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P14842

- 5HT2A_RAT

UniProt

P14842 - 5HT2A_RAT

Protein

5-hydroxytryptamine receptor 2A

Gene

Htr2a

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 1 (01 Apr 1990)
      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.2 Publications

    GO - Molecular functioni

    1. 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding Source: Ensembl
    2. drug binding Source: Ensembl
    3. G-protein alpha-subunit binding Source: RGD
    4. protein binding Source: IntAct
    5. protein complex binding Source: RGD
    6. serotonin binding Source: RGD
    7. serotonin receptor activity Source: RGD

    GO - Biological processi

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

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Keywords - Biological processi

    Behavior

    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
    ProteomesiUP000002494: Chromosome 15

    Organism-specific databases

    RGDi61800. Htr2a.

    Subcellular locationi

    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

    GO - Cellular componenti

    1. axon Source: UniProtKB-SubCell
    2. caveola Source: UniProtKB-SubCell
    3. cell body fiber Source: RGD
    4. cytoplasm Source: RGD
    5. cytoplasmic membrane-bounded vesicle Source: UniProtKB-SubCell
    6. cytosol Source: RGD
    7. dendrite Source: RGD
    8. dendritic shaft Source: RGD
    9. integral component of plasma membrane Source: InterPro
    10. membrane Source: RGD
    11. neuronal cell body Source: RGD
    12. plasma membrane Source: RGD

    Keywords - Cellular componenti

    Cell membrane, Cell projection, Cytoplasmic vesicle, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 4714715-hydroxytryptamine receptor 2APRO_0000068951Add
    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

    PaxDbiP14842.
    PRIDEiP14842.

    PTM databases

    PhosphoSiteiP14842.

    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

    GenevestigatoriP14842.

    Interactioni

    Subunit structurei

    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.By similarity

    Binary interactionsi

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

    Protein-protein interaction databases

    BioGridi248227. 1 interaction.
    IntActiP14842. 1 interaction.
    STRINGi10116.ENSRNOP00000013408.

    Structurei

    Secondary structure

    1
    471
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi469 – 4713

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4OAJX-ray2.30B465-471[»]
    ProteinModelPortaliP14842.
    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.
    GeneTreeiENSGT00750000117240.
    HOGENOMiHOG000240378.
    HOVERGENiHBG107487.
    InParanoidiP14842.
    KOiK04157.
    OMAiCTMVALG.
    OrthoDBiEOG70ZZN5.
    PhylomeDBiP14842.
    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.

    P14842-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEILCEDNIS LSSIPNSLMQ LGDGPRLYHN DFNSRDANTS EASNWTIDAE    50
    NRTNLSCEGY LPPTCLSILH LQEKNWSALL TTVVIILTIA GNILVIMAVS 100
    LEKKLQNATN YFLMSLAIAD MLLGFLVMPV SMLTILYGYR WPLPSKLCAI 150
    WIYLDVLFST ASIMHLCAIS LDRYVAIQNP IHHSRFNSRT KAFLKIIAVW 200
    TISVGISMPI PVFGLQDDSK VFKEGSCLLA DDNFVLIGSF VAFFIPLTIM 250
    VITYFLTIKS LQKEATLCVS DLSTRAKLAS FSFLPQSSLS SEKLFQRSIH 300
    REPGSYAGRR TMQSISNEQK ACKVLGIVFF LFVVMWCPFF ITNIMAVICK 350
    ESCNENVIGA LLNVFVWIGY LSSAVNPLVY TLFNKTYRSA FSRYIQCQYK 400
    ENRKPLQLIL VNTIPALAYK SSQLQVGQKK NSQEDAEQTV DDCSMVTLGK 450
    QQSEENCTDN IETVNEKVSC V 471
    Length:471
    Mass (Da):52,850
    Last modified:April 1, 1990 - v1
    Checksum:i3626DACE5F6C7FF4
    GO

    Sequence cautioni

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

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M30705 mRNA. Translation: AAA42178.1 .
    X13971 mRNA. Translation: CAA32150.1 . Frameshift.
    M64867 mRNA. No translation available.
    PIRi A34863.
    S02011.
    RefSeqi NP_058950.1. NM_017254.1.
    UniGenei Rn.10294.
    Rn.146756.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4OAJ X-ray 2.30 B 465-471 [» ]
    ProteinModelPortali P14842.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 248227. 1 interaction.
    IntActi P14842. 1 interaction.
    STRINGi 10116.ENSRNOP00000013408.

    Chemistry

    BindingDBi P14842.
    ChEMBLi CHEMBL2097175.
    GuidetoPHARMACOLOGYi 6.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei P14842.

    Proteomic databases

    PaxDbi P14842.
    PRIDEi P14842.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000013408 ; ENSRNOP00000013408 ; ENSRNOG00000010063 .
    GeneIDi 29595.
    KEGGi rno:29595.
    UCSCi RGD:61800. rat.

    Organism-specific databases

    CTDi 3356.
    RGDi 61800. Htr2a.

    Phylogenomic databases

    eggNOGi NOG247243.
    GeneTreei ENSGT00750000117240.
    HOGENOMi HOG000240378.
    HOVERGENi HBG107487.
    InParanoidi P14842.
    KOi K04157.
    OMAi CTMVALG.
    OrthoDBi EOG70ZZN5.
    PhylomeDBi P14842.
    TreeFami TF316350.

    Miscellaneous databases

    NextBioi 609738.
    PROi P14842.

    Gene expression databases

    Genevestigatori P14842.

    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. "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.

    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: October 1, 2014
    This is version 126 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

    External Data

    Dasty 3