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CNR1_MACMU
ID   CNR1_MACMU              Reviewed;         472 AA.
AC   Q71SP5;
DT   06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   03-AUG-2022, entry version 108.
DE   RecName: Full=Cannabinoid receptor 1;
DE            Short=CB-R;
DE            Short=CB1;
GN   Name=CNR1;
OS   Macaca mulatta (Rhesus macaque).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9544;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Cerebellum;
RA   Miller G.M., Madras B.K.;
RT   "Cloning of the Macaca mulatta cannabinoid receptor (CB-1).";
RL   Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: G-protein coupled receptor for cannabinoids, including
CC       endocannabinoids (eCBs), such as N-arachidonoylethanolamide (also
CC       called anandamide or AEA) and 2-arachidonoylglycerol (2-AG). Mediates
CC       many cannabinoid-induced effects, acting, among others, on food intake,
CC       memory loss, gastrointestinal motility, catalepsy, ambulatory activity,
CC       anxiety, chronic pain. Signaling typically involves reduction in cyclic
CC       AMP (By similarity). In the hypothalamus, may have a dual effect on
CC       mitochondrial respiration depending upon the agonist dose and possibly
CC       upon the cell type. Increases respiration at low doses, while decreases
CC       respiration at high doses. At high doses, CNR1 signal transduction
CC       involves G-protein alpha-i protein activation and subsequent inhibition
CC       of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP
CC       concentration, inhibition of protein kinase A (PKA)-dependent
CC       phosphorylation of specific subunits of the mitochondrial electron
CC       transport system, including NDUFS2. In the hypothalamus, inhibits
CC       leptin-induced reactive oxygen species (ROS) formation and mediates
CC       cannabinoid-induced increase in SREBF1 and FASN gene expression. In
CC       response to cannabinoids, drives the release of orexigenic beta-
CC       endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-
CC       MSH, from hypothalamic POMC neurons, hence promoting food intake. In
CC       the hippocampus, regulates cellular respiration and energy production
CC       in response to cannabinoids. Involved in cannabinoid-dependent
CC       depolarization-induced suppression of inhibition (DSI), a process in
CC       which depolarization of CA1 postsynaptic pyramidal neurons mobilizes
CC       eCBs, which retrogradely activate presynaptic CB1 receptors,
CC       transiently decreasing GABAergic inhibitory neurotransmission. Also
CC       reduces excitatory synaptic transmission (By similarity). In superior
CC       cervical ganglions and cerebral vascular smooth muscle cells, inhibits
CC       voltage-gated Ca(2+) channels in a constitutive, as well as agonist-
CC       dependent manner (By similarity). Induces leptin production in
CC       adipocytes and reduces LRP2-mediated leptin clearance in the kidney,
CC       hence participating in hyperleptinemia. In adipose tissue, CNR1
CC       signaling leads to increased expression of SREBF1, ACACA and FASN
CC       genes. In the liver, activation by cannabinoids leads to increased de
CC       novo lipogenesis and reduced fatty acid catabolism, associated with
CC       increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN
CC       genes. May also affect de novo cholesterol synthesis and HDL-
CC       cholesteryl ether uptake. Peripherally modulates energy metabolism. In
CC       high carbohydrate diet-induced obesity, may decrease the expression of
CC       mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as
CC       well as that of selected glucose/ pyruvate metabolic enzymes, hence
CC       affecting energy expenditure through mitochondrial metabolism. In
CC       response to cannabinoid anandamide, elicits a pro-inflammatory response
CC       in macrophages, which involves NLRP3 inflammasome activation and IL1B
CC       and IL18 secretion (By similarity). {ECO:0000250|UniProtKB:O02777,
CC       ECO:0000250|UniProtKB:P21554, ECO:0000250|UniProtKB:P47746}.
CC   -!- ACTIVITY REGULATION: Hemopressin, a peptide derived from hemoglobin
CC       subunit alpha (HBA1 and/or HBA2), acts as an antagonist peptide:
CC       hemopressin-binding efficiently blocks cannabinoid receptor CNR1 and
CC       subsequent signaling. {ECO:0000250|UniProtKB:P21554}.
CC   -!- SUBUNIT: Interacts (via C-terminus) with CNRIP1; this interaction
CC       attenuates constitutive, but not agonist-dependent, inhibition of
CC       voltage-gated Ca(2+) channels in neurons (By similarity). Associates
CC       with G protein alpha subunits, including G(i) alpha-1/GNAI1, G(i)
CC       alpha-3/GNAI3 and G(o)-alpha/GNAO1; palmitoylation is important for
CC       interaction with GNAI3 and GNAO1 (By similarity).
CC       {ECO:0000250|UniProtKB:P21554}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P47746};
CC       Multi-pass membrane protein {ECO:0000250|UniProtKB:P21554}.
CC       Mitochondrion outer membrane {ECO:0000250|UniProtKB:P47746}. Cell
CC       projection, axon {ECO:0000250|UniProtKB:P20272}. Presynapse
CC       {ECO:0000250|UniProtKB:P20272}. Note=Unexpectedly, in the mitochondria,
CC       the C-terminus is located in the mitochondrial intermembrane space, a
CC       compartment topologically considered as extracellular. In canonical
CC       seven-transmembrane G-protein coupled receptors, the C-terminus is
CC       cytosolic (By similarity). Found on presynaptic axon terminals in some
CC       GABAergic neurons in the somatosensory cortex (By similarity).
