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P08908 (5HT1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. 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·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
5-hydroxytryptamine receptor 1A

Short name=5-HT-1A
Short name=5-HT1A
Alternative name(s):
G-21
Serotonin receptor 1A
Gene names
Name:HTR1A
Synonyms:ADRB2RL1, ADRBRL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length422 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 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 Ca2+ 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. Ref.8 Ref.9 Ref.10 Ref.16

Subunit structure

Heterodimer; heterodimerizes with GPER1. Ref.17

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.1 Ref.8 Ref.9 Ref.16.

Tissue specificity

Detected in lymph nodes, thymus and spleen. Detected in activated T-cells, but not in resting T-cells. Ref.1 Ref.8

Involvement in disease

Periodic fever, menstrual cycle-dependent (PFMC) [MIM:614674]: A condition characterized by recurrent fevers up to 40 degrees Celsius associated with the luteal phase of the menstrual cycle. Women show menstrual cycle-dependent physiologic changes in relation to sex hormone levels. Because ovulation triggers a significant change in the hormonal milieu that is similar to local inflammation, a 0.5 to 1.0 degree Celsius increase in basal body temperature after ovulation is commonly associated with progesterone secretion and is believed to be triggered by the induction of several inflammatory cytokines.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15

Sequence similarities

Belongs to the G-protein coupled receptor 1 family. 5-hydroxytryptamine receptor subfamily. HTR1A sub-subfamily.

Ontologies

Keywords
   Biological processBehavior
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Isopeptide bond
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from mutant phenotype Ref.16. Source: UniProtKB

adenylate cyclase-inhibiting serotonin receptor signaling pathway

Inferred from direct assay Ref.8. Source: UniProtKB

behavioral fear response

Inferred from sequence or structural similarity. Source: UniProtKB

cell proliferation

Inferred from electronic annotation. Source: InterPro

exploration behavior

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Traceable author statement PubMed 1330092. Source: ProtInc

regulation of behavior

Inferred from electronic annotation. Source: InterPro

regulation of dopamine metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of hormone secretion

Inferred from electronic annotation. Source: InterPro

regulation of serotonin secretion

Inferred from sequence or structural similarity. Source: UniProtKB

serotonin metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

serotonin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

vasoconstriction

Inferred from electronic annotation. Source: InterPro

   Cellular_componentintegral component of plasma membrane

Inferred from direct assay Ref.16. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionserotonin receptor activity

Inferred from direct assay Ref.8. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

FGFR1P1136211EBI-6570214,EBI-1028277

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 4224225-hydroxytryptamine receptor 1A
PRO_0000068903

Regions

Topological domain1 – 3636Extracellular By similarity
Transmembrane37 – 6226Helical; Name=1; By similarity
Topological domain63 – 7311Cytoplasmic By similarity
Transmembrane74 – 9825Helical; Name=2; By similarity
Topological domain99 – 11012Extracellular By similarity
Transmembrane111 – 13222Helical; Name=3; By similarity
Topological domain133 – 15220Cytoplasmic By similarity
Transmembrane153 – 17826Helical; Name=4; By similarity
Topological domain179 – 19113Extracellular By similarity
Transmembrane192 – 21726Helical; Name=5; By similarity
Topological domain218 – 345128Cytoplasmic By similarity
Transmembrane346 – 36722Helical; Name=6; By similarity
Topological domain368 – 37811Extracellular By similarity
Transmembrane379 – 40325Helical; Name=7; By similarity
Topological domain404 – 42219Cytoplasmic By similarity
Region112 – 12110Agonist binding By similarity
Region358 – 3625Agonist binding By similarity
Motif133 – 1353DRY motif; important for ligand-induced conformation changes By similarity
Motif396 – 4005NPxxY motif; important for ligand-induced conformation changes and signaling By similarity

Amino acid modifications

Glycosylation101N-linked (GlcNAc...) Potential
Glycosylation111N-linked (GlcNAc...) Potential
Glycosylation241N-linked (GlcNAc...) Potential
Disulfide bond109 ↔ 187 By similarity
Cross-link334Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.11

Natural variations

Natural variant161P → L. Ref.19
Corresponds to variant rs1800041 [ dbSNP | Ensembl ].
VAR_003446
Natural variant221G → S. Ref.18
Corresponds to variant rs1799920 [ dbSNP | Ensembl ].
VAR_011826
Natural variant281I → V. Ref.18
Corresponds to variant rs1799921 [ dbSNP | Ensembl ].
VAR_011827
Natural variant1841P → L.
Corresponds to variant rs1800043 [ dbSNP | Ensembl ].
VAR_011828
Natural variant2201R → L.
Corresponds to variant rs1800044 [ dbSNP | Ensembl ].
VAR_011829
Natural variant2731G → D. Ref.19
Corresponds to variant rs1800042 [ dbSNP | Ensembl ].
VAR_011830

