5-hydroxytryptamine receptor 1A

Details

Name
5-hydroxytryptamine receptor 1A
Synonyms
  • 5-HT-1A
  • ADRB2RL1
  • ADRBRL1
  • G-21
  • Serotonin receptor 1A
Gene Name
HTR1A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0018934|5-hydroxytryptamine receptor 1A
MDVLSPGQGNNTTSPPAPFETGGNTTGISDVTVSYQVITSLLLGTLIFCAVLGNACVVAA
IALERSLQNVANYLIGSLAVTDLMVSVLVLPMAALYQVLNKWTLGQVTCDLFIALDVLCC
TSSILHLCAIALDRYWAITDPIDYVNKRTPRRAAALISLTWLIGFLISIPPMLGWRTPED
RSDPDACTISKDHGYTIYSTFGAFYIPLLLMLVLYGRIFRAARFRIRKTVKKVEKTGADT
RHGASPAPQPKKSVNGESGSRNWRLGVESKAGGALCANGAVRQGDDGAALEVIEVHRVGN
SKEHLPLPSEAGPTPCAPASFERKNERNAEAKRKMALARERKTVKTLGIIMGTFILCWLP
FFIVALVLPFCESSCHMPTLLGAIINWLGYSNSLLNPVIYAYFNKDFQNAFKKIIKCKFC
RQ
Number of residues
422
Molecular Weight
46106.335
Theoretical pI
9.05
GO Classification
Functions
serotonin receptor activity
Processes
adenylate cyclase-inhibiting serotonin receptor signaling pathway / behavioral fear response / cell proliferation / exploration behavior / G-protein coupled receptor signaling pathway / positive regulation of cell proliferation / regulation of behavior / regulation of dopamine metabolic process / regulation of hormone secretion / regulation of serotonin secretion / serotonin metabolic process / serotonin receptor signaling pathway / vasoconstriction
Components
integral component of plasma membrane / plasma membrane
General Function
Serotonin receptor activity
Specific Function
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 Ca(2+) 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.
Pfam Domain Function
Transmembrane Regions
37-62 74-98 111-132 153-178 192-217 346-367 379-403
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0018935|5-hydroxytryptamine receptor 1A (HTR1A)
ATGGATGTGCTCAGCCCTGGTCAGGGCAACAACACCACATCACCACCGGCTCCCTTTGAG
ACCGGCGGCAACACTACTGGTATCTCCGACGTGACCGTCAGCTACCAAGTGATCACCTCT
CTGCTGCTGGGCACGCTCATCTTCTGCGCGGTGCTGGGCAATGCGTGCGTGGTGGCTGCC
ATCGCCTTGGAGCGCTCCCTGCAGAACGTGGCCAATTATCTTATTGGCTCTTTGGCGGTC
ACCGACCTCATGGTGTCGGTGTTGGTGCTGCCCATGGCCGCGCTGTATCAGGTGCTCAAC
AAGTGGACACTGGGCCAGGTAACCTGCGACCTGTTCATCGCCCTCGACGTGCTGTGCTGC
ACCTCATCCATCTTGCACCTGTGCGCCATCGCGCTGGACAGGTACTGGGCCATCACGGAC
CCCATCGACTACGTGAACAAGAGGACGCCCCGGCGCGCCGCTGCGCTCATCTCGCTCACT
TGGCTTATTGGCTTCCTCATCTCTATCCCGCCCATGCTGGGCTGGCGCACCCCGGAAGAC
CGCTCGGACCCCGACGCATGCACCATTAGCAAGGATCATGGCTACACTATCTATTCCACC
TTTGGAGCTTTCTACATCCCGCTGCTGCTCATGCTGGTTCTCTATGGGCGCATATTCCGA
GCTGCGCGCTTCCGCATCCGCAAGACGGTCAAAAAGGTGGAGAAGACCGGAGCGGACACC
CGCCATGGAGCATCTCCCGCCCCGCAGCCCAAGAAGAGTGTGAATGGAGAGTCGGGGAGC
AGGAACTGGAGGCTGGGCGTGGAGAGCAAGGCTGGGGGTGCTCTGTGCGCCAATGGCGCG
GTGAGGCAAGGTGACGATGGCGCCGCCCTGGAGGTGATCGAGGTGCACCGAGTGGGCAAC
TCCAAAGAGCACTTGCCTCTGCCCAGCGAGGCTGGTCCTACCCCTTGTGCCCCCGCCTCT
TTCGAGAGGAAAAATGAGCGCAACGCCGAGGCGAAGCGCAAGATGGCCCTGGCCCGAGAG
AGGAAGACAGTGAAGACGCTGGGCATCATCATGGGCACCTTCATCCTCTGCTGGCTGCCC
TTCTTCATCGTGGCTCTTGTTCTGCCCTTCTGCGAGAGCAGCTGCCACATGCCCACCCTG
TTGGGCGCCATAATCAATTGGCTGGGCTACTCCAACTCTCTGCTTAACCCCGTCATTTAC
GCATACTTCAACAAGGACTTTCAAAACGCGTTTAAGAAGATCATTAAGTGTAAGTTCTGC
CGCCAGTGA
Chromosome Location
