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Protein

5-hydroxytryptamine receptor 2B

Gene

HTR2B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:8143856, PubMed:7926008, PubMed:8078486, PubMed:8882600, PubMed:18703043, PubMed:23519210). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances (PubMed:8143856, PubMed:7926008, PubMed:8078486, PubMed:12970106, PubMed:18703043, PubMed:23519210, PubMed:23519215, PubMed:24357322, PubMed:28129538). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors (PubMed:8143856, PubMed:8078486, PubMed:8882600, PubMed:23519215, PubMed:28129538). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:23519215, PubMed:28129538). Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca2+ ions from intracellular stores (PubMed:8143856, PubMed:8078486, PubMed:8882600, PubMed:18703043, PubMed:23519215, PubMed:28129538). Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain (By similarity). Plays a role in the regulation of behavior, including impulsive behavior (PubMed:21179162). Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine (By similarity).By similarity11 Publications

Miscellaneous

Binds lysergic acid diethylamine (LSD) in the orthosteric pocket, but is not the principal LSD receptor in the brain. Bound LSD dissociates extremely slowly, with a residence time of about 46 minutes at 37 degrees Celsius.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei209Hydrophobic barrier that decreases the speed of ligand binding and dissociation1 Publication1

GO - Molecular functioni

  • drug binding Source: UniProtKB
  • G-protein alpha-subunit binding Source: UniProtKB
  • G-protein coupled serotonin receptor activity Source: UniProtKB
  • GTPase activator activity Source: UniProtKB
  • neurotransmitter receptor activity Source: GO_Central
  • serotonin binding Source: UniProtKB

GO - Biological processi

  • activation of phospholipase C activity Source: UniProtKB
  • behavior Source: UniProtKB-KW
  • calcium-mediated signaling Source: UniProtKB
  • cardiac muscle hypertrophy Source: UniProtKB
  • cellular calcium ion homeostasis Source: UniProtKB
  • cellular response to temperature stimulus Source: UniProtKB
  • cGMP biosynthetic process Source: UniProtKB
  • embryonic morphogenesis Source: UniProtKB
  • ERK1 and ERK2 cascade Source: UniProtKB
  • G-protein coupled receptor internalization Source: Ensembl
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • heart morphogenesis Source: UniProtKB
  • intestine smooth muscle contraction Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of autophagy Source: UniProtKB
  • negative regulation of cell death Source: UniProtKB
  • neural crest cell differentiation Source: UniProtKB
  • neural crest cell migration Source: UniProtKB
  • phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • phospholipase C-activating G-protein coupled receptor signaling pathway Source: GO_Central
  • phosphorylation Source: UniProtKB
  • positive regulation of cell division Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of cytokine production Source: UniProtKB
  • positive regulation of cytokine secretion Source: UniProtKB
  • positive regulation of endothelial cell proliferation Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of MAP kinase activity Source: UniProtKB
  • positive regulation of nitric-oxide synthase activity Source: UniProtKB
  • positive regulation of phosphatidylinositol biosynthetic process Source: UniProtKB
  • protein kinase C-activating G-protein coupled receptor signaling pathway Source: UniProtKB
  • protein kinase C signaling Source: UniProtKB
  • regulation of behavior Source: UniProtKB
  • release of sequestered calcium ion into cytosol Source: UniProtKB
  • response to drug Source: UniProtKB
  • serotonin receptor signaling pathway Source: UniProtKB
  • vasoconstriction Source: UniProtKB

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processBehavior

Enzyme and pathway databases

ReactomeiR-HSA-390666 Serotonin receptors
R-HSA-416476 G alpha (q) signalling events
SIGNORiP41595

Protein family/group databases

TCDBi9.A.14.3.7 the g-protein-coupled receptor (gpcr) family

Names & Taxonomyi

Protein namesi
Recommended name:
5-hydroxytryptamine receptor 2B
Short name:
5-HT-2B
Short name:
5-HT2B
Alternative name(s):
Serotonin receptor 2B
Gene namesi
Name:HTR2B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000135914.5
HGNCiHGNC:5294 HTR2B
MIMi601122 gene
neXtProtiNX_P41595

