5HT2B_RAT
ID 5HT2B_RAT Reviewed; 479 AA.
AC P30994; Q9QW44;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=5-hydroxytryptamine receptor 2B;
DE Short=5-HT-2B;
DE Short=5-HT2B;
DE AltName: Full=5-HT-2F {ECO:0000303|PubMed:1331748};
DE AltName: Full=Serotonin receptor 2B;
DE AltName: Full=Stomach fundus serotonin receptor {ECO:0000303|PubMed:1505525};
GN Name=Htr2b; Synonyms=Srl;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=1505525; DOI=10.1002/j.1460-2075.1992.tb05427.x;
RA Foguet M., Hoyer D., Pardo L.A., Parekh A., Kluxen F.-W., Kalkman M.O.,
RA Stuehmer W., Luebbert H.;
RT "Cloning and functional characterization of the rat stomach fundus
RT serotonin receptor.";
RL EMBO J. 11:3481-3487(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Gastric fundus;
RX PubMed=1331748;
RA Kursar J.D., Nelson D.L., Wainscott D.B., Cohen M.L., Baez M.;
RT "Molecular cloning, functional expression, and pharmacological
RT characterization of a novel serotonin receptor (5-hydroxytryptamine2F) from
RT rat stomach fundus.";
RL Mol. Pharmacol. 42:549-557(1992).
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22525520; DOI=10.1016/j.pain.2012.03.024;
RA Urtikova N., Berson N., Van Steenwinckel J., Doly S., Truchetto J.,
RA Maroteaux L., Pohl M., Conrath M.;
RT "Antinociceptive effect of peripheral serotonin 5-HT2B receptor activation
RT on neuropathic pain.";
RL Pain 153:1320-1331(2012).
CC -!- FUNCTION: G-protein coupled receptor for 5-hydroxytryptamine
CC (serotonin) (PubMed:1505525, PubMed:1331748). Also functions as a
CC receptor for various ergot alkaloid derivatives and psychoactive
CC substances (PubMed:22525520). 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:1505525, PubMed:1331748). Beta-arrestin family members inhibit
CC signaling via G proteins and mediate activation of alternative
CC signaling pathways. Signaling activates a phosphatidylinositol-calcium
CC second messenger system that modulates the activity of
CC phosphatidylinositol 3-kinase and down-stream signaling cascades and
CC promotes the release of Ca(2+) ions from intracellular stores (By
CC similarity). Plays a role in the regulation of dopamine and 5-
CC hydroxytryptamine release, 5-hydroxytryptamine uptake and in the
CC regulation of extracellular dopamine and 5-hydroxytryptamine levels,
CC and thereby affects neural activity. Plays a role in the regulation of
CC behavior, including impulsive behavior. Required for normal
CC proliferation of embryonic cardiac myocytes and normal heart
CC development. Protects cardiomyocytes against apoptosis. Plays a role in
CC the adaptation of pulmonary arteries to chronic hypoxia. Plays a role
CC in 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). May play a role in the perception of pain
CC (PubMed:22525520). {ECO:0000250|UniProtKB:P41595,
CC ECO:0000250|UniProtKB:Q02152, ECO:0000269|PubMed:1331748,
CC ECO:0000269|PubMed:1505525, ECO:0000269|PubMed:22525520}.
CC -!- SUBUNIT: Interacts (via C-terminus) with MPDZ.
CC {ECO:0000250|UniProtKB:P41595}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1331748,
CC ECO:0000269|PubMed:1505525, ECO:0000269|PubMed:22525520}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:1505525}. Synapse, synaptosome
CC {ECO:0000250|UniProtKB:Q02152}.
CC -!- TISSUE SPECIFICITY: Stomach fundus. {ECO:0000269|PubMed:1331748,
CC ECO:0000269|PubMed:1505525}.
CC -!- DOMAIN: Ligands are bound in a hydrophobic pocket formed by the
CC transmembrane helices. {ECO:0000250|UniProtKB:P41595}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; X66842; CAA47318.1; -; mRNA.
DR PIR; S23562; S23562.
DR RefSeq; NP_058946.1; NM_017250.1.
DR AlphaFoldDB; P30994; -.
DR SMR; P30994; -.
DR BioGRID; 248214; 1.
DR IntAct; P30994; 1.
DR MINT; P30994; -.
DR STRING; 10116.ENSRNOP00000023829; -.
DR BindingDB; P30994; -.
DR ChEMBL; CHEMBL323; -.
DR DrugCentral; P30994; -.
DR GuidetoPHARMACOLOGY; 7; -.
DR GlyGen; P30994; 2 sites.
DR PhosphoSitePlus; P30994; -.
DR PaxDb; P30994; -.
DR GeneID; 29581; -.
DR KEGG; rno:29581; -.
DR UCSC; RGD:61801; rat.
DR CTD; 3357; -.
DR RGD; 61801; Htr2b.
DR eggNOG; KOG3656; Eukaryota.
DR InParanoid; P30994; -.
DR PhylomeDB; P30994; -.
DR Reactome; R-RNO-390666; Serotonin receptors.
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR PRO; PR:P30994; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0098666; C:G protein-coupled serotonin receptor complex; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
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; ISS:UniProtKB.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; ISS:UniProtKB.
