5HT2C_MOUSE
ID 5HT2C_MOUSE Reviewed; 459 AA.
AC P34968; B1ATN5; Q5WRU6;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=5-hydroxytryptamine receptor 2C;
DE Short=5-HT-2C;
DE Short=5-HT2C;
DE Short=5-HTR2C;
DE AltName: Full=5-hydroxytryptamine receptor 1C;
DE Short=5-HT-1C;
DE Short=5-HT1C;
DE AltName: Full=Serotonin receptor 2C;
DE Flags: Precursor;
GN Name=Htr2c; Synonyms=5ht1c, Htr1c;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1661811; DOI=10.1016/0169-328x(91)90116-f;
RA Yu L., Nguyen H., Le H., Bloem L.J., Kozak C.A., Hoffman B.J., Snutch T.P.,
RA Lester H.A., Davidson N., Luebbert H.;
RT "The mouse 5-HT1C receptor contains eight hydrophobic domains and is X-
RT linked.";
RL Brain Res. Mol. Brain Res. 11:143-149(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1381232; DOI=10.1097/00001756-199204000-00014;
RA Foguet M., Nguyen H., Le H., Luebbert H.;
RT "Structure of the mouse 5-HT1C, 5-HT2 and stomach fundus serotonin receptor
RT genes.";
RL NeuroReport 3:345-348(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=7700379; DOI=10.1038/374542a0;
RA Tecott L.H., Sun L.M., Akana S.F., Strack A.M., Lowenstein D.H.,
RA Dallman M.F., Julius D.;
RT "Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors.";
RL Nature 374:542-546(1995).
RN [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9771748; DOI=10.1038/2647;
RA Nonogaki K., Strack A.M., Dallman M.F., Tecott L.H.;
RT "Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated
RT serotonin 5-HT2C receptor gene.";
RL Nat. Med. 4:1152-1156(1998).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17451451; DOI=10.1111/j.1601-183x.2007.00316.x;
RA Heisler L.K., Zhou L., Bajwa P., Hsu J., Tecott L.H.;
RT "Serotonin 5-HT(2C) receptors regulate anxiety-like behavior.";
RL Genes Brain Behav. 6:491-496(2007).
RN [7]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17596444; DOI=10.1523/jneurosci.2584-06.2007;
RA Heisler L.K., Pronchuk N., Nonogaki K., Zhou L., Raber J., Tung L.,
RA Yeo G.S., O'Rahilly S., Colmers W.F., Elmquist J.K., Tecott L.H.;
RT "Serotonin activates the hypothalamic-pituitary-adrenal axis via serotonin
RT 2C receptor stimulation.";
RL J. Neurosci. 27:6956-6964(2007).
RN [8]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19038216; DOI=10.1016/j.neuron.2008.09.033;
RA Xu Y., Jones J.E., Kohno D., Williams K.W., Lee C.E., Choi M.J.,
RA Anderson J.G., Heisler L.K., Zigman J.M., Lowell B.B., Elmquist J.K.;
RT "5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy
RT homeostasis.";
RL Neuron 60:582-589(2008).
RN [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=19501602; DOI=10.1016/j.neuropharm.2009.05.011;
RA Fletcher P.J., Tampakeras M., Sinyard J., Slassi A., Isaac M.,
RA Higgins G.A.;
RT "Characterizing the effects of 5-HT(2C) receptor ligands on motor activity
RT and feeding behaviour in 5-HT(2C) receptor knockout mice.";
RL Neuropharmacology 57:259-267(2009).
RN [10]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=21048120; DOI=10.1523/jneurosci.5412-09.2010;
RA Xu Y., Jones J.E., Lauzon D.A., Anderson J.G., Balthasar N., Heisler L.K.,
RA Zinn A.R., Lowell B.B., Elmquist J.K.;
RT "A serotonin and melanocortin circuit mediates D-fenfluramine anorexia.";
RL J. Neurosci. 30:14630-14634(2010).
