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Protein

Cannabinoid receptor 2

Gene

CNR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Inflammatory response

Enzyme and pathway databases

BioCyciZFISH:G66-33751-MONOMER.
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

HGNCiHGNC:2160. CNR2.

Subcellular locationi

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

GO - Cellular componenti

Complete GO annotation...

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...)Sequence 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

MaxQBiP34972.
PaxDbiP34972.
PeptideAtlasiP34972.
PRIDEiP34972.

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

Gene expression databases

BgeeiENSG00000188822.
CleanExiHS_CNR2.
ExpressionAtlasiP34972. baseline and differential.
GenevisibleiP34972. HS.

Organism-specific databases

HPAiCAB009719.

Interactioni

Protein-protein interaction databases

IntActiP34972. 3 interactors.
STRINGi9606.ENSP00000363596.

Chemistry databases

BindingDBiP34972.

Structurei

Secondary structure

1360
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi242 – 245Combined sources4
Helixi246 – 254Combined sources9
Turni255 – 257Combined sources3
Beta strandi258 – 260Combined sources3
Helixi261 – 265Combined sources5
Turni266 – 269Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KI9NMR-A240-272[»]
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.
OMAiLAHWKKC.
OrthoDBiEOG091G05O3.
PhylomeDBiP34972.
TreeFamiTF330052.

Family and domain databases

InterProiIPR001551. Canbinoid_rcpt_2.
IPR002230. Cnbnoid_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR22750:SF10. PTHR22750:SF10. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00523. CANABINOID2R.
PR00362. CANNABINOIDR.
PR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

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 rs2501432dbSNPEnsembl.1
Natural variantiVAR_029209316H → Y.3 PublicationsCorresponds to variant rs2229579dbSNPEnsembl.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. Translation: CAI14799.1.
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

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. Translation: CAI14799.1.
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. 3 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

MaxQBiP34972.
PaxDbiP34972.
PeptideAtlasiP34972.
PRIDEiP34972.

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.
GeneCardsiCNR2.
H-InvDBHIX0160038.
HGNCiHGNC:2160. CNR2.
HPAiCAB009719.
MIMi605051. gene.
neXtProtiNX_P34972.
OpenTargetsiENSG00000188822.
PharmGKBiPA26682.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:G66-33751-MONOMER.
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.
PROiP34972.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000188822.
CleanExiHS_CNR2.
ExpressionAtlasiP34972. baseline and differential.
GenevisibleiP34972. HS.

Family and domain databases

InterProiIPR001551. Canbinoid_rcpt_2.
IPR002230. Cnbnoid_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR22750:SF10. PTHR22750:SF10. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00523. CANABINOID2R.
PR00362. CANNABINOIDR.
PR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCNR2_HUMAN
AccessioniPrimary (citable) accession number: P34972
Secondary accession number(s): C6ES44
, Q4VBK8, Q5JRH7, Q6B0G7, Q6NSY0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: November 30, 2016
This is version 152 of the entry and version 1 of the sequence. [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. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.