ID 5HT2C_HUMAN Reviewed; 458 AA. AC P28335; B1AMW4; Q5VUF8; Q9NP28; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 23-FEB-2022, sequence version 2. DT 27-MAR-2024, entry version 225. DE RecName: Full=5-hydroxytryptamine receptor 2C {ECO:0000305}; 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 {ECO:0000312|HGNC:HGNC:5295}; Synonyms=HTR1C; 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), AND VARIANT CYS-23. RC TISSUE=Brain; RX PubMed=1722404; DOI=10.1016/0006-291x(91)92105-s; RA Saltzman A.G., Morse B., Whitman M.M., Ivanshchenko Y., Jaye M., Felder S.; RT "Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes."; RL Biochem. Biophys. Res. Commun. 181:1469-1478(1991). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, AND RP VARIANT CYS-23. RC TISSUE=Hippocampus, and Placenta; RX PubMed=7895773; DOI=10.1016/0922-4106(94)90042-6; RA Stam N.J., Vanderheyden P., Van Alebeek C., Klomp J., De Boer T., RA Van Delft A.M.L., Olijve W.; RT "Genomic organisation and functional expression of the gene encoding the RT human serotonin 5-HT2C receptor."; RL Eur. J. Pharmacol. 269:339-348(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT RP CYS-23. RC TISSUE=Brain; RX PubMed=8812491; DOI=10.1006/geno.1996.0397; RA Xie E., Zhao L., Levine A.J., Shenk T., Chang L.-S.; RT "The human serotonin 5-HT2C receptor: complete cDNA, genomic structure, and RT alternatively spliced variant."; RL Genomics 35:551-561(1996). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), RNA EDITING OF POSITIONS 156; 158 RP AND 160, AND VARIANT CYS-23. RC TISSUE=Brain; RX PubMed=9928237; DOI=10.1111/j.1749-6632.1998.tb10171.x; RA Niswender C.M., Sanders-Bush E., Emeson R.B.; RT "Identification and characterization of RNA editing events within the 5- RT HT2C receptor."; RL Ann. N. Y. Acad. Sci. 861:38-48(1998). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT CYS-23. RC TISSUE=Brain; RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.; RT "cDNA clones of human proteins involved in signal transduction sequenced by RT the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT CYS-23. 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT CYS-23. 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 [9] RP INTERACTION WITH MPDZ, DOMAIN, MUTAGENESIS OF SER-456; SER-457 AND VAL-458, RP AND GLYCOSYLATION. RX PubMed=11150294; DOI=10.1074/jbc.m008089200; RA Becamel C., Figge A., Poliak S., Dumuis A., Peles E., Bockaert J., RA Luebbert H., Ullmer C.; RT "Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 RT of the multi-PDZ domain protein MUPP1."; RL J. Biol. Chem. 276:12974-12982(2001). RN [10] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=12970106; DOI=10.1038/sj.bjp.0705437; RA Schaerlinger B., Hickel P., Etienne N., Guesnier L., Maroteaux L.; RT "Agonist actions of dihydroergotamine at 5-HT2B and 5-HT2C receptors and RT their possible relevance to antimigraine efficacy."; RL Br. J. Pharmacol. 140:277-284(2003). RN [11] RP INTERACTION WITH MPP3. RX PubMed=14988405; DOI=10.1074/jbc.m312106200; RA Becamel C., Gavarini S., Chanrion B., Alonso G., Galeotti N., Dumuis A., RA Bockaert J., Marin P.; RT "The serotonin 5-HT2A and 5-HT2C receptors interact with specific sets of RT PDZ proteins."; RL J. Biol. Chem. 279:20257-20266(2004). RN [12] RP INTERACTION WITH ARRB2, AND MUTAGENESIS OF PRO-159. RX PubMed=16319069; DOI=10.1074/jbc.m508074200; RA Marion S., Oakley R.H., Kim K.