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Protein

5-hydroxytryptamine receptor 1B

Gene

HTR1B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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, such as lysergic acid diethylamide (LSD). 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. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.12 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei355Important for species-specific agonist sensitivity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Behavior

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135312-MONOMER.
ReactomeiR-HSA-390666. Serotonin receptors.
R-HSA-418594. G alpha (i) signalling events.

Protein family/group databases

TCDBi9.A.14.3.6. the g-protein-coupled receptor (gpcr) family.

Names & Taxonomyi

Protein namesi
Recommended name:
5-hydroxytryptamine receptor 1B
Short name:
5-HT-1B
Short name:
5-HT1B
Alternative name(s):
S12
Serotonin 1D beta receptor
Short name:
5-HT-1D-beta
Serotonin receptor 1B
Gene namesi
Name:HTR1B
Synonyms:HTR1DB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:5287. HTR1B.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 49ExtracellularAdd BLAST49
Transmembranei50 – 75Helical; Name=1Add BLAST26
Topological domaini76 – 84Cytoplasmic9
Transmembranei85 – 110Helical; Name=2Add BLAST26
Topological domaini111 – 123ExtracellularAdd BLAST13
Transmembranei124 – 145Helical; Name=3Add BLAST22
Topological domaini146 – 165CytoplasmicAdd BLAST20
Transmembranei166 – 187Helical; Name=4Add BLAST22
Topological domaini188 – 205ExtracellularAdd BLAST18
Transmembranei206 – 228Helical; Name=5Add BLAST23
Topological domaini229 – 315CytoplasmicAdd BLAST87
Transmembranei316 – 336Helical; Name=6Add BLAST21
Topological domaini337 – 349ExtracellularAdd BLAST13
Transmembranei350 – 371Helical; Name=7Add BLAST22
Topological domaini372 – 390CytoplasmicAdd BLAST19

GO - Cellular componenti

  • cytoplasm Source: Ensembl
  • dendrite Source: GO_Central
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi126L → A: No effect on agonist binding. 1 Publication1
Mutagenesisi129D → A: Abolishes agonist binding. 1 Publication1
Mutagenesisi130I → A: Abolishes agonist binding. 1 Publication1
Mutagenesisi133C → A: Abolishes agonist binding. 1 Publication1
Mutagenesisi134T → A: Slightly decreases agonist binding. 1 Publication1
Mutagenesisi200V → A: No effect on agonist binding. 1 Publication1
Mutagenesisi201V → A: No effect on agonist binding. 1 Publication1
Mutagenesisi203T → A: No effect on agonist binding. 1 Publication1
Mutagenesisi209T → A: No effect on agonist binding. 1 Publication1
Mutagenesisi212S → A: No effect on agonist binding. 1 Publication1
Mutagenesisi216A → S: No effect on agonist binding. 1 Publication1
Mutagenesisi327W → A: Abolishes agonist binding. 1 Publication1
Mutagenesisi330F → A: Abolishes agonist binding. 1 Publication1
Mutagenesisi331F → A: No effect on agonist binding. 1 Publication1
Mutagenesisi334S → A: No effect on agonist binding. 1 Publication1
Mutagenesisi337M → A: No effect on agonist binding. 1 Publication1
Mutagenesisi351F → A: No effect on agonist binding. 1 Publication1
Mutagenesisi352D → A: No effect on agonist binding. 1 Publication1
Mutagenesisi355T → A: No effect on agonist binding. 1 Publication1
Mutagenesisi359Y → A: No effect on agonist binding. 1 Publication1

Organism-specific databases

DisGeNETi3351.
OpenTargetsiENSG00000135312.
PharmGKBiPA29549.

Chemistry databases

ChEMBLiCHEMBL1898.
DrugBankiDB00918. Almotriptan.
DB00321. Amitriptyline.
DB00543. Amoxapine.
DB00714. Apomorphine.
DB01238. Aripiprazole.
DB06216. Asenapine.
DB08807. Bopindolol.
DB01200. Bromocriptine.
DB00248. Cabergoline.
DB00363. Clozapine.
DB00320. Dihydroergotamine.
DB00216. Eletriptan.
DB01049. Ergoloid mesylate.
DB00696. Ergotamine.
DB00998. Frovatriptan.
DB01221. Ketamine.
DB00589. Lisuride.
DB00408. Loxapine.
DB00247. Methysergide.
DB00952. Naratriptan.
DB00334. Olanzapine.
DB00904. Ondansetron.
DB01359. Penbutolol.
DB01186. Pergolide.
DB00960. Pindolol.
DB00413. Pramipexole.
DB00571. Propranolol.
DB01224. Quetiapine.
DB00953. Rizatriptan.
DB00268. Ropinirole.
DB00669. Sumatriptan.
DB09068. Vortioxetine.
DB01392. Yohimbine.
DB00246. Ziprasidone.
DB00315. Zolmitriptan.
GuidetoPHARMACOLOGYi2.

