Reviewed,
UniProtKB/Swiss-Prot P34972 (CNR2_HUMAN)
Last modified
June 16, 2009.
Version 82.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Cannabinoid receptor 2 Short name=CB-2 Short name=hCB2 Short name=CB2 Alternative name(s): CX5 | ||
| Gene names |
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| Organism | Homo sapiens (Human) | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 360 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis. Ref.10 Ref.14 Ref.15 Ref.19 |
| Subcellular location | Cell membrane; Multi-pass membrane protein. Cell projection › dendrite By similarity. Perikaryon By similarity. Note: Localizes to apical dendrite of pyramidal neurons By similarity. |
| Tissue specificity | Preferentially expressed in cells of the immune system with higher expression in B cells and NK cells (at protein level). Expressed in skin in suprabasal layers and hair follicles (at protein level). Highly expressed in tonsil and to a lower extent in spleen, peripheral blood mononuclear cells, and thymus. Ref.17 could not detect expression in normal brain. Expressed in brain by perivascular microglial cells and dorsal root glanglion sensory neurons (at protein level). Ref.19 Ref.8 Ref.12 Ref.16 Ref.17 Ref.18 |
| Post-translational modification | Constitutively phosphorylated on Ser-352; phosphorylation increases cell internalization and desensitizes the receptor. Ref.9 |
| Involvement in disease | Allelic variation at the CB2 locus is associated to genetic predisposition for depression in Japanese populations. |
| Sequence similarities | Belongs to the G-protein coupled receptor 1 family. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Inflammatory response |
| Cellular component | Cell membrane Cell projection Membrane |
| Coding sequence diversity | Polymorphism |
| Domain | Transmembrane |
| Molecular function | G-protein coupled receptor Receptor Transducer |
| PTM | Glycoprotein Phosphoprotein |
| Gene Ontology (GO) | |
| Biological process | G-protein signaling, coupled to cyclic nucleotide second messenger Traceable author statement. Source: ProtInc behavior Ref.8Traceable author statement. Source: ProtInc immune response Ref.8Traceable author statement. Source: ProtInc inflammatory responseInferred from electronic annotation. Source: UniProtKB-KW |
| Cellular component | dendrite Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membraneTraceable author statement. Source: ProtInc perikaryonInferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | cannabinoid receptor activity Traceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 360 | 360 | Cannabinoid receptor 2 | PRO_0000069323 | |||||
Regions | |||||||||
| Topological domain | 1 – 33 | 33 | Extracellular Potential | ||||||
| Transmembrane | 34 – 59 | 26 | 1 Potential | ||||||
| Topological domain | 60 – 71 | 12 | Cytoplasmic Potential | ||||||
| Transmembrane | 72 – 92 | 21 | 2 Potential | ||||||
| Topological domain | 93 – 104 | 12 | Extracellular Potential | ||||||
| Transmembrane | 105 – 129 | 25 | 3 Potential | ||||||
| Topological domain | 130 – 149 | 20 | Cytoplasmic Potential | ||||||
| Transmembrane | 150 – 172 | 23 | 4 Potential | ||||||
| Topological domain | 173 – 188 | 16 | Extracellular Potential | ||||||
| Transmembrane | 189 – 214 | 26 | 5 Potential | ||||||
| Topological domain | 215 – 246 | 32 | Cytoplasmic Potential | ||||||
| Transmembrane | 247 – 267 | 21 | 6 Potential | ||||||
| Topological domain | 268 – 279 | 12 | Extracellular Potential | ||||||
| Transmembrane | 280 – 301 | 22 | 7 Potential | ||||||
| Topological domain | 302 – 360 | 59 | Cytoplasmic Potential | ||||||
Amino acid modifications | |||||||||
| Modified residue | 335 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 336 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 352 | 1 | Phosphoserine Ref.9 | ||||||
| Glycosylation | 11 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Natural variant | 63 | 1 | Q → R Associated with depresssion in Japanese population. dbSNP rs2501432. Ref.7 Ref.20 | VAR_054310 | |||||
| Natural variant | 316 | 1 | H → Y: dbSNP rs2229579. Ref.7 Ref.20 Ref.4 | VAR_029209 | |||||
Experimental info | |||||||||