CC       {ECO:0000250|UniProtKB:P20272, ECO:0000250|UniProtKB:P47746}.
CC   -!- PTM: Palmitoylation at Cys-415 is important for recruitment at both
CC       plasma membrane and lipid rafts and association with G protein alpha
CC       subunits. {ECO:0000250|UniProtKB:P21554}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; AF286025; AAF97250.1; -; mRNA.
DR   RefSeq; NP_001027997.1; NM_001032825.1.
DR   AlphaFoldDB; Q71SP5; -.
DR   SMR; Q71SP5; -.
DR   STRING; 9544.ENSMMUP00000001031; -.
DR   Ensembl; ENSMMUT00000104316; ENSMMUP00000069932; ENSMMUG00000000763.
DR   GeneID; 574142; -.
DR   KEGG; mcc:574142; -.
DR   CTD; 1268; -.
DR   VEuPathDB; HostDB:ENSMMUG00000000763; -.
DR   VGNC; VGNC:71280; CNR1.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT01030000234510; -.
DR   InParanoid; Q71SP5; -.
DR   OrthoDB; 822074at2759; -.
DR   Proteomes; UP000006718; Chromosome 4.
DR   Bgee; ENSMMUG00000000763; Expressed in cerebellum and 14 other tissues.
DR   ExpressionAtlas; Q71SP5; baseline.
DR   GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl.
DR   GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0030426; C:growth cone; IEA:Ensembl.
DR   GO; GO:0032592; C:integral component of mitochondrial membrane; IEA:Ensembl.
DR   GO; GO:0099056; C:integral component of presynaptic membrane; IEA:Ensembl.
DR   GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0004949; F:cannabinoid receptor activity; ISS:UniProtKB.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR   GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR   GO; GO:0099635; F:voltage-gated calcium channel activity involved in positive regulation of presynaptic cytosolic calcium levels; IEA:Ensembl.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0007413; P:axonal fasciculation; IEA:Ensembl.
DR   GO; GO:0038171; P:cannabinoid signaling pathway; IBA:GO_Central.
DR   GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR   GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central.
DR   GO; GO:0098921; P:retrograde trans-synaptic signaling by endocannabinoid; IEA:Ensembl.
DR   GO; GO:0099553; P:trans-synaptic signaling by endocannabinoid, modulating synaptic transmission; IEA:Ensembl.
DR   InterPro; IPR000810; Canbinoid_rcpt_1.
DR   InterPro; IPR002230; Cnbnoid_rcpt.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   PANTHER; PTHR22750:SF47; PTHR22750:SF47; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PIRSF; PIRSF037995; Cnoid_rcpt_1; 1.
DR   PRINTS; PR00522; CANABINOID1R.
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   2: Evidence at transcript level;
KW   Cell membrane; Cell projection; G-protein coupled receptor; Glycoprotein;
KW   Lipoprotein; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW   Palmitate; Phosphoprotein; Receptor; Reference proteome; Synapse;
KW   Transducer; Transmembrane; Transmembrane helix.
FT   CHAIN           1..472
FT                   /note="Cannabinoid receptor 1"
FT                   /id="PRO_0000069315"
FT   TOPO_DOM        1..120
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   TRANSMEM        121..141
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   TOPO_DOM        142..154
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   TRANSMEM        155..175
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   TOPO_DOM        176..187
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   TRANSMEM        188..208
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   TOPO_DOM        209..232
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   TRANSMEM        233..253
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   TOPO_DOM        254..277
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   TRANSMEM        278..298
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   TOPO_DOM        299..344
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   TRANSMEM        345..365
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   TOPO_DOM        366..377
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   TRANSMEM        378..398
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   TOPO_DOM        399..472
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   REGION          2..23
FT                   /note="Required for mitochondrial localization"
FT                   /evidence="ECO:0000250|UniProtKB:P47746"
FT   MOD_RES         425
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P47746"
FT   MOD_RES         429
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P47746"
FT   LIPID           415
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250|UniProtKB:P21554"
FT   CARBOHYD        77
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        83
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   472 AA;  52858 MW;  1D2E49061D12ABF2 CRC64;
     MKSILDGLAD TTFRTITTDL LYVGSNDIQY EDIKGDMASK LGYFPQKFPL TSFRGSPFQE
     KMTAGDNPQL VPADQVNITE FYNKSLSSFK ENEENIQCGE NFMDIECFMV LNPSQQLAIA
     VLSLTLGTFT VLENLLVLCV ILHSRSLRCR PSYHFIGSLA VADLLGSVIF VYSFIDFHVF
     HRKDSRNVFL FKLGGVTASF TASVGSLFLT AIDRYISIHR PLAYKRIVTR PKAVVAFCLM
     WTIAIVIAVL PLLGWNCEKL QSVCSDIFPH IDETYLMFWI GVTSVLLLFI VYAYMYILWK
     AHSHAVRMIQ RGTQKSIIIH TSEDGKVQVT RPDQARMDIR LAKTLVLILV VLIICWGPLL
     AIMVYDVFGK MNKLIKTVFA FCSMLCLLNS TVNPIIYALR SKDLRHAFRS MFPSCEGTAQ
     PLDNSMGDSD CLHKHANNAA SVHRAAESCI KSTVKIAKVT MSVSTDTSAE AL
 
 
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