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Protein

5-hydroxytryptamine receptor 1A

Gene

HTR1A

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

Functioni

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.4 Publications

GO - Molecular functioni

  • G protein-coupled receptor activity Source: GO_Central
  • G protein-coupled serotonin receptor activity Source: UniProtKB
  • neurotransmitter receptor activity Source: GO_Central
  • receptor-receptor interaction Source: ParkinsonsUK-UCL
  • serotonin binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processBehavior

Enzyme and pathway databases

ReactomeiR-HSA-390666 Serotonin receptors
R-HSA-418594 G alpha (i) signalling events
SIGNORiP08908

Names & Taxonomyi

Protein namesi
Recommended name:
5-hydroxytryptamine receptor 1A
Short name:
5-HT-1A
Short name:
5-HT1A
Alternative name(s):
G-21
Serotonin receptor 1A
Gene namesi
Name:HTR1A
Synonyms:ADRB2RL1, ADRBRL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000178394.4
HGNCiHGNC:5286 HTR1A
MIMi109760 gene
neXtProtiNX_P08908

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 36ExtracellularBy similarityAdd BLAST36
Transmembranei37 – 62Helical; Name=1By similarityAdd BLAST26
Topological domaini63 – 73CytoplasmicBy similarityAdd BLAST11
Transmembranei74 – 98Helical; Name=2By similarityAdd BLAST25
Topological domaini99 – 110ExtracellularBy similarityAdd BLAST12
Transmembranei111 – 132Helical; Name=3By similarityAdd BLAST22
Topological domaini133 – 152CytoplasmicBy similarityAdd BLAST20
Transmembranei153 – 178Helical; Name=4By similarityAdd BLAST26
Topological domaini179 – 191ExtracellularBy similarityAdd BLAST13
Transmembranei192 – 217Helical; Name=5By similarityAdd BLAST26
Topological domaini218 – 345CytoplasmicBy similarityAdd BLAST128
Transmembranei346 – 367Helical; Name=6By similarityAdd BLAST22
Topological domaini368 – 378ExtracellularBy similarityAdd BLAST11
Transmembranei379 – 403Helical; Name=7By similarityAdd BLAST25
Topological domaini404 – 422CytoplasmicBy similarityAdd BLAST19

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Periodic fever, menstrual cycle-dependent (PFMC)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:614674

Organism-specific databases

DisGeNETi3350
MalaCardsiHTR1A
MIMi614674 phenotype
OpenTargetsiENSG00000178394
Orphaneti498251 Menstrual cycle-dependent periodic fever
PharmGKBiPA192

Chemistry databases

ChEMBLiCHEMBL214
DrugBankiDB01614 Acepromazine
DB00866 Alprenolol
DB01616 Alverine
DB00321 Amitriptyline
DB00543 Amoxapine
DB00714 Apomorphine
DB01238 Aripiprazole
DB06216 Asenapine
DB04888 Bifeprunox
DB08807 Bopindolol
DB09128 Brexpiprazole
DB01200 Bromocriptine
DB00490 Buspirone
DB00248 Cabergoline
DB06016 Cariprazine
DB00477 Chlorpromazine
DB08810 Cinitapride
DB00363 Clozapine
DB04884 Dapoxetine
DB01151 Desipramine
DB00988 Dopamine
DB01142 Doxepin
DB00216 Eletriptan
DB01049 Ergoloid mesylate
DB00696 Ergotamine
DB04908 Flibanserin
DB04946 Iloperidone
DB00458 Imipramine
DB01221 Ketamine
DB04970 Lesopitron
DB05509 LI-301
DB00589 Lisuride
DB00408 Loxapine
DB08815 Lurasidone
DB04829 Lysergic Acid Diethylamide
DB00247 Methysergide
DB06148 Mianserin
DB05339 MN-305
DB01618 Molindone
DB00952 Naratriptan
DB01149 Nefazodone
DB00540 Nortriptyline
DB00334 Olanzapine
DB00904 Ondansetron
DB01267 Paliperidone
DB01359 Penbutolol
DB01186 Pergolide
DB00960 Pindolol
DB01621 Pipotiazine
DB00413 Pramipexole
DB00571 Propranolol
DB01224 Quetiapine
DB00734 Risperidone
DB00268 Ropinirole
DB05271 Rotigotine
DB05280 SLV 308
DB00669 Sumatriptan
DB01622 Thioproperazine
DB13025 Tiapride
DB00656 Trazodone
DB00726 Trimipramine
DB06684 Vilazodone
DB09068 Vortioxetine
DB01392 Yohimbine
DB00246 Ziprasidone
DB00315 Zolmitriptan
GuidetoPHARMACOLOGYi1

Polymorphism and mutation databases

BioMutaiHTR1A
DMDMi231454

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000689031 – 4225-hydroxytryptamine receptor 1AAdd BLAST422

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi10N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi11N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi24N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi109 ↔ 187PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP08908
PeptideAtlasiP08908
PRIDEiP08908
ProteomicsDBi52173

