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P28221

- 5HT1D_HUMAN

UniProt

P28221 - 5HT1D_HUMAN

Protein

5-hydroxytryptamine receptor 1D

Gene

HTR1D

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 1 (01 Dec 1992)
      Previous versions | rss
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    Functioni

    G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other 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. Signaling inhibits adenylate cyclase activity. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction.3 Publications

    GO - Molecular functioni

    1. serotonin binding Source: Ensembl
    2. serotonin receptor activity Source: UniProtKB

    GO - Biological processi

    1. adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: UniProtKB
    2. G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
    3. intestine smooth muscle contraction Source: UniProtKB
    4. regulation of behavior Source: InterPro
    5. regulation of locomotion Source: InterPro
    6. response to toxic substance Source: Ensembl
    7. synaptic transmission Source: ProtInc
    8. vasoconstriction Source: InterPro

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Enzyme and pathway databases

    ReactomeiREACT_17064. Serotonin receptors.
    REACT_19231. G alpha (i) signalling events.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    5-hydroxytryptamine receptor 1D
    Short name:
    5-HT-1D
    Short name:
    5-HT1D
    Alternative name(s):
    Serotonin 1D alpha receptor
    Short name:
    5-HT-1D-alpha
    Serotonin receptor 1D
    Gene namesi
    Name:HTR1D
    Synonyms:HTR1DA, HTRL
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:5289. HTR1D.

    Subcellular locationi

    Cell membrane 3 Publications; Multi-pass membrane protein 3 Publications

    GO - Cellular componenti

    1. integral component of plasma membrane Source: UniProtKB
    2. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA29550.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 3773775-hydroxytryptamine receptor 1DPRO_0000068927Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi5 – 51N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi17 – 171N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi21 – 211N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi111 ↔ 188PROSITE-ProRule annotation

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PRIDEiP28221.

    PTM databases

    PhosphoSiteiP28221.

    Expressioni

    Tissue specificityi

    Detected in brain neocortex and caudate nucleus (at protein level).1 Publication

    Gene expression databases

    BgeeiP28221.
    CleanExiHS_HTR1D.
    GenevestigatoriP28221.

    Organism-specific databases

    HPAiCAB022770.
    CAB022775.

    Interactioni

    Subunit structurei

    Homodimer. Heterodimer with HTR1B.1 Publication

    Protein-protein interaction databases

    BioGridi109584. 3 interactions.
    STRINGi9606.ENSP00000313661.

    Structurei

    3D structure databases

    ProteinModelPortaliP28221.
    SMRiP28221. Positions 38-374.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3838ExtracellularBy similarityAdd
    BLAST
    Topological domaini65 – 7511CytoplasmicBy similarityAdd
    BLAST
    Topological domaini99 – 11214ExtracellularBy similarityAdd
    BLAST
    Topological domaini135 – 15420CytoplasmicBy similarityAdd
    BLAST
    Topological domaini177 – 19418ExtracellularBy similarityAdd
    BLAST
    Topological domaini218 – 30285CytoplasmicBy similarityAdd
    BLAST
    Topological domaini327 – 3359ExtracellularBy similarity
    Topological domaini361 – 37717CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei39 – 6426Helical; Name=1By similarityAdd
    BLAST
    Transmembranei76 – 9823Helical; Name=2By similarityAdd
    BLAST
    Transmembranei113 – 13422Helical; Name=3By similarityAdd
    BLAST
    Transmembranei155 – 17622Helical; Name=4By similarityAdd
    BLAST
    Transmembranei195 – 21723Helical; Name=5By similarityAdd
    BLAST
    Transmembranei303 – 32624Helical; Name=6By similarityAdd
    BLAST
    Transmembranei336 – 36025Helical; Name=7By similarityAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni114 – 12310Agonist bindingBy similarity
    Regioni314 – 3185Agonist bindingBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi135 – 1373DRY motif; important for ligand-induced conformation changesBy similarity
    Motifi352 – 3565NPxxY motif; important for ligand-induced conformation changes and signalingBy similarity

    Sequence similaritiesi

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

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG249628.
    HOGENOMiHOG000239242.
    HOVERGENiHBG106962.
    InParanoidiP28221.
    KOiK04153.
    OMAiCRDSCWI.
    OrthoDBiEOG7NCV3Q.
    PhylomeDBiP28221.
    TreeFamiTF316350.

    Family and domain databases

    Gene3Di1.20.1070.10. 2 hits.
    InterProiIPR000505. 5HT1D_rcpt.
    IPR002231. 5HT_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view]
    PANTHERiPTHR24247:SF17. PTHR24247:SF17. 1 hit.
    PfamiPF00001. 7tm_1. 1 hit.
    [Graphical view]
    PRINTSiPR00514. 5HT1DRECEPTR.
    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.

    P28221-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSPLNQSAEG LPQEASNRSL NATETSEAWD PRTLQALKIS LAVVLSVITL    50
    ATVLSNAFVL TTILLTRKLH TPANYLIGSL ATTDLLVSIL VMPISIAYTI 100
    THTWNFGQIL CDIWLSSDIT CCTASILHLC VIALDRYWAI TDALEYSKRR 150
    TAGHAATMIA IVWAISICIS IPPLFWRQAK AQEEMSDCLV NTSQISYTIY 200
    STCGAFYIPS VLLIILYGRI YRAARNRILN PPSLYGKRFT TAHLITGSAG 250
    SSLCSLNSSL HEGHSHSAGS PLFFNHVKIK LADSALERKR ISAARERKAT 300
    KILGIILGAF IICWLPFFVV SLVLPICRDS CWIHPALFDF FTWLGYLNSL 350
    INPIIYTVFN EEFRQAFQKI VPFRKAS 377
    Length:377
    Mass (Da):41,907
    Last modified:December 1, 1992 - v1
    Checksum:i0A4FCF81FFE2322A
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti265 – 2651S → L.1 Publication
    Corresponds to variant rs6299 [ dbSNP | Ensembl ].
    VAR_011834

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M89955 Genomic DNA. Translation: AAA35491.1.
    M81589 mRNA. Translation: AAA60315.1.
    AF498979 mRNA. Translation: AAM21126.1.
    BT007027 mRNA. Translation: AAP35673.1.
    AL049576 Genomic DNA. Translation: CAB81617.1.
    BC007720 mRNA. Translation: AAH07720.1.
    CCDSiCCDS231.1.
    PIRiA53279.
    RefSeqiNP_000855.1. NM_000864.4.
    UniGeneiHs.121482.

    Genome annotation databases

    EnsembliENST00000374619; ENSP00000363748; ENSG00000179546.
    GeneIDi3352.
    KEGGihsa:3352.
    UCSCiuc001bgn.3. human.

    Polymorphism databases

    DMDMi112819.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M89955 Genomic DNA. Translation: AAA35491.1 .
    M81589 mRNA. Translation: AAA60315.1 .
    AF498979 mRNA. Translation: AAM21126.1 .
    BT007027 mRNA. Translation: AAP35673.1 .
    AL049576 Genomic DNA. Translation: CAB81617.1 .
    BC007720 mRNA. Translation: AAH07720.1 .
    CCDSi CCDS231.1.
    PIRi A53279.
    RefSeqi NP_000855.1. NM_000864.4.
    UniGenei Hs.121482.

    3D structure databases

    ProteinModelPortali P28221.
    SMRi P28221. Positions 38-374.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109584. 3 interactions.
    STRINGi 9606.ENSP00000313661.

    Chemistry

    BindingDBi P28221.
    ChEMBLi CHEMBL1983.
    DrugBanki DB00918. Almotriptan.
    DB00320. Dihydroergotamine.
    DB00216. Eletriptan.
    DB00696. Ergotamine.
    DB00998. Frovatriptan.
    DB00952. Naratriptan.
    DB00953. Rizatriptan.
    DB00669. Sumatriptan.
    DB01079. Tegaserod.
    DB00246. Ziprasidone.
    DB00315. Zolmitriptan.
    GuidetoPHARMACOLOGYi 3.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei P28221.

    Polymorphism databases

    DMDMi 112819.

    Proteomic databases

    PRIDEi P28221.

    Protocols and materials databases

    DNASUi 3352.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000374619 ; ENSP00000363748 ; ENSG00000179546 .
    GeneIDi 3352.
    KEGGi hsa:3352.
    UCSCi uc001bgn.3. human.

    Organism-specific databases

    CTDi 3352.
    GeneCardsi GC01M023517.
    HGNCi HGNC:5289. HTR1D.
    HPAi CAB022770.
    CAB022775.
    MIMi 182133. gene.
    neXtProti NX_P28221.
    PharmGKBi PA29550.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG249628.
    HOGENOMi HOG000239242.
    HOVERGENi HBG106962.
    InParanoidi P28221.
    KOi K04153.
    OMAi CRDSCWI.
    OrthoDBi EOG7NCV3Q.
    PhylomeDBi P28221.
    TreeFami TF316350.

    Enzyme and pathway databases

    Reactomei REACT_17064. Serotonin receptors.
    REACT_19231. G alpha (i) signalling events.

    Miscellaneous databases

    GeneWikii 5-HT1D_receptor.
    GenomeRNAii 3352.
    NextBioi 13256.
    PROi P28221.
    SOURCEi Search...

    Gene expression databases

    Bgeei P28221.
    CleanExi HS_HTR1D.
    Genevestigatori P28221.

    Family and domain databases

    Gene3Di 1.20.1070.10. 2 hits.
    InterProi IPR000505. 5HT1D_rcpt.
    IPR002231. 5HT_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view ]
    PANTHERi PTHR24247:SF17. PTHR24247:SF17. 1 hit.
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00514. 5HT1DRECEPTR.
    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. "Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor."
      Hamblin M.W., Metcalf M.A.
      Mol. Pharmacol. 40:143-148(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION.
    2. "Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta."
      Weinshank R.L., Zgombick J.M., Macchi M.J., Branchek T.A., Hartig P.R.
      Proc. Natl. Acad. Sci. U.S.A. 89:3630-3634(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
      Tissue: Placenta.
    3. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
      Puhl H.L. III, Ikeda S.R., Aronstam R.S.
      Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    4. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    5. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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: Eye.
    7. "Postsynaptic localization of 5-HT1D receptor binding sites in human caudate."
      Gonzalez-Heydrich J., Peroutka S.J.
      Exp. Neurol. 113:28-30(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    8. "Serotonin 5-HT1B and 5-HT1D receptors form homodimers when expressed alone and heterodimers when co-expressed."
      Xie Z., Lee S.P., O'Dowd B.F., George S.R.
      FEBS Lett. 456:63-67(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
    9. Cited for: REVIEW.
    10. "Serotonin receptors - from molecular biology to clinical applications."
      Pytliak M., Vargova V., Mechirova V., Felsoci M.
      Physiol. Res. 60:15-25(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    11. Cited for: VARIANT LEU-265.

    Entry informationi

    Entry namei5HT1D_HUMAN
    AccessioniPrimary (citable) accession number: P28221
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 1992
    Last sequence update: December 1, 1992
    Last modified: October 1, 2014
    This is version 139 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3