RN [11]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=21037584; DOI=10.1038/nn.2664;
RA Xu Y., Berglund E.D., Sohn J.W., Holland W.L., Chuang J.C., Fukuda M.,
RA Rossi J., Williams K.W., Jones J.E., Zigman J.M., Lowell B.B.,
RA Scherer P.E., Elmquist J.K.;
RT "5-HT2CRs expressed by pro-opiomelanocortin neurons regulate insulin
RT sensitivity in liver.";
RL Nat. Neurosci. 13:1457-1459(2010).
RN [12]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=21835345; DOI=10.1016/j.neuron.2011.06.012;
RA Sohn J.W., Xu Y., Jones J.E., Wickman K., Williams K.W., Elmquist J.K.;
RT "Serotonin 2C receptor activates a distinct population of arcuate pro-
RT opiomelanocortin neurons via TRPC channels.";
RL Neuron 71:488-497(2011).
CC -!- FUNCTION: G-protein coupled receptor for 5-hydroxytryptamine
CC (serotonin). Also functions as a receptor for various drugs and
CC psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-
CC dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid
CC diethylamide (LSD). Ligand binding causes a conformation change that
CC triggers signaling via guanine nucleotide-binding proteins (G proteins)
CC and modulates the activity of down-stream effectors. Beta-arrestin
CC family members inhibit signaling via G proteins and mediate activation
CC of alternative signaling pathways. Signaling activates a
CC phosphatidylinositol-calcium second messenger system that modulates the
CC activity of phosphatidylinositol 3-kinase and down-stream signaling
CC cascades and promotes the release of Ca(2+) ions from intracellular
CC stores. Regulates neuronal activity via the activation of short
CC transient receptor potential calcium channels in the brain, and thereby
CC modulates the activation of pro-opiomelacortin neurons and the release
CC of CRH that then regulates the release of corticosterone. Plays a role
CC in the regulation of appetite and feeding behavior, responses to
CC anxiogenic stimuli and stress. Plays a role in insulin sensitivity and
CC glucose homeostasis. {ECO:0000269|PubMed:17451451,
CC ECO:0000269|PubMed:17596444, ECO:0000269|PubMed:19038216,
CC ECO:0000269|PubMed:21037584, ECO:0000269|PubMed:21048120,
CC ECO:0000269|PubMed:21835345, ECO:0000269|PubMed:7700379,
CC ECO:0000269|PubMed:9771748}.
CC -!- SUBUNIT: Interacts with MPDZ. Interacts with ARRB2 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Detected in brain cortex, hypothalamus, brainstem
CC and arcuate nucleus. Detected in the paraventricular nucleus of the
CC hypothalamus. {ECO:0000269|PubMed:17596444,
CC ECO:0000269|PubMed:19038216, ECO:0000269|PubMed:7700379}.
CC -!- DOMAIN: The PDZ domain-binding motif is involved in the interaction
CC with MPDZ. {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: No obvious phenotype at birth, but mutant mice
CC are prone to sudden death from seizures. When fed ad libitum, adult
CC mice display higher body weight and increased adiposity compared to
CC wild-type littermates. No difference in body weight is found when they
CC receive the same amount of food as their wild-type littermates,
CC indicating that the increased body weight is due to altered feeding
CC behavior. Overweight older mice develop insulin resistance and impaired
CC glucose tolerance. Young mice exhibit insulin resistance, but normal
CC glucose tolerance, due to increased insulin levels in the blood.
CC Insulin resistance is reversed when Htr2c expression is restored in
CC pro-opiomelacortin neurons. Mutant mice display impaired activation of
CC pro-opiomelacortin neurons in the paraventricular nucleus of the
CC hypothalamus, leading to decreased release of CRH and corticosterone.