5
Locus
5q11.2-q13
External Identifiers
ResourceLink
UniProtKB IDP08908
UniProtKB Entry Name5HT1A_HUMAN
GenBank Protein ID189928
GenBank Gene IDM28269
GenAtlas IDHTR1A
HGNC IDHGNC:5286
General References
  1. Kobilka BK, Frielle T, Collins S, Yang-Feng T, Kobilka TS, Francke U, Lefkowitz RJ, Caron MG: An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins. Nature. 1987 Sep 3-9;329(6134):75-9. [PubMed:3041227]
  2. Kitano T, Liu YH, Ueda S, Saitou N: Human-specific amino acid changes found in 103 protein-coding genes. Mol Biol Evol. 2004 May;21(5):936-44. Epub 2004 Mar 10. [PubMed:15014171]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  4. Parks CL, Chang LS, Shenk T: A polymerase chain reaction mediated by a single primer: cloning of genomic sequences adjacent to a serotonin receptor protein coding region. Nucleic Acids Res. 1991 Dec;19(25):7155-60. [PubMed:1766875]
  5. Aune TM, McGrath KM, Sarr T, Bombara MP, Kelley KA: Expression of 5HT1a receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-hydroxytryptamine. J Immunol. 1993 Aug 1;151(3):1175-83. [PubMed:8393041]
  6. Fargin A, Raymond JR, Lohse MJ, Kobilka BK, Caron MG, Lefkowitz RJ: The genomic clone G-21 which resembles a beta-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature. 1988 Sep 22;335(6188):358-60. [PubMed:3138543]
  7. Harrington MA, Shaw K, Zhong P, Ciaranello RD: Agonist-induced desensitization and loss of high-affinity binding sites of stably expressed human 5-HT1A receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1098-106. [PubMed:8138923]
  8. Vasilescu J, Zweitzig DR, Denis NJ, Smith JC, Ethier M, Haines DS, Figeys D: The proteomic reactor facilitates the analysis of affinity-purified proteins by mass spectrometry: application for identifying ubiquitinated proteins in human cells. J Proteome Res. 2007 Jan;6(1):298-305. [PubMed:17203973]
  9. Nichols DE, Nichols CD: Serotonin receptors. Chem Rev. 2008 May;108(5):1614-41. doi: 10.1021/cr078224o. Epub 2008 May 14. [PubMed:18476671]
  10. Polter AM, Li X: 5-HT1A receptor-regulated signal transduction pathways in brain. Cell Signal. 2010 Oct;22(10):1406-12. doi: 10.1016/j.cellsig.2010.03.019. Epub 2010 Apr 2. [PubMed:20363322]
  11. Pytliak M, Vargova V, Mechirova V, Felsoci M: Serotonin receptors - from molecular biology to clinical applications. Physiol Res. 2011;60(1):15-25. Epub 2010 Oct 15. [PubMed:20945968]
  12. Jiang YC, Wu HM, Cheng KH, Sunny Sun H: Menstrual cycle-dependent febrile episode mediated by sequence-specific repression of poly(ADP-ribose) polymerase-1 on the transcription of the human serotonin receptor 1A gene. Hum Mutat. 2012 Jan;33(1):209-17. doi: 10.1002/humu.21622. Epub 2011 Nov 7. [PubMed:21990073]
  13. Singh P, Paila YD, Chattopadhyay A: Role of glycosphingolipids in the function of human serotonin(1)A receptors. J Neurochem. 2012 Dec;123(5):716-24. doi: 10.1111/jnc.12008. Epub 2012 Oct 11. [PubMed:22957663]