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 56Extracellular3 PublicationsAdd BLAST56
Transmembranei57 – 79Helical; Name=13 PublicationsAdd BLAST23
Topological domaini80 – 90Cytoplasmic3 PublicationsAdd BLAST11
Transmembranei91 – 113Helical; Name=23 PublicationsAdd BLAST23
Topological domaini114 – 129Extracellular3 PublicationsAdd BLAST16
Transmembranei130 – 151Helical; Name=33 PublicationsAdd BLAST22
Topological domaini152 – 171Cytoplasmic3 PublicationsAdd BLAST20
Transmembranei172 – 192Helical; Name=43 PublicationsAdd BLAST21
Topological domaini193 – 216Extracellular3 PublicationsAdd BLAST24
Transmembranei217 – 239Helical; Name=53 PublicationsAdd BLAST23
Topological domaini240 – 324Cytoplasmic3 PublicationsAdd BLAST85
Transmembranei325 – 345Helical; Name=63 PublicationsAdd BLAST21
Topological domaini346 – 360Extracellular3 PublicationsAdd BLAST15
Transmembranei361 – 382Helical; Name=73 PublicationsAdd BLAST22
Topological domaini383 – 481Cytoplasmic3 PublicationsAdd BLAST99

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Synapse, Synaptosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi132L → A: No effect on agonist binding. 1 Publication1
Mutagenesisi135D → A: Abolishes agonist binding. 1 Publication1
Mutagenesisi136V → A: Slightly decreases agonist binding. 1 Publication1
Mutagenesisi139S → A: Slightly decreases agonist binding. 1 Publication1
Mutagenesisi140T → A: Slightly decreases agonist binding. 1 Publication1
Mutagenesisi208V → A: No effect on agonist binding. 1 Publication1
Mutagenesisi209L → A: No effect on agonist binding. Strongly increases dissociation of bound lysergic acid diethylamine, without affecting binding affinity. Reduces signaling via arrestins, but has no effect on signaling via the phosphatidylinositol-calcium second messenger system. 2 Publications1
Mutagenesisi211K → A: Impairs protein folding and stability. Strongly reduced cell surface expression. 1 Publication1
Mutagenesisi217F → A: Slightly decreases agonist binding. 1 Publication1
Mutagenesisi218M → A: No effect on agonist binding. 1 Publication1
Mutagenesisi225A → S: No effect on agonist binding. 1 Publication1
Mutagenesisi337W → A: Slightly decreases agonist binding. 1 Publication1
Mutagenesisi340F → A: Slightly decreases agonist binding. 1 Publication1
Mutagenesisi344N → A: Slightly decreases agonist binding. 1 Publication1
Mutagenesisi347L → A: No effect on agonist binding. 1 Publication1
Mutagenesisi348V → A: No effect on agonist binding. 1 Publication1
Mutagenesisi362L → A: No effect on agonist binding. 1 Publication1
Mutagenesisi363E → A: No effect on agonist binding. 1 Publication1
Mutagenesisi366V → A: No effect on agonist binding. 1 Publication1
Mutagenesisi370Y → A: Slightly decreases agonist binding. 1 Publication1

