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P35363 (5HT2A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 111. 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·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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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.4 Ref.6 Ref.7 Ref.8 Ref.9

Subunit structure

Interacts with MPDZ and INADL. May interact with MPP3, PRDX6, DLG4, DLG1, CASK, APBA1 and MAGI2 By similarity. Interacts with GRM2 and DRD2; this may affect signaling. Ref.6 Ref.7

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell projectiondendrite. Cell projectionaxon By similarity. Cytoplasmic vesicle By similarity. Membranecaveola By similarity. Note: Localizes to the postsynaptic thickening of axo-dendritic synapses. Ref.2 Ref.3 Ref.6 Ref.7 Ref.9

Tissue specificity

Detected in neurons in brain cortex. 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 neurons in the brain cortex. Ref.2 Ref.6 Ref.9

Domain

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

Disruption phenotype

Mutant mice display increased exploratory behavior in open spaces and reduced anxiety-like behavior. Mutant mice fail to show behavorial responses to psychoactive substances and hallucinogens, such as mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane and lysergic acid diethylamide (LSD). Besides, the colon from mutant mice does not contract in response to 5-hydroxytryptamine. Ref.2 Ref.4 Ref.5

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

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 termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of phospholipase C activity

Inferred from electronic annotation. Source: Ensembl

aging

Inferred from electronic annotation. Source: Ensembl

artery smooth muscle contraction

Inferred from electronic annotation. Source: Ensembl

behavioral response to cocaine

Inferred from electronic annotation. Source: Ensembl

cell death

Inferred from electronic annotation. Source: Ensembl

detection of mechanical stimulus involved in sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

detection of temperature stimulus involved in sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

memory

Inferred from electronic annotation. Source: Ensembl

negative regulation of potassium ion transport

Inferred from electronic annotation. Source: Ensembl

negative regulation of synaptic transmission, glutamatergic

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol 3-kinase signaling

Inferred from electronic annotation. Source: Ensembl

phospholipase C-activating serotonin receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of ERK1 and ERK2 cascade

Inferred from electronic annotation. Source: Ensembl

positive regulation of MAP kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of glycolysis

Inferred from mutant phenotype PubMed 17408640. Source: MGI

positive regulation of kinase activity

Inferred from mutant phenotype PubMed 17720578. Source: MGI

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from mutant phenotype PubMed 17720578. Source: MGI

positive regulation of phosphatidylinositol biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of vasoconstriction

Inferred from electronic annotation. Source: Ensembl

protein localization to cytoskeleton

Inferred from direct assay PubMed 17720578. Source: MGI

regulation of behavior

Inferred from electronic annotation. Source: InterPro

regulation of dopamine secretion

Inferred from electronic annotation. Source: Ensembl

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 electronic annotation. Source: Ensembl

sleep

Inferred from electronic annotation. Source: Ensembl

temperature homeostasis

Inferred from electronic annotation. Source: Ensembl

urinary bladder smooth muscle contraction

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentaxon

Inferred from electronic annotation. Source: UniProtKB-SubCell

caveola

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell body fiber

Inferred from electronic annotation. Source: Ensembl

cytoplasmic membrane-bounded vesicle

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from electronic annotation. Source: Ensembl

dendritic shaft

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Inferred from electronic annotation. Source: InterPro

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

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

Inferred from electronic annotation. Source: Ensembl

drug binding

Inferred from electronic annotation. Source: Ensembl

serotonin binding

Inferred from sequence orthology PubMed 7582481. Source: MGI

serotonin receptor activity

Inferred from sequence orthology PubMed 7582481. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 4714715-hydroxytryptamine receptor 2A
PRO_0000068948

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
P35363 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: DE763E5617EE8435

FASTA47152,842
        10         20         30         40         50         60 
MEILCEDNIS LSSIPNSLMQ LGDDSRLYPN DFNSRDANTS EASNWTIDAE NRTNLSCEGY 

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

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

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

       250        260        270        280        290        300 
VAFFIPLTIM VITYFLTIKS LQKEATLCVS DLSTRAKLSS 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 VNTIPTLAYK 