CC Likewise, they exhibit blunted behavorial responses to anxiogenic
CC environments and stress. {ECO:0000269|PubMed:17451451,
CC ECO:0000269|PubMed:17596444, ECO:0000269|PubMed:19038216,
CC ECO:0000269|PubMed:19501602, ECO:0000269|PubMed:21037584,
CC ECO:0000269|PubMed:21048120, ECO:0000269|PubMed:21835345,
CC ECO:0000269|PubMed:7700379, ECO:0000269|PubMed:9771748}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; X72230; CAA51031.1; -; mRNA.
DR EMBL; S44559; AAA10521.1; -; Genomic_DNA.
DR EMBL; S44556; AAA10521.1; JOINED; Genomic_DNA.
DR EMBL; S44557; AAA10521.1; JOINED; Genomic_DNA.
DR EMBL; S44558; AAA10521.1; JOINED; Genomic_DNA.
DR EMBL; AL662932; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL808014; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS30459.1; -.
DR PIR; A43951; A43951.
DR RefSeq; NP_032338.3; NM_008312.4.
DR AlphaFoldDB; P34968; -.
DR SMR; P34968; -.
DR STRING; 10090.ENSMUSP00000043936; -.
DR BindingDB; P34968; -.
DR ChEMBL; CHEMBL3006; -.
DR DrugCentral; P34968; -.
DR GlyGen; P34968; 3 sites.
DR iPTMnet; P34968; -.
DR PhosphoSitePlus; P34968; -.
DR PaxDb; P34968; -.
DR PRIDE; P34968; -.
DR ProteomicsDB; 285690; -.
DR Antibodypedia; 527; 504 antibodies from 37 providers.
DR DNASU; 15560; -.
DR Ensembl; ENSMUST00000036303; ENSMUSP00000043936; ENSMUSG00000041380.
DR Ensembl; ENSMUST00000096299; ENSMUSP00000094021; ENSMUSG00000041380.
DR GeneID; 15560; -.
DR KEGG; mmu:15560; -.
DR UCSC; uc009und.2; mouse.
DR CTD; 3358; -.
DR MGI; MGI:96281; Htr2c.
DR VEuPathDB; HostDB:ENSMUSG00000041380; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244937; -.
DR HOGENOM; CLU_009579_11_3_1; -.
DR InParanoid; P34968; -.
DR OMA; CEKACNQ; -.
DR OrthoDB; 962038at2759; -.
DR PhylomeDB; P34968; -.
DR TreeFam; TF316350; -.
DR Reactome; R-MMU-390666; Serotonin receptors.
DR Reactome; R-MMU-416476; G alpha (q) signalling events.
DR BioGRID-ORCS; 15560; 4 hits in 77 CRISPR screens.
DR ChiTaRS; Htr2c; mouse.
DR PRO; PR:P34968; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; P34968; protein.
DR Bgee; ENSMUSG00000041380; Expressed in choroid plexus epithelium and 80 other tissues.
DR ExpressionAtlas; P34968; baseline and differential.
DR Genevisible; P34968; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0098666; C:G protein-coupled serotonin receptor complex; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0071886; F:1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding; ISO:MGI.
DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IMP:UniProtKB.
DR GO; GO:0001587; F:Gq/11-coupled serotonin receptor activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0051378; F:serotonin binding; ISO:MGI.
DR GO; GO:0001662; P:behavioral fear response; IMP:UniProtKB.
DR GO; GO:0035095; P:behavioral response to nicotine; ISO:MGI.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:MGI.
DR GO; GO:0019934; P:cGMP-mediated signaling; ISO:MGI.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0007631; P:feeding behavior; IMP:UniProtKB.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; IBA:GO_Central.
DR GO; GO:0098664; P:G protein-coupled serotonin receptor signaling pathway; ISO:MGI.
DR GO; GO:0048016; P:inositol phosphate-mediated signaling; ISO:MGI.
DR GO; GO:0007626; P:locomotory behavior; IEA:InterPro.
DR GO; GO:0045963; P:negative regulation of dopamine metabolic process; ISO:MGI.