Polymorphism and mutation databases

BioMutaiHTR1B.
DMDMi112821.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000689161 – 3905-hydroxytryptamine receptor 1BAdd BLAST390

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi24N-linked (GlcNAc...)Sequence analysis1
Glycosylationi32N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi122 ↔ 199PROSITE-ProRule annotation1 Publication
Lipidationi388S-palmitoyl cysteineSequence analysis1

Post-translational modificationi

Phosphorylated. Desensitization of the receptor may be mediated by its phosphorylation.1 Publication
Palmitoylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiP28222.
PRIDEiP28222.

PTM databases

iPTMnetiP28222.
PhosphoSitePlusiP28222.

Expressioni

Tissue specificityi

Detected in cerebral artery smooth muscle cells (at protein level). Detected in brain cortex, striatum, amygdala, medulla, hippocampus, caudate nucleus and putamen.3 Publications

Gene expression databases

BgeeiENSG00000135312.
CleanExiHS_HTR1B.
ExpressionAtlasiP28222. baseline and differential.
GenevisibleiP28222. HS.

Interactioni

Subunit structurei

Homodimer. Heterodimer with HTR1D.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
MDFIQ997503EBI-1056863,EBI-724076

Protein-protein interaction databases

BioGridi109583. 5 interactors.
IntActiP28222. 3 interactors.
STRINGi9606.ENSP00000358963.

Chemistry databases

BindingDBiP28222.

Structurei

Secondary structure

1390
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi40 – 43Combined sources4
Helixi46 – 76Combined sources31
Helixi78 – 80Combined sources3
Helixi83 – 101Combined sources19
Helixi104 – 112Combined sources9
Helixi118 – 152Combined sources35
Helixi154 – 158Combined sources5
Helixi163 – 181Combined sources19
Helixi206 – 216Combined sources11
Helixi218 – 239Combined sources22
Helixi311 – 336Combined sources26
Helixi349 – 372Combined sources24
Helixi374 – 383Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2G1Xmodel-A1-390[»]
4IAQX-ray2.80A33-239[»]
A304-390[»]
4IARX-ray2.70A33-239[»]
A306-390[»]
ProteinModelPortaliP28222.
SMRiP28222.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni125 – 134Agonist binding10
Regioni327 – 331Agonist binding5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi146 – 148DRY motif; important for ligand-induced conformation changes and signaling3
Motifi365 – 369NPxxY motif; important for ligand-induced conformation changes and signaling5

Domaini

Ligands are bound in a hydrophobic pocket formed by the transmembrane helices.1 Publication

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118795.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP28222.
KOiK04153.
OMAiVNTDHVL.
OrthoDBiEOG091G06VI.
PhylomeDBiP28222.
TreeFamiTF316350.

Family and domain databases

InterProiIPR002147. 5HT1B_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24247:SF16. PTHR24247:SF16. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00513. 5HT1BRECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P28222-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEEPGAQCAP PPPAGSETWV PQANLSSAPS QNCSAKDYIY QDSISLPWKV
60 70 80 90 100
LLVMLLALIT LATTLSNAFV IATVYRTRKL HTPANYLIAS LAVTDLLVSI
110 120 130 140 150
LVMPISTMYT VTGRWTLGQV VCDFWLSSDI TCCTASILHL CVIALDRYWA
160 170 180 190 200
ITDAVEYSAK RTPKRAAVMI ALVWVFSISI SLPPFFWRQA KAEEEVSECV
210 220 230 240 250
VNTDHILYTV YSTVGAFYFP TLLLIALYGR IYVEARSRIL KQTPNRTGKR
260 270 280 290 300
LTRAQLITDS PGSTSSVTSI NSRVPDVPSE SGSPVYVNQV KVRVSDALLE
310 320 330 340 350
KKKLMAARER KATKTLGIIL GAFIVCWLPF FIISLVMPIC KDACWFHLAI
360 370 380 390
FDFFTWLGYL NSLINPIIYT MSNEDFKQAF HKLIRFKCTS
Length:390
Mass (Da):43,568
Last modified:December 1, 1992 - v1
Checksum:iCD874DC7EB44CF12
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011715124F → C.1 PublicationCorresponds to variant rs130060dbSNPEnsembl.1
Natural variantiVAR_011831219F → L.Corresponds to variant rs130061dbSNPEnsembl.1
Natural variantiVAR_011832367I → V.Corresponds to variant rs130063dbSNPEnsembl.1
Natural variantiVAR_011833374E → K.Corresponds to variant rs130064dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M89478 Genomic DNA. No translation available.
D10995 Genomic DNA. Translation: BAA01763.1.
M83180 Genomic DNA. Translation: AAA36029.1.
L09732 Genomic DNA. Translation: AAA36030.1.
M81590 mRNA. Translation: AAA60316.1.
M75128 Genomic DNA. Translation: AAA58675.1.
AB041370 Genomic DNA. Translation: BAA94455.1.
AY225227 Genomic DNA. Translation: AAO67712.1.
AL049595 Genomic DNA. Translation: CAB51537.1.
BC069065 mRNA. Translation: AAH69065.1.
BC096206 mRNA. Translation: AAH96206.1.
BC096207 mRNA. Translation: AAH96207.1.
BC096208 mRNA. Translation: AAH96208.1.
CCDSiCCDS4986.1.
PIRiJN0268.
RefSeqiNP_000854.1. NM_000863.2.
UniGeneiHs.123016.