       430        440        450        460        470 
SSQLQVGQKK NSQEDAEPTA NDCSMVTLGN QHSEEMCTDN IETVNEKVSC V 

« Hide

References

[1]"Gene structure and expression of the mouse 5-HT2 receptor."
Yang W., Chen K., Lan N.C., Gallaher T.K., Shih J.C.
J. Neurosci. Res. 33:196-204(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]"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: DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[3]"The serotonin 5-HT2A and 5-HT2C receptors interact with specific sets of PDZ proteins."
Becamel C., Gavarini S., Chanrion B., Alonso G., Galeotti N., Dumuis A., Bockaert J., Marin P.
J. Biol. Chem. 279:20257-20266(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[4]"Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice."
Weisstaub N.V., Zhou M., Lira A., Lambe E., Gonzalez-Maeso J., Hornung J.P., Sibille E., Underwood M., Itohara S., Dauer W.T., Ansorge M.S., Morelli E., Mann J.J., Toth M., Aghajanian G., Sealfon S.C., Hen R., Gingrich J.A.
Science 313:536-540(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[5]"Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior."
Gonzalez-Maeso J., Weisstaub N.V., Zhou M., Chan P., Ivic L., Ang R., Lira A., Bradley-Moore M., Ge Y., Zhou Q., Sealfon S.C., Gingrich J.A.
Neuron 53:439-452(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[6]"Identification of a serotonin/glutamate receptor complex implicated in psychosis."
Gonzalez-Maeso J., Ang R.L., Yuen T., Chan P., Weisstaub N.V., Lopez-Gimenez J.F., Zhou M., Okawa Y., Callado L.F., Milligan G., Gingrich J.A., Filizola M., Meana J.J., Sealfon S.C.
Nature 452:93-97(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRM2, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[7]"Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors."
Albizu L., Holloway T., Gonzalez-Maeso J., Sealfon S.C.
Neuropharmacology 61:770-777(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DRD2, FUNCTION, SUBCELLULAR LOCATION.
[8]"5HT(2A) and 5HT(2B) receptors contribute to serotonin-induced vascular dysfunction in diabetes."
Nelson P.M., Harrod J.S., Lamping K.G.
Exp. Diabetes Res. 2012:398406-398406(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Identification of three residues essential for 5-hydroxytryptamine 2A-metabotropic glutamate 2 (5-HT2A.mGlu2) receptor heteromerization and its psychoactive behavioral function."
Moreno J.L., Muguruza C., Umali A., Mortillo S., Holloway T., Pilar-Cuellar F., Mocci G., Seto J., Callado L.F., Neve R.L., Milligan G., Sealfon S.C., Lopez-Gimenez J.F., Meana J.J., Benson D.L., Gonzalez-Maeso J.
J. Biol. Chem. 287:44301-44319(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S49542 mRNA. Translation: AAB24369.1.
PIRS40689.
RefSeqNP_766400.1. NM_172812.2.
UniGeneMm.214351.

3D structure databases

ProteinModelPortalP35363.
SMRP35363. Positions 38-400.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP35363. 1 interaction.
STRING10090.ENSMUSP00000047774.

Chemistry

BindingDBP35363.
ChEMBLCHEMBL2109245.
GuidetoPHARMACOLOGY6.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP35363.

Proteomic databases

PRIDEP35363.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000036653; ENSMUSP00000047774; ENSMUSG00000034997.
GeneID15558.
KEGGmmu:15558.
UCSCuc007uqc.1. mouse.

Organism-specific databases

CTD3356.
MGIMGI:109521. Htr2a.

Phylogenomic databases

eggNOGNOG247243.
HOGENOMHOG000240378.
HOVERGENHBG107487.
InParanoidP35363.
KOK04157.
OMAFITNVMA.
OrthoDBEOG70ZZN5.
PhylomeDBP35363.
TreeFamTF316350.

Gene expression databases

BgeeP35363.
CleanExMM_HTR2A.
GenevestigatorP35363.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
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

NextBio288500.
PROP35363.
SOURCESearch...

Entry information

Entry name5HT2A_MOUSE
AccessionPrimary (citable) accession number: P35363
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: April 16, 2014
This is version 111 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries