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P14842 (5HT2A_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
5-hydroxytryptamine receptor 2A

Short name=5-HT-2
Short name=5-HT-2A
Alternative name(s):
Serotonin receptor 2A
Gene names
Name:Htr2a
Synonyms:Htr2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length471 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2

Subunit structure

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

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell projectionaxon. Cytoplasmic vesicle. Membranecaveola. Cell projectiondendrite By similarity. Note: Localizes to the postsynaptic thickening of axo-dendritic synapses By similarity. Ref.1 Ref.2 Ref.4

Tissue specificity

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. Ref.1 Ref.4

Domain

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

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Sequence caution

The sequence CAA32150.1 differs from that shown. Reason: Frameshift at position 37.

Ontologies

Keywords
   Biological processBehavior
   Cellular componentCell membrane
Cell projection
Cytoplasmic vesicle
Membrane
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of phospholipase C activity

Inferred from electronic annotation. Source: Ensembl

aging

Inferred from expression pattern PubMed 17374516. Source: RGD

artery smooth muscle contraction

Inferred from mutant phenotype PubMed 14752059. Source: RGD

behavioral response to cocaine

Inferred from direct assay PubMed 23390419. Source: RGD

cell death

Inferred from mutant phenotype PubMed 16504407. Source: RGD

detection of mechanical stimulus involved in sensory perception of pain

Inferred from mutant phenotype PubMed 20531396. Source: RGD

detection of temperature stimulus involved in sensory perception of pain

Inferred from mutant phenotype PubMed 20531396. Source: RGD

memory

Inferred from mutant phenotype PubMed 16149040. Source: RGD

negative regulation of potassium ion transport

Inferred from mutant phenotype PubMed 16527989. Source: RGD

negative regulation of synaptic transmission, glutamatergic

Inferred from mutant phenotype PubMed 17016851. Source: RGD

phosphatidylinositol 3-kinase signaling

Inferred from electronic annotation. Source: Ensembl

phospholipase C-activating serotonin receptor signaling pathway

Inferred from direct assay PubMed 17010161. Source: RGD

positive regulation of ERK1 and ERK2 cascade

Inferred from electronic annotation. Source: Ensembl

positive regulation of MAP kinase activity

Inferred from mutant phenotype PubMed 15087293. Source: RGD

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 15087293. Source: RGD

positive regulation of cytosolic calcium ion concentration

Inferred from mutant phenotype PubMed 20531396. Source: RGD

positive regulation of phosphatidylinositol biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of vasoconstriction

Inferred from mutant phenotype PubMed 16527989. Source: RGD

regulation of behavior

Inferred from electronic annotation. Source: InterPro

regulation of dopamine secretion

Inferred from mutant phenotype PubMed 15999145. Source: RGD

regulation of hormone secretion

Inferred from electronic annotation. Source: InterPro

release of sequestered calcium ion into cytosol

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from mutant phenotype PubMed 17077317. Source: RGD

sleep

Inferred from mutant phenotype PubMed 17059817. Source: RGD

temperature homeostasis

Inferred from mutant phenotype PubMed 17067560. Source: RGD

urinary bladder smooth muscle contraction

Inferred from mutant phenotype PubMed 23274492. Source: RGD

   Cellular_componentaxon

Inferred from electronic annotation. Source: UniProtKB-SubCell

caveola

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell body fiber

Inferred from direct assay PubMed 23390419. Source: RGD

cytoplasmic membrane-bounded vesicle

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from direct assay PubMed 14534355. Source: RGD

dendritic shaft

Inferred from direct assay PubMed 18622042. Source: RGD

integral component of plasma membrane

Inferred from electronic annotation. Source: InterPro

neuronal cell body

Inferred from direct assay PubMed 23390419. Source: RGD

plasma membrane

Inferred from direct assay PubMed 14534355. Source: RGD

   Molecular_function1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding

Inferred from electronic annotation. Source: Ensembl

G-protein alpha-subunit binding

Inferred from mutant phenotype PubMed 19016481. Source: RGD

drug binding

Inferred from electronic annotation. Source: Ensembl

serotonin binding

Inferred from direct assay PubMed 19016481. Source: RGD

serotonin receptor activity

Inferred from direct assay PubMed 19016481. Source: RGD

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Grm2P314213EBI-7090176,EBI-7090147

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 4714715-hydroxytryptamine receptor 2A
PRO_0000068951

Regions

Topological domain1 – 7575Extracellular By similarity
Transmembrane76 – 9924Helical; Name=1; By similarity
Topological domain100 – 11011Cytoplasmic By similarity
Transmembrane111 – 13222Helical; Name=2; By similarity
Topological domain133 – 14816Extracellular By similarity
Transmembrane149 – 17123Helical; Name=3; By similarity
Topological domain172 – 19120Cytoplasmic By similarity
Transmembrane192 – 21524Helical; Name=4; By similarity
Topological domain216 – 23318Extracellular By similarity
Transmembrane234 – 25421Helical; Name=5; By similarity
Topological domain255 – 32470Cytoplasmic By similarity
Transmembrane325 – 34622Helical; Name=6; By similarity
Topological domain347 – 36216Extracellular By similarity
Transmembrane363 – 38422Helical; Name=7; By similarity
Topological domain385 – 47187Cytoplasmic By similarity
Region155 – 1606Agonist binding By similarity
Region336 – 3405Agonist binding By similarity
Motif172 – 1743DRY motif; important for ligand-induced conformation changes By similarity
Motif376 – 3805NPxxY motif; important for ligand-induced conformation changes and signaling By similarity
Motif469 – 4713PDZ-binding

