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Protein

5-hydroxytryptamine receptor 1D

Gene

HTR1D

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. serotonin receptor signaling pathway Source: GOC
  8. synaptic transmission Source: ProtInc
  9. vasoconstriction Source: InterPro
Complete GO annotation...

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 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:5289. HTR1D.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3838ExtracellularBy similarityAdd
BLAST
Transmembranei39 – 6426Helical; Name=1By similarityAdd
BLAST
Topological domaini65 – 7511CytoplasmicBy similarityAdd
BLAST
Transmembranei76 – 9823Helical; Name=2By similarityAdd
BLAST
Topological domaini99 – 11214ExtracellularBy similarityAdd
BLAST
Transmembranei113 – 13422Helical; Name=3By similarityAdd
BLAST
Topological domaini135 – 15420CytoplasmicBy similarityAdd
BLAST
Transmembranei155 – 17622Helical; Name=4By similarityAdd
BLAST
Topological domaini177 – 19418ExtracellularBy similarityAdd
BLAST
Transmembranei195 – 21723Helical; Name=5By similarityAdd
BLAST
Topological domaini218 – 30285CytoplasmicBy similarityAdd
BLAST
Transmembranei303 – 32624Helical; Name=6By similarityAdd
BLAST
Topological domaini327 – 3359ExtracellularBy similarity
Transmembranei336 – 36025Helical; Name=7By similarityAdd
BLAST
Topological domaini361 – 37717CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29550.

Chemistry

DrugBankiDB00918. Almotriptan.
DB00321. Amitriptyline.
DB00714. Apomorphine.
DB01238. Aripiprazole.
DB01200. Bromocriptine.
DB00248. Cabergoline.
DB00363. Clozapine.
DB00320. Dihydroergotamine.
DB00216. Eletriptan.
DB01049. Ergoloid mesylate.
DB00696. Ergotamine.
DB00998. Frovatriptan.
DB01221. Ketamine.
DB00589. Lisuride.
DB00408. Loxapine.
DB00952. Naratriptan.
DB00334. Olanzapine.
DB01267. Paliperidone.
DB01186. Pergolide.
DB00413. Pramipexole.
DB01224. Quetiapine.
DB00734. Risperidone.
DB00953. Rizatriptan.
DB00268. Ropinirole.
DB00669. Sumatriptan.
DB00726. Trimipramine.
DB01392. Yohimbine.
DB00246. Ziprasidone.
DB00315. Zolmitriptan.

Polymorphism and mutation databases

BioMutaiHTR1D.
DMDMi112819.

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 4-374.
ModBaseiSearch...
MobiDBiSearch...

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.
GeneTreeiENSGT00760000118795.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP28221.
KOiK04153.
OMAiCRDSCWI.
OrthoDBiEOG7NCV3Q.
PhylomeDBiP28221.
TreeFamiTF316350.

Family and domain databases

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

        10         20         30         40         50
MSPLNQSAEG LPQEASNRSL NATETSEAWD PRTLQALKIS LAVVLSVITL
60 70 80 90 100
ATVLSNAFVL TTILLTRKLH TPANYLIGSL ATTDLLVSIL VMPISIAYTI
110 120 130 140 150
THTWNFGQIL CDIWLSSDIT CCTASILHLC VIALDRYWAI TDALEYSKRR
160 170 180 190 200
TAGHAATMIA IVWAISICIS IPPLFWRQAK AQEEMSDCLV NTSQISYTIY
210 220 230 240 250
STCGAFYIPS VLLIILYGRI YRAARNRILN PPSLYGKRFT TAHLITGSAG
260 270 280 290 300
SSLCSLNSSL HEGHSHSAGS PLFFNHVKIK LADSALERKR ISAARERKAT
310 320 330 340 350
KILGIILGAF IICWLPFFVV SLVLPICRDS CWIHPALFDF FTWLGYLNSL
360 370
INPIIYTVFN EEFRQAFQKI VPFRKAS
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:
EMBLi
GenBanki
DDBJi
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 and mutation databases

BioMutaiHTR1D.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliP28221.
SMRiP28221. Positions 4-374.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109584. 3 interactions.
STRINGi9606.ENSP00000313661.

Chemistry

BindingDBiP28221.
ChEMBLiCHEMBL2096904.
DrugBankiDB00918. Almotriptan.
DB00321. Amitriptyline.
DB00714. Apomorphine.
DB01238. Aripiprazole.
DB01200. Bromocriptine.
DB00248. Cabergoline.
DB00363. Clozapine.
DB00320. Dihydroergotamine.
DB00216. Eletriptan.
DB01049. Ergoloid mesylate.
DB00696. Ergotamine.
DB00998. Frovatriptan.
DB01221. Ketamine.
DB00589. Lisuride.
DB00408. Loxapine.
DB00952. Naratriptan.
DB00334. Olanzapine.
DB01267. Paliperidone.
DB01186. Pergolide.
DB00413. Pramipexole.
DB01224. Quetiapine.
DB00734. Risperidone.
DB00953. Rizatriptan.
DB00268. Ropinirole.
DB00669. Sumatriptan.
DB00726. Trimipramine.
DB01392. Yohimbine.
DB00246. Ziprasidone.
DB00315. Zolmitriptan.
GuidetoPHARMACOLOGYi3.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiP28221.

Polymorphism and mutation databases

BioMutaiHTR1D.
DMDMi112819.

Proteomic databases

PRIDEiP28221.

Protocols and materials databases

DNASUi3352.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3352.
GeneCardsiGC01M023517.
HGNCiHGNC:5289. HTR1D.
HPAiCAB022770.
CAB022775.
MIMi182133. gene.
neXtProtiNX_P28221.
PharmGKBiPA29550.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG249628.
GeneTreeiENSGT00760000118795.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP28221.
KOiK04153.
OMAiCRDSCWI.
OrthoDBiEOG7NCV3Q.
PhylomeDBiP28221.
TreeFamiTF316350.

Enzyme and pathway databases

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

Miscellaneous databases

GeneWikii5-HT1D_receptor.
GenomeRNAii3352.
NextBioi13256.
PROiP28221.
SOURCEiSearch...

Gene expression databases

BgeeiP28221.
CleanExiHS_HTR1D.
GenevestigatoriP28221.

Family and domain databases

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: April 29, 2015
This is version 142 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.