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P08909

- 5HT2C_RAT

UniProt

P08909 - 5HT2C_RAT

Protein

5-hydroxytryptamine receptor 2C

Gene

Htr2c

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 Nov 1988)
      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 ergot alkaloid derivatives, 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 a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca2+ ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and feeding behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.1 Publication

    GO - Molecular functioni

    1. Gq/11-coupled serotonin receptor activity Source: UniProtKB
    2. protein binding Source: RGD
    3. serotonin receptor activity Source: MGI

    GO - Biological processi

    1. behavioral fear response Source: UniProtKB
    2. behavioral response to nicotine Source: RGD
    3. feeding behavior Source: RGD
    4. G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: RGD
    5. inositol phosphate-mediated signaling Source: MGI
    6. locomotory behavior Source: InterPro
    7. negative regulation of dopamine metabolic process Source: RGD
    8. negative regulation of locomotion Source: RGD
    9. organ regeneration Source: RGD
    10. phospholipase C-activating serotonin receptor signaling pathway Source: RGD
    11. phospholipase D-activating G-protein coupled receptor signaling pathway Source: RGD
    12. positive regulation of acetylcholine secretion, neurotransmission Source: RGD
    13. positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Source: UniProtKB
    14. positive regulation of gamma-aminobutyric acid secretion Source: RGD
    15. positive regulation of vasoconstriction Source: RGD
    16. regulation of appetite Source: UniProtKB
    17. regulation of corticotropin-releasing hormone secretion Source: UniProtKB
    18. regulation of neurological system process Source: UniProtKB
    19. regulation of sensory perception of pain Source: RGD
    20. response to drug Source: RGD

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Keywords - Biological processi

    Behavior

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    5-hydroxytryptamine receptor 2C
    Short name:
    5-HT-2C
    Short name:
    5-HT2C
    Short name:
    5-HTR2C
    Alternative name(s):
    5-hydroxytryptamine receptor 1C
    Short name:
    5-HT-1C
    Short name:
    5-HT1C
    Serotonin receptor 2C
    Gene namesi
    Name:Htr2c
    Synonyms:5ht1c, Htr1c
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi2848. Htr2c.

    Subcellular locationi

    Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

    GO - Cellular componenti

    1. cell surface Source: RGD
    2. external side of plasma membrane Source: MGI
    3. integral component of plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi458 – 4581S → A or D: Loss of interaction with MPDZ. 1 Publication
    Mutagenesisi459 – 4591S → D: No effect on interaction with MPDZ. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3232By similarityAdd
    BLAST
    Chaini33 – 4604285-hydroxytryptamine receptor 2CPRO_0000068961Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi39 – 391N-linked (GlcNAc...)By similarity
    Disulfide bondi128 ↔ 208PROSITE-ProRule annotation
    Glycosylationi204 – 2041N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi205 – 2051N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi339 ↔ 343PROSITE-ProRule annotation

    Post-translational modificationi

    N-glycosylated.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    PTM databases

    PhosphoSiteiP08909.

    Expressioni

    Gene expression databases

    GenevestigatoriP08909.

    Interactioni

    Subunit structurei

    Interacts with MPDZ. Interacts with ARRB2 By similarity.By similarity

    Protein-protein interaction databases

    MINTiMINT-443850.
    STRINGi10116.ENSRNOP00000062375.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2MHONMR-B452-460[»]
    ProteinModelPortaliP08909.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini33 – 5321ExtracellularBy similarityAdd
    BLAST
    Topological domaini80 – 9011CytoplasmicBy similarityAdd
    BLAST
    Topological domaini112 – 12817ExtracellularBy similarityAdd
    BLAST
    Topological domaini152 – 17120CytoplasmicBy similarityAdd
    BLAST
    Topological domaini195 – 21420ExtracellularBy similarityAdd
    BLAST
    Topological domaini237 – 31377CytoplasmicBy similarityAdd
    BLAST
    Topological domaini336 – 35015ExtracellularBy similarityAdd
    BLAST
    Topological domaini374 – 46087CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei54 – 7926Helical; Name=1By similarityAdd
    BLAST
    Transmembranei91 – 11121Helical; Name=2By similarityAdd
    BLAST
    Transmembranei129 – 15123Helical; Name=3By similarityAdd
    BLAST
    Transmembranei172 – 19423Helical; Name=4By similarityAdd
    BLAST
    Transmembranei215 – 23622Helical; Name=5By similarityAdd
    BLAST
    Transmembranei314 – 33522Helical; Name=6By similarityAdd
    BLAST
    Transmembranei351 – 37323Helical; Name=7By similarityAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni135 – 1406Agonist bindingBy similarity
    Regioni326 – 3305Agonist bindingBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi152 – 1543DRY motif; important for ligand-induced conformation changesBy similarity
    Motifi366 – 3705NPxxY motif; important for ligand-induced conformation changes and signalingBy similarity
    Motifi458 – 4603PDZ-binding

    Domaini

    The PDZ domain-binding motif is involved in the interaction with MPDZ.