Amino acid modifications

Glycosylation81N-linked (GlcNAc...) Potential
Glycosylation381N-linked (GlcNAc...) Potential
Glycosylation441N-linked (GlcNAc...) Potential
Glycosylation511N-linked (GlcNAc...) Potential
Glycosylation541N-linked (GlcNAc...) Potential
Disulfide bond148 ↔ 227 By similarity
Disulfide bond349 ↔ 353 By similarity

Sequences

Sequence LengthMass (Da)Tools
P14842 [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: 3626DACE5F6C7FF4

FASTA47152,850
        10         20         30         40         50         60 
MEILCEDNIS LSSIPNSLMQ LGDGPRLYHN DFNSRDANTS EASNWTIDAE NRTNLSCEGY 

        70         80         90        100        110        120 
LPPTCLSILH LQEKNWSALL TTVVIILTIA GNILVIMAVS LEKKLQNATN YFLMSLAIAD 

       130        140        150        160        170        180 
MLLGFLVMPV SMLTILYGYR WPLPSKLCAI WIYLDVLFST ASIMHLCAIS LDRYVAIQNP 

       190        200        210        220        230        240 
IHHSRFNSRT KAFLKIIAVW TISVGISMPI PVFGLQDDSK VFKEGSCLLA DDNFVLIGSF 

       250        260        270        280        290        300 
VAFFIPLTIM VITYFLTIKS LQKEATLCVS DLSTRAKLAS FSFLPQSSLS SEKLFQRSIH 

       310        320        330        340        350        360 
REPGSYAGRR TMQSISNEQK ACKVLGIVFF LFVVMWCPFF ITNIMAVICK ESCNENVIGA 

       370        380        390        400        410        420 
LLNVFVWIGY LSSAVNPLVY TLFNKTYRSA FSRYIQCQYK ENRKPLQLIL VNTIPALAYK 

       430        440        450        460        470 
SSQLQVGQKK NSQEDAEQTV DDCSMVTLGK QQSEENCTDN IETVNEKVSC V 

« Hide

References

[1]"The 5HT2 receptor defines a family of structurally distinct but functionally conserved serotonin receptors."
Julius D., Huang K.N., Livelli T.J., Axel R., Jessell T.M.
Proc. Natl. Acad. Sci. U.S.A. 87:928-932(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]"Structure and functional expression of cloned rat serotonin 5HT-2 receptor."
Pritchett D.B., Bach A.W.J., Wozny M., Taleb O., Dal-Toso R., Shih J.C., Seeburg P.H.
EMBO J. 7:4135-4140(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
[3]"The 5-HT2 serotonin receptor gene Htr-2 is tightly linked to Es-10 on mouse chromosome 14."
Liu J., Chen Y., Kozak C.A., Yu L.
Genomics 11:231-234(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"5-HT(2A) receptors: location and functional analysis in intestines of wild-type and 5-HT(2A) knockout mice."
Fiorica-Howells E., Hen R., Gingrich J., Li Z., Gershon M.D.
Am. J. Physiol. 282:G877-G893(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M30705 mRNA. Translation: AAA42178.1.
X13971 mRNA. Translation: CAA32150.1. Frameshift.
M64867 mRNA. No translation available.
PIRA34863.
S02011.
RefSeqNP_058950.1. NM_017254.1.
UniGeneRn.10294.
Rn.146756.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4OAJX-ray2.30B465-471[»]
ProteinModelPortalP14842.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid248227. 1 interaction.
IntActP14842. 1 interaction.
STRING10116.ENSRNOP00000013408.

Chemistry

BindingDBP14842.
ChEMBLCHEMBL2093870.
GuidetoPHARMACOLOGY6.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP14842.

Proteomic databases

PaxDbP14842.
PRIDEP14842.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000013408; ENSRNOP00000013408; ENSRNOG00000010063.
GeneID29595.
KEGGrno:29595.
UCSCRGD:61800. rat.

Organism-specific databases

CTD3356.
RGD61800. Htr2a.

Phylogenomic databases

eggNOGNOG247243.
GeneTreeENSGT00740000114976.
HOGENOMHOG000240378.
HOVERGENHBG107487.
InParanoidP14842.
KOK04157.
OMAFITNVMA.
OrthoDBEOG70ZZN5.
TreeFamTF316350.

Gene expression databases

GenevestigatorP14842.

Family and domain databases

InterProIPR000455. 5HT2A_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24247:SF30. PTHR24247:SF30. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00516. 5HT2ARECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio609738.
PROP14842.

Entry information

Entry name5HT2A_RAT
AccessionPrimary (citable) accession number: P14842
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: March 19, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries