ID 5HT2B_HUMAN Reviewed; 481 AA. AC P41595; B2R9D5; Q53TI1; Q62221; Q6P523; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 27-MAR-2024, entry version 210. DE RecName: Full=5-hydroxytryptamine receptor 2B; DE Short=5-HT-2B; DE Short=5-HT2B; DE AltName: Full=Serotonin receptor 2B; GN Name=HTR2B; 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], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=8143856; DOI=10.1016/0014-5793(94)80590-3; RA Schmuck K., Ullmer C., Engels P., Luebbert H.; RT "Cloning and functional characterization of the human 5-HT2B serotonin RT receptor."; RL FEBS Lett. 342:85-90(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Brain; RX PubMed=7926008; DOI=10.1016/0014-5793(94)00968-6; RA Choi D.S., Birraux G., Launay J.-M., Maroteaux L.; RT "The human serotonin 5-HT2B receptor: pharmacological link between 5-HT2 RT and 5-HT1D receptors."; RL FEBS Lett. 352:393-399(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Uterus; RX PubMed=8078486; RA Kursar J.D., Nelson D.L., Wainscott D.B., Baez M.; RT "Molecular cloning, functional expression, and mRNA tissue distribution of RT the human 5-hydroxytryptamine2B receptor."; RL Mol. Pharmacol. 46:227-234(1994). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10722792; DOI=10.1006/mcpr.1999.0281; RA Kim S.J., Veenstra-VanderWeele J., Hanna G.L., Gonen D., Leventhal B.L., RA Cook E.H. Jr.; RT "Mutation screening of human 5-HT(2B) receptor gene in early-onset RT obsessive-compulsive disorder."; RL Mol. Cell. Probes 14:47-52(2000). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Colon; 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 (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin; 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 [10] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=8882600; DOI=10.1111/j.1476-5381.1996.tb16700.x; RA Ullmer C., Boddeke H.G., Schmuck K., Lubbert H.; RT "5-HT2B receptor-mediated calcium release from ryanodine-sensitive RT intracellular stores in human pulmonary artery endothelial cells."; RL Br. J. Pharmacol. 117:1081-1088(1996). RN [11] RP INTERACTION WITH MPDZ. 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 [12] 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 [13] RP REVIEW. RX PubMed=18476671; DOI=10.1021/cr078224o; RA Nichols D.E., Nichols C.D.; RT "Serotonin receptors."; RL Chem. Rev. 108:1614-1641(2008). RN [14] RP FUNCTION. 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, INVOLVEMENT IN IMPULSIVE BEHAVIOR, TISSUE SPECIFICITY, RP POLYMORPHISM, AND VARIANTS GLU-45; LEU-173 AND TRP-388. RX PubMed=21179162; DOI=10.1038/nature09629; RA Bevilacqua L., Doly S., Kaprio J., Yuan Q., Tikkanen R., Paunio T., RA Zhou Z., Wedenoja J., Maroteaux L., Diaz S., Belmer A., Hodgkinson C.A., RA Dell'osso L., Suvisaari J., Coccaro E., Rose R.J., Peltonen L., RA Virkkunen M., Goldman D.; RT "A population-specific HTR2B stop codon predisposes to severe RT impulsivity."; RL Nature 468:1061-1066(2010). 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 FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-132; ASP-135; RP VAL-136; SER-139; THR-140; VAL-208; LEU-209; LYS-211; PHE-217; MET-218; RP ALA-225; TRP-337; PHE-340; ASN-344; LEU-347; VAL-348; LEU-362; GLU-363; RP VAL-366 AND TYR-370. RX PubMed=23519210; DOI=10.1126/science.1232807; RA Wang C., Jiang Y., Ma J., Wu H., Wacker D., Katritch V., Han G.W., Liu W., RA Huang X.P., Vardy E., McCorvy J.D., Gao X., Zhou X.E., Melcher K., RA Zhang C., Bai F., Yang H., Yang L., Jiang H., Roth B.L., Cherezov V., RA Stevens R.C., Xu H.E.; RT "Structural basis for molecular recognition at serotonin receptors."; RL Science 340:610-614(2013). RN [18] {ECO:0007744|PDB:4IB4} RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 