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Protein

Cannabinoid receptor 2

Gene

CNR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.4 Publications

GO - Molecular functioni

  • cannabinoid receptor activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processInflammatory response

Enzyme and pathway databases

ReactomeiR-HSA-373076 Class A/1 (Rhodopsin-like receptors)
R-HSA-418594 G alpha (i) signalling events

Protein family/group databases

TCDBi9.A.14.2.6 the g-protein-coupled receptor (gpcr) family

Chemistry databases

SwissLipidsiSLP:000001608

Names & Taxonomyi

Protein namesi
Recommended name:
Cannabinoid receptor 2
Short name:
CB-2
Short name:
CB2
Short name:
hCB2
Alternative name(s):
CX5
Gene namesi
Name:CNR2
Synonyms:CB2A, CB2B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000188822.7
HGNCiHGNC:2160 CNR2
MIMi605051 gene
neXtProtiNX_P34972

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 33ExtracellularSequence analysisAdd BLAST33
Transmembranei34 – 59Helical; Name=1Sequence analysisAdd BLAST26
Topological domaini60 – 71CytoplasmicSequence analysisAdd BLAST12
Transmembranei72 – 92Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini93 – 104ExtracellularSequence analysisAdd BLAST12
Transmembranei105 – 129Helical; Name=3Sequence analysisAdd BLAST25
Topological domaini130 – 149CytoplasmicSequence analysisAdd BLAST20
Transmembranei150 – 172Helical; Name=4Sequence analysisAdd BLAST23
Topological domaini173 – 188ExtracellularSequence analysisAdd BLAST16
Transmembranei189 – 214Helical; Name=5Sequence analysisAdd BLAST26
Topological domaini215 – 246CytoplasmicSequence analysisAdd BLAST32
Transmembranei247 – 267Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini268 – 279ExtracellularSequence analysisAdd BLAST12
Transmembranei280 – 301Helical; Name=7Sequence analysisAdd BLAST22
Topological domaini302 – 360CytoplasmicSequence analysisAdd BLAST59

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi109K → A: No effect on agonist binding. Affects cannabinoid agonist binding; when associated with G-112. 1 Publication1
Mutagenesisi109K → R: No effect on agonist binding. 1 Publication1
Mutagenesisi112S → G: Affects cannabinoid agonist binding; when associated with A-109. 1 Publication1
Mutagenesisi130D → A: Loss of ligand binding. Alters agonist-induced inhibitory effect on adenylate cyclase. 1 Publication1
Mutagenesisi131R → A: No effect on ligand binding. Alters agonist-induced inhibitory effect on adenylate cyclase. 1 Publication1
Mutagenesisi201L → P: Abolishes ligand binding and agonist-induced inhibitory effect on adenylate cyclase. 1 Publication1
Mutagenesisi207Y → A: Abolishes agonist-induced inhibitory effect on adenylate cyclase. No effect on ligand binding. 1 Publication1
Mutagenesisi244A → E: Loss of ligand binding. Alters agonist-induced inhibitory effect on adenylate cyclase. 1 Publication1

Organism-specific databases

DisGeNETi1269
OpenTargetsiENSG00000188822
PharmGKBiPA26682

Chemistry databases

ChEMBLiCHEMBL253
DrugBankiDB00470 Dronabinol
DB00486 Nabilone
GuidetoPHARMACOLOGYi57

Polymorphism and mutation databases

BioMutaiCNR2
DMDMi461697

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000693231 – 360Cannabinoid receptor 2Add BLAST360

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi11N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei335PhosphoserineBy similarity1
Modified residuei336PhosphoserineBy similarity1
Modified residuei338PhosphothreonineBy similarity1
Modified residuei352Phosphoserine1 Publication1

Post-translational modificationi

Constitutively phosphorylated on Ser-352; phosphorylation increases cell internalization and desensitizes the receptor.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP34972
MaxQBiP34972
PaxDbiP34972
PeptideAtlasiP34972
PRIDEiP34972
ProteomicsDBi54964