DR GO; GO:0001587; F:Gq/11-coupled serotonin receptor activity; ISO:RGD.
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:RGD.
DR GO; GO:0007202; P:activation of phospholipase C activity; ISO:RGD.
DR GO; GO:0007610; P:behavior; IEA:UniProtKB-KW.
DR GO; GO:0019722; P:calcium-mediated signaling; ISS:UniProtKB.
DR GO; GO:0003300; P:cardiac muscle hypertrophy; ISS:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:RGD.
DR GO; GO:0071418; P:cellular response to amine stimulus; IDA:RGD.
DR GO; GO:1904015; P:cellular response to serotonin; IDA:RGD.
DR GO; GO:0071502; P:cellular response to temperature stimulus; ISS:UniProtKB.
DR GO; GO:0019934; P:cGMP-mediated signaling; ISS: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; ISS:UniProtKB.
DR GO; GO:0002031; P:G protein-coupled receptor internalization; ISO:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; 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; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0003007; P:heart morphogenesis; ISS:UniProtKB.
DR GO; GO:0035733; P:hepatic stellate cell activation; IEP:RGD.
DR GO; GO:0043647; P:inositol phosphate metabolic process; IEP:RGD.
DR GO; GO:0014827; P:intestine smooth muscle contraction; ISS:UniProtKB.
DR GO; GO:0034220; P:ion transmembrane transport; IDA:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0060548; P:negative regulation of cell death; 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:0014065; P:phosphatidylinositol 3-kinase signaling; ISS: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; ISO:RGD.
DR GO; GO:0016310; P:phosphorylation; ISS:UniProtKB.
DR GO; GO:0051781; P:positive regulation of cell division; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISS:UniProtKB.
DR GO; GO:0010513; P:positive regulation of phosphatidylinositol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0070528; P:protein kinase C signaling; ISS: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; ISS:UniProtKB.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:RGD.
DR GO; GO:0042310; P:vasoconstriction; ISS:UniProtKB.
DR InterPro; IPR000482; 5HT2B_rcpt.
DR InterPro; IPR002231; 5HT_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24247:SF31; PTHR24247:SF31; 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 PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 2: Evidence at transcript level;
KW Behavior; Cell membrane; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Lipoprotein; Membrane; Palmitate; Receptor;
KW Reference proteome; Synapse; Synaptosome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..479
FT /note="5-hydroxytryptamine receptor 2B"
FT /id="PRO_0000068956"
FT TOPO_DOM 1..55
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT TRANSMEM 56..78
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT TOPO_DOM 79..89
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT TRANSMEM 90..112
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT TOPO_DOM 113..128
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT TRANSMEM 129..150
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT TOPO_DOM 151..170
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT TRANSMEM 171..191
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT TOPO_DOM 192..215
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT TRANSMEM 216..238
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT TOPO_DOM 239..323
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT TRANSMEM 324..344
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT TOPO_DOM 345..359
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT TRANSMEM 360..381
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT TOPO_DOM 382..479
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT MOTIF 151..153
FT /note="DRY motif; important for ligand-induced conformation
FT changes"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT MOTIF 211..214
FT /note="[DE]RFG motif; may stabilize a conformation that
FT preferentially activates signaling via beta-arrestin family
FT members"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT MOTIF 375..379
FT /note="NPxxY motif; important for ligand-induced
FT conformation changes and signaling"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT MOTIF 477..479
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:P41595"
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 208
FT /ligand="ergotamine"
FT /ligand_id="ChEBI:CHEBI:190463"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT SITE 208
FT /note="Hydrophobic barrier that decreases the speed of
FT ligand binding and dissociation"
FT /evidence="ECO:0000250|UniProtKB:P41595"
FT LIPID 396
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 203
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 127..206
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT DISULFID 349..352
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT CONFLICT 281
FT /note="V -> A (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 296
FT /note="T -> I (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 479 AA; 53652 MW; 17FFC73213B42038 CRC64;
MASSYKMSEQ STISEHILQK TCDHLILTDR SGLKAESAAE EMKQTAENQG NTVHWAALLI
FAVIIPTIGG NILVILAVSL EKRLQYATNY FLMSLAVADL LVGLFVMPIA LLTIMFEATW
PLPLALCPAW LFLDVLFSTA SIMHLCAISL DRYIAIKKPI QANQCNSRTT AFVKITVVWL
ISIGIAIPVP IKGIEADVVN AHNITCELTK DRFGSFMLFG SLAAFFAPLT IMIVTYFLTI
HALRKKAYLV RNRPPQRLTR WTVSTVLQRE DSSFSSPEKM VMLDGSHKDK ILPNSTDETL
MRRMSSAGKK PAQTISNEQR ASKVLGIVFL FFLLMWCPFF ITNVTLALCD SCNQTTLKTL
LQIFVWVGYV SSGVNPLIYT LFNKTFREAF GRYITCNYQA TKSVKVLRKC SSTLYFGNSM
VENSKFFTKH GIRNGINPAM YQSPVRLRSS TIQSSSIILL NTFLTENDGD KVEDQVSYI