36-248 AND 314-405 IN COMPLEX WITH RP THE AGONIST ERGOTAMINE, FUNCTION, ROLE IN ARRESTIN-MEDIATED SIGNALING AND RP CALCIUM RELEASE, SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY, AND DISULFIDE RP BONDS. RX PubMed=23519215; DOI=10.1126/science.1232808; RA Wacker D., Wang C., Katritch V., Han G.W., Huang X.P., Vardy E., RA McCorvy J.D., Jiang Y., Chu M., Siu F.Y., Liu W., Xu H.E., Cherezov V., RA Roth B.L., Stevens R.C.; RT "Structural features for functional selectivity at serotonin receptors."; RL Science 340:615-619(2013). RN [19] {ECO:0007744|PDB:4NC3} RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 36-248 AND 314-405 IN COMPLEX RP WITH ERGOTAMINE, FUNCTION, DISULFIDE BONDS, AND TOPOLOGY. RX PubMed=24357322; DOI=10.1126/science.1244142; RA Liu W., Wacker D., Gati C., Han G.W., James D., Wang D., Nelson G., RA Weierstall U., Katritch V., Barty A., Zatsepin N.A., Li D., RA Messerschmidt M., Boutet S., Williams G.J., Koglin J.E., Seibert M.M., RA Wang C., Shah S.T., Basu S., Fromme R., Kupitz C., Rendek K.N., RA Grotjohann I., Fromme P., Kirian R.A., Beyerlein K.R., White T.A., RA Chapman H.N., Caffrey M., Spence J.C., Stevens R.C., Cherezov V.; RT "Serial femtosecond crystallography of G protein-coupled receptors."; RL Science 342:1521-1524(2013). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 41-248 AND 314-400 IN COMPLEX RP WITH LYSERGIC ACID DIETHYLAMIDE, FUNCTION, DISULFIDE BONDS, SUBCELLULAR RP LOCATION, TOPOLOGY, AND MUTAGENESIS OF LEU-209. RX PubMed=28129538; DOI=10.1016/j.cell.2016.12.033; RA Wacker D., Wang S., McCorvy J.D., Betz R.M., Venkatakrishnan A.J., RA Levit A., Lansu K., Schools Z.L., Che T., Nichols D.E., Shoichet B.K., RA Dror R.O., Roth B.L.; RT "Crystal structure of an LSD-bound human serotonin receptor."; RL Cell 168:377-389(2017). CC -!- FUNCTION: G-protein coupled receptor for 5-hydroxytryptamine CC (serotonin) (PubMed:8143856, PubMed:7926008, PubMed:8078486, CC PubMed:8882600, PubMed:18703043, PubMed:23519210). Also functions as a CC receptor for various ergot alkaloid derivatives and psychoactive CC substances (PubMed:8143856, PubMed:7926008, PubMed:8078486, CC PubMed:12970106, PubMed:18703043, PubMed:23519210, PubMed:23519215, CC PubMed:24357322, PubMed:28129538). Ligand binding causes a conformation CC change that triggers signaling via guanine nucleotide-binding proteins CC (G proteins) and modulates the activity of down-stream effectors CC (PubMed:8143856, PubMed:8078486, PubMed:8882600, PubMed:23519215, CC PubMed:28129538). Beta-arrestin family members inhibit signaling via G CC proteins and mediate activation of alternative signaling pathways CC (PubMed:23519215, PubMed:28129538). 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 (PubMed:8143856, PubMed:8078486, PubMed:8882600, CC PubMed:18703043, PubMed:23519215, PubMed:28129538). Plays a role in the CC regulation of dopamine and 5-hydroxytryptamine release, 5- CC hydroxytryptamine uptake and in the regulation of extracellular CC dopamine and 5-hydroxytryptamine levels, and thereby affects neural CC activity. May play a role in the perception of pain (By similarity). CC Plays a role in the regulation of behavior, including impulsive CC behavior (PubMed:21179162). Required for normal proliferation of CC embryonic cardiac myocytes and normal heart development. Protects CC cardiomyocytes against apoptosis. Plays a role in the adaptation of CC pulmonary arteries to chronic hypoxia. Plays a role in CC vasoconstriction. Required for normal osteoblast function and CC proliferation, and for maintaining normal bone density. Required for CC normal proliferation of the interstitial cells of Cajal in the CC intestine (By similarity). {ECO:0000250|UniProtKB:P30994, CC ECO:0000250|UniProtKB:Q02152, ECO:0000269|PubMed:12970106, CC ECO:0000269|PubMed:18703043, ECO:0000269|PubMed:21179162, CC ECO:0000269|PubMed:23519210, ECO:0000269|PubMed:23519215, CC ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538, CC ECO:0000269|PubMed:7926008, ECO:0000269|PubMed:8078486, CC ECO:0000269|PubMed:8143856, ECO:0000269|PubMed:8882600}. CC -!