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Protein

5-hydroxytryptamine receptor 2A

Gene

Htr2a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 Publications

GO - Molecular functioni

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

GO - Biological processi

  • activation of phospholipase C activity Source: Ensembl
  • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: GO_Central
  • aging Source: RGD
  • artery smooth muscle contraction Source: RGD
  • behavioral response to cocaine Source: RGD
  • cell death Source: RGD
  • 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 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: Ensembl
  • phospholipase C-activating serotonin receptor signaling pathway Source: RGD
  • positive regulation of cell proliferation Source: RGD
  • positive regulation of cytosolic calcium ion concentration Source: RGD
  • positive regulation of ERK1 and ERK2 cascade Source: Ensembl
  • positive regulation of fat cell differentiation Source: Ensembl
  • positive regulation of glycolytic process Source: Ensembl
  • positive regulation of MAP kinase activity Source: RGD
  • positive regulation of peptidyl-tyrosine phosphorylation Source: Ensembl
  • positive regulation of phosphatidylinositol biosynthetic process Source: Ensembl
  • positive regulation of vasoconstriction Source: RGD
  • protein localization to cytoskeleton Source: Ensembl
  • regulation of behavior Source: InterPro
  • regulation of dopamine secretion Source: RGD
  • regulation of hormone secretion Source: InterPro
  • release of sequestered calcium ion into cytosol Source: GO_Central
  • response to drug Source: RGD
  • sensory perception of pain Source: RGD
  • sleep Source: RGD
  • temperature homeostasis Source: RGD
  • urinary bladder smooth muscle contraction Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Behavior

Enzyme and pathway databases

ReactomeiR-RNO-390666. Serotonin receptors.
R-RNO-416476. G alpha (q) signalling events.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 15

Organism-specific databases

RGDi61800. Htr2a.

Subcellular locationi

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

GO - Cellular componenti

  • axon Source: UniProtKB-SubCell
  • caveola Source: UniProtKB-SubCell
  • cell body fiber Source: RGD
  • cytoplasm Source: RGD
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
  • cytosol Source: RGD
  • dendrite Source: RGD
  • dendritic shaft Source: RGD
  • integral component of plasma membrane Source: GO_Central
  • membrane Source: RGD
  • neuronal cell body Source: RGD
  • plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL322.
GuidetoPHARMACOLOGYi6.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000689511 – 4715-hydroxytryptamine receptor 2AAdd BLAST471

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi8N-linked (GlcNAc...)Sequence analysis1
Glycosylationi38N-linked (GlcNAc...)Sequence analysis1
Glycosylationi44N-linked (GlcNAc...)Sequence analysis1
Glycosylationi51N-linked (GlcNAc...)Sequence analysis1
Glycosylationi54N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi148 ↔ 227PROSITE-ProRule annotation
Modified residuei280PhosphoserineBy similarity1
Disulfide bondi349 ↔ 353PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP14842.
PRIDEiP14842.

PTM databases

iPTMnetiP14842.
PhosphoSitePlusiP14842.

Expressioni

Tissue specificityi

Detected in adult intestine, especially in mucosal epithelium, longitudinal and circular layers of muscularis externa and myenteric plexuses. Highly expressed in Paneth cells, and detected at lower levels in enterocytes (at protein level). Detected in brain cortex.2 Publications

Gene expression databases

BgeeiENSRNOG00000010063.
GenevisibleiP14842. RN.

Interactioni

Subunit structurei

Interacts with MPDZ and PATJ. May interact with MPP3, PRDX6, DLG4, DLG1, CASK, APBA1 and MAGI2. Interacts with GRM2 and DRD2; this may affect signaling (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Grm2P314213EBI-7090176,EBI-7090147

GO - Molecular functioni

  • G-protein alpha-subunit binding Source: RGD
  • protein complex binding Source: RGD

Protein-protein interaction databases

BioGridi248227. 1 interactor.
DIPiDIP-57661N.
IntActiP14842. 1 interactor.
STRINGi10116.ENSRNOP00000013408.

Chemistry databases

BindingDBiP14842.

Structurei

Secondary structure

1471
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi469 – 471Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4OAJX-ray2.30B465-471[»]
ProteinModelPortaliP14842.
SMRiP14842.
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-binding3

Domaini

The PDZ domain-binding motif is involved in the interaction with PATJ, CASK, APBA1, DLG1 and DLG4.By similarity

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.
GeneTreeiENSGT00780000121897.
HOGENOMiHOG000240378.
HOVERGENiHBG107487.
InParanoidiP14842.
KOiK04157.
OMAiCTMVALG.
OrthoDBiEOG091G06VI.
PhylomeDBiP14842.
TreeFamiTF316350.

Family and domain databases

InterProiIPR000455. 5HT2A_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24247:SF30. PTHR24247:SF30. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00516. 5HT2ARECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P14842-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:471
Mass (Da):52,850
Last modified:April 1, 1990 - v1
Checksum:i3626DACE5F6C7FF4
GO

Sequence cautioni

The sequence CAA32150 differs from that shown. Reason: Frameshift at position 37.Curated

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.
PIRiA34863.
S02011.
RefSeqiNP_058950.1. NM_017254.1.
UniGeneiRn.10294.
Rn.146756.

Genome annotation databases

EnsembliENSRNOT00000013408; ENSRNOP00000013408; ENSRNOG00000010063.
GeneIDi29595.
KEGGirno:29595.
UCSCiRGD:61800. rat.

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.
PIRiA34863.
S02011.
RefSeqiNP_058950.1. NM_017254.1.
UniGeneiRn.10294.
Rn.146756.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4OAJX-ray2.30B465-471[»]
ProteinModelPortaliP14842.
SMRiP14842.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248227. 1 interactor.
DIPiDIP-57661N.
IntActiP14842. 1 interactor.
STRINGi10116.ENSRNOP00000013408.

Chemistry databases

BindingDBiP14842.
ChEMBLiCHEMBL322.
GuidetoPHARMACOLOGYi6.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP14842.
PhosphoSitePlusiP14842.

Proteomic databases

PaxDbiP14842.
PRIDEiP14842.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000013408; ENSRNOP00000013408; ENSRNOG00000010063.
GeneIDi29595.
KEGGirno:29595.
UCSCiRGD:61800. rat.

Organism-specific databases

CTDi3356.
RGDi61800. Htr2a.

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00780000121897.
HOGENOMiHOG000240378.
HOVERGENiHBG107487.
InParanoidiP14842.
KOiK04157.
OMAiCTMVALG.
OrthoDBiEOG091G06VI.
PhylomeDBiP14842.
TreeFamiTF316350.

Enzyme and pathway databases

ReactomeiR-RNO-390666. Serotonin receptors.
R-RNO-416476. G alpha (q) signalling events.

Miscellaneous databases

PROiP14842.

Gene expression databases

BgeeiENSRNOG00000010063.
GenevisibleiP14842. RN.

Family and domain databases

InterProiIPR000455. 5HT2A_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24247:SF30. PTHR24247:SF30. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00516. 5HT2ARECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry namei5HT2A_RAT
AccessioniPrimary (citable) accession number: P14842
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: November 2, 2016
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.