IntAct=EBI-2835940, EBI-12867720;
CC P34972; Q9NP94: SLC39A2; NbExp=3; IntAct=EBI-2835940, EBI-12898013;
CC P34972; Q13501: SQSTM1; NbExp=5; IntAct=EBI-2835940, EBI-307104;
CC P34972; Q96HH6: TMEM19; NbExp=3; IntAct=EBI-2835940, EBI-741829;
CC P34972; Q969S6: TMEM203; NbExp=3; IntAct=EBI-2835940, EBI-12274070;
CC P34972; Q9NWH2: TMEM242; NbExp=3; IntAct=EBI-2835940, EBI-10315004;
CC P34972; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-2835940, EBI-2852148;
CC P34972; Q8N2M4: TMEM86A; NbExp=3; IntAct=EBI-2835940, EBI-12015604;
CC P34972; Q6ZT21: TMPPE; NbExp=3; IntAct=EBI-2835940, EBI-11724433;
CC P34972; Q5TGU0: TSPO2; NbExp=3; IntAct=EBI-2835940, EBI-12195249;
CC P34972; Q9Y548: YIPF1; NbExp=3; IntAct=EBI-2835940, EBI-7850136;
CC P34972; Q9BSR8: YIPF4; NbExp=3; IntAct=EBI-2835940, EBI-751253;
CC P34972; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-2835940, EBI-751210;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Cell
CC projection, dendrite {ECO:0000250}. Perikaryon {ECO:0000250}.
CC Note=Localizes to apical dendrite of pyramidal neurons. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Preferentially expressed in cells of the immune
CC system with higher expression in B-cells and NK cells (at protein
CC level). Expressed in skin in suprabasal layers and hair follicles (at
CC protein level). Highly expressed in tonsil and to a lower extent in
CC spleen, peripheral blood mononuclear cells, and thymus. PubMed:14657172
CC could not detect expression in normal brain. Expressed in brain by
CC perivascular microglial cells and dorsal root ganglion sensory neurons
CC (at protein level). Two isoforms are produced by alternative promoter
CC usage and differ only in the 5' UTR: isoform CB2A is observed
CC predominantly in testis with some expression in brain, while isoform
CC CB2B is predominant in spleen and leukocytes.
CC {ECO:0000269|PubMed:12153574, ECO:0000269|PubMed:12511587,
CC ECO:0000269|PubMed:14657172, ECO:0000269|PubMed:15266552,
CC ECO:0000269|PubMed:18692962, ECO:0000269|PubMed:19496827,
CC ECO:0000269|PubMed:7556170}.
CC -!- INDUCTION: In macrophages, down-regulated by endocannabinoid
CC anandamide/AEA. {ECO:0000269|PubMed:23955712}.
CC -!- PTM: Constitutively phosphorylated on Ser-352; phosphorylation
CC increases cell internalization and desensitizes the receptor.
CC {ECO:0000269|PubMed:10400664}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {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; X74328; CAA52376.1; -; mRNA.
DR EMBL; EU517121; ACD31539.1; -; mRNA.
DR EMBL; AJ430063; CAD22548.1; -; mRNA.
DR EMBL; AJ430064; CAD22549.1; -; Genomic_DNA.
DR EMBL; AY242132; AAO92299.1; -; Genomic_DNA.
DR EMBL; AM156854; CAJ42137.1; -; mRNA.
DR EMBL; AM156855; CAJ42138.1; -; mRNA.
DR EMBL; AM156856; CAJ42139.1; -; mRNA.
DR EMBL; AL590609; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471134; EAW95099.1; -; Genomic_DNA.
DR EMBL; BC069722; AAH69722.1; -; mRNA.
DR EMBL; BC074767; AAH74767.1; -; mRNA.
DR EMBL; BC095545; AAH95545.1; -; mRNA.
DR CCDS; CCDS245.1; -.
DR PIR; S36750; S36750.
DR RefSeq; NP_001832.1; NM_001841.2.
DR RefSeq; XP_011538931.1; XM_011540629.2.
DR RefSeq; XP_016855750.1; XM_017000261.1.
DR PDB; 2KI9; NMR; -; A=240-272.
DR PDB; 5ZTY; X-ray; 2.80 A; A=21-222, A=235-325.
DR PDB; 6KPC; X-ray; 3.20 A; A=21-222, A=235-325.
DR PDB; 6KPF; EM; 2.90 A; R=1-360.
DR PDB; 6PT0; EM; 3.20 A; R=1-360.
DR PDBsum; 2KI9; -.
DR PDBsum; 5ZTY; -.
DR PDBsum; 6KPC; -.
DR PDBsum; 6KPF; -.
DR PDBsum; 6PT0; -.
DR AlphaFoldDB; P34972; -.
