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Protein

5-hydroxytryptamine receptor 2A

Gene

HTR2A

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

Functioni

G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (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:28129538). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:28129538). Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca2+ ions from intracellular stores (PubMed:18703043, PubMed:28129538). Affects neural activity, perception, cognition and mood (PubMed:18297054). Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.7 Publications
(Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.1 Publication

Miscellaneous

Binds lysergic acid diethylamine (LSD) in the orthosteric pocket (Probable). Bound LSD dissociates extremely slowly, with a residence time of about 221 minutes at 37 degrees Celsius.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei229Hydrophobic barrier that decreases the speed of ligand binding and dissociation1 Publication1

GO - Molecular functioni

  • 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding Source: UniProtKB
  • drug binding Source: UniProtKB
  • G-protein alpha-subunit binding Source: Ensembl
  • G-protein coupled serotonin receptor activity Source: UniProtKB
  • neurotransmitter receptor activity Source: GO_Central
  • protein-containing complex binding Source: Ensembl
  • serotonin binding Source: UniProtKB
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Host cell receptor for virus entry, Receptor, Transducer
Biological processBehavior, Host-virus interaction

Enzyme and pathway databases

ReactomeiR-HSA-390666 Serotonin receptors
R-HSA-416476 G alpha (q) signalling events
SignaLinkiP28223

Names & Taxonomyi

Protein namesi
Recommended name:
5-hydroxytryptamine receptor 2A
Short name:
5-HT-2
Short name:
5-HT-2A
Alternative name(s):
Serotonin receptor 2A
Gene namesi
Name:HTR2A
Synonyms:HTR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000102468.10
HGNCiHGNC:5293 HTR2A
MIMi182135 gene
neXtProtiNX_P28223

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 – 75ExtracellularBy similarityAdd BLAST75
Transmembranei76 – 99Helical; Name=1By similarityAdd BLAST24
Topological domaini100 – 110CytoplasmicBy similarityAdd BLAST11
Transmembranei111 – 132Helical; Name=2By similarityAdd BLAST22
Topological domaini133 – 148ExtracellularBy similarityAdd BLAST16
Transmembranei149 – 171Helical; Name=3By similarityAdd BLAST23
Topological domaini172 – 191CytoplasmicBy similarityAdd BLAST20
Transmembranei192 – 215Helical; Name=4By similarityAdd BLAST24
Topological domaini216 – 233ExtracellularBy similarityAdd BLAST18
Transmembranei234 – 254Helical; Name=5By similarityAdd BLAST21
Topological domaini255 – 324CytoplasmicBy similarityAdd BLAST70
Transmembranei325 – 346Helical; Name=6By similarityAdd BLAST22
Topological domaini347 – 362ExtracellularBy similarityAdd BLAST16
Transmembranei363 – 384Helical; Name=7By similarityAdd BLAST22
Topological domaini385 – 471CytoplasmicBy similarityAdd BLAST87

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi229L → A: 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. 1 Publication1
Mutagenesisi280S → A: Increased ability of hallucinogens to desensitize the receptor. 1 Publication1
Mutagenesisi280S → D: Reduced receptor desensitization by nonhallucinogenic agonists. 1 Publication1
Mutagenesisi463G → V: Loss of interaction with PATJ. 1 Publication1
Mutagenesisi465N → S: No effect on interaction with PATJ. Acquires the binding properties of HTR2C; when associated with S-470. 1 Publication1
Mutagenesisi470C → S: No effect on interaction with PATJ. Acquires the binding properties of HTR2C; when associated with S-465. 1 Publication1
Mutagenesisi471V → A: Loss of interaction with PATJ, CASK, APBA1, DLG1 and DLG4. 1 Publication1

