CNR1_HUMAN
ID CNR1_HUMAN Reviewed; 472 AA.
AC P21554; B2R9T4; E1P512; Q13949; Q495Z0; Q4PLI4; Q4VBM6; Q5JVL5; Q5UB37;
AC Q9UNN0;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Cannabinoid receptor 1;
DE Short=CB-R;
DE Short=CB1;
DE AltName: Full=CANN6;
GN Name=CNR1; Synonyms=CNR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain stem;
RX PubMed=2263478; DOI=10.1093/nar/18.23.7142;
RA Gerard C., Mollereau C., Vassart G., Parmentier M.;
RT "Nucleotide sequence of a human cannabinoid receptor cDNA.";
RL Nucleic Acids Res. 18:7142-7142(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC TISSUE=Brain stem;
RX PubMed=1718258; DOI=10.1042/bj2790129;
RA Gerard C., Mollereau C., Vassart G., Parmentier M.;
RT "Molecular cloning of a human cannabinoid receptor which is also expressed
RT in testis.";
RL Biochem. J. 279:129-134(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung;
RX PubMed=7876112; DOI=10.1074/jbc.270.8.3726;
RA Shire D., Carillon C., Kaghad M., Calandra B., Rinaldi-Carmona M.,
RA Le Fur G., Caput D., Ferrara P.;
RT "An amino-terminal variant of the central cannabinoid receptor resulting
RT from alternative splicing.";
RL J. Biol. Chem. 270:3726-3731(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION (ISOFORMS 1; 2 AND 3), AND
RP TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=15620723; DOI=10.1016/j.febslet.2004.11.085;
RA Ryberg E., Vu H.K., Larsson N., Groblewski T., Hjorth S., Elebring T.,
RA Sjoegren S., Greasley P.J.;
RT "Identification and characterisation of a novel splice variant of the human
RT CB1 receptor.";
RL FEBS Lett. 579:259-264(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Hippocampus;
RA Kathmann M., Schlicker E.;
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Bonner T.I.;
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain tumor;
RA Kumar S., Gupta S., Sharma G.;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [13]
RP FUNCTION, AND INTERACTION WITH CNRIP1.
RC TISSUE=Brain;
RX PubMed=17895407; DOI=10.1124/mol.107.039263;
RA Niehaus J.L., Liu Y., Wallis K.T., Egertova M., Bhartur S.G.,
RA Mukhopadhyay S., Shi S., He H., Selley D.E., Howlett A.C., Elphick M.R.,
RA Lewis D.L.;
RT "CB1 cannabinoid receptor activity is modulated by the cannabinoid receptor
RT interacting protein CRIP 1a.";
RL Mol. Pharmacol. 72:1557-1566(2007).
RN [14]
RP ACTIVITY REGULATION.
RX PubMed=18077343; DOI=10.1073/pnas.0706980105;
RA Heimann A.S., Gomes I., Dale C.S., Pagano R.L., Gupta A., de Souza L.L.,
RA Luchessi A.D., Castro L.M., Giorgi R., Rioli V., Ferro E.S., Devi L.A.;
RT "Hemopressin is an inverse agonist of CB1 cannabinoid receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:20588-20593(2007).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-415, AND MUTAGENESIS
RP OF CYS-415.
RX PubMed=21895628; DOI=10.1111/j.1476-5381.2011.01658.x;
RA Oddi S., Dainese E., Sandiford S., Fezza F., Lanuti M., Chiurchiu V.,
RA Totaro A., Catanzaro G., Barcaroli D., De Laurenzi V., Centonze D.,
RA Mukhopadhyay S., Selent J., Howlett A.C., Maccarrone M.;
RT "Effects of palmitoylation of Cys(415) in helix 8 of the CB(1) cannabinoid
RT receptor on membrane localization and signalling.";
RL Br. J. Pharmacol. 165:2635-2651(2012).
RN [16]
RP INVOLVEMENT IN OBESITY.
