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Q64264

- 5HT1A_MOUSE

UniProt

Q64264 - 5HT1A_MOUSE

Protein

5-hydroxytryptamine receptor 1A

Gene

Htr1a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 128 (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. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca2+ ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.6 Publications

    GO - Molecular functioni

    1. serotonin receptor activity Source: UniProtKB

    GO - Biological processi

    1. adenylate cyclase-inhibiting serotonin receptor signaling pathway Source: UniProtKB
    2. behavioral fear response Source: UniProtKB
    3. cell proliferation Source: InterPro
    4. exploration behavior Source: UniProtKB
    5. regulation of behavior Source: InterPro
    6. regulation of dopamine metabolic process Source: UniProtKB
    7. regulation of hormone secretion Source: InterPro
    8. regulation of serotonin secretion Source: UniProtKB
    9. serotonin metabolic process Source: UniProtKB
    10. serotonin receptor signaling pathway Source: UniProtKB
    11. vasoconstriction Source: InterPro

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Keywords - Biological processi

    Behavior

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    5-hydroxytryptamine receptor 1A
    Short name:
    5-HT-1A
    Short name:
    5-HT1A
    Alternative name(s):
    Serotonin receptor 1A
    Gene namesi
    Name:Htr1a
    Synonyms:Gpcr18
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 13

    Organism-specific databases

    MGIiMGI:96273. Htr1a.

    Subcellular locationi

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

    GO - Cellular componenti

    1. integral component of plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Mutant mice display decreased exploratory behavior and increased fear-related behavior in anxiogenic environments. Mutant mice display altered monoamine metabolism in specific parts of the brain, especially in dorsal and medial raphe nuclei, thalamus and hypothalamus, leading to altered levels of 5-hydroxytryptamine, dopamine and their metabolites, as well as altered noradrenaline levels.3 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 4214215-hydroxytryptamine receptor 1APRO_0000068904Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi10 – 101N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi11 – 111N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi24 – 241N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi30 – 301N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi109 ↔ 187PROSITE-ProRule annotation
    Cross-linki334 – 334Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Isopeptide bond, Ubl conjugation

    Proteomic databases

    PRIDEiQ64264.

    PTM databases

    PhosphoSiteiQ64264.

    Expressioni

    Tissue specificityi

    Most abundantly expressed in midbrain, in dorsal raphe and hippocampus. Detected at lower levels in amygdala and brain cortex.1 Publication

    Gene expression databases

    BgeeiQ64264.
    CleanExiMM_HTR1A.
    GenevestigatoriQ64264.

    Interactioni

    Subunit structurei

    Heterodimer; heterodimerizes with GPER1.By similarity

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000022235.

    Structurei

    3D structure databases

    ProteinModelPortaliQ64264.
    SMRiQ64264. Positions 30-418.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3636ExtracellularBy similarityAdd
    BLAST
    Topological domaini63 – 7311CytoplasmicBy similarityAdd
    BLAST
    Topological domaini99 – 11012ExtracellularBy similarityAdd
    BLAST
    Topological domaini133 – 15220CytoplasmicBy similarityAdd
    BLAST
    Topological domaini179 – 19113ExtracellularBy similarityAdd
    BLAST
    Topological domaini218 – 345128CytoplasmicBy similarityAdd
    BLAST
    Topological domaini368 – 37811ExtracellularBy similarityAdd
    BLAST
    Topological domaini404 – 42118CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei37 – 6226Helical; Name=1By similarityAdd
    BLAST
    Transmembranei74 – 9825Helical; Name=2By similarityAdd
    BLAST
    Transmembranei111 – 13222Helical; Name=3By similarityAdd
    BLAST
    Transmembranei153 – 17826Helical; Name=4By similarityAdd
    BLAST
    Transmembranei192 – 21726Helical; Name=5By similarityAdd
    BLAST
    Transmembranei346 – 36722Helical; Name=6By similarityAdd
    BLAST
    Transmembranei379 – 40325Helical; Name=7By similarityAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni112 – 12110Agonist bindingBy similarity
    Regioni358 – 3625Agonist bindingBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi133 – 1353DRY motif; important for ligand-induced conformation changesBy similarity
    Motifi396 – 4005NPxxY motif; important for ligand-induced conformation changes and signalingBy similarity

    Sequence similaritiesi

    Belongs to the G-protein coupled receptor 1 family. 5-hydroxytryptamine receptor subfamily. HTR1A sub-subfamily.PROSITE-ProRule annotation

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG249628.
    GeneTreeiENSGT00750000117301.
    HOGENOMiHOG000239242.
    HOVERGENiHBG106962.
    InParanoidiQ8BGS4.
    KOiK04153.
    OMAiREWRQGV.
    OrthoDBiEOG7NCV3Q.
    TreeFamiTF316350.