  14. Akama KT, Thompson LI, Milner TA, McEwen BS: Post-synaptic density-95 (PSD-95) binding capacity of G-protein-coupled receptor 30 (GPR30), an estrogen receptor that can be identified in hippocampal dendritic spines. J Biol Chem. 2013 Mar 1;288(9):6438-50. doi: 10.1074/jbc.M112.412478. Epub 2013 Jan 8. [PubMed:23300088]
  15. Nakhai B, Nielsen DA, Linnoila M, Goldman D: Two naturally occurring amino acid substitutions in the human 5-HT1A receptor: glycine 22 to serine 22 and isoleucine 28 to valine 28. Biochem Biophys Res Commun. 1995 May 16;210(2):530-6. [PubMed:7755630]
  16. Kawanishi Y, Harada S, Tachikawa H, Okubo T, Shiraishi H: Novel mutations in the promoter and coding region of the human 5-HT1A receptor gene and association analysis in schizophrenia. Am J Med Genet. 1998 Sep 7;81(5):434-9. [PubMed:9754630]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00490Buspironeapproved, investigationalyespartial agonistDetails
DB00216Eletriptanapproved, investigationalunknownagonistDetails
DB00246ZiprasidoneapprovedunknownagonistDetails
DB01238Aripiprazoleapproved, investigationalunknownpartial agonistDetails
DB00247MethysergideapprovedyesagonistDetails
DB00363ClozapineapprovedunknownantagonistDetails
DB00589Lisurideapproved, investigationalunknownagonistDetails
DB00656Trazodoneapproved, investigationalyesantagonistpartial agonistDetails
DB00866Alprenololexperimental, withdrawnyesantagonistDetails
DB00960Pindololapproved, investigationalunknownantagonistDetails
DB01224Quetiapineapprovedunknownantagonistpartial agonistDetails
DB04884DapoxetineinvestigationalunknownDetails
DB04888BifeprunoxinvestigationalunknownDetails
DB04908Flibanserinapproved, investigationalyesagonistDetails
DB04970LesopitroninvestigationalunknownDetails
DB12061PardoprunoxinvestigationalunknownDetails
DB05339MN-305investigationalunknownDetails
DB05509LI-301investigationalunknownDetails
DB00571Propranololapproved, investigationalunknownother/unknownDetails
DB06216AsenapineapprovedunknownantagonistDetails
DB06393XaliprodeninvestigationalunknownDetails
DB06506RepinotaninvestigationalunknownDetails
DB06446DotarizineinvestigationalunknownDetails
DB06454SarizotaninvestigationalunknownDetails
DB06538RobalzotaninvestigationalunknownDetails
DB06684VilazodoneapprovedunknownagonistDetails
DB01186Pergolideapproved, investigational, vet_approved, withdrawnunknownagonistDetails
DB01200Bromocriptineapproved, investigationalunknownagonistDetails
DB00248CabergolineapprovedunknownagonistDetails
DB00413Pramipexoleapproved, investigationalunknownagonistDetails
DB05271RotigotineapprovedunknownagonistDetails
DB00714Apomorphineapproved, investigationalunknownagonistDetails
DB00734Risperidoneapproved, investigationalunknownantagonistDetails
DB01267PaliperidoneapprovedunknownantagonistDetails
DB01618MolindoneapprovedunknownantagonistDetails
DB00321AmitriptylineapprovedunknowninhibitorinducerDetails
DB01142Doxepinapproved, investigationalunknownantagonistDetails
DB01149Nefazodoneapproved, withdrawnyesantagonistDetails
DB00540NortriptylineapprovedunknownantagonistDetails
DB00726TrimipramineapprovedunknownantagonistDetails
