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P35363

- 5HT2A_MOUSE

UniProt

P35363 - 5HT2A_MOUSE

Protein

5-hydroxytryptamine receptor 2A

Gene

Htr2a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 116 (01 Oct 2014)
      Sequence version 1 (01 Jun 1994)
      Previous versions | rss
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    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: Ensembl
    2. drug binding Source: Ensembl
    3. serotonin binding Source: MGI
    4. serotonin receptor activity Source: MGI

    GO - Biological processi

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

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Keywords - Biological processi

    Behavior

    Enzyme and pathway databases

    ReactomeiREACT_207651. 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: Chromosome 14

    Organism-specific databases

    MGIiMGI:109521. Htr2a.

    Subcellular locationi

    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.

    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

    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
    Disulfide bondi349 ↔ 353PROSITE-ProRule annotation

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    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.
    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 7575ExtracellularBy similarityAdd
    BLAST
    Topological domaini100 – 11011CytoplasmicBy similarityAdd
    BLAST
    Topological domaini133 – 14816ExtracellularBy similarityAdd
    BLAST
    Topological domaini172 – 19120CytoplasmicBy similarityAdd
    BLAST
    Topological domaini216 – 23318ExtracellularBy similarityAdd
    BLAST
    Topological domaini255 – 32470CytoplasmicBy similarityAdd
    BLAST
    Topological domaini347 – 36216ExtracellularBy similarityAdd
    BLAST
    Topological domaini385 – 47187CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei76 – 9924Helical; Name=1By similarityAdd
    BLAST
    Transmembranei111 – 13222Helical; Name=2By similarityAdd
    BLAST
    Transmembranei149 – 17123Helical; Name=3By similarityAdd
    BLAST
    Transmembranei192 – 21524Helical; Name=4By similarityAdd
    BLAST
    Transmembranei234 – 25421Helical; Name=5By similarityAdd
    BLAST
    Transmembranei325 – 34622Helical; Name=6By similarityAdd
    BLAST
    Transmembranei363 – 38422Helical; Name=7By similarityAdd
    BLAST

    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

    Gene3Di1.20.1070.10. 1 hit.
    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

    MEILCEDNIS LSSIPNSLMQ LGDDSRLYPN DFNSRDANTS EASNWTIDAE    50
    NRTNLSCEGY LPPTCLSILH LQEKNWSALL TTVVIILTIA GNILVIMAVS 100
    LEKKLQNATN YFLMSLAIAD MLLGFLVMPV SMLTILYGYR WPLPSKLCAV 150
    WIYLDVLFST ASIMHLCAIS LDRYVAIQNP IHHSRFNSRT KAFLKIIAVW 200
    TISVGISMPI PVFGLQDDSK VFKEGSCLLA DDNFVLIGSF VAFFIPLTIM 250
    VITYFLTIKS LQKEATLCVS DLSTRAKLSS FSFLPQSSLS SEKLFQRSIH 300
    REPGSYAGRR TMQSISNEQK ACKVLGIVFF LFVVMWCPFF ITNIMAVICK 350
    ESCNENVIGA LLNVFVWIGY LSSAVNPLVY TLFNKTYRSA FSRYIQCQYK 400
    ENRKPLQLIL VNTIPTLAYK SSQLQVGQKK NSQEDAEPTA NDCSMVTLGN 450
    QHSEEMCTDN IETVNEKVSC V 471
    Length:471
    Mass (Da):52,842
    Last modified:June 1, 1994 - v1
    Checksum:iDE763E5617EE8435
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    S49542 mRNA. Translation: AAB24369.1 .
    CCDSi CCDS27275.1.
    PIRi S40689.
    RefSeqi NP_766400.1. NM_172812.2.
    UniGenei Mm.214351.

    3D structure databases

    ProteinModelPortali P35363.
    SMRi P35363. Positions 38-400.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P35363. 1 interaction.
    STRINGi 10090.ENSMUSP00000047774.

    Chemistry

    BindingDBi P35363.
    ChEMBLi CHEMBL5377.
    GuidetoPHARMACOLOGYi 6.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei P35363.

    Proteomic databases

    PRIDEi P35363.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000036653 ; ENSMUSP00000047774 ; ENSMUSG00000034997 .
    GeneIDi 15558.
    KEGGi mmu:15558.
    UCSCi uc007uqc.1. mouse.

    Organism-specific databases

    CTDi 3356.
    MGIi MGI:109521. Htr2a.

    Phylogenomic databases

    eggNOGi NOG247243.
    HOGENOMi HOG000240378.
    HOVERGENi HBG107487.
    InParanoidi P35363.
    KOi K04157.
    OMAi CTMVALG.
    OrthoDBi EOG70ZZN5.
    PhylomeDBi P35363.
    TreeFami TF316350.

    Enzyme and pathway databases

    Reactomei REACT_207651. G alpha (q) signalling events.

    Miscellaneous databases

    NextBioi 288500.
    PROi P35363.
    SOURCEi Search...

    Gene expression databases

    Bgeei P35363.
    CleanExi MM_HTR2A.
    Genevestigatori P35363.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR000455. 5HT2A_rcpt.
    IPR002231. 5HT_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view ]
    PANTHERi PTHR24247:SF30. PTHR24247:SF30. 1 hit.
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00516. 5HT2ARECEPTR.
    PR01101. 5HTRECEPTOR.
    PR00237. GPCRRHODOPSN.
    PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    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: October 1, 2014
    This is version 116 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