PTM databases

iPTMnetiP08908
PhosphoSitePlusiP08908

Expressioni

Tissue specificityi

Detected in lymph nodes, thymus and spleen. Detected in activated T-cells, but not in resting T-cells.2 Publications

Gene expression databases

BgeeiENSG00000178394 Expressed in 23 organ(s), highest expression level in temporal lobe
CleanExiHS_HTR1A
ExpressionAtlasiP08908 baseline and differential
GenevisibleiP08908 HS

Organism-specific databases

HPAiHPA018073

Interactioni

Subunit structurei

Heterodimer; heterodimerizes with GPER1.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
FGFR1P113626EBI-6570214,EBI-1028277

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109582, 6 interactors
CORUMiP08908
IntActiP08908, 2 interactors
STRINGi9606.ENSP00000316244

Chemistry databases

BindingDBiP08908

Structurei

3D structure databases

ProteinModelPortaliP08908
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni112 – 121Agonist bindingBy similarity10
Regioni358 – 362Agonist bindingBy similarity5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi133 – 135DRY motif; important for ligand-induced conformation changesBy similarity3
Motifi396 – 400NPxxY motif; important for ligand-induced conformation changes and signalingBy similarity5

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00760000118795
HOGENOMiHOG000239242
HOVERGENiHBG106962
InParanoidiP08908
KOiK04153
OMAiYQVLNKW
OrthoDBiEOG091G06VI
PhylomeDBiP08908
TreeFamiTF316350

Family and domain databases

CDDicd15330 7tmA_5-HT1A_vertebrates, 1 hit
InterProiView protein in InterPro
IPR000610 5HT1A_rcpt
IPR002231 5HT_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PANTHERiPTHR24247:SF20 PTHR24247:SF20, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00512 5HT1ARECEPTR
PR01101 5HTRECEPTOR
PR00237 GPCRRHODOPSN
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P08908-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDVLSPGQGN NTTSPPAPFE TGGNTTGISD VTVSYQVITS LLLGTLIFCA
60 70 80 90 100
VLGNACVVAA IALERSLQNV ANYLIGSLAV TDLMVSVLVL PMAALYQVLN
110 120 130 140 150
KWTLGQVTCD LFIALDVLCC TSSILHLCAI ALDRYWAITD PIDYVNKRTP
160 170 180 190 200
RRAAALISLT WLIGFLISIP PMLGWRTPED RSDPDACTIS KDHGYTIYST
210 220 230 240 250
FGAFYIPLLL MLVLYGRIFR AARFRIRKTV KKVEKTGADT RHGASPAPQP
260 270 280 290 300
KKSVNGESGS RNWRLGVESK AGGALCANGA VRQGDDGAAL EVIEVHRVGN
310 320 330 340 350
SKEHLPLPSE AGPTPCAPAS FERKNERNAE AKRKMALARE RKTVKTLGII
360 370 380 390 400
MGTFILCWLP FFIVALVLPF CESSCHMPTL LGAIINWLGY SNSLLNPVIY
410 420
AYFNKDFQNA FKKIIKCKFC RQ
Length:422
Mass (Da):46,107
Last modified:April 1, 1993 - v3
Checksum:i762664FCF62CFD8F
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RA34D6RA34_HUMAN
5-hydroxytryptamine receptor 1A
HTR1A
41Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti152 – 154RAA → PR in AAA36440 (PubMed:3041227).Curated3
Sequence conflicti152 – 154RAA → PR in CAA31908 (PubMed:3041227).Curated3
Sequence conflicti172M → I in AAA36440 (PubMed:3041227).Curated1
Sequence conflicti172M → I in CAA31908 (PubMed:3041227).Curated1
Sequence conflicti200 – 202TFG → RPR no nucleotide entry (PubMed:8393041).Curated3
Sequence conflicti228K → R no nucleotide entry (PubMed:8393041).Curated1
Sequence conflicti244A → AA no nucleotide entry (PubMed:8393041).Curated1
Sequence conflicti355I → T no nucleotide entry (PubMed:8393041).Curated1
Sequence conflicti363 – 365IVA → MRP no nucleotide entry (PubMed:8393041).Curated3
Sequence conflicti418K → N in AAA36440 (PubMed:3041227).Curated1
Sequence conflicti418K → N in CAA31908 (PubMed:3041227).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00344616P → L1 PublicationCorresponds to variant dbSNP:rs1800041Ensembl.1
Natural variantiVAR_01182622G → S1 PublicationCorresponds to variant dbSNP:rs1799920Ensembl.1
Natural variantiVAR_01182728I → V1 PublicationCorresponds to variant dbSNP:rs1799921Ensembl.1
Natural variantiVAR_011828184P → L. Corresponds to variant dbSNP:rs1800043Ensembl.1
Natural variantiVAR_011829220R → L. Corresponds to variant dbSNP:rs1800044Ensembl.1
Natural variantiVAR_011830273G → D1 PublicationCorresponds to variant dbSNP:rs1800042Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS34168.1
PIRiI38209
RefSeqiNP_000515.2, NM_000524.3
UniGeneiHs.247940

