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P28221 (5HT1D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:HTR1D
Synonyms:HTR1DA, HTRL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length377 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2 Ref.8

Subunit structure

Homodimer. Heterodimer with HTR1B. Ref.8

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.1 Ref.2 Ref.8.

Tissue specificity

Detected in brain neocortex and caudate nucleus (at protein level). Ref.7

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 3773775-hydroxytryptamine receptor 1D
PRO_0000068927

Regions

Topological domain1 – 3838Extracellular By similarity
Transmembrane39 – 6426Helical; Name=1; By similarity
Topological domain65 – 7511Cytoplasmic By similarity
Transmembrane76 – 9823Helical; Name=2; By similarity
Topological domain99 – 11214Extracellular By similarity
Transmembrane113 – 13422Helical; Name=3; By similarity
Topological domain135 – 15420Cytoplasmic By similarity
Transmembrane155 – 17622Helical; Name=4; By similarity
Topological domain177 – 19418Extracellular By similarity
Transmembrane195 – 21723Helical; Name=5; By similarity
Topological domain218 – 30285Cytoplasmic By similarity
Transmembrane303 – 32624Helical; Name=6; By similarity
Topological domain327 – 3359Extracellular By similarity
Transmembrane336 – 36025Helical; Name=7; By similarity
Topological domain361 – 37717Cytoplasmic By similarity
Region114 – 12310Agonist binding By similarity
Region314 – 3185Agonist binding By similarity
Motif135 – 1373DRY motif; important for ligand-induced conformation changes By similarity
Motif352 – 3565NPxxY motif; important for ligand-induced conformation changes and signaling By similarity

Amino acid modifications

Glycosylation51N-linked (GlcNAc...) Potential
Glycosylation171N-linked (GlcNAc...) Potential
Glycosylation211N-linked (GlcNAc...) Potential
Disulfide bond111 ↔ 188 By similarity

Natural variations

Natural variant2651S → L. Ref.11
Corresponds to variant rs6299 [ dbSNP | Ensembl ].
VAR_011834

Sequences

Sequence LengthMass (Da)Tools
P28221 [UniParc].

Last modified December 1, 1992. Version 1.
Checksum: 0A4FCF81FFE2322A

FASTA37741,907
        10         20         30         40         50         60 
MSPLNQSAEG LPQEASNRSL NATETSEAWD PRTLQALKIS LAVVLSVITL ATVLSNAFVL 

        70         80         90        100        110        120 
TTILLTRKLH TPANYLIGSL ATTDLLVSIL VMPISIAYTI THTWNFGQIL CDIWLSSDIT 

       130        140        150        160        170        180 
CCTASILHLC VIALDRYWAI TDALEYSKRR TAGHAATMIA IVWAISICIS IPPLFWRQAK 

       190        200        210        220        230        240 
AQEEMSDCLV NTSQISYTIY STCGAFYIPS VLLIILYGRI YRAARNRILN PPSLYGKRFT 

       250        260        270        280        290        300 
TAHLITGSAG SSLCSLNSSL HEGHSHSAGS PLFFNHVKIK LADSALERKR ISAARERKAT 

       310        320        330        340        350        360 
KILGIILGAF IICWLPFFVV SLVLPICRDS CWIHPALFDF FTWLGYLNSL INPIIYTVFN 

       370 
EEFRQAFQKI VPFRKAS 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Serotonin receptors."
Nichols D.E., Nichols C.D.
Chem. Rev. 108:1614-1641(2008) [PubMed] [Europe PMC] [Abstract]
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]"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LEU-265.
[12]Erratum
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 23:373-373(1999)
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS231.1.
PIRA53279.
RefSeqNP_000855.1. NM_000864.4.
UniGeneHs.121482.

3D structure databases

ProteinModelPortalP28221.
SMRP28221. Positions 38-374.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109584. 3 interactions.
STRING9606.ENSP00000313661.

Chemistry

BindingDBP28221.
ChEMBLCHEMBL1983.
DrugBankDB00918. Almotriptan.
DB00320. Dihydroergotamine.
DB00216. Eletriptan.
DB00696. Ergotamine.
DB00998. Frovatriptan.
DB00952. Naratriptan.
DB00953. Rizatriptan.
DB00669. Sumatriptan.
DB01079. Tegaserod.
DB00246. Ziprasidone.
DB00315. Zolmitriptan.
GuidetoPHARMACOLOGY3.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP28221.

Polymorphism databases

DMDM112819.

Proteomic databases

PRIDEP28221.

Protocols and materials databases

DNASU3352.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000314113; ENSP00000313661; ENSG00000179546.
ENST00000374619; ENSP00000363748; ENSG00000179546.
GeneID3352.
KEGGhsa:3352.
UCSCuc001bgn.3. human.

Organism-specific databases

CTD3352.
GeneCardsGC01M023517.
HGNCHGNC:5289. HTR1D.
HPACAB022770.
CAB022775.
MIM182133. gene.
neXtProtNX_P28221.
PharmGKBPA29550.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG249628.
HOGENOMHOG000239242.
HOVERGENHBG106962.
InParanoidP28221.
KOK04153.
OMACRDSCWI.
OrthoDBEOG7NCV3Q.
PhylomeDBP28221.
TreeFamTF316350.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeP28221.
CleanExHS_HTR1D.
GenevestigatorP28221.

Family and domain databases

Gene3D1.20.1070.10. 2 hits.
InterProIPR000505. 5HT1D_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24247:SF17. PTHR24247:SF17. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00514. 5HT1DRECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWiki5-HT1D_receptor.
GenomeRNAi3352.
NextBio13256.
PROP28221.
SOURCESearch...

Entry information

Entry name5HT1D_HUMAN
AccessionPrimary (citable) accession number: P28221
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: July 9, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries