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Protein

5-hydroxytryptamine receptor 2A

Gene

Htr2a

Organism
Mus musculus (Mouse)
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.5 Publications

GO - Molecular functioni

  1. 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding Source: MGI
  2. drug binding Source: MGI
  3. serotonin binding Source: MGI
  4. serotonin receptor activity Source: MGI

GO - Biological processi

  1. activation of phospholipase C activity Source: MGI
  2. aging Source: Ensembl
  3. artery smooth muscle contraction Source: Ensembl
  4. behavioral response to cocaine Source: Ensembl
  5. cell death Source: Ensembl
  6. cellular calcium ion homeostasis Source: MGI
  7. detection of mechanical stimulus involved in sensory perception of pain Source: Ensembl
  8. detection of temperature stimulus involved in sensory perception of pain Source: Ensembl
  9. memory Source: Ensembl
  10. negative regulation of potassium ion transport Source: Ensembl
  11. negative regulation of synaptic transmission, glutamatergic Source: Ensembl
  12. phosphatidylinositol 3-kinase signaling Source: MGI
  13. phospholipase C-activating serotonin receptor signaling pathway Source: Ensembl
  14. positive regulation of cell proliferation Source: Ensembl
  15. positive regulation of ERK1 and ERK2 cascade Source: MGI
  16. positive regulation of fat cell differentiation Source: MGI
  17. positive regulation of glycolytic process Source: MGI
  18. positive regulation of kinase activity Source: MGI
  19. positive regulation of MAP kinase activity Source: Ensembl
  20. positive regulation of peptidyl-tyrosine phosphorylation Source: MGI
  21. positive regulation of phosphatidylinositol biosynthetic process Source: MGI
  22. positive regulation of vasoconstriction Source: Ensembl
  23. protein localization to cytoskeleton Source: MGI
  24. regulation of behavior Source: InterPro
  25. regulation of dopamine secretion Source: Ensembl
  26. regulation of hormone secretion Source: InterPro
  27. release of sequestered calcium ion into cytosol Source: MGI
  28. response to drug Source: MGI
  29. serotonin receptor signaling pathway Source: MGI
  30. sleep Source: Ensembl
  31. temperature homeostasis Source: Ensembl
  32. urinary bladder smooth muscle contraction Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Behavior

Enzyme and pathway databases

ReactomeiREACT_332615. Serotonin receptors.
REACT_347934. 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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:109521. Htr2a.

Subcellular locationi

  1. Cell membrane; Multi-pass membrane protein
  2. Cell projectiondendrite
  3. Cell projectionaxon By similarity
  4. Cytoplasmic vesicle By similarity
  5. Membranecaveola By similarity

  6. Note: Localizes to the postsynaptic thickening of axo-dendritic synapses.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 7575ExtracellularBy similarityAdd
BLAST
Transmembranei76 – 9924Helical; Name=1By similarityAdd
BLAST
Topological domaini100 – 11011CytoplasmicBy similarityAdd
BLAST
Transmembranei111 – 13222Helical; Name=2By similarityAdd
BLAST
Topological domaini133 – 14816ExtracellularBy similarityAdd
BLAST
Transmembranei149 – 17123Helical; Name=3By similarityAdd
BLAST
Topological domaini172 – 19120CytoplasmicBy similarityAdd
BLAST
Transmembranei192 – 21524Helical; Name=4By similarityAdd
BLAST
Topological domaini216 – 23318ExtracellularBy similarityAdd
BLAST
Transmembranei234 – 25421Helical; Name=5By similarityAdd
BLAST
Topological domaini255 – 32470CytoplasmicBy similarityAdd
BLAST
Transmembranei325 – 34622Helical; Name=6By similarityAdd
BLAST
Topological domaini347 – 36216ExtracellularBy similarityAdd
BLAST
Transmembranei363 – 38422Helical; Name=7By similarityAdd
BLAST
Topological domaini385 – 47187CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  1. axon Source: UniProtKB-SubCell
  2. caveola Source: UniProtKB-SubCell
  3. cell body fiber Source: Ensembl
  4. cytoplasmic membrane-bounded vesicle Source: UniProtKB-SubCell
  5. cytosol Source: Ensembl
  6. dendritic shaft Source: Ensembl
  7. integral component of plasma membrane Source: InterPro
  8. neuronal cell body Source: Ensembl
  9. plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Disruption phenotypei

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.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 4714715-hydroxytryptamine receptor 2APRO_0000068948Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi8 – 81N-linked (GlcNAc...)Sequence Analysis
Glycosylationi38 – 381N-linked (GlcNAc...)Sequence Analysis
Glycosylationi44 – 441N-linked (GlcNAc...)Sequence Analysis
Glycosylationi51 – 511N-linked (GlcNAc...)Sequence Analysis
Glycosylationi54 – 541N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi148 ↔ 227PROSITE-ProRule annotation
Modified residuei280 – 2801PhosphoserineBy similarity
Disulfide bondi349 ↔ 353PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP35363.
PRIDEiP35363.