RX PubMed=18177726; DOI=10.1016/j.cmet.2007.11.012;
RA Addy C., Wright H., Van Laere K., Gantz I., Erondu N., Musser B.J., Lu K.,
RA Yuan J., Sanabria-Bohorquez S.M., Stoch A., Stevens C., Fong T.M.,
RA De Lepeleire I., Cilissen C., Cote J., Rosko K., Gendrano I.N. III,
RA Nguyen A.M., Gumbiner B., Rothenberg P., de Hoon J., Bormans G., Depre M.,
RA Eng W.S., Ravussin E., Klein S., Blundell J., Herman G.A., Burns H.D.,
RA Hargreaves R.J., Wagner J., Gottesdiener K., Amatruda J.M.,
RA Heymsfield S.B.;
RT "The acyclic CB1R inverse agonist taranabant mediates weight loss by
RT increasing energy expenditure and decreasing caloric intake.";
RL Cell Metab. 7:68-78(2008).
RN [17]
RP FUNCTION, AND INDUCTION BY ENDOCANNABINOID ANANDAMIDE.
RX PubMed=23955712; DOI=10.1038/nm.3265;
RA Jourdan T., Godlewski G., Cinar R., Bertola A., Szanda G., Liu J., Tam J.,
RA Han T., Mukhopadhyay B., Skarulis M.C., Ju C., Aouadi M., Czech M.P.,
RA Kunos G.;
RT "Activation of the Nlrp3 inflammasome in infiltrating macrophages by
RT endocannabinoids mediates beta cell loss in type 2 diabetes.";
RL Nat. Med. 19:1132-1140(2013).
RN [18]
RP STRUCTURE BY NMR OF 338-346, INTERACTION WITH GNAI1, AND MUTAGENESIS OF
RP 341-LEU-ALA-342.
RX PubMed=12237474; DOI=10.1110/ps.0218402;
RA Ulfers A.L., McMurry J.L., Miller A., Wang L., Kendall D.A., Mierke D.F.;
RT "Cannabinoid receptor-G protein interactions: G(alphai1)-bound structures
RT of IC3 and a mutant with altered G protein specificity.";
RL Protein Sci. 11:2526-2531(2002).
RN [19] {ECO:0007744|PDB:5TGZ}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 99-306 AND 332-414, FUNCTION, AND
RP TOPOLOGY.
RX PubMed=27768894; DOI=10.1016/j.cell.2016.10.004;
RA Hua T., Vemuri K., Pu M., Qu L., Han G.W., Wu Y., Zhao S., Shui W., Li S.,
RA Korde A., Laprairie R.B., Stahl E.L., Ho J.H., Zvonok N., Zhou H.,
RA Kufareva I., Wu B., Zhao Q., Hanson M.A., Bohn L.M., Makriyannis A.,
RA Stevens R.C., Liu Z.J.;
RT "Crystal structure of the human cannabinoid receptor CB1.";
RL Cell 167:750-762(2016).
RN [20] {ECO:0007744|PDB:5U09}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 90-301 AND 334-421 IN COMPLEX
RP WITH INVERSE AGONIST TARANABANT, MUTAGENESIS OF THR-210, TOPOLOGY, AND
RP FUNCTION.
RX PubMed=27851727; DOI=10.1038/nature20613;
RA Shao Z., Yin J., Chapman K., Grzemska M., Clark L., Wang J.,
RA Rosenbaum D.M.;
RT "High-resolution crystal structure of the human CB1 cannabinoid receptor.";
RL Nature 540:602-606(2016).
CC -!- FUNCTION: G-protein coupled receptor for endogenous cannabinoids
CC (eCBs), including N-arachidonoylethanolamide (also called anandamide or
CC AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids,
CC such as delta(9)-tetrahydrocannabinol (THC) (PubMed:15620723,
CC PubMed:27768894, PubMed:27851727). Mediates many cannabinoid-induced
CC effects, acting, among others, on food intake, memory loss,
CC gastrointestinal motility, catalepsy, ambulatory activity, anxiety,
CC chronic pain. Signaling typically involves reduction in cyclic AMP
CC (PubMed:1718258, PubMed:21895628, PubMed:27768894). In the
CC hypothalamus, may have a dual effect on mitochondrial respiration
CC depending upon the agonist dose and possibly upon the cell type.
