UniProtKB - P14842 (5HT2A_RAT)
5-hydroxytryptamine receptor 2A
Htr2a
Functioni
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). 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). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. 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. Affects neural activity, perception, cognition and mood. 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.
2 PublicationsSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 229 | Hydrophobic barrier that decreases the speed of ligand binding and dissociationBy similarity | 1 |
GO - Molecular functioni
- 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding Source: RGD
- G protein-coupled serotonin receptor activity Source: RGD
- Gq/11-coupled serotonin receptor activity Source: RGD
- identical protein binding Source: RGD
- neurotransmitter receptor activity Source: GO_Central
- protein-containing complex binding Source: RGD
- serotonin binding Source: RGD
GO - Biological processi
- activation of phospholipase C activity Source: RGD
- aging Source: RGD
- artery smooth muscle contraction Source: RGD
- behavioral response to cocaine Source: RGD
- cell death Source: RGD
- cellular calcium ion homeostasis Source: RGD
- chemical synaptic transmission Source: GO_Central
- detection of mechanical stimulus involved in sensory perception of pain Source: RGD
- detection of temperature stimulus involved in sensory perception of pain Source: RGD
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: GO_Central
- G protein-coupled serotonin receptor signaling pathway Source: RGD
- memory Source: RGD
- negative regulation of potassium ion transport Source: RGD
- negative regulation of synaptic transmission, glutamatergic Source: RGD
- phosphatidylinositol 3-kinase signaling Source: RGD
- phospholipase C-activating G protein-coupled receptor signaling pathway Source: GO_Central
- phospholipase C-activating serotonin receptor signaling pathway Source: RGD
- positive regulation of cell population proliferation Source: RGD
- positive regulation of cytosolic calcium ion concentration Source: RGD
- positive regulation of ERK1 and ERK2 cascade Source: RGD
- positive regulation of fat cell differentiation Source: RGD
- positive regulation of glycolytic process Source: RGD
- positive regulation of kinase activity Source: RGD
- positive regulation of MAP kinase activity Source: RGD
- positive regulation of peptidyl-tyrosine phosphorylation Source: RGD
- positive regulation of phosphatidylinositol biosynthetic process Source: RGD
- positive regulation of vasoconstriction Source: RGD
- protein localization to cytoskeleton Source: RGD
- regulation of dopamine secretion Source: RGD
- regulation of synaptic vesicle exocytosis Source: SynGO
- release of sequestered calcium ion into cytosol Source: RGD
- response to xenobiotic stimulus Source: RGD
- sensory perception of pain Source: RGD
- sleep Source: RGD
- temperature homeostasis Source: RGD
- urinary bladder smooth muscle contraction Source: RGD
Keywordsi
Molecular function | G-protein coupled receptor, Receptor, Transducer |
Biological process | Behavior |
Enzyme and pathway databases
Reactomei | R-RNO-390666, Serotonin receptors R-RNO-416476, G alpha (q) signalling events |
Names & Taxonomyi
Protein namesi | Recommended name: 5-hydroxytryptamine receptor 2AShort name: 5-HT-2 Short name: 5-HT-2A Alternative name(s): Serotonin receptor 2A |
Gene namesi | Name:Htr2a Synonyms:Htr2 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 61800, Htr2a |
Subcellular locationi
Plasma membrane
- Cell membrane 3 Publications; Multi-pass membrane protein Curated
Other locations
- axon 1 Publication
- Cytoplasmic vesicle 1 Publication
- caveola 1 Publication
- dendrite By similarity
- presynapse 1 Publication
Cytosol
- cytosol Source: RGD
Plasma Membrane
- caveola Source: UniProtKB-SubCell
- integral component of plasma membrane Source: GO_Central
- integral component of postsynaptic membrane Source: SynGO
- integral component of presynaptic membrane Source: SynGO
- plasma membrane Source: RGD