| Mutagenesis | 109 | 1 | K → A: No effect on agonist binding. Affects cannabinoid agonist binding; when associated with G-112. Ref.10 | ||||||
| Mutagenesis | 109 | 1 | K → R: No effect on agonist binding. Ref.10 | ||||||
| Mutagenesis | 112 | 1 | S → G: Affects cannabinoid agonist binding; when associated with A-109. Ref.10 | ||||||
| Mutagenesis | 130 | 1 | D → A: Loss of ligand binding. Alters agonist-induced inhibitory effect on adenylate cyclase. Ref.14 | ||||||
| Mutagenesis | 131 | 1 | R → A: No effect on ligand binding. Alters agonist-induced inhibitory effect on adenylate cyclase. Ref.14 | ||||||
| Mutagenesis | 201 | 1 | L → P: Abolishes ligand binding and agonist-induced inhibitory effect on adenylate cyclase. Ref.13 | ||||||
| Mutagenesis | 207 | 1 | Y → A: Abolishes agonist-induced inhibitory effect on adenylate cyclase. No effect on ligand binding. Ref.13 | ||||||
| Mutagenesis | 244 | 1 | A → E: Loss of ligand binding. Alters agonist-induced inhibitory effect on adenylate cyclase. Ref.14 | ||||||
| Sequence conflict | 173 | 1 | T → A in AAH95545. Ref.7 | ||||||
| Sequence conflict | 307 | 1 | R → H in AAH69722. Ref.7 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Molecular characterization of a peripheral receptor for cannabinoids." Munro S., Thomas K.L., Abu-Shaar M. Nature 365:61-65(1993) [PubMed: 7689702] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [2] | "Cannabinoid receptors and their genes." Bruess M., Boenisch H. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Blood. |
| [3] | "Isolation of complete coding sequence for cannabinoid receptor 2 (CNR2)." Warren C.N., Aronstam R.S., Sharma S.V. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [4] | "Amplification and cloning of human cannabinoid receptor 2 gene from Asiatic origin." Saravanan T., Chugh A., Kant R. Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT TYR-316. Tissue: Blood. |
| [5] | "The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-63 AND TYR-316. Tissue: Brain. |
| [8] | "Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations." Galiegue S., Mary S., Marchand J., Dussossoy D., Carriere D., Carayon P., Bouaboula M., Shire D., Le Fur G., Casellas P. Eur. J. Biochem. 232:54-61(1995) [PubMed: 7556170] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [9] | "Regulation of peripheral cannabinoid receptor CB2 phosphorylation by the inverse agonist SR 144528. Implications for receptor biological responses." Bouaboula M., Dussossoy D., Casellas P. J. Biol. Chem. 274:20397-20405(1999) [PubMed: 10400664] [Abstract] Cited for: PHOSPHORYLATION AT SER-352, SUBCELLULAR LOCATION. |
| [10] | "Role of a conserved lysine residue in the peripheral cannabinoid receptor (CB2): evidence for subtype specificity." Tao Q., McAllister S.D., Andreassi J., Nowell K.W., Cabral G.A., Hurst D.P., Bachtel K., Ekman M.C., Reggio P.H., Abood M.E. Mol. Pharmacol. 55:605-613(1999) [PubMed: 10051546] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-109 AND SER-112. |
| [11] | "Evidence that 2-arachidonoylglycerol but not N-palmitoylethanolamine or anandamide is the physiological ligand for the cannabinoid CB2 receptor. Comparison of the agonistic activities of various cannabinoid receptor ligands in HL-60 cells." Sugiura T., Kondo S., Kishimoto S., Miyashita T., Nakane S., Kodaka T., Suhara Y., Takayama H., Waku K. J. Biol. Chem. 275:605-612(2000) [PubMed: 10617657] [Abstract] Cited for: IDENTIFICATION OF 2-ARACHIDONOYLGLYCEROL AS AN ENDOGENOUS LIGAND. |
| [12] | "Presence and regulation of the endocannabinoid system in human dendritic cells." Matias I., Pochard P., Orlando P., Salzet M., Pestel J., Di Marzo V. Eur. J. Biochem. 269:3771-3778(2002) [PubMed: 12153574] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [13] | "Absence of a conserved proline and presence of a conserved tyrosine in the CB2 cannabinoid receptor are crucial for its function." Song Z.H., Feng W. FEBS Lett. 531:290-294(2002) [PubMed: 12417328] [Abstract] Cited for: MUTAGENESIS OF LEU-201 AND TYR-207. |
| [14] | "Effects of D3.49A, R3.50A, and A6.34E mutations on ligand binding and activation of the cannabinoid-2 (CB2) receptor." Feng W., Song Z.H. Biochem. Pharmacol. 65:1077-1085(2003) [PubMed: 12663043] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-130; ARG-131 AND ALA-244. |
| [15] | "2-arachidonoylglycerol induces the migration of HL-60 cells differentiated into macrophage-like cells and human peripheral blood monocytes through the cannabinoid CB2 receptor-dependent mechanism." Kishimoto S., Gokoh M., Oka S., Muramatsu M., Kajiwara T., Waku K., Sugiura T. J. Biol. Chem. 278:24469-24475(2003) [PubMed: 12711605] [Abstract] Cited for: FUNCTION. |
| [16] | "Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors." Casanova M.L., Blazquez C., Martinez-Palacio J., Villanueva C., Fernandez-Acenero M.J., Huffman J.W., Jorcano J.L., Guzman M. J. Clin. Invest. 111:43-50(2003) [PubMed: 12511587] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [17] | "Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer's disease brains." Benito C., Nunez E., Tolon R.M., Carrier E.J., Rabano A., Hillard C.J., Romero J. J. Neurosci. 23:11136-11141(2003) [PubMed: 14657172] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [18] | "Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: an immunohistochemical study." Nunez E., Benito C., Pazos M.R., Barbachano A., Fajardo O., Gonzalez S., Tolon R.M., Romero J. Synapse 53:208-213(2004) [PubMed: 15266552] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [19] | "Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons." Anand U., Otto W.R., Sanchez-Herrera D., Facer P., Yiangou Y., Korchev Y., Birch R., Benham C., Bountra C., Chessell I.P., Anand P. Pain 138:667-680(2008) [PubMed: 18692962] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY. |
| [20] | "Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects." Onaivi E.S., Ishiguro H., Gong J.-P., Patel S., Meozzi P.A., Myers L., Perchuk A., Mora Z., Tagliaferro P.A., Gardner E., Brusco A., Akinshola B.E., Hope B., Lujilde J., Inada T., Iwasaki S., Macharia D., Teasenfitz L., Arinami T., Uhl G.R. PLoS ONE 3:E1640-E1640(2008) [PubMed: 18286196] [Abstract] Cited for: VARIANTS ARG-63 AND TYR-316, POSSIBLE INVOLVEMENT IN DEPRESSION. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| X74328 mRNA. Translation: CAA52376.1. AJ430063 mRNA. Translation: CAD22548.1. AJ430064 Genomic DNA. Translation: CAD22549.1. AY242132 Genomic DNA. Translation: AAO92299.1. AM156854 mRNA. Translation: CAJ42137.1. AM156855 mRNA. Translation: CAJ42138.1. AM156856 mRNA. Translation: CAJ42139.1. AL590609 Genomic DNA. Translation: CAI14799.1. CH471134 Genomic DNA. Translation: EAW95099.1. BC069722 mRNA. Translation: AAH69722.1. BC074767 mRNA. Translation: AAH74767.1. BC095545 mRNA. Translation: AAH95545.1. | |
| IPI | IPI00003060. |
| PIR | S36750. |
| RefSeq | NP_001832.1. |
| UniGene | Hs.73037 |
3D structure databases | |
| ModBase | Search... |
Protein family/group databases | |
| GPCRDB | Search... |
PTM databases | |
| PhosphoSite | P34972. |
Genome annotation databases | |
| Ensembl | ENSG00000188822. Homo sapiens. [Contig view] |
| GeneID | 1269. |
| KEGG | hsa:1269. |
Organism-specific databases | |
| GeneCards | GC01M024069. |
| H-InvDB | HIX0028631. |
| HGNC | HGNC:2160. CNR2. |
| HPA | CAB009719. |
| MIM | 605051. gene. |
| PharmGKB | PA26682. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | P34972. |
| HOVERGEN | P34972. |
| OMA | P34972. DRYLCLR. |
Gene expression databases | |
| ArrayExpress | P34972. |
| Bgee | P34972. |
| CleanEx | HS_CNR2. |
| GermOnline | ENSG00000188822. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR000276. 7TM_GPCR_Rhodpsn. IPR001551. Canbinoid_rcpt_2. IPR002230. Cnbnoid_rcpt. IPR017452. GPCR_Rhodpsn_supfam. [Graphical view] |
| PANTHER | PTHR22750:SF11. Canbinoid_rcpt_2. 1 hit. |
| Pfam | PF00001. 7tm_1. 1 hit. [Graphical view] |
| PRINTS | PR00523. CANABINOID2R. PR00362. CANNABINOIDR. PR00237. GPCRRHODOPSN. |
| PROSITE | PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| BindingDB | P34972. |
| DrugBank | DB00486. Nabilone. |
| NextBio | 5139. |
| SOURCE | Search... |
Entry information
| Entry name | CNR2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P34972 Secondary accession number(s): Q4VBK8 Q6NSY0 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| 7-transmembrane G-linked receptors List of 7-transmembrane G-linked receptor entries |
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