    Sequence similaritiesi

    Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG247243.
    HOGENOMiHOG000240378.
    HOVERGENiHBG107487.
    InParanoidiP08909.
    KOiK04157.
    PhylomeDBiP08909.

    Family and domain databases

    Gene3Di1.20.1070.10. 2 hits.
    InterProiIPR000377. 5HT2C_rcpt.
    IPR002231. 5HT_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view]
    PANTHERiPTHR24247:SF32. PTHR24247:SF32. 1 hit.
    PfamiPF00001. 7tm_1. 1 hit.
    [Graphical view]
    PRINTSiPR00517. 5HT2CRECEPTR.
    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.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P08909-1 [UniParc]FASTAAdd to Basket

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    MVNLGNAVRS LLMHLIGLLV WQFDISISPV AAIVTDTFNS SDGGRLFQFP    50
    DGVQNWPALS IVVIIIMTIG GNILVIMAVS MEKKLHNATN YFLMSLAIAD 100
    MLVGLLVMPL SLLAILYDYV WPLPRYLCPV WISLDVLFST ASIMHLCAIS 150
    LDRYVAIRNP IEHSRFNSRT KAIMKIAIVW AISIGVSVPI PVIGLRDESK 200
    VFVNNTTCVL NDPNFVLIGS FVAFFIPLTI MVITYFLTIY VLRRQTLMLL 250
    RGHTEEELAN MSLNFLNCCC KKNGGEEENA PNPNPDQKPR RKKKEKRPRG 300
    TMQAINNEKK ASKVLGIVFF VFLIMWCPFF ITNILSVLCG KACNQKLMEK 350
    LLNVFVWIGY VCSGINPLVY TLFNKIYRRA FSKYLRCDYK PDKKPPVRQI 400
    PRVAATALSG RELNVNIYRH TNERVARKAN DPEPGIEMQV ENLELPVNPS 450
    NVVSERISSV 460
    Length:460
    Mass (Da):51,917
    Last modified:November 1, 1988 - v1
    Checksum:iD44E977D8F80047E
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M21410 Genomic DNA. Translation: AAA42177.1.
    PIRiA32605.
    RefSeqiNP_036897.2. NM_012765.3.
    UniGeneiRn.9935.

    Genome annotation databases

    GeneIDi25187.
    KEGGirno:25187.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M21410 Genomic DNA. Translation: AAA42177.1 .
    PIRi A32605.
    RefSeqi NP_036897.2. NM_012765.3.
    UniGenei Rn.9935.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2MHO NMR - B 452-460 [» ]
    ProteinModelPortali P08909.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    MINTi MINT-443850.
    STRINGi 10116.ENSRNOP00000062375.

    Chemistry

    BindingDBi P08909.
    ChEMBLi CHEMBL324.
    GuidetoPHARMACOLOGYi 8.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei P08909.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 25187.
    KEGGi rno:25187.

    Organism-specific databases

    CTDi 3358.
    RGDi 2848. Htr2c.

    Phylogenomic databases

    eggNOGi NOG247243.
    HOGENOMi HOG000240378.
    HOVERGENi HBG107487.
    InParanoidi P08909.
    KOi K04157.
    PhylomeDBi P08909.

    Miscellaneous databases

    NextBioi 605689.

    Gene expression databases

    Genevestigatori P08909.

    Family and domain databases

    Gene3Di 1.20.1070.10. 2 hits.
    InterProi IPR000377. 5HT2C_rcpt.
    IPR002231. 5HT_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view ]
    PANTHERi PTHR24247:SF32. PTHR24247:SF32. 1 hit.
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00517. 5HT2CRECEPTR.
    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. "Molecular characterization of a functional cDNA encoding the serotonin 1c receptor."
      Julius D., McDermott A.B., Axel R., Jessell T.M.
      Science 241:558-564(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION.
    2. "Agonist-induced phosphorylation of the serotonin 5-HT2C receptor regulates its interaction with multiple PDZ protein 1."
      Parker L.L., Backstrom J.R., Sanders-Bush E., Shieh B.H.
      J. Biol. Chem. 278:21576-21583(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MPDZ, MUTAGENESIS OF SER-458 AND SER-459.

    Entry informationi

    Entry namei5HT2C_RAT
    AccessioniPrimary (citable) accession number: P08909
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1988
    Last sequence update: November 1, 1988
    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