PTM databases

iPTMnetiP34972
PhosphoSitePlusiP34972

Expressioni

Tissue specificityi

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. PubMed:14657172 could not detect expression in normal brain. Expressed in brain by perivascular microglial cells and dorsal root ganglion sensory neurons (at protein level). Two isoforms are produced by alternative promoter usage and differ only in the 5' UTR: isoform CB2A is observed predominantly in testis with some expression in brain, while isoform CB2B is predominant in spleen and leukocytes.7 Publications

Inductioni

In macrophages, down-regulated by endocannabinoid anandamide/AEA.1 Publication

Gene expression databases

BgeeiENSG00000188822 Expressed in 36 organ(s), highest expression level in spleen
CleanExiHS_CNR2
ExpressionAtlasiP34972 baseline and differential
GenevisibleiP34972 HS

Organism-specific databases

HPAiCAB009719

Interactioni

Protein-protein interaction databases

IntActiP34972, 23 interactors
STRINGi9606.ENSP00000363596

Chemistry databases

BindingDBiP34972

Structurei

Secondary structure

1360
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP34972
SMRiP34972
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP34972

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00760000118804
HOGENOMiHOG000049272
HOVERGENiHBG051045
InParanoidiP34972
KOiK04278
OMAiVNFHVFH
OrthoDBiEOG091G05O3
PhylomeDBiP34972
TreeFamiTF330052

Family and domain databases

CDDicd15341 7tmA_CB2, 1 hit
InterProiView protein in InterPro
IPR001551 Canbinoid_rcpt_2
IPR002230 Cnbnoid_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PANTHERiPTHR22750:SF10 PTHR22750:SF10, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00523 CANABINOID2R
PR00362 CANNABINOIDR
PR00237 GPCRRHODOPSN
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequencei

Sequence statusi: Complete.

P34972-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEECWVTEIA NGSKDGLDSN PMKDYMILSG PQKTAVAVLC TLLGLLSALE
60 70 80 90 100
NVAVLYLILS SHQLRRKPSY LFIGSLAGAD FLASVVFACS FVNFHVFHGV
110 120 130 140 150
DSKAVFLLKI GSVTMTFTAS VGSLLLTAID RYLCLRYPPS YKALLTRGRA
160 170 180 190 200
LVTLGIMWVL SALVSYLPLM GWTCCPRPCS ELFPLIPNDY LLSWLLFIAF
210 220 230 240 250
LFSGIIYTYG HVLWKAHQHV ASLSGHQDRQ VPGMARMRLD VRLAKTLGLV
260 270 280 290 300
LAVLLICWFP VLALMAHSLA TTLSDQVKKA FAFCSMLCLI NSMVNPVIYA
310 320 330 340 350
LRSGEIRSSA HHCLAHWKKC VRGLGSEAKE EAPRSSVTET EADGKITPWP
360
DSRDLDLSDC
Length:360
Mass (Da):39,681
Last modified:February 1, 1994 - v1
Checksum:iA7ECF68C16E7514B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti173T → A in AAH95545 (PubMed:15489334).Curated1
Sequence conflicti307R → H in AAH69722 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05431063Q → R High incidence in Japanese depressed subjects. 2 PublicationsCorresponds to variant dbSNP:rs2501432Ensembl.1
Natural variantiVAR_029209316H → Y3 PublicationsCorresponds to variant dbSNP:rs2229579Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X74328 mRNA Translation: CAA52376.1
EU517121 mRNA Translation: ACD31539.1
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 No translation available.
CH471134 Genomic DNA Translation: EAW95099.1
BC069722 mRNA Translation: AAH69722.1
BC074767 mRNA Translation: AAH74767.1
BC095545 mRNA Translation: AAH95545.1
CCDSiCCDS245.1
PIRiS36750
RefSeqiNP_001832.1, NM_001841.2
XP_011538931.1, XM_011540629.2
XP_016855750.1, XM_017000261.1
UniGeneiHs.73037