DB01392Yohimbineapproved, investigational, vet_approvedunknownpartial agonistDetails
DB00952Naratriptanapproved, investigationalyesagonistDetails
DB00315Zolmitriptanapproved, investigationalyesagonistDetails
DB00669Sumatriptanapproved, investigationalyesagonistDetails
DB00477Chlorpromazineapproved, investigational, vet_approvedyesantagonistDetails
DB08807BopindololexperimentalunknownDetails
DB00904Ondansetronapprovedunknownother/unknownDetails
DB01616Alverineapproved, investigationalyesantagonistDetails
DB01614Acepromazineexperimental, vet_approvedyesantagonistDetails
DB01621Pipotiazineapproved, investigationalyesantagonistDetails
DB01622ThioproperazineexperimentalyesantagonistDetails
DB08810CinitaprideinvestigationalyesagonistDetails
DB04946IloperidoneapprovedunknownantagonistDetails
DB08815Lurasidoneapproved, investigationalunknownantagonistDetails
DB01359Penbutololapproved, investigationalyesantagonistDetails
DB04829Lysergic acid diethylamideillicit, investigational, withdrawnunknownDetails
DB00408LoxapineapprovedunknownbinderDetails
DB00458ImipramineapprovedunknownactivatorDetails
DB00543AmoxapineapprovedunknownantagonistDetails
DB00988DopamineapprovedunknownbinderDetails
DB00696ErgotamineapprovedunknownagonistDetails
DB01151Desipramineapproved, investigationalunknownbinderDetails
DB06148Mianserinapproved, investigationalunknownblockerDetails
DB09068Vortioxetineapproved, investigationalyesagonistDetails
DB09128Brexpiprazoleapproved, investigationalyesagonistpartial agonistDetails
DB06016Cariprazineapproved, investigationalyesagonistpartial agonistDetails
DB08922Perospironeexperimentalyespartial agonistDetails
DB09167DosulepinapprovedyesantagonistDetails
DB09061Cannabidiolapproved, investigationalunknownagonistDetails
DB09244PirlindoleexperimentalunknownantagonistDetails
DB06153PizotifenapprovedunknownantagonistDetails
DB140105-methoxy-N,N-dimethyltryptamineexperimental, illicitunknownagonistDetails
DB14011NabiximolsinvestigationalunknownDetails
DB14009Medical Cannabisexperimental, investigationalunknownDetails
DB11755TetrahydrocannabivarininvestigationalyesagonistDetails
DB04948Lofexidineapproved, investigationalnoagonistDetails
DB05562NaluzotaninvestigationalunknownagonistDetails
DB09289TianeptineinvestigationalunknowninhibitorDetails
DB14185Aripiprazole lauroxilapproved, investigationalyespartial agonistDetails
DB00422Methylphenidateapproved, investigationalunknownDetails
DB00502HaloperidolapprovedunknownDetails
DB01175EscitalopramapprovedunknowninhibitorDetails
DB13025TiaprideinvestigationalyesantagonistDetails
DB09304SetiptilineexperimentalunknownantagonistDetails
DB13345Dihydroergocristineapproved, experimentalyesantagonistDetails
DB01049Ergoloid mesylateapprovedyesantagonistagonistDetails
DB11273DihydroergocornineapprovedyesantagonistagonistDetails
DB12141Gilteritinibapproved, investigationalnoinhibitorDetails
DB00715Paroxetineapproved, investigationalunknownDetails
DB01221Ketamineapproved, vet_approvedunknownantagonistDetails
DB00334Olanzapineapproved, investigationalunknowninhibitorDetails