CC Increases respiration at low doses, while decreases respiration at high
CC doses. At high doses, CNR1 signal transduction involves G-protein
CC alpha-i protein activation and subsequent inhibition of mitochondrial
CC soluble adenylate cyclase, decrease in cyclic AMP concentration,
CC inhibition of protein kinase A (PKA)-dependent phosphorylation of
CC specific subunits of the mitochondrial electron transport system,
CC including NDUFS2. In the hypothalamus, inhibits leptin-induced reactive
CC oxygen species (ROS) formation and mediates cannabinoid-induced
CC increase in SREBF1 and FASN gene expression. In response to
CC cannabinoids, drives the release of orexigenic beta-endorphin, but not
CC that of melanocyte-stimulating hormone alpha/alpha-MSH, from
CC hypothalamic POMC neurons, hence promoting food intake. In the
CC hippocampus, regulates cellular respiration and energy production in
CC 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 (PubMed:17895407). In cerebral vascular smooth muscle
CC cells, cannabinoid-induced inhibition of voltage-gated Ca(2+) channels
CC leads to vasodilation and decreased vascular tone (By similarity).
CC Induces leptin production in adipocytes and reduces LRP2-mediated
CC leptin clearance in the kidney, hence participating in hyperleptinemia.
CC In adipose tissue, CNR1 signaling leads to increased expression of
CC SREBF1, ACACA and FASN genes (By similarity). In the liver, activation
CC by endocannabinoids leads to increased de novo lipogenesis and reduced
CC fatty acid catabolism, associated with increased expression of
CC SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes. May also affect de
CC novo cholesterol synthesis and HDL-cholesteryl ether uptake.
CC Peripherally modulates energy metabolism (By similarity). In high
CC 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 (By
CC similarity). In response to cannabinoid anandamide, elicits a pro-
CC inflammatory response in macrophages, which involves NLRP3 inflammasome
CC activation and IL1B and IL18 secretion (By similarity). In macrophages
CC infiltrating pancreatic islets, this process may participate in the
CC progression of type-2 diabetes and associated loss of pancreatic beta-
CC cells (PubMed:23955712). {ECO:0000250|UniProtKB:O02777,
CC ECO:0000250|UniProtKB:P47746, ECO:0000269|PubMed:15620723,
CC ECO:0000269|PubMed:1718258, ECO:0000269|PubMed:17895407,
CC ECO:0000269|PubMed:21895628, ECO:0000269|PubMed:23955712,
CC ECO:0000269|PubMed:27768894, ECO:0000269|PubMed:27851727}.
CC -!- FUNCTION: [Isoform 1]: Binds both 2-arachidonoylglycerol (2-AG) and
CC anandamide. {ECO:0000269|PubMed:15620723}.
CC -!- FUNCTION: [Isoform 2]: Only binds 2-arachidonoylglycerol (2-AG) with
CC high affinity. Contrary to its effect on isoform 1, 2-AG behaves as an
CC inverse agonist on isoform 2 in assays measuring GTP binding to
CC membranes. {ECO:0000269|PubMed:15620723}.
CC -!- FUNCTION: [Isoform 3]: Only binds 2-arachidonoylglycerol (2-AG) with
CC high affinity. Contrary to its effect on isoform 1, 2-AG behaves as an
CC inverse agonist on isoform 3 in assays measuring GTP binding to
CC membranes. {ECO:0000269|PubMed:15620723}.
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:0000269|PubMed:18077343}.
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 (PubMed:17895407). 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 (PubMed:12237474).
CC {ECO:0000269|PubMed:12237474, ECO:0000269|PubMed:17895407}.
CC -!- INTERACTION:
CC P21554; P29274: ADORA2A; NbExp=8; IntAct=EBI-2909859, EBI-2902702;
CC P21554; P21554: CNR1; NbExp=8; IntAct=EBI-2909859, EBI-2909859;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21895628};
CC Multi-pass membrane protein {ECO:0000269|PubMed:27768894,
CC ECO:0000269|PubMed:27851727}. Membrane raft
CC {ECO:0000269|PubMed:21895628}. Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:P47746}. Cell projection, axon
CC {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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Long;
CC IsoId=P21554-1; Sequence=Displayed;
CC Name=2; Synonyms=CB1a {ECO:0000303|PubMed:15620723}, Short;
CC IsoId=P21554-2; Sequence=VSP_001868;
CC Name=3; Synonyms=CB1b {ECO:0000303|PubMed:15620723};
CC IsoId=P21554-3; Sequence=VSP_016529;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in fetal and
CC adult brain. Expression levels of isoform 2 and isoform 3 are much
CC lower than those of isoform 1. {ECO:0000269|PubMed:15620723}.