Organism-specific databases

DisGeNETi3357
OpenTargetsiENSG00000135914
PharmGKBiPA29554

Chemistry databases

ChEMBLiCHEMBL1833
DrugBankiDB00543 Amoxapine
DB00714 Apomorphine
DB06216 Asenapine
DB01200 Bromocriptine
DB00248 Cabergoline
DB06016 Cariprazine
DB00477 Chlorpromazine
DB01239 Chlorprothixene
DB01242 Clomipramine
DB00320 Dihydroergotamine
DB01142 Doxepin
DB00216 Eletriptan
DB05492 Epicept NP-1
DB01049 Ergoloid mesylate
DB06678 Esmirtazapine
DB00574 Fenfluramine
DB01221 Ketamine
DB00589 Lisuride
DB00247 Methysergide
DB06148 Mianserin
DB00805 Minaprine
DB00370 Mirtazapine
DB00334 Olanzapine
DB05461 OPC-28326
DB01186 Pergolide
DB00413 Pramipexole
DB00268 Ropinirole
DB01079 Tegaserod
DB13025 Tiapride
DB00508 Triflupromazine
DB01392 Yohimbine
GuidetoPHARMACOLOGYi7

Polymorphism and mutation databases

BioMutaiHTR2B
DMDMi1168220

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000689531 – 4815-hydroxytryptamine receptor 2BAdd BLAST481

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi30N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi128 ↔ 207PROSITE-ProRule annotationCombined sources3 Publications
Disulfide bondi350 ↔ 353PROSITE-ProRule annotationCombined sources3 Publications
Lipidationi397S-palmitoyl cysteineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP41595
PRIDEiP41595

PTM databases

iPTMnetiP41595
PhosphoSitePlusiP41595

Expressioni

Tissue specificityi

Ubiquitous. Detected in liver, kidney, heart, pulmonary artery, and intestine. Detected at lower levels in blood, placenta and brain, especially in cerebellum, occipital cortex and frontal cortex.5 Publications

Gene expression databases

BgeeiENSG00000135914
CleanExiHS_HTR2B
GenevisibleiP41595 HS

Organism-specific databases

HPAiCAB011448
HPA012867
HPA063658

Interactioni

Subunit structurei

Interacts (via C-terminus) with MPDZ.1 Publication

GO - Molecular functioni

  • G-protein alpha-subunit binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109589, 3 interactors
IntActiP41595, 1 interactor
MINTiP41595
STRINGi9606.ENSP00000258400

Chemistry databases

BindingDBiP41595

Structurei

Secondary structure

1481
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi54 – 63Combined sources10
Helixi65 – 81Combined sources17
Helixi83 – 85Combined sources3
Helixi88 – 106Combined sources19
Helixi108 – 111Combined sources4
Helixi113 – 116Combined sources4
Helixi127 – 158Combined sources32
Helixi165 – 187Combined sources23
Helixi189 – 193Combined sources5
Beta strandi195 – 198Combined sources4
Helixi202 – 204Combined sources3
Helixi211 – 225Combined sources15
Helixi227 – 248Combined sources22
Helixi314 – 349Combined sources36
Beta strandi351 – 353Combined sources3
Helixi355 – 381Combined sources27
Helixi385 – 394Combined sources10
Turni395 – 397Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4IB4X-ray2.70A36-248[»]
A314-405[»]
4NC3X-ray2.80A36-248[»]
A314-405[»]
5TUDX-ray3.00A/D36-248[»]
A/D314-405[»]
5TVNX-ray2.90A41-248[»]
A313-400[»]
ProteinModelPortaliP41595
SMRiP41595
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni135 – 140Agonist bindingCombined sources3 Publications6
Regioni337 – 341Agonist bindingCombined sources3 Publications5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi152 – 154DRY motif; important for ligand-induced conformation changes2 Publications3
Motifi212 – 215[DE]RFG motif; may stabilize a conformation that preferentially activates signaling via beta-arrestin family members2 Publications4
Motifi376 – 380NPxxY motif; important for ligand-induced conformation changes and signaling2 Publications5
Motifi479 – 481PDZ-binding1 Publication3

Domaini

Ligands are bound in a hydrophobic pocket formed by the transmembrane helices.3 Publications

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00890000139331
HOGENOMiHOG000240378
HOVERGENiHBG107487
InParanoidiP41595
KOiK04157
OMAiVWLISIG
OrthoDBiEOG091G06VI
PhylomeDBiP41595
TreeFamiTF316350

Family and domain databases

InterProiView protein in InterPro
IPR000482 5HT2B_rcpt
IPR002231 5HT_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PANTHERiPTHR24247:SF31 PTHR24247:SF31, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00651 5HT2BRECEPTR
PR01101 5HTRECEPTOR
PR00237 GPCRRHODOPSN
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequencei

Sequence statusi: Complete.