Experimental info

Sequence conflict152 – 1543RAA → PR in AAA36440. Ref.1
Sequence conflict152 – 1543RAA → PR in CAA31908. Ref.1
Sequence conflict1721M → I in AAA36440. Ref.1
Sequence conflict1721M → I in CAA31908. Ref.1
Sequence conflict200 – 2023TFG → RPR no nucleotide entry Ref.8
Sequence conflict2281K → R no nucleotide entry Ref.8
Sequence conflict2441A → AA no nucleotide entry Ref.8
Sequence conflict3551I → T no nucleotide entry Ref.8
Sequence conflict363 – 3653IVA → MRP no nucleotide entry Ref.8
Sequence conflict4181K → N in AAA36440. Ref.1
Sequence conflict4181K → N in CAA31908. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P08908 [UniParc].

Last modified April 1, 1993. Version 3.
Checksum: 762664FCF62CFD8F

FASTA42246,107
        10         20         30         40         50         60 
MDVLSPGQGN NTTSPPAPFE TGGNTTGISD VTVSYQVITS LLLGTLIFCA VLGNACVVAA 

        70         80         90        100        110        120 
IALERSLQNV ANYLIGSLAV TDLMVSVLVL PMAALYQVLN KWTLGQVTCD LFIALDVLCC 

       130        140        150        160        170        180 
TSSILHLCAI ALDRYWAITD PIDYVNKRTP RRAAALISLT WLIGFLISIP PMLGWRTPED 

       190        200        210        220        230        240 
RSDPDACTIS KDHGYTIYST FGAFYIPLLL MLVLYGRIFR AARFRIRKTV KKVEKTGADT 

       250        260        270        280        290        300 
RHGASPAPQP KKSVNGESGS RNWRLGVESK AGGALCANGA VRQGDDGAAL EVIEVHRVGN 

       310        320        330        340        350        360 
SKEHLPLPSE AGPTPCAPAS FERKNERNAE AKRKMALARE RKTVKTLGII MGTFILCWLP 

       370        380        390        400        410        420 
FFIVALVLPF CESSCHMPTL LGAIINWLGY SNSLLNPVIY AYFNKDFQNA FKKIIKCKFC 