- SUBUNIT: Interacts (via C-terminus) with MPDZ. CC {ECO:0000269|PubMed:11150294}. CC -!- INTERACTION: CC P41595; P28223: HTR2A; NbExp=3; IntAct=EBI-7474947, EBI-6656333; CC P41595; P28335: HTR2C; NbExp=4; IntAct=EBI-7474947, EBI-994141; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12970106, CC ECO:0000269|PubMed:23519210, ECO:0000269|PubMed:23519215, CC ECO:0000269|PubMed:28129538, ECO:0000269|PubMed:7926008, CC ECO:0000269|PubMed:8078486, ECO:0000269|PubMed:8143856}; Multi-pass CC membrane protein {ECO:0000269|PubMed:23519215, CC ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538}. Synapse, CC synaptosome {ECO:0000250|UniProtKB:Q02152}. CC -!- TISSUE SPECIFICITY: Ubiquitous. Detected in liver, kidney, heart, CC pulmonary artery, and intestine. Detected at lower levels in blood, CC placenta and brain, especially in cerebellum, occipital cortex and CC frontal cortex. {ECO:0000269|PubMed:21179162, CC ECO:0000269|PubMed:7926008, ECO:0000269|PubMed:8078486, CC ECO:0000269|PubMed:8143856, ECO:0000269|PubMed:8882600}. CC -!- DOMAIN: Ligands are bound in a hydrophobic pocket formed by the CC transmembrane helices. {ECO:0000269|PubMed:23519215, CC ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538}. CC -!- POLYMORPHISM: A variation at a single nucleotide base, which results in CC an erroneous stop codon and affects Gln-20, triggers non-sense mediated CC RNA decay, such that no HTR2B-receptor protein is expressed. It is CC associated with impulsive behavior and co-segregates with disorders CC characterized by impulsivity. However, the presence of this variant is CC not in itself sufficient to cause impulsive behavior: male sex, CC testosterone level, alcohol and stress exposure are other factors CC playing important roles. {ECO:0000269|PubMed:21179162}. CC -!- MISCELLANEOUS: Binds lysergic acid diethylamine (LSD) in the CC orthosteric pocket, but is not the principal LSD receptor in the brain. CC Bound LSD dissociates extremely slowly, with a residence time of about CC 46 minutes at 37 degrees Celsius. {ECO:0000269|PubMed:28129538}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=On the spur of a whim CC - Issue 127 of March 2011; CC URL="https://web.expasy.org/spotlight/back_issues/127"; 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; X77307; CAA54513.1; -; mRNA. DR EMBL; Z36748; CAA85319.1; -; mRNA. DR EMBL; AF156160; AAD39259.1; -; Genomic_DNA. DR EMBL; AF156158; AAD39259.1; JOINED; Genomic_DNA. DR EMBL; AF156159; AAD39259.1; JOINED; Genomic_DNA. DR EMBL; AY136751; AAN01277.1; -; mRNA. DR EMBL; AC009407; AAX93128.1; -; Genomic_DNA. DR EMBL; AK313741; BAG36482.1; -; mRNA. DR EMBL; CH471063; EAW70949.1; -; Genomic_DNA. DR EMBL; BC063123; AAH63123.1; -; mRNA. DR CCDS; CCDS2483.1; -. DR PIR; S43687; S43687. DR PIR; S49442; S49442. DR RefSeq; NP_000858.3; NM_000867.4. DR RefSeq; NP_001307687.1; NM_001320758.1. DR PDB; 4IB4; X-ray; 2.70 A; A=36-248, A=314-405. DR PDB; 4NC3; X-ray; 2.80 A; A=36-248, A=314-405. DR PDB; 5TUD; X-ray; 3.00 A; A/D=36-248, A/D=314-405. DR PDB; 5TVN; X-ray; 2.90 A; A=41-248, A=313-400. DR PDB; 6DRX; X-ray; 3.10 A; A=36-248, A=314-404. DR PDB; 6DRY; X-ray; 2.92 A; A=36-248, A=313-404. DR PDB; 6DRZ; X-ray; 3.10 A; A=36-248, A=313-404. DR PDB; 6DS0; X-ray; 3.19 A; A=36-248, A=314-404. DR PDB; 7SRQ; EM; 2.70 A; R=36-405. DR PDB; 7SRR; EM; 2.90 A; R=36-405. DR PDB; 7SRS; EM; 3.30 A; R=36-464. DR PDBsum; 4IB4; -. DR PDBsum; 4NC3; -. DR PDBsum; 5TUD; -. DR PDBsum; 5TVN; -. DR PDBsum; 6DRX; -. DR PDBsum; 6DRY; -. DR PDBsum; 6DRZ; -. DR PDBsum; 6DS0; -. DR PDBsum; 7SRQ; -. DR PDBsum; 7SRR; -. DR PDBsum; 7SRS; -. DR AlphaFoldDB; P41595; -. DR EMDB; EMD-25401; -. DR EMDB; EMD-25402; -. DR EMDB; EMD-25403; -. DR SMR; P41595; -. DR BioGRID; 109589; 27. DR IntAct; P41595; 28. DR MINT; P41595; -. DR STRING; 9606.ENSP00000258400; -. DR BindingDB; P41595; -. DR ChEMBL; CHEMBL1833; -. DR DrugBank; DB00543; Amoxapine. DR DrugBank; DB00714; Apomorphine. DR DrugBank; DB01238; Aripiprazole. DR DrugBank; DB06216; Asenapine. DR DrugBank; DB01200; Bromocriptine. DR DrugBank; DB00248; Cabergoline. DR DrugBank; DB06016; Cariprazine. DR DrugBank; DB00477; Chlorpromazine. DR DrugBank; DB01239; Chlorprothixene. DR DrugBank; DB01242; Clomipramine. DR DrugBank; DB00924; Cyclobenzaprine. DR DrugBank; DB00434; Cyproheptadine. DR DrugBank; DB11273; Dihydroergocornine. DR DrugBank; DB13345; Dihydroergocristine. DR DrugBank; DB00320; Dihydroergotamine. DR DrugBank; DB01142; Doxepin. DR DrugBank; DB05492; Epicept NP-1. DR DrugBank; DB01049; Ergoloid mesylate. DR DrugBank; DB00696; Ergotamine. DR DrugBank; DB06678; Esmirtazapine. DR DrugBank; DB00574; Fenfluramine. DR DrugBank; DB12141; Gilteritinib. DR DrugBank; DB01221; Ketamine. DR DrugBank; DB00589; Lisuride. DR DrugBank; DB04829; Lysergic acid diethylamide. DR DrugBank; DB00353; Methylergometrine. DR DrugBank; DB00247; Methysergide. DR DrugBank; DB06148; Mianserin. DR DrugBank; DB01454; Midomafetamine. DR DrugBank; DB00805; Minaprine. DR DrugBank; DB08804; Nandrolone decanoate. DR DrugBank; DB06229; Ocaperidone. DR DrugBank; DB05461; OPC-28326. DR DrugBank; DB00715; Paroxetine. DR DrugBank; DB01186; Pergolide. DR DrugBank; DB09286; Pipamperone. DR DrugBank; DB06153; Pizotifen. DR DrugBank; DB05607; PRX-08066. DR DrugBank; DB09304; Setiptiline. DR DrugBank; DB01079; Tegaserod. DR DrugBank; DB13025; Tiapride. DR DrugBank; DB00508; Triflupromazine. DR DrugBank; DB09185; Viloxazine. DR DrugBank; DB01392; Yohimbine. DR DrugBank; DB00315; Zolmitriptan. DR DrugCentral; P41595; -. DR GuidetoPHARMACOLOGY; 7; -. DR TCDB; 9.A.14.3.7; the g-protein-coupled receptor (gpcr) family. DR GlyCosmos; P41595; 1 site, No reported glycans. DR GlyGen; P41595; 1 site. DR iPTMnet; P41595; -. DR PhosphoSitePlus; P41595; -. DR BioMuta; HTR2B; -. DR DMDM; 1168220; -. DR MassIVE; P41595; -. DR PaxDb; 9606-ENSP00000258400; -. DR ABCD; P41595; 1 sequenced antibody. DR Antibodypedia; 2921; 448 antibodies from 33 providers. DR DNASU; 3357; -. DR Ensembl; ENST00000258400.4; ENSP00000258400.3; ENSG00000135914.6. DR GeneID; 3357; -. DR KEGG; hsa:3357; -. DR MANE-Select; ENST00000258400.4; ENSP00000258400.3; NM_000867.5; NP_000858.3. DR UCSC; uc002vro.4; human. DR AGR; HGNC:5294; -. DR CTD; 3357; -. DR DisGeNET; 3357; -. DR GeneCards; HTR2B; -. DR HGNC; HGNC:5294; HTR2B. DR HPA; ENSG00000135914; Tissue enhanced (adrenal gland, cervix, endometrium, smooth muscle). DR MIM; 601122; gene. DR neXtProt; NX_P41595; -. DR OpenTargets; ENSG00000135914; -. DR PharmGKB; PA29554; -. DR VEuPathDB; HostDB:ENSG00000135914; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT01050000244937; -. DR HOGENOM; CLU_009579_11_3_1; -. DR InParanoid; P41595; -. DR OMA; CPVWLFL; -. DR OrthoDB; 2880253at2759; -. DR PhylomeDB; P41595; -. DR TreeFam; TF316350; -. DR PathwayCommons; P41595; -. DR Reactome; R-HSA-390666; Serotonin receptors. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR SignaLink; P41595; -. DR SIGNOR; P41595; -. DR BioGRID-ORCS; 3357; 16 hits in 1157 CRISPR screens. DR GeneWiki; 5-HT2B_receptor; -. DR GenomeRNAi; 3357; -. DR Pharos; P41595; Tclin. DR PRO; PR:P41595; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P41595; Protein. DR Bgee; ENSG00000135914; Expressed in decidua and 111 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. 