-M., Caron M.G., Barak L.S.; RT "A beta-arrestin binding determinant common to the second intracellular RT loops of rhodopsin family G protein-coupled receptors."; RL J. Biol. Chem. 281:2932-2938(2006). RN [13] RP INTERACTION WITH MPP3. RX PubMed=16914526; DOI=10.1091/mbc.e06-03-0218; RA Gavarini S., Becamel C., Altier C., Lory P., Poncet J., Wijnholds J., RA Bockaert J., Marin P.; RT "Opposite effects of PSD-95 and MPP3 PDZ proteins on serotonin 5- RT hydroxytryptamine2C receptor desensitization and membrane stability."; RL Mol. Biol. Cell 17:4619-4631(2006). RN [14] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=18703043; DOI=10.1016/j.ejphar.2008.07.040; RA Cussac D., Boutet-Robinet E., Ailhaud M.C., Newman-Tancredi A., RA Martel J.C., Danty N., Rauly-Lestienne I.; RT "Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and RT 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in RT CHO cells."; RL Eur. J. Pharmacol. 594:32-38(2008). RN [15] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19057895; DOI=10.1007/s00210-008-0378-4; RA Knauer C.S., Campbell J.E., Chio C.L., Fitzgerald L.W.; RT "Pharmacological characterization of mitogen-activated protein kinase RT activation by recombinant human 5-HT2C, 5-HT2A, and 5-HT2B receptors."; RL Naunyn Schmiedebergs Arch. Pharmacol. 379:461-471(2009). RN [16] RP REVIEW. RX PubMed=20945968; DOI=10.33549/physiolres.931903; RA Pytliak M., Vargova V., Mechirova V., Felsoci M.; RT "Serotonin receptors - from molecular biology to clinical applications."; RL Physiol. Res. 60:15-25(2011). RN [17] RP SIGNAL SEQUENCE CLEAVAGE SITE, AND VARIANT CYS-23. RX PubMed=22497996; DOI=10.1016/j.ejphar.2012.03.043; RA Jahnsen J.A., Uhlen S.; RT "The N-terminal region of the human 5-HT(2)C receptor has as a cleavable RT signal peptide."; RL Eur. J. Pharmacol. 684:44-50(2012). RN [18] RP VARIANT CYS-23. RX PubMed=7557992; DOI=10.1006/geno.1995.1042; RA Lappalainen J., Zhang L., Dean M., Oz M., Ozaki N., Yu D., Virkkunen M., RA Weight F., Linnoila M., Goldman D.; RT "Identification, expression, and pharmacology of a Cys23-Ser23 substitution RT in the human 5-HT2c receptor gene (HTR2C)."; RL Genomics 27:274-279(1995). RN [19] RP VARIANT CYS-23. RX PubMed=10206230; RX DOI=10.1002/(sici)1096-8628(19990416)88:2<126::aid-ajmg6>3.3.co;2-d; RA Samochowiec J., Smolka M., Winterer G., Rommelspacher H., Schmidt L.G., RA Sander T.; RT "Association analysis between a Cys23Ser substitution polymorphism of the RT human 5-HT2c receptor gene and neuronal hyperexcitability."; RL Am. J. Med. Genet. 88:126-130(1999). RN [20] RP VARIANT CYS-23. RX PubMed=10581480; RX DOI=10.1002/(sici)1096-8628(19991215)88:6<621::aid-ajmg9>3.0.co;2-h; RA Marshall S.E., Bird T.G., Hart K., Welsh K.I.; RT "Unified approach to the analysis of genetic variation in serotonergic RT pathways."; RL Am. J. Med. Genet. 88:621-627(1999). RN [21] RP VARIANT CYS-23. RX PubMed=10391209; DOI=10.1038/10290; RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RT "Characterization of single-nucleotide polymorphisms in coding regions of RT human genes."; RL Nat. Genet. 