RQ 

« Hide

References

« Hide 'large scale' references
[1]"An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins."
Kobilka B.K., Frielle T., Collins S., Yang-Feng T.L., Kobilka T.S., Francke U., Lefkowitz R.J., Caron M.G.
Nature 329:75-79(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[2]"Nucleotide and deduced amino acid sequence of the human serotonin 5-HT1a receptor gene."
Saltzman A.G., Morse B., Felder S.
Submitted (FEB-1991) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]Levy F.O., Gudermann T., Birnbaumer M., Kaumann A.J., Birnbaumer L.
Submitted (MAY-1992) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Human-specific amino acid changes found in 103 protein-coding genes."
Kitano T., Liu Y.-H., Ueda S., Saitou N.
Mol. Biol. Evol. 21:936-944(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"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].
Tissue: Brain.
[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].
[7]"A polymerase chain reaction mediated by a single primer: cloning of genomic sequences adjacent to a serotonin receptor protein coding region."
Parks C.L., Chang L.S., Shenk T.
Nucleic Acids Res. 19:7155-7160(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
[8]"Expression of 5HT1a receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-hydroxytryptamine."
Aune T.M., McGrath K.M., Sarr T., Bombara M.P., Kelley K.A.
J. Immunol. 151:1175-1183(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 200-365, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]"The genomic clone G-21 which resembles a beta-adrenergic receptor sequence encodes the 5-HT1A receptor."
Fargin A., Raymond J.R., Lohse M.L., Kobilka B.K., Caron M.G., Lefkowitz R.J.
Nature 335:358-360(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]"Agonist-induced desensitization and loss of high-affinity binding sites of stably expressed human 5-HT1A receptors."
Harrington M.A., Shaw K., Zhong P., Ciaranello R.D.
J. Pharmacol. Exp. Ther. 268:1098-1106(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"The proteomic reactor facilitates the analysis of affinity-purified proteins by mass spectrometry: application for identifying ubiquitinated proteins in human cells."
Vasilescu J., Zweitzig D.R., Denis N.J., Smith J.C., Ethier M., Haines D.S., Figeys D.
J. Proteome Res. 6:298-305(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-334.
Tissue: Lung adenocarcinoma.
[12]"Serotonin receptors."
Nichols D.E., Nichols C.D.
Chem. Rev. 108:1614-1641(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[13]"5-HT1A receptor-regulated signal transduction pathways in brain."
Polter A.M., Li X.
Cell. Signal. 22:1406-1412(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[14]"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.
[15]"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."
Jiang Y.C., Wu H.M., Cheng K.H., Sunny Sun H.
Hum. Mutat. 33:209-217(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PFMC.
[16]"Role of glycosphingolipids in the function of human serotonin(1)A receptors."
Singh P., Paila Y.D., Chattopadhyay A.
J. Neurochem. 123:716-724(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[17]"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."
Akama K.T., Thompson L.I., Milner T.A., McEwen B.S.
J. Biol. Chem. 288:6438-6450(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[18]"Two naturally occurring amino acid substitutions in the human 5-HT1A receptor: glycine 22 to serine 22 and isoleucine 28 to valine 28."
Nakhai B., Nielsen D.A., Linnoila M., Goldman D.
Biochem. Biophys. Res. Commun. 210:530-536(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SER-22 AND VAL-28.
[19]"Novel mutations in the promoter and coding region of the human 5-HT1A receptor gene and association analysis in schizophrenia."
Kawanishi Y., Harada S., Tachikawa H., Okubo T., Shiraishi H.
Am. J. Med. Genet. 81:434-439(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LEU-16 AND ASP-273.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M28269 Genomic DNA. Translation: AAA36440.1.
X13556 Genomic DNA. Translation: CAA31908.1.
X57829 Genomic DNA. Translation: CAA40962.1.
M83181 Genomic DNA. Translation: AAA66493.1.
AB041403 Genomic DNA. Translation: BAA94488.1.
AF498978 mRNA. Translation: AAM21125.1.
BC069159 mRNA. Translation: AAH69159.1.
Z11168 Genomic DNA. Translation: CAA77560.1.
PIRI38209.
RefSeqNP_000515.2. NM_000524.3.
UniGeneHs.247940.

3D structure databases

ProteinModelPortalP08908.
SMRP08908. Positions 31-418.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109582. 6 interactions.
IntActP08908. 4 interactions.
STRING9606.ENSP00000316244.

Chemistry

BindingDBP08908.
ChEMBLCHEMBL2096904.
DrugBankDB00866. Alprenolol.
DB01238. Aripiprazole.
DB00490. Buspirone.
DB00363. Clozapine.
DB00216. Eletriptan.
DB01049. Ergoloid mesylate.
DB00176. Fluvoxamine.
DB00589. Lisuride.
DB00247. Methysergide.
DB00370. Mirtazapine.
DB00960. Pindolol.
DB00571. Propranolol.
DB01224. Quetiapine.
DB01104. Sertraline.
DB01079. Tegaserod.
DB00656. Trazodone.
DB00285. Venlafaxine.
DB00246. Ziprasidone.
GuidetoPHARMACOLOGY1.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP08908.

Polymorphism databases

DMDM231454.

Proteomic databases

PaxDbP08908.
PRIDEP08908.

Protocols and materials databases

DNASU3350.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000323865; ENSP00000316244; ENSG00000178394.
GeneID3350.
KEGGhsa:3350.
UCSCuc011cqt.3. human.

Organism-specific databases

CTD3350.
GeneCardsGC05M063292.
HGNCHGNC:5286. HTR1A.
HPAHPA018073.
MIM109760. gene.
614674. phenotype.
neXtProtNX_P08908.
PharmGKBPA192.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG249628.
HOGENOMHOG000239242.
HOVERGENHBG106962.
InParanoidP08908.
KOK04153.
OMATGAPCAN.
PhylomeDBP08908.
TreeFamTF316350.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP08908.
BgeeP08908.
CleanExHS_HTR1A.
GenevestigatorP08908.

Family and domain databases

Gene3D1.20.1070.10. 2 hits.
InterProIPR000610. 5HT1A_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24247:SF20. PTHR24247:SF20. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00512. 5HT1ARECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi3350.
NextBio13248.
PROP08908.
SOURCESearch...

Entry information

Entry name5HT1A_HUMAN
AccessionPrimary (citable) accession number: P08908
Secondary accession number(s): Q6LAE7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: April 1, 1993
Last modified: April 16, 2014
This is version 144 of the entry and version 3 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

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Index of human polymorphisms and disease mutations

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List of human entries with polymorphisms or disease mutations

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