Cannabinoid receptor 2

NameCannabinoid receptor 2
Synonyms
  • CB-2
  • CB2A
  • CB2B
  • CX5
Gene NameCNR2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009930|Cannabinoid receptor 2
MEECWVTEIANGSKDGLDSNPMKDYMILSGPQKTAVAVLCTLLGLLSALENVAVLYLILS
SHQLRRKPSYLFIGSLAGADFLASVVFACSFVNFHVFHGVDSKAVFLLKIGSVTMTFTAS
VGSLLLTAIDRYLCLRYPPSYKALLTRGRALVTLGIMWVLSALVSYLPLMGWTCCPRPCS
ELFPLIPNDYLLSWLLFIAFLFSGIIYTYGHVLWKAHQHVASLSGHQDRQVPGMARMRLD
VRLAKTLGLVLAVLLICWFPVLALMAHSLATTLSDQVKKAFAFCSMLCLINSMVNPVIYA
LRSGEIRSSAHHCLAHWKKCVRGLGSEAKEEAPRSSVTETEADGKITPWPDSRDLDLSDC
Number of residues360
Molecular Weight39680.275
Theoretical pI8.25
GO Classification
Functions
  • cannabinoid receptor activity
Processes
  • negative regulation of synaptic transmission, GABAergic
  • response to lipopolysaccharide
  • immune response
  • sensory perception of pain
  • inflammatory response
  • response to amphetamine
  • G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
  • cannabinoid signaling pathway
  • negative regulation of action potential
  • negative regulation of inflammatory response
  • negative regulation of mast cell activation
  • negative regulation of nitric-oxide synthase activity
Components
  • plasma membrane
  • extrinsic component of cytoplasmic side of plasma membrane
  • integral component of plasma membrane
  • dendrite
  • perikaryon
General FunctionCannabinoid receptor activity
Specific FunctionHeterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.
Pfam Domain Function
Transmembrane Regions34-59 72-92 105-129 150-172 189-214 247-267 280-301
GenBank Protein ID407807
UniProtKB IDP34972
UniProtKB Entry NameCNR2_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0009931|Cannabinoid receptor 2 (CNR2)
ATGGAGGAATGCTGGGTGACAGAGATAGCCAATGGCTCCAAGGATGGCTTGGATTCCAAC
CCTATGAAGGATTACATGATCCTGAGTGGTCCCCAGAAGACAGCTGTTGCTGTGTTGTGC
ACTCTTCTGGGCCTGCTAAGTGCCCTGGAGAACGTGGCTGTGCTCTATCTGATCCTGTCC
TCCCACCAACTCCGCCGGAAGCCCTCATACCTGTTCATTGGCAGCTTGGCTGGGGCTGAC
TTCCTGGCCAGTGTGGTCTTTGCATGCAGCTTTGTGAATTTCCATGTTTTCCATGGTGTG
GATTCCAAGGCTGTCTTCCTGCTGAAGATTGGCAGCGTGACTATGACCTTCACAGCCTCT
GTGGGTAGCCTCCTGCTGACCGCCATTGACCGATACCTCTGCCTGCGCTATCCACCTTCC
TACAAAGCTCTGCTCACCCGTGGAAGGGCACTGGTGACCCTGGGCATCATGTGGGTCCTC
TCAGCACTAGTCTCCTACCTGCCCCTCATGGGATGGACTTGCTGTCCCAGGCCCTGCTCT
GAGCTTTTCCCACTGATCCCCAATGACTACCTGCTGAGCTGGCTCCTGTTCATCGCCTTC
CTCTTTTCCGGAATCATCTACACCTATGGGCATGTTCTCTGGAAGGCCCATCAGCATGTG
GCCAGCTTGTCTGGCCACCAGGACAGGCAGGTGCCAGGAATGGCCCGAATGAGGCTGGAT
GTGAGGTTGGCCAAGACCCTAGGGCTAGTGTTGGCTGTGCTCCTCATCTGTTGGTTCCCA
GTGCTGGCCCTCATGGCCCACAGCCTGGCCACTACGCTCAGTGACCAGGTCAAGAAGGCC
TTTGCTTTCTGCTCCATGCTGTGCCTCATCAACTCCATGGTCAACCCTGTCATCTATGCT
CTACGGAGTGGAGAGATCCGCTCCTCTGCCCATCACTGCCTGGCTCACTGGAAGAAGTGT
GTGAGGGGCCTTGGGTCAGAGGCAAAAGAAGAAGCCCCGAGATCCTCAGTCACCGAGACA
GAGGCTGATGGGAAAATCACTCCGTGGCCAGATTCCAGAGATCTAGACCTCTCTGATTGC
TGA
GenBank Gene IDX74328
GeneCard IDNot Available
GenAtlas IDCNR2
HGNC IDHGNC:2160
Chromosome Location1
Locus1p36.11
References
  1. Munro S, Thomas KL, Abu-Shaar M: Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993 Sep 2;365(6441):61-5. 7689702
  2. Liu QR, Pan CH, Hishimoto A, Li CY, Xi ZX, Llorente-Berzal A, Viveros MP, Ishiguro H, Arinami T, Onaivi ES, Uhl GR: Species differences in cannabinoid receptor 2 (CNR2 gene): identification of novel human and rodent CB2 isoforms, differential tissue expression and regulation by cannabinoid receptor ligands. Genes Brain Behav. 2009 Jul;8(5):519-30. doi: 10.1111/j.1601-183X.2009.00498.x. Epub 2009 Jun 3. 19496827