22:231-238(1999). RN [22] RP ERRATUM OF PUBMED:10391209. RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RL Nat. Genet. 23:373-373(1999). 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 eating behavior, responses to CC anxiogenic stimuli and stress. Plays a role in insulin sensitivity and CC glucose homeostasis. {ECO:0000269|PubMed:12970106, CC ECO:0000269|PubMed:18703043, ECO:0000269|PubMed:19057895, CC ECO:0000269|PubMed:7895773}. CC -!- SUBUNIT: Interacts with MPDZ (PubMed:11150294). Interacts with ARRB2 CC (PubMed:16319069). Interacts with MPP3; this interaction stabilizes the CC receptor at the plasma membrane and prevents the desensitization of the CC HTR2C receptor-mediated calcium response (PubMed:14988405, CC PubMed:16914526). {ECO:0000269|PubMed:11150294, CC ECO:0000269|PubMed:14988405, ECO:0000269|PubMed:16319069, CC ECO:0000269|PubMed:16914526}. CC -!- INTERACTION: CC P28335; O95406: CNIH1; NbExp=3; IntAct=EBI-994141, EBI-12172273; CC P28335; P54849: EMP1; NbExp=3; IntAct=EBI-994141, EBI-4319440; CC P28335; P28223: HTR2A; NbExp=5; IntAct=EBI-994141, EBI-6656333; CC P28335; P41595: HTR2B; NbExp=4; IntAct=EBI-994141, EBI-7474947; CC P28335; P28335: HTR2C; NbExp=9; IntAct=EBI-994141, EBI-994141; CC P28335; P49286: MTNR1B; NbExp=3; IntAct=EBI-994141, EBI-1188341; CC P28335; Q9NUM3: SLC39A9; NbExp=3; IntAct=EBI-994141, EBI-2823239; CC P28335; P55061: TMBIM6; NbExp=3; IntAct=EBI-994141, EBI-1045825; CC P28335; Q9BVK8: TMEM147; NbExp=4; IntAct=EBI-994141, EBI-348587; CC P28335-1; P28223-1: HTR2A; NbExp=3; IntAct=EBI-21299643, EBI-15573967; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12970106, CC ECO:0000269|PubMed:18703043, ECO:0000269|PubMed:19057895, CC ECO:0000269|PubMed:7895773}; Multi-pass membrane protein CC {ECO:0000269|PubMed:12970106, ECO:0000269|PubMed:18703043, CC ECO:0000269|PubMed:19057895, ECO:0000269|PubMed:7895773}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P28335-1; Sequence=Displayed; CC Name=2; CC IsoId=P28335-2; Sequence=VSP_045171; CC -!- TISSUE SPECIFICITY: Detected in brain. {ECO:0000269|PubMed:8812491}. CC -!- DOMAIN: The PDZ domain-binding motif is involved in the interaction CC with MPDZ. {ECO:0000269|PubMed:11150294}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:11150294}. CC -!- RNA EDITING: Modified_positions=156 {ECO:0000269|PubMed:9928237}, 158 CC {ECO:0000269|PubMed:9928237}, 160 {ECO:0000269|PubMed:9928237}; CC Note=Partially edited. RNA editing generates receptor isoforms that CC differ in their ability to interact with the phospholipase C signaling CC cascade in a transfected cell line, suggesting that this RNA processing CC event may contribute to the modulation of serotonergic CC neurotransmission in the central nervous system.; CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M81778; AAA60317.1; -; mRNA. DR EMBL; X80763; CAB59978.1; -; Genomic_DNA. DR EMBL; U49516; AAB40898.1; -; mRNA. DR EMBL; AF208053; AAF35842.1; -; mRNA. DR EMBL; AF498983; AAM21130.1; -; mRNA. DR EMBL; AK295753; BAG58583.1; -; mRNA. DR EMBL; AC233299; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL590097; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL355812; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC095543; AAH95543.1; -; mRNA. DR CCDS; CCDS14564.1; -. [P28335-1] DR CCDS; CCDS59174.1; -. [P28335-2] DR