    Family and domain databases

    Gene3Di1.20.1070.10. 2 hits.
    InterProiIPR000610. 5HT1A_rcpt.
    IPR002231. 5HT_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view]
    PANTHERiPTHR24247:SF20. PTHR24247:SF20. 1 hit.
    PfamiPF00001. 7tm_1. 1 hit.
    [Graphical view]
    PRINTSiPR00512. 5HT1ARECEPTR.
    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.

    Q64264-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDMFSLGQGN NTTTSLEPFG TGGNDTGLSN VTFSYQVITS LLLGTLIFCA    50
    VLGNACVVAA IALERSLQNV ANYLIGSLAV TDLMVSVLVL PMAALYQVLN 100
    KWTLGQVTCD LFIALDVLCC TSSILHLCAI ALDRYWAITD PIDYVNKRTP 150
    RRAAALISLT WLIGFLISIP PMLGWRTPED RSNPNECTIS KDHGYTIYST 200
    FGAFYIPLLL MLVLYGRIFR AARFRIRKTV KKVEKKGAGT SFGTSSAPPP 250
    KKSLNGQPGS GDCRRSAENR AVGTPCANGA VRQGEDDATL EVIEVHRVGN 300
    SKGHLPLPSE SGATSYVPAC LERKNERTAE AKRKMALARE RKTVKTLGII 350
    MGTFILCWLP FFIVALVLPF CESSCHMPEL LGAIINWLGY SNSLLNPVIY 400
    AYFNKDFQNA FKKIIKCKFC R 421
    Length:421
    Mass (Da):46,176
    Last modified:July 27, 2011 - v2
    Checksum:i74F519DF7CC0C7AA
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti177 – 1771T → A in AAA81519. (PubMed:8254366)Curated
    Sequence conflicti242 – 2421F → L in AAA16850. (PubMed:8288218)Curated
    Sequence conflicti247 – 2471A → V in AAA16850. (PubMed:8288218)Curated
    Sequence conflicti263 – 2631C → W in AAA16850. (PubMed:8288218)Curated
    Sequence conflicti304 – 3041H → D in AAA81519. (PubMed:8254366)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti17 – 193EPF → DHL in strain: C3H/An.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U39391 mRNA. Translation: AAA81519.1.
    AK043668 mRNA. Translation: BAC31611.1.
    AK049814 mRNA. Translation: BAC33931.1.
    AK049884 mRNA. Translation: BAC33970.1.
    AK140194 mRNA. Translation: BAE24273.1.
    CH466568 Genomic DNA. Translation: EDL18479.1.
    BC138669 mRNA. Translation: AAI38670.1.
    BC138681 mRNA. Translation: AAI38682.1.
    U33820 Genomic DNA. Translation: AAC52572.1.
    L20339 mRNA. Translation: AAA16850.1.
    CCDSiCCDS26756.1.
    PIRiI49375.
    RefSeqiNP_032334.2. NM_008308.4.
    UniGeneiMm.4716.

    Genome annotation databases

    EnsembliENSMUST00000022235; ENSMUSP00000022235; ENSMUSG00000021721.
    GeneIDi15550.
    KEGGimmu:15550.
    UCSCiuc007rtu.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U39391 mRNA. Translation: AAA81519.1 .
    AK043668 mRNA. Translation: BAC31611.1 .
    AK049814 mRNA. Translation: BAC33931.1 .
    AK049884 mRNA. Translation: BAC33970.1 .
    AK140194 mRNA. Translation: BAE24273.1 .
    CH466568 Genomic DNA. Translation: EDL18479.1 .
    BC138669 mRNA. Translation: AAI38670.1 .
    BC138681 mRNA. Translation: AAI38682.1 .
    U33820 Genomic DNA. Translation: AAC52572.1 .
    L20339 mRNA. Translation: AAA16850.1 .
    CCDSi CCDS26756.1.
    PIRi I49375.
    RefSeqi NP_032334.2. NM_008308.4.
    UniGenei Mm.4716.