Other locations
- axon Source: UniProtKB-SubCell
- cell body fiber Source: RGD
- cytoplasm Source: RGD
- cytoplasmic vesicle Source: UniProtKB-KW
- dendrite Source: RGD
- dendritic shaft Source: RGD
- G protein-coupled serotonin receptor complex Source: RGD
- glutamatergic synapse Source: SynGO
- neuronal cell body Source: RGD
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 75 | ExtracellularBy similarityAdd BLAST | 75 | |
Transmembranei | 76 – 99 | Helical; Name=1By similarityAdd BLAST | 24 | |
Topological domaini | 100 – 110 | CytoplasmicBy similarityAdd BLAST | 11 | |
Transmembranei | 111 – 132 | Helical; Name=2By similarityAdd BLAST | 22 | |
Topological domaini | 133 – 148 | ExtracellularBy similarityAdd BLAST | 16 | |
Transmembranei | 149 – 171 | Helical; Name=3By similarityAdd BLAST | 23 | |
Topological domaini | 172 – 191 | CytoplasmicBy similarityAdd BLAST | 20 | |
Transmembranei | 192 – 215 | Helical; Name=4By similarityAdd BLAST | 24 | |
Topological domaini | 216 – 233 | ExtracellularBy similarityAdd BLAST | 18 | |
Transmembranei | 234 – 254 | Helical; Name=5By similarityAdd BLAST | 21 | |
Topological domaini | 255 – 324 | CytoplasmicBy similarityAdd BLAST | 70 | |
Transmembranei | 325 – 346 | Helical; Name=6By similarityAdd BLAST | 22 | |
Topological domaini | 347 – 362 | ExtracellularBy similarityAdd BLAST | 16 | |
Transmembranei | 363 – 384 | Helical; Name=7By similarityAdd BLAST | 22 | |
Topological domaini | 385 – 471 | CytoplasmicBy similarityAdd BLAST | 87 |
Keywords - Cellular componenti
Cell junction, Cell membrane, Cell projection, Cytoplasmic vesicle, Membrane, SynapsePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000068951 | 1 – 471 | 5-hydroxytryptamine receptor 2AAdd BLAST | 471 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 8 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 38 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 44 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 51 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 54 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 148 ↔ 227 | PROSITE-ProRule annotation | ||
Modified residuei | 280 | PhosphoserineBy similarity | 1 | |
Disulfide bondi | 349 ↔ 353 | PROSITE-ProRule annotation |
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
PaxDbi | P14842 |
PTM databases
GlyGeni | P14842, 5 sites |
iPTMneti | P14842 |
PhosphoSitePlusi | P14842 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSRNOG00000010063, Expressed in brain and 19 other tissues |
Genevisiblei | P14842, RN |
Interactioni
Subunit structurei
Interacts (via C-terminus) with MPDZ and PATJ. May interact (via C-terminus) with MPP3, PRDX6, DLG4, DLG1, CASK, APBA1 and MAGI2.
Interacts with GRM2 and DRD2; this may affect signaling.
By similarityBinary interactionsi
P14842
With | #Exp. | IntAct |
---|---|---|
Grm2 [P31421] | 3 | EBI-7090176,EBI-7090147 |
GO - Molecular functioni
- identical protein binding Source: RGD
Protein-protein interaction databases
BioGRIDi | 248227, 2 interactors |
DIPi | DIP-57661N |
IntActi | P14842, 4 interactors |
MINTi | P14842 |
STRINGi | 10116.ENSRNOP00000013408 |
Chemistry databases
BindingDBi | P14842 |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P14842 |
SMRi | P14842 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 155 – 160 | Agonist bindingBy similarity | 6 | |
Regioni | 336 – 340 | Agonist bindingBy similarity | 5 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 172 – 174 | DRY motif; important for ligand-induced conformation changesBy similarity | 3 | |
Motifi | 376 – 380 | NPxxY motif; important for ligand-induced conformation changes and signalingBy similarity | 5 | |
Motifi | 469 – 471 | PDZ-bindingBy similarity | 3 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3656, Eukaryota |
GeneTreei | ENSGT01030000234619 |
HOGENOMi | CLU_009579_11_3_1 |
InParanoidi | P14842 |
OMAi | RLYNNDF |
OrthoDBi | 962038at2759 |
PhylomeDBi | P14842 |
TreeFami | TF316350 |
Family and domain databases
InterProi | View protein in InterPro IPR000455, 5HT2A_rcpt IPR002231, 5HT_rcpt IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM |
PANTHERi | PTHR24247:SF30, PTHR24247:SF30, 1 hit |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR00516, 5HT2ARECEPTR PR01101, 5HTRECEPTOR PR00237, GPCRRHODOPSN |
SMARTi | View protein in SMART SM01381, 7TM_GPCR_Srsx, 1 hit |
PROSITEi | View protein in PROSITE PS00237, G_PROTEIN_RECEP_F1_1, 1 hit PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MEILCEDNIS LSSIPNSLMQ LGDGPRLYHN DFNSRDANTS EASNWTIDAE
60 70 80 90 100
NRTNLSCEGY LPPTCLSILH LQEKNWSALL TTVVIILTIA GNILVIMAVS
110 120 130 140 150
LEKKLQNATN YFLMSLAIAD MLLGFLVMPV SMLTILYGYR WPLPSKLCAI
160 170 180 190 200
WIYLDVLFST ASIMHLCAIS LDRYVAIQNP IHHSRFNSRT KAFLKIIAVW
210 220 230 240 250
TISVGISMPI PVFGLQDDSK VFKEGSCLLA DDNFVLIGSF VAFFIPLTIM
260 270 280 290 300
VITYFLTIKS LQKEATLCVS DLSTRAKLAS FSFLPQSSLS SEKLFQRSIH
310 320 330 340 350
REPGSYAGRR TMQSISNEQK ACKVLGIVFF LFVVMWCPFF ITNIMAVICK
360 370 380 390 400
ESCNENVIGA LLNVFVWIGY LSSAVNPLVY TLFNKTYRSA FSRYIQCQYK
410 420 430 440 450
ENRKPLQLIL VNTIPALAYK SSQLQVGQKK NSQEDAEQTV DDCSMVTLGK
460 470
QQSEENCTDN IETVNEKVSC V
Sequence cautioni
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M30705 mRNA Translation: AAA42178.1 X13971 mRNA Translation: CAA32150.1 Frameshift. M64867 mRNA No translation available. |
PIRi | A34863 S02011 |
RefSeqi | NP_058950.1, NM_017254.1 |
Genome annotation databases
Ensembli | ENSRNOT00000013408; ENSRNOP00000013408; ENSRNOG00000010063 |
GeneIDi | 29595 |
KEGGi | rno:29595 |
UCSCi | RGD:61800, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M30705 mRNA Translation: AAA42178.1 X13971 mRNA Translation: CAA32150.1 Frameshift. M64867 mRNA No translation available. |
PIRi | A34863 S02011 |
RefSeqi | NP_058950.1, NM_017254.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4OAJ | X-ray | 2.30 | B | 465-471 | [»] | |
AlphaFoldDBi | P14842 | |||||
SMRi | P14842 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 248227, 2 interactors |
DIPi | DIP-57661N |
IntActi | P14842, 4 interactors |
MINTi | P14842 |
STRINGi | 10116.ENSRNOP00000013408 |
Chemistry databases
BindingDBi | P14842 |
ChEMBLi | CHEMBL322 |
DrugCentrali | P14842 |
GuidetoPHARMACOLOGYi | 6 |
Protein family/group databases
GPCRDBi | Search... |
PTM databases
GlyGeni | P14842, 5 sites |
iPTMneti | P14842 |
PhosphoSitePlusi | P14842 |
Proteomic databases
PaxDbi | P14842 |
Genome annotation databases
Ensembli | ENSRNOT00000013408; ENSRNOP00000013408; ENSRNOG00000010063 |
GeneIDi | 29595 |
KEGGi | rno:29595 |
UCSCi | RGD:61800, rat |
Organism-specific databases
CTDi | 3356 |
RGDi | 61800, Htr2a |
Phylogenomic databases
eggNOGi | KOG3656, Eukaryota |
GeneTreei | ENSGT01030000234619 |
HOGENOMi | CLU_009579_11_3_1 |
InParanoidi | P14842 |
OMAi | RLYNNDF |
OrthoDBi | 962038at2759 |
PhylomeDBi | P14842 |
TreeFami | TF316350 |
Enzyme and pathway databases
Reactomei | R-RNO-390666, Serotonin receptors R-RNO-416476, G alpha (q) signalling events |
Miscellaneous databases
PROi | PR:P14842 |
Gene expression databases
Bgeei | ENSRNOG00000010063, Expressed in brain and 19 other tissues |
Genevisiblei | P14842, RN |
Family and domain databases
InterProi | View protein in InterPro IPR000455, 5HT2A_rcpt IPR002231, 5HT_rcpt IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM |
PANTHERi | PTHR24247:SF30, PTHR24247:SF30, 1 hit |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR00516, 5HT2ARECEPTR PR01101, 5HTRECEPTOR PR00237, GPCRRHODOPSN |
SMARTi | View protein in SMART SM01381, 7TM_GPCR_Srsx, 1 hit |
PROSITEi | View protein in PROSITE PS00237, G_PROTEIN_RECEP_F1_1, 1 hit PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | 5HT2A_RAT | |
Accessioni | P14842Primary (citable) accession number: P14842 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1990 |
Last sequence update: | April 1, 1990 | |
Last modified: | May 25, 2022 | |
This is version 178 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- 7-transmembrane G-linked receptors
List of 7-transmembrane G-linked receptor entries - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families