PIR; JS0616; JS0616. DR RefSeq; NP_000859.1; NM_000868.3. [P28335-1] DR RefSeq; NP_001243689.1; NM_001256760.2. [P28335-1] DR RefSeq; NP_001243690.1; NM_001256761.2. [P28335-2] DR PDB; 6BQG; X-ray; 3.00 A; A=40-245, A=301-393. DR PDB; 6BQH; X-ray; 2.70 A; A=40-245, A=301-393. DR PDB; 8DPF; EM; 2.84 A; A=1-458. DR PDB; 8DPG; EM; 3.60 A; A=1-458. DR PDB; 8DPH; EM; 3.20 A; A=1-458. DR PDB; 8DPI; EM; 3.40 A; A=1-458. DR PDBsum; 6BQG; -. DR PDBsum; 6BQH; -. DR PDBsum; 8DPF; -. DR PDBsum; 8DPG; -. DR PDBsum; 8DPH; -. DR PDBsum; 8DPI; -. DR AlphaFoldDB; P28335; -. DR EMDB; EMD-27633; -. DR EMDB; EMD-27634; -. DR EMDB; EMD-27635; -. DR EMDB; EMD-27636; -. DR SMR; P28335; -. DR BioGRID; 109590; 139. DR IntAct; P28335; 119. DR MINT; P28335; -. DR STRING; 9606.ENSP00000276198; -. DR BindingDB; P28335; -. DR ChEMBL; CHEMBL225; -. DR DrugBank; DB13940; 2,5-Dimethoxy-4-ethylthioamphetamine. DR DrugBank; DB01537; 4-Bromo-2,5-dimethoxyphenethylamine. DR DrugBank; DB06594; Agomelatine. DR DrugBank; DB00321; Amitriptyline. DR DrugBank; DB00543; Amoxapine. DR DrugBank; DB00714; Apomorphine. DR DrugBank; DB01238; Aripiprazole. DR DrugBank; DB14185; Aripiprazole lauroxil. DR DrugBank; DB06216; Asenapine. DR DrugBank; DB01200; Bromocriptine. DR DrugBank; DB00248; Cabergoline. DR DrugBank; DB09014; Captodiame. DR DrugBank; DB06016; Cariprazine. DR DrugBank; DB00477; Chlorpromazine. DR DrugBank; DB01239; Chlorprothixene. DR DrugBank; DB01242; Clomipramine. DR DrugBank; DB00363; Clozapine. DR DrugBank; DB00924; Cyclobenzaprine. DR DrugBank; DB00434; Cyproheptadine. DR DrugBank; DB04884; Dapoxetine. DR DrugBank; DB06512; Deramciclane. DR DrugBank; DB01151; Desipramine. DR DrugBank; DB01191; Dexfenfluramine. DR DrugBank; DB11273; Dihydroergocornine. DR DrugBank; DB13345; Dihydroergocristine. DR DrugBank; DB00320; Dihydroergotamine. DR DrugBank; DB06446; Dotarizine. DR DrugBank; DB01142; Doxepin. DR DrugBank; DB05492; Epicept NP-1. DR DrugBank; DB12177; Eplivanserin. DR DrugBank; DB01049; Ergoloid mesylate. DR DrugBank; DB00696; Ergotamine. DR DrugBank; DB01175; Escitalopram. DR DrugBank; DB06678; Esmirtazapine. DR DrugBank; DB09194; Etoperidone. DR DrugBank; DB00574; Fenfluramine. DR DrugBank; DB00472; Fluoxetine. DR DrugBank; DB00875; Flupentixol. DR DrugBank; DB00623; Fluphenazine. DR DrugBank; DB12141; Gilteritinib. DR DrugBank; DB00502; Haloperidol. DR DrugBank; DB00458; Imipramine. DR DrugBank; DB01221; Ketamine. DR DrugBank; DB00589; Lisuride. DR DrugBank; DB04948; Lofexidine. DR DrugBank; DB04871; Lorcaserin. DR DrugBank; DB09195; Lorpiprazole. DR DrugBank; DB00408; Loxapine. DR DrugBank; DB12110; m-Chlorophenylpiperazine. DR DrugBank; DB00934; Maprotiline. DR DrugBank; DB01403; Methotrimeprazine. DR DrugBank; DB00247; Methysergide. DR DrugBank; DB06148; Mianserin. DR DrugBank; DB01454; Midomafetamine. DR DrugBank; DB00805; Minaprine. DR DrugBank; DB00370; Mirtazapine. DR DrugBank; DB08804; Nandrolone decanoate. DR DrugBank; DB01149; Nefazodone. DR DrugBank; DB00540; Nortriptyline. DR DrugBank; DB06229; Ocaperidone. DR DrugBank; DB00334; Olanzapine. DR DrugBank; DB01267; Paliperidone. DR DrugBank; DB00715; Paroxetine. DR DrugBank; DB01186; Pergolide. DR DrugBank; DB05316; Pimavanserin. DR DrugBank; DB06153; Pizotifen. DR DrugBank; DB00420; Promazine. DR