    3D structure databases

    ProteinModelPortali Q64264.
    SMRi Q64264. Positions 30-418.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10090.ENSMUSP00000022235.

    Chemistry

    BindingDBi Q64264.
    ChEMBLi CHEMBL3737.
    GuidetoPHARMACOLOGYi 1.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q64264.

    Proteomic databases

    PRIDEi Q64264.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000022235 ; ENSMUSP00000022235 ; ENSMUSG00000021721 .
    GeneIDi 15550.
    KEGGi mmu:15550.
    UCSCi uc007rtu.2. mouse.

    Organism-specific databases

    CTDi 3350.
    MGIi MGI:96273. Htr1a.

    Phylogenomic databases

    eggNOGi NOG249628.
    GeneTreei ENSGT00750000117301.
    HOGENOMi HOG000239242.
    HOVERGENi HBG106962.
    InParanoidi Q8BGS4.
    KOi K04153.
    OMAi REWRQGV.
    OrthoDBi EOG7NCV3Q.
    TreeFami TF316350.

    Miscellaneous databases

    NextBioi 288480.
    PROi Q64264.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q64264.
    CleanExi MM_HTR1A.
    Genevestigatori Q64264.

    Family and domain databases

    Gene3Di 1.20.1070.10. 2 hits.
    InterProi IPR000610. 5HT1A_rcpt.
    IPR002231. 5HT_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view ]
    PANTHERi PTHR24247:SF20. PTHR24247:SF20. 1 hit.
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00512. 5HT1ARECEPTR.
    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. "Cloning and differentiation-induced expression of a murine serotonin 1A receptor in a septal cell line."
      Charest A., Wainer B.H., Albert P.R.
      J. Neurosci. 13:5164-5171(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
      Strain: NIH Swiss.
      Tissue: Brain.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Brain cortex, Corpora quadrigemina and Hippocampus.
    3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    5. "The serotonin 1a receptor gene contains a TATA-less promoter that responds to MAZ and Sp1."
      Parks C.L., Shenk T.
      J. Biol. Chem. 271:4417-4430(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-23.
      Strain: C3H/An.
    6. "Identification, chromosomal location, and genome organization of mammalian G-protein-coupled receptors."
      Wilkie T.M., Chen Y., Gilbert D.J., Moore K.J., Yu L., Simon M.I., Copeland N.G., Jenkins N.A.
      Genomics 18:175-184(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 136-353.
      Tissue: Testis.
    7. Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, FUNCTION.
    8. "Altered serotonin and dopamine metabolism in the CNS of serotonin 5-HT(1A) or 5-HT(1B) receptor knockout mice."
      Ase A.R., Reader T.A., Hen R., Riad M., Descarries L.
      J. Neurochem. 75:2415-2426(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    9. "Embryonic and postnatal development of the serotonergic raphe system and its target regions in 5-HT1A receptor deletion or overexpressing mouse mutants."
      Deng D.R., Djalali S., Holtje M., Grosse G., Stroh T., Voigt I., Kusserow H., Theuring F., Ahnert-Hilger G., Hortnagl H.
      Neuroscience 147:388-402(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    10. "Sporadic autonomic dysregulation and death associated with excessive serotonin autoinhibition."
      Audero E., Coppi E., Mlinar B., Rossetti T., Caprioli A., Banchaabouchi M.A., Corradetti R., Gross C.
      Science 321:130-133(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    11. "Serotonin-1A autoreceptors are necessary and sufficient for the normal formation of circuits underlying innate anxiety."
      Richardson-Jones J.W., Craige C.P., Nguyen T.H., Kung H.F., Gardier A.M., Dranovsky A., David D.J., Guiard B.P., Beck S.G., Hen R., Leonardo E.D.
      J. Neurosci. 31:6008-6018(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry namei5HT1A_MOUSE
    AccessioniPrimary (citable) accession number: Q64264
    Secondary accession number(s): Q60956, Q61617, Q8BGS4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 128 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