5HT2C_HUMAN
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 03-AUG-2022, entry version 216.
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=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 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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
RP VARIANT CYS-23.
RX PubMed=10206230;
RX DOI=10.1002/(sici)1096-8628(19990416)88:2<126::aid-ajmg6>3.0.co;2-m;
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 [18]
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 [19]
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 [20]
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. Interacts with ARRB2.
CC {ECO:0000269|PubMed:11150294, ECO:0000269|PubMed:16319069}.
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}.
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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 PDBsum; 6BQG; -.
DR PDBsum; 6BQH; -.
DR AlphaFoldDB; 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; 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; DB01392; Yohimbine.
DR DrugBank; DB00246; Ziprasidone.
DR DrugCentral; P28335; -.
DR GuidetoPHARMACOLOGY; 8; -.
DR GlyGen; P28335; 1 site.
DR iPTMnet; P28335; -.
DR PhosphoSitePlus; P28335; -.
DR BioMuta; HTR2C; -.
DR DMDM; 112816; -.
DR MassIVE; P28335; -.
DR PaxDb; P28335; -.
DR PeptideAtlas; P28335; -.
DR PRIDE; P28335; -.
DR Antibodypedia; 527; 504 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 CTD; 3358; -.
DR DisGeNET; 3358; -.
DR GeneCards; HTR2C; -.
DR HGNC; HGNC:5295; HTR2C.
DR HPA; ENSG00000147246; Tissue enriched (choroid).
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 OrthoDB; 962038at2759; -.
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 697 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 tissues.
DR Genevisible; P28335; HS.
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:0005887; C:integral component of plasma membrane; IMP: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:0006874; P:cellular calcium ion homeostasis; IDA: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:0007626; P:locomotory behavior; IEA:InterPro.
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:UniProtKB.
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; 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 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; 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:0000305|PubMed:11150294"
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 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