DrugBank; DB00777; Propiomazine. DR DrugBank; DB01224; Quetiapine. DR DrugBank; DB00734; Risperidone. DR DrugBank; DB12163; Sarpogrelate. DR DrugBank; DB06144; Sertindole. DR DrugBank; DB09304; Setiptiline. DR DrugBank; DB01079; Tegaserod. DR DrugBank; DB13025; Tiapride. DR DrugBank; DB00193; Tramadol. DR DrugBank; DB00656; Trazodone. DR DrugBank; DB00726; Trimipramine. DR DrugBank; DB09185; Viloxazine. DR DrugBank; DB01392; Yohimbine. DR DrugBank; DB00246; Ziprasidone. DR DrugCentral; P28335; -. DR GuidetoPHARMACOLOGY; 8; -. DR GlyCosmos; P28335; 1 site, No reported glycans. DR GlyGen; P28335; 2 sites. DR iPTMnet; P28335; -. DR PhosphoSitePlus; P28335; -. DR BioMuta; HTR2C; -. DR DMDM; 112816; -. DR MassIVE; P28335; -. DR PaxDb; 9606-ENSP00000276198; -. DR PeptideAtlas; P28335; -. DR Antibodypedia; 527; 545 antibodies from 37 providers. DR DNASU; 3358; -. DR Ensembl; ENST00000276198.6; ENSP00000276198.1; ENSG00000147246.10. [P28335-1] DR Ensembl; ENST00000371950.3; ENSP00000361018.3; ENSG00000147246.10. [P28335-2] DR Ensembl; ENST00000371951.5; ENSP00000361019.1; ENSG00000147246.10. [P28335-1] DR GeneID; 3358; -. DR KEGG; hsa:3358; -. DR MANE-Select; ENST00000276198.6; ENSP00000276198.1; NM_000868.4; NP_000859.2. DR UCSC; uc004epu.1; human. [P28335-1] DR AGR; HGNC:5295; -. DR CTD; 3358; -. DR DisGeNET; 3358; -. DR GeneCards; HTR2C; -. DR HGNC; HGNC:5295; HTR2C. DR HPA; ENSG00000147246; Group enriched (brain, choroid plexus). DR MIM; 312861; gene. DR neXtProt; NX_P28335; -. DR OpenTargets; ENSG00000147246; -. DR PharmGKB; PA194; -. DR VEuPathDB; HostDB:ENSG00000147246; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT01050000244937; -. DR HOGENOM; CLU_009579_11_3_1; -. DR InParanoid; P28335; -. DR OMA; KEPGIEM; -. DR PhylomeDB; P28335; -. DR TreeFam; TF316350; -. DR PathwayCommons; P28335; -. DR Reactome; R-HSA-390666; Serotonin receptors. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR SignaLink; P28335; -. DR SIGNOR; P28335; -. DR BioGRID-ORCS; 3358; 12 hits in 777 CRISPR screens. DR ChiTaRS; HTR2C; human. DR GeneWiki; 5-HT2C_receptor; -. DR GenomeRNAi; 3358; -. DR Pharos; P28335; Tclin. DR PRO; PR:P28335; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; P28335; Protein. DR Bgee; ENSG00000147246; Expressed in choroid plexus epithelium and 55 other cell types or tissues. DR GO; GO:0030425; C:dendrite; IBA:GO_Central. DR GO; GO:0098666; C:G protein-coupled serotonin receptor complex; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; IEA:GOC. DR GO; GO:0071886; F:1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding; IDA:UniProtKB. DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IDA:UniProtKB. DR GO; GO:0001587; F:Gq/11-coupled serotonin receptor activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central. DR GO; GO:0051378; F:serotonin binding; IDA:UniProtKB. DR GO; GO:0001662; P:behavioral fear response; ISS:UniProtKB. DR GO; GO:0019934; P:cGMP-mediated signaling; IDA:UniProtKB. DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central. DR GO; GO:0007631; P:feeding behavior; ISS: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; IDA:UniProtKB. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IDA:UniProtKB. DR GO; GO:0007626; P:locomotory behavior; IEA:InterPro. DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0007208; P:phospholipase C-activating serotonin receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IEA:Ensembl. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IEA:Ensembl. DR GO; GO:0010513; P:positive regulation of phosphatidylinositol biosynthetic process; IDA:UniProtKB. 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:0051209; P:release of sequestered calcium ion into cytosol; IMP:UniProtKB. DR CDD; cd15305; 7tmA_5-HT2C; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR000377; 5HT2C_rcpt. DR InterPro; IPR002231; 5HT_rcpt. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR24247; 5-HYDROXYTRYPTAMINE RECEPTOR; 1. DR PANTHER; PTHR24247:SF32; 5-HYDROXYTRYPTAMINE RECEPTOR 2C; 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 SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; P28335; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Behavior; Cell membrane; KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane; KW Receptor; Reference proteome; RNA editing; Signal; Transducer; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..32 FT /evidence="ECO:0000269|PubMed:22497996" FT CHAIN 33..458 FT /note="5-hydroxytryptamine receptor 2C" FT /id="PRO_0000068958" FT TOPO_DOM 33..52 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 53..78 FT /note="Helical; Name=1" FT /evidence="ECO:0000250" FT TOPO_DOM 79..89 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 90..110 FT /note="Helical; Name=2" FT /evidence="ECO:0000250" FT TOPO_DOM 111..127 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 128..150 FT /note="Helical; Name=3" FT /evidence="ECO:0000250" FT TOPO_DOM 151..170 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 171..193 FT /note="Helical; Name=4" FT /evidence="ECO:0000250" FT TOPO_DOM 194..213 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 214..235 FT /note="Helical; Name=5" FT /evidence="ECO:0000250" FT TOPO_DOM 236..311 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 312..333 FT /note="Helical; Name=6" FT /evidence="ECO:0000250" FT TOPO_DOM 334..348 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 349..371 FT /note="Helical; Name=7" FT /evidence="ECO:0000250" FT TOPO_DOM 372..458 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT REGION 274..301 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 151..153 FT /note="DRY motif; important for ligand-induced conformation FT changes" FT /evidence="ECO:0000250" FT MOTIF 364..368 FT /note="NPxxY motif; important for ligand-induced FT conformation changes and signaling" FT /evidence="ECO:0000250" FT MOTIF 456..458 FT /note="PDZ-binding" FT BINDING 134 FT /ligand="ergotamine" FT /ligand_id="ChEBI:CHEBI:190463" FT /ligand_note="agonist" FT /evidence="ECO:0000250|UniProtKB:P41595" FT BINDING 139 FT /ligand="ergotamine" FT /ligand_id="ChEBI:CHEBI:190463" FT /ligand_note="agonist" FT /evidence="ECO:0000250|UniProtKB:P41595" FT BINDING 209 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:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 204 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT DISULFID 127..207 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT DISULFID 337..341 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT VAR_SEQ 153..458 FT /note="YVAIRNPIEHSRFNSRTKAIMKIAIVWAISIGVSVPIPVIGLRDEEKVFVNN