Genome annotation databases

EnsembliENST00000374472; ENSP00000363596; ENSG00000188822
GeneIDi1269
KEGGihsa:1269
UCSCiuc001bif.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X74328 mRNA Translation: CAA52376.1
EU517121 mRNA Translation: ACD31539.1
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 No translation available.
CH471134 Genomic DNA Translation: EAW95099.1
BC069722 mRNA Translation: AAH69722.1
BC074767 mRNA Translation: AAH74767.1
BC095545 mRNA Translation: AAH95545.1
CCDSiCCDS245.1
PIRiS36750
RefSeqiNP_001832.1, NM_001841.2
XP_011538931.1, XM_011540629.2
XP_016855750.1, XM_017000261.1
UniGeneiHs.73037

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KI9NMR-A240-272[»]
ProteinModelPortaliP34972
SMRiP34972
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP34972, 23 interactors
STRINGi9606.ENSP00000363596

Chemistry databases

BindingDBiP34972
ChEMBLiCHEMBL253
DrugBankiDB00470 Dronabinol
DB00486 Nabilone
GuidetoPHARMACOLOGYi57
SwissLipidsiSLP:000001608

Protein family/group databases

TCDBi9.A.14.2.6 the g-protein-coupled receptor (gpcr) family
GPCRDBiSearch...

PTM databases

iPTMnetiP34972
PhosphoSitePlusiP34972

Polymorphism and mutation databases

BioMutaiCNR2
DMDMi461697

Proteomic databases

EPDiP34972
MaxQBiP34972
PaxDbiP34972
PeptideAtlasiP34972
PRIDEiP34972
ProteomicsDBi54964

Protocols and materials databases

DNASUi1269
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000374472; ENSP00000363596; ENSG00000188822
GeneIDi1269
KEGGihsa:1269
UCSCiuc001bif.4 human

Organism-specific databases

CTDi1269
DisGeNETi1269
EuPathDBiHostDB:ENSG00000188822.7
GeneCardsiCNR2
H-InvDBiHIX0160038
HGNCiHGNC:2160 CNR2
HPAiCAB009719
MIMi605051 gene
neXtProtiNX_P34972
OpenTargetsiENSG00000188822
PharmGKBiPA26682
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00760000118804
HOGENOMiHOG000049272
HOVERGENiHBG051045
InParanoidiP34972
KOiK04278
OMAiVNFHVFH
OrthoDBiEOG091G05O3
PhylomeDBiP34972
TreeFamiTF330052

Enzyme and pathway databases

ReactomeiR-HSA-373076 Class A/1 (Rhodopsin-like receptors)
R-HSA-418594 G alpha (i) signalling events

Miscellaneous databases

EvolutionaryTraceiP34972
GeneWikiiCannabinoid_receptor_type_2
GenomeRNAii1269
PROiPR:P34972
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000188822 Expressed in 36 organ(s), highest expression level in spleen
CleanExiHS_CNR2
ExpressionAtlasiP34972 baseline and differential
GenevisibleiP34972 HS

Family and domain databases

CDDicd15341 7tmA_CB2, 1 hit
InterProiView protein in InterPro
IPR001551 Canbinoid_rcpt_2
IPR002230 Cnbnoid_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PANTHERiPTHR22750:SF10 PTHR22750:SF10, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00523 CANABINOID2R
PR00362 CANNABINOIDR
PR00237 GPCRRHODOPSN
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCNR2_HUMAN
AccessioniPrimary (citable) accession number: P34972
Secondary accession number(s): C6ES44
, Q4VBK8, Q5JRH7, Q6B0G7, Q6NSY0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: September 12, 2018
This is version 164 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  4. SIMILARITY comments
    Index of protein domains and families
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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