5HT2C_RAT
ID 5HT2C_RAT Reviewed; 460 AA.
AC P08909;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 168.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=3399891; DOI=10.1126/science.3399891;
RA Julius D., McDermott A.B., Axel R., Jessell T.M.;
RT "Molecular characterization of a functional cDNA encoding the serotonin 1c
RT receptor.";
RL Science 241:558-564(1988).
RN [2]
RP INTERACTION WITH MPDZ, AND MUTAGENESIS OF SER-458 AND SER-459.
RX PubMed=12682077; DOI=10.1074/jbc.m210973200;
RA Parker L.L., Backstrom J.R., Sanders-Bush E., Shieh B.H.;
RT "Agonist-induced phosphorylation of the serotonin 5-HT2C receptor regulates
RT its interaction with multiple PDZ protein 1.";
RL J. Biol. Chem. 278:21576-21583(2003).
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:3399891}.
CC -!- SUBUNIT: Interacts with MPDZ. Interacts with ARRB2 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:3399891};
CC Multi-pass membrane protein {ECO:0000269|PubMed:3399891}.
CC -!- DOMAIN: The PDZ domain-binding motif is involved in the interaction
CC with MPDZ.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; M21410; AAA42177.1; -; Genomic_DNA.
DR PIR; A32605; A32605.
DR RefSeq; NP_036897.2; NM_012765.3.
DR PDB; 2MHO; NMR; -; B=452-460.
DR PDBsum; 2MHO; -.
DR AlphaFoldDB; P08909; -.
DR BMRB; P08909; -.
DR SMR; P08909; -.
DR IntAct; P08909; 1.
DR MINT; P08909; -.
DR STRING; 10116.ENSRNOP00000060345; -.
DR BindingDB; P08909; -.
DR ChEMBL; CHEMBL324; -.
DR DrugBank; DB00321; Amitriptyline.
DR DrugBank; DB00540; Nortriptyline.
DR DrugBank; DB00935; Oxymetazoline.
DR DrugBank; DB00656; Trazodone.
DR DrugBank; DB00726; Trimipramine.
DR DrugCentral; P08909; -.
DR GuidetoPHARMACOLOGY; 8; -.
DR GlyGen; P08909; 3 sites.
DR iPTMnet; P08909; -.
DR PhosphoSitePlus; P08909; -.
DR PaxDb; P08909; -.
DR Ensembl; ENSRNOT00000065293; ENSRNOP00000060345; ENSRNOG00000030877.
DR GeneID; 25187; -.
DR KEGG; rno:25187; -.
DR CTD; 3358; -.
DR RGD; 2848; Htr2c.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000161671; -.
DR InParanoid; P08909; -.
DR OrthoDB; 962038at2759; -.
DR PhylomeDB; P08909; -.
DR Reactome; R-RNO-390666; Serotonin receptors.
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR PRO; PR:P08909; -.
DR Proteomes; UP000002494; Chromosome X.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0098666; C:G protein-coupled serotonin receptor complex; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0071886; F:1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding; ISO:RGD.
DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IDA:MGI.
DR GO; GO:0001587; F:Gq/11-coupled serotonin receptor activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0051378; F:serotonin binding; ISO:RGD.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0001662; P:behavioral fear response; ISS:UniProtKB.
DR GO; GO:0035095; P:behavioral response to nicotine; IMP:RGD.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:RGD.
DR GO; GO:0019934; P:cGMP-mediated signaling; ISO:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0007631; P:feeding behavior; IMP:RGD.
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:RGD.
DR GO; GO:0048016; P:inositol phosphate-mediated signaling; IDA:MGI.
DR GO; GO:0007626; P:locomotory behavior; IEA:InterPro.
DR GO; GO:0045963; P:negative regulation of dopamine metabolic process; IMP:RGD.
DR GO; GO:0040013; P:negative regulation of locomotion; IMP:RGD.
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; IDA:RGD.
DR GO; GO:0031583; P:phospholipase D-activating G protein-coupled receptor signaling pathway; IMP:RGD.
DR GO; GO:0014057; P:positive regulation of acetylcholine secretion, neurotransmission; IMP:RGD.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISO:RGD.
DR GO; GO:0014054; P:positive regulation of gamma-aminobutyric acid secretion; IMP:RGD.
DR GO; GO:0010513; P:positive regulation of phosphatidylinositol biosynthetic process; ISO:RGD.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IMP:RGD.
DR GO; GO:0032098; P:regulation of appetite; ISS:UniProtKB.
DR GO; GO:0043397; P:regulation of corticotropin-releasing hormone secretion; ISS:UniProtKB.
DR GO; GO:0031644; P:regulation of nervous system process; ISS:UniProtKB.
DR GO; GO:0051930; P:regulation of sensory perception of pain; IMP:RGD.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:RGD.
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 1: Evidence at protein level;
KW 3D-structure; Behavior; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix.
FT SIGNAL 1..32
FT /evidence="ECO:0000250"
FT CHAIN 33..460
FT /note="5-hydroxytryptamine receptor 2C"
FT /id="PRO_0000068961"
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..313
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 314..335
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 336..350
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 351..373
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 374..460
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 276..301
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 366..370
FT /note="NPxxY motif; important for ligand-induced
FT conformation changes and signaling"
FT /evidence="ECO:0000250"
FT MOTIF 458..460
FT /note="PDZ-binding"
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 339..343
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT MUTAGEN 458
FT /note="S->A,D: Loss of interaction with MPDZ."
FT /evidence="ECO:0000269|PubMed:12682077"
FT MUTAGEN 459
FT /note="S->D: No effect on interaction with MPDZ."
FT /evidence="ECO:0000269|PubMed:12682077"
SQ SEQUENCE 460 AA; 51917 MW; D44E977D8F80047E CRC64;
MVNLGNAVRS LLMHLIGLLV WQFDISISPV AAIVTDTFNS SDGGRLFQFP DGVQNWPALS
IVVIIIMTIG GNILVIMAVS MEKKLHNATN YFLMSLAIAD MLVGLLVMPL SLLAILYDYV
WPLPRYLCPV WISLDVLFST ASIMHLCAIS LDRYVAIRNP IEHSRFNSRT KAIMKIAIVW
AISIGVSVPI PVIGLRDESK VFVNNTTCVL NDPNFVLIGS FVAFFIPLTI MVITYFLTIY
VLRRQTLMLL RGHTEEELAN MSLNFLNCCC KKNGGEEENA PNPNPDQKPR RKKKEKRPRG
TMQAINNEKK ASKVLGIVFF VFLIMWCPFF ITNILSVLCG KACNQKLMEK LLNVFVWIGY
VCSGINPLVY TLFNKIYRRA FSKYLRCDYK PDKKPPVRQI PRVAATALSG RELNVNIYRH
TNERVARKAN DPEPGIEMQV ENLELPVNPS NVVSERISSV