Genome annotation databases

EnsembliENST00000323865; ENSP00000316244; ENSG00000178394
GeneIDi3350
KEGGihsa:3350

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS34168.1
PIRiI38209
RefSeqiNP_000515.2, NM_000524.3
UniGeneiHs.247940

3D structure databases

ProteinModelPortaliP08908
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109582, 6 interactors
CORUMiP08908
IntActiP08908, 2 interactors
STRINGi9606.ENSP00000316244

Chemistry databases

BindingDBiP08908
ChEMBLiCHEMBL214
DrugBankiDB01614 Acepromazine
DB00866 Alprenolol
DB01616 Alverine
DB00321 Amitriptyline
DB00543 Amoxapine
DB00714 Apomorphine
DB01238 Aripiprazole
DB06216 Asenapine
DB04888 Bifeprunox
DB08807 Bopindolol
DB09128 Brexpiprazole
DB01200 Bromocriptine
DB00490 Buspirone
DB00248 Cabergoline
DB06016 Cariprazine
DB00477 Chlorpromazine
DB08810 Cinitapride
DB00363 Clozapine
DB04884 Dapoxetine
DB01151 Desipramine
DB00988 Dopamine
DB01142 Doxepin
DB00216 Eletriptan
DB01049 Ergoloid mesylate
DB00696 Ergotamine
DB04908 Flibanserin
DB04946 Iloperidone
DB00458 Imipramine
DB01221 Ketamine
DB04970 Lesopitron
DB05509 LI-301
DB00589 Lisuride
DB00408 Loxapine
DB08815 Lurasidone
DB04829 Lysergic Acid Diethylamide
DB00247 Methysergide
DB06148 Mianserin
DB05339 MN-305
DB01618 Molindone
DB00952 Naratriptan
DB01149 Nefazodone
DB00540 Nortriptyline
DB00334 Olanzapine
DB00904 Ondansetron
DB01267 Paliperidone
DB01359 Penbutolol
DB01186 Pergolide
DB00960 Pindolol
DB01621 Pipotiazine
DB00413 Pramipexole
DB00571 Propranolol
DB01224 Quetiapine
DB00734 Risperidone
DB00268 Ropinirole
DB05271 Rotigotine
DB05280 SLV 308
DB00669 Sumatriptan
DB01622 Thioproperazine
DB13025 Tiapride
DB00656 Trazodone
DB00726 Trimipramine
DB06684 Vilazodone
DB09068 Vortioxetine
DB01392 Yohimbine
DB00246 Ziprasidone
DB00315 Zolmitriptan
GuidetoPHARMACOLOGYi1

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP08908
PhosphoSitePlusiP08908

Polymorphism and mutation databases

BioMutaiHTR1A
DMDMi231454

Proteomic databases

PaxDbiP08908
PeptideAtlasiP08908
PRIDEiP08908
ProteomicsDBi52173

Protocols and materials databases

DNASUi3350
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000323865; ENSP00000316244; ENSG00000178394
GeneIDi3350
KEGGihsa:3350

Organism-specific databases

CTDi3350
DisGeNETi3350
EuPathDBiHostDB:ENSG00000178394.4
GeneCardsiHTR1A
HGNCiHGNC:5286 HTR1A
HPAiHPA018073
MalaCardsiHTR1A
MIMi109760 gene
614674 phenotype
neXtProtiNX_P08908
OpenTargetsiENSG00000178394
Orphaneti498251 Menstrual cycle-dependent periodic fever
PharmGKBiPA192
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00760000118795
HOGENOMiHOG000239242
HOVERGENiHBG106962
InParanoidiP08908
KOiK04153
OMAiYQVLNKW
OrthoDBiEOG091G06VI
PhylomeDBiP08908
TreeFamiTF316350

Enzyme and pathway databases

ReactomeiR-HSA-390666 Serotonin receptors
R-HSA-418594 G alpha (i) signalling events
SIGNORiP08908

Miscellaneous databases

GenomeRNAii3350
PROiPR:P08908
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000178394 Expressed in 23 organ(s), highest expression level in temporal lobe
CleanExiHS_HTR1A
ExpressionAtlasiP08908 baseline and differential
GenevisibleiP08908 HS

Family and domain databases

CDDicd15330 7tmA_5-HT1A_vertebrates, 1 hit
InterProiView protein in InterPro
IPR000610 5HT1A_rcpt
IPR002231 5HT_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PANTHERiPTHR24247:SF20 PTHR24247:SF20, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00512 5HT1ARECEPTR
PR01101 5HTRECEPTOR
PR00237 GPCRRHODOPSN
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry namei5HT1A_HUMAN
AccessioniPrimary (citable) accession number: P08908
Secondary accession number(s): Q6LAE7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: April 1, 1993
Last modified: November 7, 2018
This is version 178 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  6. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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