P41595-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALSYRVSEL QSTIPEHILQ STFVHVISSN WSGLQTESIP EEMKQIVEEQ
60 70 80 90 100
GNKLHWAALL ILMVIIPTIG GNTLVILAVS LEKKLQYATN YFLMSLAVAD
110 120 130 140 150
LLVGLFVMPI ALLTIMFEAM WPLPLVLCPA WLFLDVLFST ASIMHLCAIS
160 170 180 190 200
VDRYIAIKKP IQANQYNSRA TAFIKITVVW LISIGIAIPV PIKGIETDVD
210 220 230 240 250
NPNNITCVLT KERFGDFMLF GSLAAFFTPL AIMIVTYFLT IHALQKKAYL
260 270 280 290 300
VKNKPPQRLT WLTVSTVFQR DETPCSSPEK VAMLDGSRKD KALPNSGDET
310 320 330 340 350
LMRRTSTIGK KSVQTISNEQ RASKVLGIVF FLFLLMWCPF FITNITLVLC
360 370 380 390 400
DSCNQTTLQM LLEIFVWIGY VSSGVNPLVY TLFNKTFRDA FGRYITCNYR
410 420 430 440 450
ATKSVKTLRK RSSKIYFRNP MAENSKFFKK HGIRNGINPA MYQSPMRLRS
460 470 480
STIQSSSIIL LDTLLLTENE GDKTEEQVSY V
Length:481
Mass (Da):54,298
Last modified:November 1, 1995 - v1
Checksum:iCDA4447ECDBA3B46
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti452T → P in CAA85319 (PubMed:7926008).Curated1
Sequence conflicti477Q → R in AAH63123 (PubMed:15489334).Curated1

Polymorphismi

A variation at a single nucleotide base, which results in an erroneous stop codon and affects Gln-20, triggers non-sense mediated RNA decay, such that no HTR2B-receptor protein is expressed. It is associated with impulsive behavior and co-segregates with disorders characterized by impulsivity. However, the presence of this variant is not in itself sufficient to cause impulsive behavior: male sex, testosterone level, alcohol and stress exposure are other factors playing important roles.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06457445Q → E1 PublicationCorresponds to variant dbSNP:rs78484969Ensembl.1
Natural variantiVAR_064575173F → L1 PublicationCorresponds to variant dbSNP:rs77570025Ensembl.1
Natural variantiVAR_064576388R → W1 PublicationCorresponds to variant dbSNP:rs77982984Ensembl.1
Natural variantiVAR_055907421M → V. Corresponds to variant dbSNP:rs6736017Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X77307 mRNA Translation: CAA54513.1
Z36748 mRNA Translation: CAA85319.1
AF156160, AF156158, AF156159 Genomic DNA Translation: AAD39259.1
AY136751 mRNA Translation: AAN01277.1
AC009407 Genomic DNA Translation: AAX93128.1
AK313741 mRNA Translation: BAG36482.1
CH471063 Genomic DNA Translation: EAW70949.1
BC063123 mRNA Translation: AAH63123.1
CCDSiCCDS2483.1
PIRiS43687
S49442
RefSeqiNP_000858.3, NM_000867.4
NP_001307687.1, NM_001320758.1
UniGeneiHs.421649

Genome annotation databases

EnsembliENST00000258400; ENSP00000258400; ENSG00000135914
GeneIDi3357
KEGGihsa:3357
UCSCiuc002vro.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry namei5HT2B_HUMAN
AccessioniPrimary (citable) accession number: P41595
Secondary accession number(s): B2R9D5
, Q53TI1, Q62221, Q6P523
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: March 28, 2018
This is version 172 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health