CC -!- INDUCTION: Up-regulated by endocannabinoid anandamide.
CC {ECO:0000269|PubMed:23955712}.
CC -!- PTM: Palmitoylation at Cys-415 is important for recruitment at plasma
CC membrane and lipid rafts and association with G protein alpha subunits.
CC {ECO:0000269|PubMed:21895628}.
CC -!- DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by
CC an increase of body weight beyond the limitation of skeletal and
CC physical requirements, as the result of excessive accumulation of body
CC fat. {ECO:0000269|PubMed:18177726}. Note=The protein represented in
CC this entry may be involved in disease pathogenesis. May contribute to
CC the development of diet-induced obesity and several obesity-associated
CC features, such as dyslipidemia and liver steatosis, regulating
CC peripheral lipogenesis, energy expenditure and feeding behavior. CNR1
CC inverse agonists have been shown to reduce body weight and improve
CC metabolic abnormalities in obese subjects, although adverse
CC neuropsychiatric effects, including anxiety, irritability, and
CC depressed mood, halted their therapeutic development (PubMed:18177726).
CC In obese mice, peripherally restricted CNR1 inverse agonists have been
CC shown to normalize metabolic abnormalities, including insulin
CC resistance and fatty liver, and to reverse leptin resistance.
CC {ECO:0000269|PubMed:18177726}.
CC -!- MISCELLANEOUS: High-fat diet also increases the hepatic levels of CNR1
CC ligand anandamide, but not that of 2-arachidonoylglycerol.
CC {ECO:0000250|UniProtKB:P47746}.
CC -!- MISCELLANEOUS: [Isoform 2]: Dubious isoform. A putative downstream
CC initiation AUG is used to produce isoform 2 (PubMed:1718258). The use
CC of the first AUG (same as isoform 1) gives a truncated protein of 36
CC AA. {ECO:0000305|PubMed:1718258}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; X54937; CAA38699.1; -; mRNA.
DR EMBL; X81120; CAA57018.1; -; mRNA.
DR EMBL; X81121; CAA57019.1; -; mRNA.
DR EMBL; AY766182; AAV35030.1; -; mRNA.
DR EMBL; AF107262; AAD34320.1; -; mRNA.
DR EMBL; U73304; AAB18200.1; -; Genomic_DNA.
DR EMBL; DQ067455; AAY68486.1; -; mRNA.
DR EMBL; AY225225; AAO67710.1; -; Genomic_DNA.
DR EMBL; AL136096; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK313908; BAG36631.1; -; mRNA.
DR EMBL; CH471051; EAW48574.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW48575.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW48576.1; -; Genomic_DNA.
DR EMBL; BC074811; AAH74811.1; -; mRNA.
DR EMBL; BC074812; AAH74812.1; -; mRNA.
DR EMBL; BC095513; AAH95513.1; -; mRNA.
DR EMBL; BC100968; AAI00969.1; -; mRNA.
DR EMBL; BC100969; AAI00970.1; -; mRNA.
DR EMBL; BC100970; AAI00971.1; -; mRNA.
DR EMBL; BC100971; AAI00972.1; -; mRNA.
DR CCDS; CCDS5015.1; -. [P21554-1]
DR CCDS; CCDS5016.2; -. [P21554-3]
DR PIR; S17595; S17595.
DR RefSeq; NP_001153698.1; NM_001160226.1. [P21554-1]
DR RefSeq; NP_001153730.1; NM_001160258.1. [P21554-1]
DR RefSeq; NP_001153731.1; NM_001160259.1. [P21554-1]
DR RefSeq; NP_057167.2; NM_016083.4. [P21554-1]
DR RefSeq; NP_149421.2; NM_033181.3. [P21554-3]
DR RefSeq; XP_006715393.1; XM_006715330.3.
DR RefSeq; XP_011533726.1; XM_011535424.1.
DR RefSeq; XP_011533727.1; XM_011535425.1. [P21554-1]
DR RefSeq; XP_011533728.1; XM_011535426.1.
DR RefSeq; XP_011533730.1; XM_011535428.1.
DR RefSeq; XP_016865727.1; XM_017010238.1.