FT TTCVLNDPNFVLIGSFVAFFIPLTIMVITYCLTIYVLRRQALMLLHGHTEEPPGLSLDF FT LKCCKRNTAEEENSANPNQDQNARRRKKKERRPRGTMQAINNERKASKVLGIVFFVFLI FT MWCPFFITNILSVLCEKSCNQKLMEKLLNVFVWIGYVCSGINPLVYTLFNKIYRRAFSN FT YLRCNYKVEKKPPVRQIPRVAATALSGRELNVNIYRHTNEPVIEKASDNEPGIEMQVEN FT LELPVNPSSVVSERISSV -> CISSYPCDWTEGRRKGVREQHDVRAQRPKFRSYWVLR FT SFLHTADDYGDYVLPDHLRSAPTSFDVTARPHRGTAWTKSGFPEVLQEEYGRGRELCKP FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045171" FT VARIANT 23 FT /note="S -> C (in dbSNP:rs6318)" FT /evidence="ECO:0000269|PubMed:10206230, FT ECO:0000269|PubMed:10391209, ECO:0000269|PubMed:10581480, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:1722404, FT ECO:0000269|PubMed:22497996, ECO:0000269|PubMed:7557992, FT ECO:0000269|PubMed:7895773, ECO:0000269|PubMed:8812491, FT ECO:0000269|PubMed:9928237, ECO:0000269|Ref.5" FT /id="VAR_003450" FT VARIANT 156 FT /note="I -> V (in RNA edited version)" FT /id="VAR_010166" FT VARIANT 158 FT /note="N -> S (in RNA edited version)" FT /id="VAR_010167" FT VARIANT 160 FT /note="I -> V (in RNA edited version; dbSNP:rs781938388)" FT /id="VAR_010168" FT MUTAGEN 159 FT /note="P->A: Decreases interaction with ARRB2." FT /evidence="ECO:0000269|PubMed:16319069" FT MUTAGEN 456 FT /note="S->A: Loss of interaction with MPDZ." FT /evidence="ECO:0000269|PubMed:11150294" FT MUTAGEN 456 FT /note="S->T: No effect on interaction with MPDZ." FT /evidence="ECO:0000269|PubMed:11150294" FT MUTAGEN 457 FT /note="S->A: No effect on interaction with MPDZ." FT /evidence="ECO:0000269|PubMed:11150294" FT MUTAGEN 458 FT /note="V->A: Loss of interaction with MPDZ." FT /evidence="ECO:0000269|PubMed:11150294" FT TURN 48..50 FT /evidence="ECO:0007829|PDB:6BQG" FT HELIX 56..60 FT /evidence="ECO:0007829|PDB:6BQH" FT HELIX 61..80 FT /evidence="ECO:0007829|PDB:6BQH" FT HELIX 82..84 FT /evidence="ECO:0007829|PDB:6BQH" FT HELIX 87..105 FT /evidence="ECO:0007829|PDB:6BQH" FT HELIX 107..115 FT /evidence="ECO:0007829|PDB:6BQH" FT TURN 116..118 FT /evidence="ECO:0007829|PDB:6BQH" FT HELIX 126..154 FT /evidence="ECO:0007829|PDB:6BQH" FT HELIX 159..165 FT /evidence="ECO:0007829|PDB:8DPF" FT HELIX 167..186 FT /evidence="ECO:0007829|PDB:6BQH" FT HELIX 188..195 FT /evidence="ECO:0007829|PDB:6BQH" FT HELIX 197..199 FT /evidence="ECO:0007829|PDB:6BQH" FT STRAND 200..202 FT /evidence="ECO:0007829|PDB:6BQH" FT TURN 203..205 FT /evidence="ECO:0007829|PDB:6BQH" FT HELIX 212..222 FT /evidence="ECO:0007829|PDB:6BQH" FT HELIX 224..245 FT /evidence="ECO:0007829|PDB:6BQH" FT HELIX 301..335 FT /evidence="ECO:0007829|PDB:6BQH" FT STRAND 338..341 FT /evidence="ECO:0007829|PDB:6BQH" FT HELIX 343..371 FT /evidence="ECO:0007829|PDB:6BQH" FT HELIX 373..385 FT /evidence="ECO:0007829|PDB:6BQH" SQ SEQUENCE 458 AA; 51805 MW; 0622E8F8AE55696D CRC64; MVNLRNAVHS FLVHLIGLLV WQSDISVSPV AAIVTDIFNT SDGGRFKFPD GVQNWPALSI VIIIIMTIGG NILVIMAVSM EKKLHNATNY FLMSLAIADM LVGLLVMPLS LLAILYDYVW PLPRYLCPVW ISLDVLFSTA SIMHLCAISL DRYVAIRNPI EHSRFNSRTK AIMKIAIVWA ISIGVSVPIP VIGLRDEEKV FVNNTTCVLN DPNFVLIGSF VAFFIPLTIM VITYCLTIYV LRRQALMLLH GHTEEPPGLS LDFLKCCKRN TAEEENSANP NQDQNARRRK KKERRPRGTM QAINNERKAS KVLGIVFFVF LIMWCPFFIT NILSVLCEKS CNQKLMEKLL NVFVWIGYVC SGINPLVYTL FNKIYRRAFS NYLRCNYKVE KKPPVRQIPR VAATALSGRE LNVNIYRHTN EPVIEKASDN EPGIEMQVEN LELPVNPSSV VSERISSV //