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P34968

- 5HT2C_MOUSE

UniProt

P34968 - 5HT2C_MOUSE

Protein

5-hydroxytryptamine receptor 2C

Gene

Htr2c

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 117 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      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.8 Publications

    GO - Molecular functioni

    1. 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding Source: Ensembl
    2. drug binding Source: Ensembl
    3. Gq/11-coupled serotonin receptor activity Source: UniProtKB
    4. serotonin binding Source: MGI
    5. serotonin receptor activity Source: UniProtKB

    GO - Biological processi

    1. behavioral fear response Source: UniProtKB
    2. cGMP biosynthetic process Source: Ensembl
    3. feeding behavior Source: UniProtKB
    4. locomotory behavior Source: InterPro
    5. phospholipase C-activating serotonin receptor signaling pathway Source: UniProtKB
    6. positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Source: UniProtKB
    7. positive regulation of ERK1 and ERK2 cascade Source: Ensembl
    8. positive regulation of phosphatidylinositol biosynthetic process Source: Ensembl
    9. regulation of appetite Source: UniProtKB
    10. regulation of corticotropin-releasing hormone secretion Source: UniProtKB
    11. regulation of neurological system process Source: UniProtKB
    12. release of sequestered calcium ion into cytosol Source: Ensembl
    13. response to drug 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 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
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome X

    Organism-specific databases

    MGIiMGI:96281. Htr2c.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    No obvious phenotype at birth, but mutant mice are prone to sudden death from seizures. When fed ad libitum, adult mice display higher body weight and increased adiposity compared to wild-type littermates. No difference in body weight is found when they receive the same amount of food as their wild-type littermates, indicating that the increased body weight is due to altered feeding behavior. Overweight older mice develop insulin resistance and impaired glucose tolerance. Young mice exibit insulin resistance, but normal glucose tolerance, due to increased insulin levels in the blood. Insulin resistance is reversed when Htr2c expression is restored in pro-opiomelacortin neurons. Mutant mice display impaired activation of pro-opiomelacortin neurons in the paraventricular nucleus of the hypothalamus, leading to decreased release of CRH and corticosterone. Likewise, they exhibit blunted behavorial responses to anxiogenic environments and stress.9 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3232By similarityAdd
    BLAST
    Chaini33 – 4594275-hydroxytryptamine receptor 2CPRO_0000068959Add
    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 bondi338 ↔ 342PROSITE-ProRule annotation

    Post-translational modificationi

    N-glycosylated.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PRIDEiP34968.

    PTM databases

    PhosphoSiteiP34968.

    Expressioni

    Tissue specificityi

    Detected in brain cortex, hypothalamus, brainstem and arcuate nucleus. Detected in the paraventricular nucleus of the hypothalamus.3 Publications

    Gene expression databases

    BgeeiP34968.
    CleanExiMM_HTR2C.
    GenevestigatoriP34968.

    Interactioni

    Subunit structurei

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

    Structurei

    3D structure databases

    ProteinModelPortaliP34968.
    SMRiP34968. Positions 55-389.
    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 – 31276CytoplasmicBy similarityAdd
    BLAST
    Topological domaini335 – 34915ExtracellularBy similarityAdd
    BLAST
    Topological domaini373 – 45987CytoplasmicBy 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
    Transmembranei313 – 33422Helical; Name=6By similarityAdd
    BLAST
    Transmembranei350 – 37223Helical; Name=7By similarityAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni135 – 1406Agonist bindingBy similarity
    Regioni325 – 3295Agonist bindingBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi152 – 1543DRY motif; important for ligand-induced conformation changesBy similarity
    Motifi365 – 3695NPxxY motif; important for ligand-induced conformation changes and signalingBy similarity
    Motifi457 – 4593PDZ-binding

    Domaini

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

    Sequence similaritiesi

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

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG247243.
    GeneTreeiENSGT00750000117240.
    HOGENOMiHOG000240378.
    HOVERGENiHBG107487.
    InParanoidiB1ATN5.
    KOiK04157.
    OMAiSSYIRCQ.
    OrthoDBiEOG70ZZN5.
    TreeFamiTF316350.

    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.

    P34968-1 [UniParc]FASTAAdd to Basket

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    MVNLGTAVRS LLVHLIGLLV 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
    RGHTEEELRN ISLNFLKCCC KKGDEEENAP NPNPDQKPRR KKKEKRPRGT 300
    MQAINNEKKA SKVLGIVFFV FLIMWCPFFI TNILSVLCGK ACNQKLMEKL 350
    LNVFVWIGYV CSGINPLVYT LFNKIYRRAF SKYLRCDYKP DKKPPVRQIP 400
    RVAATALSGR ELNVNIYRHT NERVVRKAND TEPGIEMQVE NLELPVNPSN 450
    VVSERISSV 459
    Length:459
    Mass (Da):51,929
    Last modified:July 27, 2011 - v2
    Checksum:iAA3C537B2ADCB0C9
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti157 – 1615IRNPI → VRSPV in CAA51031. (PubMed:1661811)Curated
    Sequence conflicti157 – 1615IRNPI → VRSPV in AAA10521. (PubMed:1381232)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X72230 mRNA. Translation: CAA51031.1.
    S44559
    , S44556, S44557, S44558 Genomic DNA. Translation: AAA10521.1.
    AL808014, AL662932 Genomic DNA. Translation: CAM15060.1.
    AL662932, AL808014 Genomic DNA. Translation: CAM15766.1.
    CCDSiCCDS30459.1.
    PIRiA43951.
    RefSeqiNP_032338.3. NM_008312.4.
    UniGeneiMm.439670.