Organism-specific databases

DisGeNETi3356
MalaCardsiHTR2A
OpenTargetsiENSG00000102468
PharmGKBiPA193

Chemistry databases

ChEMBLiCHEMBL224
DrugBankiDB01614 Acepromazine
DB06288 Amisulpride
DB00321 Amitriptyline
DB00543 Amoxapine
DB08927 Amperozide
DB04599 Aniracetam
DB05026 APD125
DB05227 APD791
DB00714 Apomorphine
DB01238 Aripiprazole
DB06216 Asenapine
DB05687 BL-1020
DB09128 Brexpiprazole
DB01200 Bromocriptine
DB09016 Butriptyline
DB00248 Cabergoline
DB06016 Cariprazine
DB00477 Chlorpromazine
DB01239 Chlorprothixene
DB08810 Cinitapride
DB00604 Cisapride
DB01242 Clomipramine
DB00363 Clozapine
DB00924 Cyclobenzaprine
DB00434 Cyproheptadine
DB06512 Deramciclane
DB01151 Desipramine
DB01488 Dimethyltryptamine
DB00843 Donepezil
DB01142 Doxepin
DB05492 Epicept NP-1
DB00751 Epinastine
DB01049 Ergoloid mesylate
DB00696 Ergotamine
DB06678 Esmirtazapine
DB04908 Flibanserin
DB00875 Flupentixol
DB04842 Fluspirilene
DB00502 Haloperidol
DB05079 HY10275
DB04946 Iloperidone
DB00458 Imipramine
DB01221 Ketamine
DB00589 Lisuride
DB00408 Loxapine
DB06077 Lumateperone
DB08815 Lurasidone
DB05743 MAP-0004
DB00934 Maprotiline
DB00933 Mesoridazine
DB01403 Methotrimeprazine
DB00247 Methysergide
DB06148 Mianserin
DB00805 Minaprine
DB00370 Mirtazapine
DB01442 MMDA
DB01618 Molindone
DB01149 Nefazodone
DB00540 Nortriptyline
DB00334 Olanzapine
DB01267 Paliperidone
DB00715 Paroxetine
DB01186 Pergolide
DB05316 Pimavanserin
DB01621 Pipotiazine
DB00413 Pramipexole
DB00420 Promazine
DB01069 Promethazine
DB00777 Propiomazine
DB01224 Quetiapine
DB00409 Remoxipride
DB00734 Risperidone
DB00268 Ropinirole
DB06144 Sertindole
DB01079 Tegaserod
DB01622 Thioproperazine
DB00679 Thioridazine
DB01623 Thiothixene
DB13025 Tiapride
DB00656 Trazodone
DB00726 Trimipramine
DB01392 Yohimbine
DB00246 Ziprasidone
DB01624 Zuclopenthixol
GuidetoPHARMACOLOGYi6

Polymorphism and mutation databases

BioMutaiHTR2A
DMDMi543727

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000689461 – 4715-hydroxytryptamine receptor 2AAdd BLAST471

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi8N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi38N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi44N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi51N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi54N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi148 ↔ 227PROSITE-ProRule annotation
Modified residuei280Phosphoserine1 Publication1
Disulfide bondi349 ↔ 353PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP28223
PeptideAtlasiP28223
PRIDEiP28223
ProteomicsDBi54453

PTM databases

iPTMnetiP28223
PhosphoSitePlusiP28223

Expressioni

Tissue specificityi

Detected in brain cortex (at protein level). Detected in blood platelets.1 Publication

Gene expression databases

BgeeiENSG00000102468
CleanExiHS_HTR2A
ExpressionAtlasiP28223 baseline and differential
GenevisibleiP28223 HS

Organism-specific databases

HPAiHPA014011

Interactioni

Subunit structurei

Interacts (via C-terminus) with MPDZ and PATJ (PubMed:11150294, PubMed:14988405). May interact (via C-terminus) with MPP3, PRDX6, DLG4, DLG1, CASK, APBA1 and MAGI2 (PubMed:14988405). Interacts with GRM2 and DRD2; this may affect signaling (PubMed:18297054, PubMed:21645528, PubMed:22300836).5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109588, 6 interactors
DIPiDIP-41844N
IntActiP28223, 16 interactors
MINTiP28223
STRINGi9606.ENSP00000367959

Chemistry databases

BindingDBiP28223

Structurei

3D structure databases

ProteinModelPortaliP28223
SMRiP28223
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni155 – 160Agonist bindingBy similarity6
Regioni336 – 340Agonist bindingBy similarity5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi172 – 174DRY motif; important for ligand-induced conformation changesBy similarity3
Motifi376 – 380NPxxY motif; important for ligand-induced conformation changes and signalingBy similarity5
Motifi469 – 471PDZ-binding2 Publications3

Domaini

The PDZ domain-binding motif is involved in the interaction with PATJ, CASK, APBA1, DLG1 and DLG4.2 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
InParanoidiP28223
KOiK04157
OMAiAGRRTMQ
OrthoDBiEOG091G06VI
PhylomeDBiP28223
TreeFamiTF316350