DR RefSeq; XP_016865728.1; XM_017010239.1.
DR RefSeq; XP_016865729.1; XM_017010240.1.
DR PDB; 1LVQ; NMR; -; A=338-346.
DR PDB; 1LVR; NMR; -; A=338-346.
DR PDB; 2B0Y; NMR; -; A=400-414.
DR PDB; 2KOE; NMR; -; A=377-414.
DR PDB; 2MZ2; NMR; -; A=400-414.
DR PDB; 2MZ3; NMR; -; A=400-414.
DR PDB; 2MZA; NMR; -; A=400-414.
DR PDB; 5TGZ; X-ray; 2.80 A; A=99-306, A=332-414.
DR PDB; 5U09; X-ray; 2.60 A; A=90-301, A=333-421.
DR PDB; 5XR8; X-ray; 2.95 A; A=99-306, A=332-414.
DR PDB; 5XRA; X-ray; 2.80 A; A=99-306, A=332-414.
DR PDB; 6KPG; EM; 3.00 A; R=71-425.
DR PDB; 6KQI; X-ray; 3.25 A; A=94-301, A=334-413.
DR PDB; 6N4B; EM; 3.00 A; R=1-472.
DR PDB; 7V3Z; X-ray; 3.29 A; A=102-306, A=336-414.
DR PDBsum; 1LVQ; -.
DR PDBsum; 1LVR; -.
DR PDBsum; 2B0Y; -.
DR PDBsum; 2KOE; -.
DR PDBsum; 2MZ2; -.
DR PDBsum; 2MZ3; -.
DR PDBsum; 2MZA; -.
DR PDBsum; 5TGZ; -.
DR PDBsum; 5U09; -.
DR PDBsum; 5XR8; -.
DR PDBsum; 5XRA; -.
DR PDBsum; 6KPG; -.
DR PDBsum; 6KQI; -.
DR PDBsum; 6N4B; -.
DR PDBsum; 7V3Z; -.
DR AlphaFoldDB; P21554; -.
DR SMR; P21554; -.
DR BioGRID; 107668; 9.
DR DIP; DIP-61575N; -.
DR IntAct; P21554; 11.
DR STRING; 9606.ENSP00000358513; -.
DR BindingDB; P21554; -.
DR ChEMBL; CHEMBL218; -.
DR DrugBank; DB05750; AVE-1625.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB00470; Dronabinol.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB00486; Nabilone.
DR DrugBank; DB14011; Nabiximols.
DR DrugBank; DB11745; Otenabant.
DR DrugBank; DB09288; Propacetamol.
DR DrugBank; DB02955; Ricinoleic acid.
DR DrugBank; DB06155; Rimonabant.
DR DrugBank; DB05077; SLV319.
DR DrugBank; DB11755; Tetrahydrocannabivarin.
DR DrugBank; DB05201; V24343.
DR DrugCentral; P21554; -.
DR GuidetoPHARMACOLOGY; 56; -.
DR SwissLipids; SLP:000001607; -.
DR TCDB; 9.A.14.2.2; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P21554; 2 sites.
DR iPTMnet; P21554; -.
DR PhosphoSitePlus; P21554; -.
DR SwissPalm; P21554; -.
DR BioMuta; CNR1; -.
DR DMDM; 115562; -.
DR MassIVE; P21554; -.
DR PaxDb; P21554; -.
DR PeptideAtlas; P21554; -.
DR PRIDE; P21554; -.
DR ProteomicsDB; 53875; -. [P21554-1]
DR ProteomicsDB; 53876; -. [P21554-2]
DR ProteomicsDB; 53877; -. [P21554-3]
DR ABCD; P21554; 62 sequenced antibodies.
DR Antibodypedia; 3355; 571 antibodies from 41 providers.
DR DNASU; 1268; -.
DR Ensembl; ENST00000369499.3; ENSP00000358511.2; ENSG00000118432.13. [P21554-1]
DR Ensembl; ENST00000369501.3; ENSP00000358513.2; ENSG00000118432.13. [P21554-1]
DR Ensembl; ENST00000428600.3; ENSP00000412192.2; ENSG00000118432.13. [P21554-1]
DR Ensembl; ENST00000468898.2; ENSP00000420188.1; ENSG00000118432.13. [P21554-3]
DR Ensembl; ENST00000549890.2; ENSP00000446819.1; ENSG00000118432.13. [P21554-1]
DR Ensembl; ENST00000551417.2; ENSP00000446702.2; ENSG00000118432.13. [P21554-1]
DR GeneID; 1268; -.