DR GO; GO:0040013; P:negative regulation of locomotion; ISO:MGI.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007208; P:phospholipase C-activating serotonin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0031583; P:phospholipase D-activating G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0014057; P:positive regulation of acetylcholine secretion, neurotransmission; ISO:MGI.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; IMP:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:MGI.
DR GO; GO:0014054; P:positive regulation of gamma-aminobutyric acid secretion; ISO:MGI.
DR GO; GO:0010513; P:positive regulation of phosphatidylinositol biosynthetic process; ISO:MGI.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:MGI.
DR GO; GO:0032098; P:regulation of appetite; IMP:UniProtKB.
DR GO; GO:0043397; P:regulation of corticotropin-releasing hormone secretion; IMP:UniProtKB.
DR GO; GO:0031644; P:regulation of nervous system process; IMP:UniProtKB.
DR GO; GO:0051930; P:regulation of sensory perception of pain; ISO:MGI.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISO:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR InterPro; IPR000377; 5HT2C_rcpt.
DR InterPro; IPR002231; 5HT_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24247:SF32; PTHR24247:SF32; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00517; 5HT2CRECEPTR.
DR PRINTS; PR01101; 5HTRECEPTOR.
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 Behavior; Cell membrane; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Membrane; Receptor; Reference proteome; Signal; Transducer;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..32
FT /evidence="ECO:0000250"
FT CHAIN 33..459
FT /note="5-hydroxytryptamine receptor 2C"
FT /id="PRO_0000068959"
FT TOPO_DOM 33..53
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 54..79
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 80..90
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 91..111
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 112..128
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 129..151
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 152..171
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 172..194
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 195..214
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 215..236
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 237..312
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 313..334
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 335..349
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 350..372
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 373..459
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 274..302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 152..154
FT /note="DRY motif; important for ligand-induced conformation
FT changes"
FT /evidence="ECO:0000250"
FT MOTIF 365..369
FT /note="NPxxY motif; important for ligand-induced
FT conformation changes and signaling"
FT /evidence="ECO:0000250"
FT MOTIF 457..459
FT /note="PDZ-binding"
FT COMPBIAS 274..288
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 135
FT /ligand="ergotamine"
FT /ligand_id="ChEBI:CHEBI:190463"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT BINDING 140
FT /ligand="ergotamine"
FT /ligand_id="ChEBI:CHEBI:190463"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT BINDING 210
FT /ligand="ergotamine"
FT /ligand_id="ChEBI:CHEBI:190463"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 128..208
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 338..342
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT CONFLICT 157..161
FT /note="IRNPI -> VRSPV (in Ref. 1; CAA51031 and 2;
FT AAA10521)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 459 AA; 51929 MW; AA3C537B2ADCB0C9 CRC64;
MVNLGTAVRS LLVHLIGLLV WQFDISISPV AAIVTDTFNS SDGGRLFQFP DGVQNWPALS
IVVIIIMTIG GNILVIMAVS MEKKLHNATN YFLMSLAIAD MLVGLLVMPL SLLAILYDYV
WPLPRYLCPV WISLDVLFST ASIMHLCAIS LDRYVAIRNP IEHSRFNSRT KAIMKIAIVW
AISIGVSVPI PVIGLRDESK VFVNNTTCVL NDPNFVLIGS FVAFFIPLTI MVITYFLTIY
VLRRQTLMLL RGHTEEELRN ISLNFLKCCC KKGDEEENAP NPNPDQKPRR KKKEKRPRGT
MQAINNEKKA SKVLGIVFFV FLIMWCPFFI TNILSVLCGK ACNQKLMEKL LNVFVWIGYV
CSGINPLVYT LFNKIYRRAF SKYLRCDYKP DKKPPVRQIP RVAATALSGR ELNVNIYRHT
NERVVRKAND TEPGIEMQVE NLELPVNPSN VVSERISSV