PTM databases

PhosphoSiteiP35363.

Expressioni

Tissue specificityi

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.3 Publications

Gene expression databases

BgeeiP35363.
CleanExiMM_HTR2A.
ExpressionAtlasiP35363. baseline and differential.
GenevestigatoriP35363.

Interactioni

Subunit structurei

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.By similarity2 Publications

Protein-protein interaction databases

IntActiP35363. 1 interaction.
STRINGi10090.ENSMUSP00000047774.

Structurei

3D structure databases

ProteinModelPortaliP35363.
SMRiP35363. Positions 38-400.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni155 – 1606Agonist bindingBy similarity
Regioni336 – 3405Agonist bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi172 – 1743DRY motif; important for ligand-induced conformation changesBy similarity
Motifi376 – 3805NPxxY motif; important for ligand-induced conformation changes and signalingBy similarity
Motifi469 – 4713PDZ-binding

Domaini

The PDZ domain-binding motif is involved in the interaction with INADL, 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

eggNOGiNOG247243.
HOGENOMiHOG000240378.
HOVERGENiHBG107487.
InParanoidiP35363.
KOiK04157.
OMAiCTMVALG.
OrthoDBiEOG70ZZN5.
PhylomeDBiP35363.
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.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P35363-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEILCEDNIS LSSIPNSLMQ LGDDSRLYPN DFNSRDANTS EASNWTIDAE
60 70 80 90 100
NRTNLSCEGY LPPTCLSILH LQEKNWSALL TTVVIILTIA 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 VAFFIPLTIM
260 270 280 290 300
VITYFLTIKS LQKEATLCVS DLSTRAKLSS 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 VNTIPTLAYK SSQLQVGQKK NSQEDAEPTA NDCSMVTLGN
460 470
QHSEEMCTDN IETVNEKVSC V
Length:471
Mass (Da):52,842
Last modified:June 1, 1994 - v1
Checksum:iDE763E5617EE8435
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S49542 mRNA. Translation: AAB24369.1.
CCDSiCCDS27275.1.
PIRiS40689.
RefSeqiNP_766400.1. NM_172812.2.
UniGeneiMm.214351.

Genome annotation databases

EnsembliENSMUST00000036653; ENSMUSP00000047774; ENSMUSG00000034997.
GeneIDi15558.
KEGGimmu:15558.
UCSCiuc007uqc.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S49542 mRNA. Translation: AAB24369.1.
CCDSiCCDS27275.1.
PIRiS40689.
RefSeqiNP_766400.1. NM_172812.2.
UniGeneiMm.214351.

3D structure databases

ProteinModelPortaliP35363.
SMRiP35363. Positions 38-400.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP35363. 1 interaction.
STRINGi10090.ENSMUSP00000047774.

Chemistry

BindingDBiP35363.
ChEMBLiCHEMBL2109245.
GuidetoPHARMACOLOGYi6.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiP35363.

Proteomic databases

MaxQBiP35363.
PRIDEiP35363.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000036653; ENSMUSP00000047774; ENSMUSG00000034997.
GeneIDi15558.
KEGGimmu:15558.
UCSCiuc007uqc.1. mouse.

Organism-specific databases

CTDi3356.
MGIiMGI:109521. Htr2a.

Phylogenomic databases

eggNOGiNOG247243.
HOGENOMiHOG000240378.
HOVERGENiHBG107487.
InParanoidiP35363.
KOiK04157.
OMAiCTMVALG.
OrthoDBiEOG70ZZN5.
PhylomeDBiP35363.
TreeFamiTF316350.

Enzyme and pathway databases

ReactomeiREACT_332615. Serotonin receptors.
REACT_347934. G alpha (q) signalling events.

Miscellaneous databases

NextBioi288500.
PROiP35363.
SOURCEiSearch...

Gene expression databases

BgeeiP35363.
CleanExiMM_HTR2A.
ExpressionAtlasiP35363. baseline and differential.
GenevestigatoriP35363.

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.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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. 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. 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.

Entry informationi

Entry namei5HT2A_MOUSE
AccessioniPrimary (citable) accession number: P35363
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: April 1, 2015
This is version 122 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

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.