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P28221

- 5HT1D_HUMAN

UniProt

P28221 - 5HT1D_HUMAN

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Protein

5-hydroxytryptamine receptor 1D

Gene

HTR1D

Organism
Homo sapiens (Human)
Status
Reviewed - 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: Chromosome 1

Organism-specific databases

HGNCiHGNC:5289. HTR1D.

Subcellular locationi

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.

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

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

        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 databases

DMDMi112819.

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 .
CCDSi CCDS231.1.
PIRi A53279.
RefSeqi NP_000855.1. NM_000864.4.
UniGenei Hs.121482.

3D structure databases

ProteinModelPortali P28221.
SMRi P28221. Positions 4-374.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109584. 3 interactions.
STRINGi 9606.ENSP00000313661.

Chemistry

BindingDBi P28221.
ChEMBLi CHEMBL2096904.
DrugBanki DB00918. 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.
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.
GeneTreei ENSGT00760000118795.
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

« 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: October 29, 2014
This is version 140 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