Family and domain databases

InterProiView protein in InterPro
IPR000455 5HT2A_rcpt
IPR002231 5HT_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PANTHERiPTHR24247:SF30 PTHR24247:SF30, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00516 5HT2ARECEPTR
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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P28223-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDILCEENTS LSSTTNSLMQ LNDDTRLYSN DFNSGEANTS DAFNWTVDSE
60 70 80 90 100
NRTNLSCEGC LSPSCLSLLH LQEKNWSALL TAVVIILTIA GNILVIMAVS
110 120 130 140 150
LEKKLQNATN YFLMSLAIAD MLLGFLVMPV SMLTILYGYR WPLPSKLCAV
160 170 180 190 200
WIYLDVLFST ASIMHLCAIS LDRYVAIQNP IHHSRFNSRT KAFLKIIAVW
210 220 230 240 250
TISVGISMPI PVFGLQDDSK VFKEGSCLLA DDNFVLIGSF VSFFIPLTIM
260 270 280 290 300
VITYFLTIKS LQKEATLCVS DLGTRAKLAS FSFLPQSSLS SEKLFQRSIH
310 320 330 340 350
REPGSYTGRR TMQSISNEQK ACKVLGIVFF LFVVMWCPFF ITNIMAVICK
360 370 380 390 400
ESCNEDVIGA LLNVFVWIGY LSSAVNPLVY TLFNKTYRSA FSRYIQCQYK
410 420 430 440 450
ENKKPLQLIL VNTIPALAYK SSQLQMGQKK NSKQDAKTTD NDCSMVALGK
460 470
QHSEEASKDN SDGVNEKVSC V
Length:471
Mass (Da):52,603
Last modified:June 1, 1994 - v2
Checksum:iEF8AAC0BC5379DA2
GO
Isoform 2 (identifier: P28223-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-138: MDILCEENTS...PVSMLTILYG → MQFLKSAKQK...ISCVDPEDKW

Show »
Length:387
Mass (Da):43,940
Checksum:iDA98167A87C1AAB7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Isoform 2 (identifier: P28223-2)
Sequence conflicti49D → N in BAG63991 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00344825T → N2 PublicationsCorresponds to variant dbSNP:rs1805055Ensembl.1
Natural variantiVAR_013901197I → V1 PublicationCorresponds to variant dbSNP:rs6304Ensembl.1
Natural variantiVAR_013902447A → V1 PublicationCorresponds to variant dbSNP:rs6308Ensembl.1
Natural variantiVAR_003449452H → Y3 PublicationsCorresponds to variant dbSNP:rs6314Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0466631 – 138MDILC…TILYG → MQFLKSAKQKPNYYHIMLVE DQEEGTLHQFNYCERCSESQ NNKCISCVDPEDKW in isoform 2. 1 PublicationAdd BLAST138

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57830 mRNA Translation: CAA40963.1
S42168, S42165, S42167 Genomic DNA Translation: AAB22791.2
S71229 mRNA Translation: AAB31320.1
AF498982 mRNA Translation: AAM21129.1
AK302787 mRNA Translation: BAG63991.1
AK314132 mRNA Translation: BAG36822.1
AL160397 Genomic DNA No translation available.
AL136958 Genomic DNA No translation available.
CH471075 Genomic DNA Translation: EAX08770.1
BC069356 mRNA Translation: AAH69356.1
BC069576 mRNA Translation: AAH69576.1
BC074848 mRNA Translation: AAH74848.1
BC074849 mRNA Translation: AAH74849.1
BC096839 mRNA Translation: AAH96839.1
M86841 mRNA Translation: AAA58354.1
S50130, S49737, S50113 Genomic DNA Translation: AAB24166.2
CCDSiCCDS53867.1 [P28223-2]
CCDS9405.1 [P28223-1]
PIRiA43956
RefSeqiNP_000612.1, NM_000621.4 [P28223-1]
NP_001159419.1, NM_001165947.2 [P28223-2]
UniGeneiHs.72630

Genome annotation databases

EnsembliENST00000378688; ENSP00000367959; ENSG00000102468 [P28223-1]
ENST00000542664; ENSP00000437737; ENSG00000102468 [P28223-1]
ENST00000543956; ENSP00000441861; ENSG00000102468 [P28223-2]
GeneIDi3356
KEGGihsa:3356
UCSCiuc001vbr.5 human [P28223-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry namei5HT2A_HUMAN
AccessioniPrimary (citable) accession number: P28223
Secondary accession number(s): B2RAC5
, B4DZ79, F5GWE8, Q5T8C0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: June 1, 1994
Last modified: July 18, 2018
This is version 189 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

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