  3. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. 16710414
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  5. Galiegue S, Mary S, Marchand J, Dussossoy D, Carriere D, Carayon P, Bouaboula M, Shire D, Le Fur G, Casellas P: Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem. 1995 Aug 15;232(1):54-61. 7556170
  6. Bouaboula M, Dussossoy D, Casellas P: Regulation of peripheral cannabinoid receptor CB2 phosphorylation by the inverse agonist SR 144528. Implications for receptor biological responses. J Biol Chem. 1999 Jul 16;274(29):20397-405. 10400664
  7. Tao Q, McAllister SD, Andreassi J, Nowell KW, Cabral GA, Hurst DP, Bachtel K, Ekman MC, Reggio PH, Abood ME: Role of a conserved lysine residue in the peripheral cannabinoid receptor (CB2): evidence for subtype specificity. Mol Pharmacol. 1999 Mar;55(3):605-13. 10051546
  8. Sugiura T, Kondo S, Kishimoto S, Miyashita T, Nakane S, Kodaka T, Suhara Y, Takayama H, Waku K: 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. J Biol Chem. 2000 Jan 7;275(1):605-12. 10617657
  9. Matias I, Pochard P, Orlando P, Salzet M, Pestel J, Di Marzo V: Presence and regulation of the endocannabinoid system in human dendritic cells. Eur J Biochem. 2002 Aug;269(15):3771-8. 12153574
  10. Song ZH, Feng W: Absence of a conserved proline and presence of a conserved tyrosine in the CB2 cannabinoid receptor are crucial for its function. FEBS Lett. 2002 Nov 6;531(2):290-4. 12417328
  11. Feng W, Song ZH: Effects of D3.49A, R3.50A, and A6.34E mutations on ligand binding and activation of the cannabinoid-2 (CB2) receptor. Biochem Pharmacol. 2003 Apr 1;65(7):1077-85. 12663043
  12. Kishimoto S, Gokoh M, Oka S, Muramatsu M, Kajiwara T, Waku K, Sugiura T: 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. J Biol Chem. 2003 Jul 4;278(27):24469-75. Epub 2003 Apr 23. 12711605
  13. Casanova ML, Blazquez C, Martinez-Palacio J, Villanueva C, Fernandez-Acenero MJ, Huffman JW, Jorcano JL, Guzman M: Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. J Clin Invest. 2003 Jan;111(1):43-50. 12511587
  14. Benito C, Nunez E, Tolon RM, Carrier EJ, Rabano A, Hillard CJ, Romero J: Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer's disease brains. J Neurosci. 2003 Dec 3;23(35):11136-41. 14657172
  15. Nunez E, Benito C, Pazos MR, Barbachano A, Fajardo O, Gonzalez S, Tolon RM, Romero J: Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: an immunohistochemical study. Synapse. 2004 Sep 15;53(4):208-13. 15266552
  16. Anand U, Otto WR, Sanchez-Herrera D, Facer P, Yiangou Y, Korchev Y, Birch R, Benham C, Bountra C, Chessell IP, Anand P: Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons. Pain. 2008 Sep 15;138(3):667-80. doi: 10.1016/j.pain.2008.06.007. Epub 2008 Aug 9. 18692962
  17. Tiburu EK, Tyukhtenko S, Deshmukh L, Vinogradova O, Janero DR, Makriyannis A: Structural biology of human cannabinoid receptor-2 helix 6 in membrane-mimetic environments. Biochem Biophys Res Commun. 2009 Jun 26;384(2):243-8. doi: 10.1016/j.bbrc.2009.04.099. Epub 2009 May 3. 19397896
  18. Onaivi ES, Ishiguro H, Gong JP, Patel S, Meozzi PA, Myers L, Perchuk A, Mora Z, Tagliaferro PA, Gardner E, Brusco A, Akinshola BE, Hope B, Lujilde J, Inada T, Iwasaki S, Macharia D, Teasenfitz L, Arinami T, Uhl GR: Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects. PLoS One. 2008 Feb 20;3(2):e1640. doi: 10.1371/journal.pone.0001640. 18286196