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:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell. DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IDA:UniProtKB. DR GO; GO:0001965; F:G-protein alpha-subunit binding; IMP:UniProtKB. DR GO; GO:0001587; F:Gq/11-coupled serotonin receptor activity; IDA:UniProtKB. DR GO; GO:0005096; F:GTPase activator activity; ISS:UniProtKB. DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central. DR GO; GO:0051378; F:serotonin binding; IDA:UniProtKB. DR GO; GO:0007202; P:activation of phospholipase C activity; IDA:UniProtKB. DR GO; GO:0007610; P:behavior; IEA:UniProtKB-KW. DR GO; GO:0019722; P:calcium-mediated signaling; IMP:UniProtKB. DR GO; GO:0003300; P:cardiac muscle hypertrophy; ISS:UniProtKB. DR GO; GO:0071502; P:cellular response to temperature stimulus; 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:0048598; P:embryonic morphogenesis; ISS:UniProtKB. DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IMP:UniProtKB. DR GO; GO:0002031; P:G protein-coupled receptor internalization; IEA:Ensembl. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; 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; IDA:UniProtKB. DR GO; GO:0003007; P:heart morphogenesis; ISS:UniProtKB. DR GO; GO:0014827; P:intestine smooth muscle contraction; IMP:UniProtKB. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IDA:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0014033; P:neural crest cell differentiation; ISS:UniProtKB. DR GO; GO:0001755; P:neural crest cell migration; ISS:UniProtKB. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB. 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:0016310; P:phosphorylation; IMP:UniProtKB. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IEP:UniProtKB. DR GO; GO:0051781; P:positive regulation of cell division; ISS:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:UniProtKB. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB. DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IDA:UniProtKB. DR GO; GO:0010513; P:positive regulation of phosphatidylinositol biosynthetic process; IDA:UniProtKB. DR GO; GO:0070528; P:protein kinase C signaling; IMP:UniProtKB. DR GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0050795; P:regulation of behavior; IMP:UniProtKB. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IDA:UniProtKB. DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:UniProtKB. DR GO; GO:0042310; P:vasoconstriction; IMP:UniProtKB. DR CDD; cd15306; 7tmA_5-HT2B; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR000482; 5HT2B_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:SF31; 5-HYDROXYTRYPTAMINE RECEPTOR 2B; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00651; 5HT2BRECEPTR. 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; P41595; HS. PE 1: Evidence at protein level; KW 3D-structure; Behavior; Cell membrane; Disulfide bond; KW G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Palmitate; KW Receptor; Reference proteome; Synapse; Synaptosome; Transducer; KW Transmembrane; Transmembrane helix. FT CHAIN 1..481 FT /note="5-hydroxytryptamine receptor 2B" FT /id="PRO_0000068953" FT TOPO_DOM 1..56 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT TRANSMEM 57..79 FT /note="Helical; Name=1" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT TOPO_DOM 80..90 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT TRANSMEM 91..113 FT /note="Helical; Name=2" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT TOPO_DOM 114..129 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT TRANSMEM 130..151 FT /note="Helical; Name=3" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT TOPO_DOM 152..171 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT TRANSMEM 172..192 FT /note="Helical; Name=4" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT TOPO_DOM 193..216 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT TRANSMEM 217..239 FT /note="Helical; Name=5" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT TOPO_DOM 240..324 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT TRANSMEM 325..345 FT /note="Helical; Name=6" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT TOPO_DOM 346..360 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT TRANSMEM 361..382 FT /note="Helical; Name=7" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT TOPO_DOM 383..481 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0000269|PubMed:24357322, ECO:0000269|PubMed:28129538" FT MOTIF 152..154 FT /note="DRY motif; important for ligand-induced conformation FT changes" FT /evidence="ECO:0000305|PubMed:23519215, FT ECO:0000305|PubMed:28129538" FT MOTIF 212..215 FT /note="[DE]RFG motif; may stabilize a conformation that FT preferentially activates signaling via beta-arrestin family FT members" FT /evidence="ECO:0000305|PubMed:23519215, FT ECO:0000305|PubMed:28129538" FT MOTIF 376..380 FT /note="NPxxY motif; important for ligand-induced FT conformation changes and signaling" FT /evidence="ECO:0000305|PubMed:23519215, FT ECO:0000305|PubMed:28129538" FT MOTIF 479..481 FT /note="PDZ-binding" FT /evidence="ECO:0000269|PubMed:11150294" FT BINDING 135 FT /ligand="ergotamine" FT /ligand_id="ChEBI:CHEBI:190463" FT /ligand_note="agonist" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0007744|PDB:4IB4, ECO:0007744|PDB:4NC3" FT BINDING 140 FT /ligand="ergotamine" FT /ligand_id="ChEBI:CHEBI:190463" FT /ligand_note="agonist" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0007744|PDB:4IB4, ECO:0007744|PDB:4NC3" FT BINDING 209 FT /ligand="ergotamine" FT /ligand_id="ChEBI:CHEBI:190463" FT /ligand_note="agonist" FT /evidence="ECO:0000269|PubMed:23519215, FT ECO:0007744|PDB:4IB4, ECO:0007744|PDB:4NC3" FT SITE 209 FT /note="Hydrophobic barrier that decreases the speed of FT ligand binding and dissociation" FT /evidence="ECO:0000269|PubMed:28129538" FT LIPID 397 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000255" FT CARBOHYD 30 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 128..207 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521, FT ECO:0000269|PubMed:23519215, ECO:0000269|PubMed:24357322, FT ECO:0000269|PubMed:28129538, ECO:0007744|PDB:4IB4, FT ECO:0007744|PDB:4NC3, ECO:0007744|PDB:5TVN" FT DISULFID 350..353 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521, FT ECO:0000269|PubMed:23519215, ECO:0000269|PubMed:24357322, FT ECO:0000269|PubMed:28129538, ECO:0007744|PDB:4IB4, FT ECO:0007744|PDB:4NC3, ECO:0007744|PDB:5TVN" FT VARIANT 45 FT /note="Q -> E (in dbSNP:rs78484969)" FT /evidence="ECO:0000269|PubMed:21179162" FT /id="VAR_064574" FT VARIANT 173 FT /note="F -> L (in dbSNP:rs77570025)" FT /evidence="ECO:0000269|PubMed:21179162" FT /id="VAR_064575" FT VARIANT 388 FT /note="R -> W (in dbSNP:rs77982984)" FT /evidence="ECO:0000269|PubMed:21179162" FT /id="VAR_064576" FT VARIANT 421 FT /note="M -> V (in dbSNP:rs6736017)" FT /id="VAR_055907" FT MUTAGEN 132 FT /note="L->A: No effect on agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 135 FT /note="D->A: Abolishes agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 136 FT /note="V->A: Slightly decreases agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 139 FT /note="S->A: Slightly decreases agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 140 FT /note="T->A: Slightly decreases agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 208 FT /note="V->A: No effect on agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 209 FT /note="L->A: No effect on agonist binding. Strongly FT increases dissociation of bound lysergic acid diethylamine, FT without affecting binding affinity. Reduces signaling via FT arrestins, but has no effect on signaling via the FT phosphatidylinositol-calcium second messenger system." FT /evidence="ECO:0000269|PubMed:23519210, FT ECO:0000269|PubMed:28129538" FT MUTAGEN 211 FT /note="K->A: Impairs protein folding and stability. FT Strongly reduced cell surface expression." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 217 FT /note="F->A: Slightly decreases agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 218 FT /note="M->A: No effect on agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 225 FT /note="A->S: No effect on agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 337 FT /note="W->A: Slightly decreases agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 340 FT /note="F->A: Slightly decreases agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 344 FT /note="N->A: Slightly decreases agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 347 FT /note="L->A: No effect on agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 348 FT /note="V->A: No effect on agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 362 FT /note="L->A: No effect on agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 363 FT /note="E->A: No effect on agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 366 FT /note="V->A: No effect on agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT MUTAGEN 370 FT /note="Y->A: Slightly decreases agonist binding." FT /evidence="ECO:0000269|PubMed:23519210" FT CONFLICT 452 FT /note="T -> P (in Ref. 2; CAA85319)" FT /evidence="ECO:0000305" FT CONFLICT 477 FT /note="Q -> R (in Ref. 9; AAH63123)" FT /evidence="ECO:0000305" FT HELIX 40..49 FT /evidence="ECO:0007829|PDB:6DRZ" FT HELIX 54..63 FT /evidence="ECO:0007829|PDB:4IB4" FT HELIX 65..81 FT /evidence="ECO:0007829|PDB:4IB4" FT HELIX 83..85 FT /evidence="ECO:0007829|PDB:4IB4" FT HELIX 88..106 FT /evidence="ECO:0007829|PDB:4IB4" FT HELIX 108..111 FT /evidence="ECO:0007829|PDB:4IB4" FT HELIX 113..116 FT /evidence="ECO:0007829|PDB:4IB4" FT TURN 117..119 FT /evidence="ECO:0007829|PDB:7SRQ" FT HELIX 127..158 FT /evidence="ECO:0007829|PDB:4IB4" FT HELIX 160..163 FT /evidence="ECO:0007829|PDB:7SRR" FT HELIX 165..187 FT /evidence="ECO:0007829|PDB:4IB4" FT HELIX 189..193 FT /evidence="ECO:0007829|PDB:4IB4" FT STRAND 198..201 FT /evidence="ECO:0007829|PDB:7SRR" FT HELIX 202..204 FT /evidence="ECO:0007829|PDB:7SRQ" FT HELIX 211..225 FT /evidence="ECO:0007829|PDB:4IB4" FT HELIX 227..248 FT /evidence="ECO:0007829|PDB:4IB4" FT HELIX 281..284 FT /evidence="ECO:0007829|PDB:7SRS" FT HELIX 314..349 FT /evidence="ECO:0007829|PDB:4IB4" FT STRAND 351..353 FT /evidence="ECO:0007829|PDB:4IB4" FT HELIX 355..381 FT /evidence="ECO:0007829|PDB:4IB4" FT HELIX 385..394 FT /evidence="ECO:0007829|PDB:4IB4" FT TURN 395..397 FT /evidence="ECO:0007829|PDB:4IB4" SQ SEQUENCE 481 AA; 54298 MW; CDA4447ECDBA3B46 CRC64; MALSYRVSEL QSTIPEHILQ STFVHVISSN WSGLQTESIP EEMKQIVEEQ GNKLHWAALL ILMVIIPTIG GNTLVILAVS LEKKLQYATN YFLMSLAVAD LLVGLFVMPI ALLTIMFEAM WPLPLVLCPA WLFLDVLFST ASIMHLCAIS VDRYIAIKKP IQANQYNSRA TAFIKITVVW LISIGIAIPV PIKGIETDVD NPNNITCVLT KERFGDFMLF GSLAAFFTPL AIMIVTYFLT IHALQKKAYL VKNKPPQRLT WLTVSTVFQR DETPCSSPEK VAMLDGSRKD KALPNSGDET LMRRTSTIGK KSVQTISNEQ RASKVLGIVF FLFLLMWCPF FITNITLVLC DSCNQTTLQM LLEIFVWIGY VSSGVNPLVY TLFNKTFRDA FGRYITCNYR ATKSVKTLRK RSSKIYFRNP MAENSKFFKK HGIRNGINPA MYQSPMRLRS STIQSSSIIL LDTLLLTENE GDKTEEQVSY V //