    Genome annotation databases

    EnsembliENSMUST00000036303; ENSMUSP00000043936; ENSMUSG00000041380.
    ENSMUST00000096299; ENSMUSP00000094021; ENSMUSG00000041380.
    GeneIDi15560.
    KEGGimmu:15560.
    UCSCiuc009und.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X72230 mRNA. Translation: CAA51031.1 .
    S44559
    , S44556 , S44557 , S44558 Genomic DNA. Translation: AAA10521.1 .
    AL808014 , AL662932 Genomic DNA. Translation: CAM15060.1 .
    AL662932 , AL808014 Genomic DNA. Translation: CAM15766.1 .
    CCDSi CCDS30459.1.
    PIRi A43951.
    RefSeqi NP_032338.3. NM_008312.4.
    UniGenei Mm.439670.

    3D structure databases

    ProteinModelPortali P34968.
    SMRi P34968. Positions 55-389.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P34968.
    ChEMBLi CHEMBL2109245.
    GuidetoPHARMACOLOGYi 8.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei P34968.

    Proteomic databases

    PRIDEi P34968.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000036303 ; ENSMUSP00000043936 ; ENSMUSG00000041380 .
    ENSMUST00000096299 ; ENSMUSP00000094021 ; ENSMUSG00000041380 .
    GeneIDi 15560.
    KEGGi mmu:15560.
    UCSCi uc009und.2. mouse.

    Organism-specific databases

    CTDi 3358.
    MGIi MGI:96281. Htr2c.

    Phylogenomic databases

    eggNOGi NOG247243.
    GeneTreei ENSGT00750000117240.
    HOGENOMi HOG000240378.
    HOVERGENi HBG107487.
    InParanoidi B1ATN5.
    KOi K04157.
    OMAi SSYIRCQ.
    OrthoDBi EOG70ZZN5.
    TreeFami TF316350.

    Enzyme and pathway databases

    Reactomei REACT_207651. G alpha (q) signalling events.

    Miscellaneous databases

    ChiTaRSi HTR2C. mouse.
    NextBioi 288508.
    PROi P34968.
    SOURCEi Search...

    Gene expression databases

    Bgeei P34968.
    CleanExi MM_HTR2C.
    Genevestigatori P34968.

    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. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Structure of the mouse 5-HT1C, 5-HT2 and stomach fundus serotonin receptor genes."
      Foguet M., Nguyen H., Le H., Luebbert H.
      NeuroReport 3:345-348(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    4. "Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors."
      Tecott L.H., Sun L.M., Akana S.F., Strack A.M., Lowenstein D.H., Dallman M.F., Julius D.
      Nature 374:542-546(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
    5. "Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene."
      Nonogaki K., Strack A.M., Dallman M.F., Tecott L.H.
      Nat. Med. 4:1152-1156(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    6. "Serotonin 5-HT(2C) receptors regulate anxiety-like behavior."
      Heisler L.K., Zhou L., Bajwa P., Hsu J., Tecott L.H.
      Genes Brain Behav. 6:491-496(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    7. "Serotonin activates the hypothalamic-pituitary-adrenal axis via serotonin 2C receptor stimulation."
      Heisler L.K., Pronchuk N., Nonogaki K., Zhou L., Raber J., Tung L., Yeo G.S., O'Rahilly S., Colmers W.F., Elmquist J.K., Tecott L.H.
      J. Neurosci. 27:6956-6964(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
    8. "5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis."
      Xu Y., Jones J.E., Kohno D., Williams K.W., Lee C.E., Choi M.J., Anderson J.G., Heisler L.K., Zigman J.M., Lowell B.B., Elmquist J.K.
      Neuron 60:582-589(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
    9. "Characterizing the effects of 5-HT(2C) receptor ligands on motor activity and feeding behaviour in 5-HT(2C) receptor knockout mice."
      Fletcher P.J., Tampakeras M., Sinyard J., Slassi A., Isaac M., Higgins G.A.
      Neuropharmacology 57:259-267(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    10. Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    11. Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    12. "Serotonin 2C receptor activates a distinct population of arcuate pro-opiomelanocortin neurons via TRPC channels."
      Sohn J.W., Xu Y., Jones J.E., Wickman K., Williams K.W., Elmquist J.K.
      Neuron 71:488-497(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.

    Entry informationi

    Entry namei5HT2C_MOUSE
    AccessioniPrimary (citable) accession number: P34968
    Secondary accession number(s): B1ATN5, Q5WRU6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 117 of the entry and version 2 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