DR BMRB; P34972; -.
DR SMR; P34972; -.
DR BioGRID; 107669; 107.
DR IntAct; P34972; 111.
DR MINT; P34972; -.
DR STRING; 9606.ENSP00000363596; -.
DR BindingDB; P34972; -.
DR ChEMBL; CHEMBL253; -.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB00470; Dronabinol.
DR DrugBank; DB06202; Lasofoxifene.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB00486; Nabilone.
DR DrugBank; DB14011; Nabiximols.
DR DrugBank; DB02955; Ricinoleic acid.
DR DrugBank; DB11755; Tetrahydrocannabivarin.
DR DrugCentral; P34972; -.
DR GuidetoPHARMACOLOGY; 57; -.
DR SwissLipids; SLP:000001608; -.
DR TCDB; 9.A.14.2.6; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P34972; 1 site.
DR iPTMnet; P34972; -.
DR PhosphoSitePlus; P34972; -.
DR SwissPalm; P34972; -.
DR BioMuta; CNR2; -.
DR DMDM; 461697; -.
DR MassIVE; P34972; -.
DR MaxQB; P34972; -.
DR PaxDb; P34972; -.
DR PeptideAtlas; P34972; -.
DR PRIDE; P34972; -.
DR ProteomicsDB; 54964; -.
DR Antibodypedia; 4047; 491 antibodies from 41 providers.
DR DNASU; 1269; -.
DR Ensembl; ENST00000374472.5; ENSP00000363596.4; ENSG00000188822.8.
DR GeneID; 1269; -.
DR KEGG; hsa:1269; -.
DR MANE-Select; ENST00000374472.5; ENSP00000363596.4; NM_001841.3; NP_001832.1.
DR UCSC; uc001bif.4; human.
DR CTD; 1269; -.
DR DisGeNET; 1269; -.
DR GeneCards; CNR2; -.
DR HGNC; HGNC:2160; CNR2.
DR HPA; ENSG00000188822; Tissue enhanced (intestine, lymphoid tissue).
DR MIM; 605051; gene.
DR neXtProt; NX_P34972; -.
DR OpenTargets; ENSG00000188822; -.
DR PharmGKB; PA26682; -.
DR VEuPathDB; HostDB:ENSG00000188822; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01030000234510; -.
DR HOGENOM; CLU_009579_7_0_1; -.
DR InParanoid; P34972; -.
DR OMA; CNFVNFH; -.
DR OrthoDB; 822074at2759; -.
DR PhylomeDB; P34972; -.
DR TreeFam; TF330052; -.
DR PathwayCommons; P34972; -.
DR Reactome; R-HSA-373076; Class A/1 (Rhodopsin-like receptors).
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P34972; -.
DR SIGNOR; P34972; -.
DR BioGRID-ORCS; 1269; 5 hits in 1071 CRISPR screens.
DR ChiTaRS; CNR2; human.
DR EvolutionaryTrace; P34972; -.
DR GeneWiki; Cannabinoid_receptor_type_2; -.
DR GenomeRNAi; 1269; -.
DR Pharos; P34972; Tchem.
DR PRO; PR:P34972; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P34972; protein.
DR Bgee; ENSG00000188822; Expressed in spleen and 42 other tissues.
DR ExpressionAtlas; P34972; baseline and differential.
DR Genevisible; P34972; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:CACAO.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004949; F:cannabinoid receptor activity; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0038171; P:cannabinoid signaling pathway; IBA:GO_Central.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; TAS:ProtInc.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0030595; P:leukocyte chemotaxis; IEA:Ensembl.
DR GO; GO:0045759; P:negative regulation of action potential; IEA:Ensembl.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0033004; P:negative regulation of mast cell activation; IEA:Ensembl.
DR GO; GO:0051001; P:negative regulation of nitric-oxide synthase activity; IEA:Ensembl.
DR GO; GO:0032229; P:negative regulation of synaptic transmission, GABAergic; IEA:Ensembl.
DR GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central.
DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
DR InterPro; IPR001551; Canbinoid_rcpt_2.
DR InterPro; IPR002230; Cnbnoid_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR22750:SF10; PTHR22750:SF10; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00523; CANABINOID2R.
DR PRINTS; PR00362; CANNABINOIDR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cell projection; G-protein coupled receptor;
KW Glycoprotein; Inflammatory response; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..360
FT /note="Cannabinoid receptor 2"
FT /id="PRO_0000069323"
FT TOPO_DOM 1..33
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 34..59
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 60..71
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 72..92
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 93..104
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 105..129
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 130..149
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..172
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 173..188
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..214
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 215..246
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 247..267
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 268..279
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 280..301
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 302..360
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 327..360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 346..360
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47936"
FT MOD_RES 336
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47936"
FT MOD_RES 338
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P47936"
FT MOD_RES 352
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10400664"
FT CARBOHYD 11
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 63
FT /note="Q -> R (high incidence in Japanese depressed
FT subjects; dbSNP:rs2501432)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:18286196"
FT /id="VAR_054310"
FT VARIANT 316
FT /note="H -> Y (in dbSNP:rs2229579)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:18286196, ECO:0000269|Ref.5"
FT /id="VAR_029209"
FT MUTAGEN 109
FT /note="K->A: No effect on agonist binding. Affects
FT cannabinoid agonist binding; when associated with G-112."
FT /evidence="ECO:0000269|PubMed:10051546"
FT MUTAGEN 109
FT /note="K->R: No effect on agonist binding."
FT /evidence="ECO:0000269|PubMed:10051546"
FT MUTAGEN 112
FT /note="S->G: Affects cannabinoid agonist binding; when
FT associated with A-109."
FT /evidence="ECO:0000269|PubMed:10051546"
FT MUTAGEN 130
FT /note="D->A: Loss of ligand binding. Alters agonist-induced
FT inhibitory effect on adenylate cyclase."
FT /evidence="ECO:0000269|PubMed:12663043"
FT MUTAGEN 131
FT /note="R->A: No effect on ligand binding. Alters agonist-
FT induced inhibitory effect on adenylate cyclase."
FT /evidence="ECO:0000269|PubMed:12663043"
FT MUTAGEN 201
FT /note="L->P: Abolishes ligand binding and agonist-induced
FT inhibitory effect on adenylate cyclase."
FT /evidence="ECO:0000269|PubMed:12417328"
FT MUTAGEN 207
FT /note="Y->A: Abolishes agonist-induced inhibitory effect on
FT adenylate cyclase. No effect on ligand binding."
FT /evidence="ECO:0000269|PubMed:12417328"
FT MUTAGEN 244
FT /note="A->E: Loss of ligand binding. Alters agonist-induced
FT inhibitory effect on adenylate cyclase."
FT /evidence="ECO:0000269|PubMed:12663043"
FT CONFLICT 173
FT /note="T -> A (in Ref. 8; AAH95545)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="R -> H (in Ref. 8; AAH69722)"
FT /evidence="ECO:0000305"
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:5ZTY"
FT HELIX 31..60
FT /evidence="ECO:0007829|PDB:5ZTY"
FT HELIX 62..65
FT /evidence="ECO:0007829|PDB:5ZTY"
FT HELIX 68..94
FT /evidence="ECO:0007829|PDB:5ZTY"
FT TURN 95..97
FT /evidence="ECO:0007829|PDB:6KPC"
FT HELIX 103..136
FT /evidence="ECO:0007829|PDB:5ZTY"
FT HELIX 138..144
FT /evidence="ECO:0007829|PDB:5ZTY"
FT HELIX 147..165
FT /evidence="ECO:0007829|PDB:5ZTY"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:5ZTY"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:5ZTY"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:5ZTY"
FT HELIX 188..219
FT /evidence="ECO:0007829|PDB:5ZTY"
FT HELIX 220..223
FT /evidence="ECO:0007829|PDB:6KPF"
FT TURN 224..226
FT /evidence="ECO:0007829|PDB:6KPF"
FT HELIX 230..233
FT /evidence="ECO:0007829|PDB:6PT0"
FT HELIX 238..270
FT /evidence="ECO:0007829|PDB:5ZTY"
FT HELIX 275..284
FT /evidence="ECO:0007829|PDB:5ZTY"
FT HELIX 287..302
FT /evidence="ECO:0007829|PDB:5ZTY"
FT HELIX 304..318
FT /evidence="ECO:0007829|PDB:5ZTY"
SQ SEQUENCE 360 AA; 39681 MW; A7ECF68C16E7514B CRC64;
MEECWVTEIA NGSKDGLDSN PMKDYMILSG PQKTAVAVLC TLLGLLSALE NVAVLYLILS
SHQLRRKPSY LFIGSLAGAD FLASVVFACS FVNFHVFHGV DSKAVFLLKI GSVTMTFTAS
VGSLLLTAID RYLCLRYPPS YKALLTRGRA LVTLGIMWVL SALVSYLPLM GWTCCPRPCS
ELFPLIPNDY LLSWLLFIAF LFSGIIYTYG HVLWKAHQHV ASLSGHQDRQ VPGMARMRLD
VRLAKTLGLV LAVLLICWFP VLALMAHSLA TTLSDQVKKA FAFCSMLCLI NSMVNPVIYA
LRSGEIRSSA HHCLAHWKKC VRGLGSEAKE EAPRSSVTET EADGKITPWP DSRDLDLSDC