DR KEGG; hsa:1268; -.
DR MANE-Select; ENST00000369501.3; ENSP00000358513.2; NM_016083.6; NP_057167.2.
DR CTD; 1268; -.
DR DisGeNET; 1268; -.
DR GeneCards; CNR1; -.
DR HGNC; HGNC:2159; CNR1.
DR HPA; ENSG00000118432; Tissue enhanced (adipose tissue, brain).
DR MIM; 114610; gene.
DR MIM; 601665; phenotype.
DR neXtProt; NX_P21554; -.
DR OpenTargets; ENSG00000118432; -.
DR PharmGKB; PA26681; -.
DR VEuPathDB; HostDB:ENSG00000118432; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01030000234510; -.
DR HOGENOM; CLU_009579_7_0_1; -.
DR InParanoid; P21554; -.
DR OMA; CMMWAIS; -.
DR PhylomeDB; P21554; -.
DR TreeFam; TF330052; -.
DR PathwayCommons; P21554; -.
DR Reactome; R-HSA-373076; Class A/1 (Rhodopsin-like receptors).
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P21554; -.
DR SIGNOR; P21554; -.
DR BioGRID-ORCS; 1268; 16 hits in 1075 CRISPR screens.
DR ChiTaRS; CNR1; human.
DR EvolutionaryTrace; P21554; -.
DR GeneWiki; Cannabinoid_receptor_type_1; -.
DR GenomeRNAi; 1268; -.
DR Pharos; P21554; Tclin.
DR PRO; PR:P21554; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P21554; protein.
DR Bgee; ENSG00000118432; Expressed in ganglionic eminence and 148 other tissues.
DR ExpressionAtlas; P21554; baseline and differential.
DR Genevisible; P21554; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
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:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IEA:Ensembl.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004949; F:cannabinoid receptor activity; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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; IDA:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0007413; P:axonal fasciculation; IEA:Ensembl.
DR GO; GO:0038171; P:cannabinoid signaling pathway; IDA:UniProtKB.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; TAS:ProtInc.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0045759; P:negative regulation of action potential; IEA:Ensembl.
DR GO; GO:0045776; P:negative regulation of blood pressure; IEA:Ensembl.
DR GO; GO:0033602; P:negative regulation of dopamine secretion; IEA:Ensembl.
DR GO; GO:0031999; P:negative regulation of fatty acid beta-oxidation; IEA:Ensembl.
DR GO; GO:0033004; P:negative regulation of mast cell activation; IEA:Ensembl.
DR GO; GO:0051001; P:negative regulation of nitric-oxide synthase activity; IEA:Ensembl.
DR GO; GO:0014063; P:negative regulation of serotonin secretion; IEA:Ensembl.
DR GO; GO:0002866; P:positive regulation of acute inflammatory response to antigenic stimulus; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0045777; P:positive regulation of blood pressure; IEA:Ensembl.
DR GO; GO:0031622; P:positive regulation of fever generation; IEA:Ensembl.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0060259; P:regulation of feeding behavior; IEA:Ensembl.
DR GO; GO:0050796; P:regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central.
DR GO; GO:0060405; P:regulation of penile erection; IEA:Ensembl.
DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; IEA:Ensembl.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IEA:Ensembl.
DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0043278; P:response to morphine; IEA:Ensembl.
DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0098921; P:retrograde trans-synaptic signaling by endocannabinoid; IEA:Ensembl.
DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; 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 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane;
KW Mitochondrion; Mitochondrion outer membrane; Obesity; Palmitate;
KW Phosphoprotein; Receptor; Reference proteome; Synapse; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..472
FT /note="Cannabinoid receptor 1"
FT /id="PRO_0000069314"
FT TOPO_DOM 1..116
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
FT TRANSMEM 117..142
FT /note="Helical; Name=1"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
FT TOPO_DOM 143..154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
FT TRANSMEM 155..175
FT /note="Helical; Name=2"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
FT TOPO_DOM 176..187
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
FT TRANSMEM 188..212
FT /note="Helical; Name=3"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
FT TOPO_DOM 213..232
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
FT TRANSMEM 233..255
FT /note="Helical; Name=4"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
FT TOPO_DOM 256..273
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
FT TRANSMEM 274..299
FT /note="Helical; Name=5"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
FT TOPO_DOM 300..344
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
FT TRANSMEM 345..365
FT /note="Helical; Name=6"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
FT TOPO_DOM 366..377
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
FT TRANSMEM 378..399
FT /note="Helical; Name=7"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
FT TOPO_DOM 400..472
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27768894,
FT ECO:0000269|PubMed:27851727"
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:0000269|PubMed:21895628"
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"
FT VAR_SEQ 1..89
FT /note="MKSILDGLADTTFRTITTDLLYVGSNDIQYEDIKGDMASKLGYFPQKFPLTS
FT FRGSPFQEKMTAGDNPQLVPADQVNITEFYNKSLSSF -> MALQIPPSAPSPLTSCTW
FT AQMTFSTKTS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7876112"
FT /id="VSP_001868"
FT VAR_SEQ 22..54
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15620723"
FT /id="VSP_016529"
FT MUTAGEN 210
FT /note="T->A: 7-fold lower affinity for a synthetic agonist,
FT CP55940, possibly due the stabilization of an inactive
FT conformation."
FT /evidence="ECO:0000269|PubMed:27851727"
FT MUTAGEN 341..342
FT /note="LA->AL: Loss of activity, when assayed for GNAI1
FT GTPase stimulatory activity."
FT /evidence="ECO:0000269|PubMed:12237474"
FT MUTAGEN 415
FT /note="C->A: Loss of palmitoylation, marked loss of
FT association with lipid rafts on the plasma membrane and
FT loss of activity, when assayed for downstream GTP-binding
FT and reduction in cAMP levels."
FT /evidence="ECO:0000269|PubMed:21895628"
FT CONFLICT 94
FT /note="E -> G (in Ref. 12; AAH95513)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="M -> I (in Ref. 12; AAH95513)"
FT /evidence="ECO:0000305"
FT CONFLICT 149
FT /note="C -> R (in Ref. 12; AAH95513)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="F -> L (in Ref. 5; AAD34320)"
FT /evidence="ECO:0000305"
FT CONFLICT 216
FT /note="I -> V (in Ref. 5; AAD34320)"
FT /evidence="ECO:0000305"
FT CONFLICT 246
FT /note="V -> A (in Ref. 5; AAD34320)"
FT /evidence="ECO:0000305"
FT CONFLICT 298
FT /note="L -> P (in Ref. 12; AAH95513)"
FT /evidence="ECO:0000305"
FT CONFLICT 332
FT /note="P -> S (in Ref. 12; AAI00972)"
FT /evidence="ECO:0000305"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:5U09"
FT HELIX 113..143
FT /evidence="ECO:0007829|PDB:5U09"
FT HELIX 145..148
FT /evidence="ECO:0007829|PDB:5U09"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:5U09"
FT HELIX 154..178
FT /evidence="ECO:0007829|PDB:5U09"
FT HELIX 186..219
FT /evidence="ECO:0007829|PDB:5U09"
FT TURN 221..223
FT /evidence="ECO:0007829|PDB:5U09"
FT HELIX 224..227
FT /evidence="ECO:0007829|PDB:5U09"
FT HELIX 230..249
FT /evidence="ECO:0007829|PDB:5U09"
FT HELIX 250..253
FT /evidence="ECO:0007829|PDB:5U09"
FT HELIX 257..260
FT /evidence="ECO:0007829|PDB:5U09"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:5U09"
FT HELIX 273..300
FT /evidence="ECO:0007829|PDB:5U09"
FT HELIX 302..305
FT /evidence="ECO:0007829|PDB:6KPG"
FT HELIX 307..310
FT /evidence="ECO:0007829|PDB:6KPG"
FT HELIX 334..367
FT /evidence="ECO:0007829|PDB:5U09"
FT HELIX 375..400
FT /evidence="ECO:0007829|PDB:5U09"
FT HELIX 402..409
FT /evidence="ECO:0007829|PDB:5U09"
FT HELIX 411..415
FT /evidence="ECO:0007829|PDB:2B0Y"
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