Genome annotation databases

EnsembliENST00000369947; ENSP00000358963; ENSG00000135312.
GeneIDi3351.
KEGGihsa:3351.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M89478 Genomic DNA. No translation available.
D10995 Genomic DNA. Translation: BAA01763.1.
M83180 Genomic DNA. Translation: AAA36029.1.
L09732 Genomic DNA. Translation: AAA36030.1.
M81590 mRNA. Translation: AAA60316.1.
M75128 Genomic DNA. Translation: AAA58675.1.
AB041370 Genomic DNA. Translation: BAA94455.1.
AY225227 Genomic DNA. Translation: AAO67712.1.
AL049595 Genomic DNA. Translation: CAB51537.1.
BC069065 mRNA. Translation: AAH69065.1.
BC096206 mRNA. Translation: AAH96206.1.
BC096207 mRNA. Translation: AAH96207.1.
BC096208 mRNA. Translation: AAH96208.1.
CCDSiCCDS4986.1.
PIRiJN0268.
RefSeqiNP_000854.1. NM_000863.2.
UniGeneiHs.123016.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2G1Xmodel-A1-390[»]
4IAQX-ray2.80A33-239[»]
A304-390[»]
4IARX-ray2.70A33-239[»]
A306-390[»]
ProteinModelPortaliP28222.
SMRiP28222.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109583. 5 interactors.
IntActiP28222. 3 interactors.
STRINGi9606.ENSP00000358963.

Chemistry databases

BindingDBiP28222.
ChEMBLiCHEMBL1898.
DrugBankiDB00918. Almotriptan.
DB00321. Amitriptyline.
DB00543. Amoxapine.
DB00714. Apomorphine.
DB01238. Aripiprazole.
DB06216. Asenapine.
DB08807. Bopindolol.
DB01200. Bromocriptine.
DB00248. Cabergoline.
DB00363. Clozapine.
DB00320. Dihydroergotamine.
DB00216. Eletriptan.
DB01049. Ergoloid mesylate.
DB00696. Ergotamine.
DB00998. Frovatriptan.
DB01221. Ketamine.
DB00589. Lisuride.
DB00408. Loxapine.
DB00247. Methysergide.
DB00952. Naratriptan.
DB00334. Olanzapine.
DB00904. Ondansetron.
DB01359. Penbutolol.
DB01186. Pergolide.
DB00960. Pindolol.
DB00413. Pramipexole.
DB00571. Propranolol.
DB01224. Quetiapine.
DB00953. Rizatriptan.
DB00268. Ropinirole.
DB00669. Sumatriptan.
DB09068. Vortioxetine.
DB01392. Yohimbine.
DB00246. Ziprasidone.
DB00315. Zolmitriptan.
GuidetoPHARMACOLOGYi2.

Protein family/group databases

TCDBi9.A.14.3.6. the g-protein-coupled receptor (gpcr) family.
GPCRDBiSearch...

PTM databases

iPTMnetiP28222.
PhosphoSitePlusiP28222.

Polymorphism and mutation databases

BioMutaiHTR1B.
DMDMi112821.

Proteomic databases

PaxDbiP28222.
PRIDEiP28222.

Protocols and materials databases

DNASUi3351.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000369947; ENSP00000358963; ENSG00000135312.
GeneIDi3351.
KEGGihsa:3351.

Organism-specific databases

CTDi3351.
DisGeNETi3351.
GeneCardsiHTR1B.
HGNCiHGNC:5287. HTR1B.
MIMi182131. gene.
neXtProtiNX_P28222.
OpenTargetsiENSG00000135312.
PharmGKBiPA29549.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118795.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP28222.
KOiK04153.
OMAiVNTDHVL.
OrthoDBiEOG091G06VI.
PhylomeDBiP28222.
TreeFamiTF316350.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135312-MONOMER.
ReactomeiR-HSA-390666. Serotonin receptors.
R-HSA-418594. G alpha (i) signalling events.

Miscellaneous databases

GeneWikii5-HT1B_receptor.
GenomeRNAii3351.
PROiP28222.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135312.
CleanExiHS_HTR1B.
ExpressionAtlasiP28222. baseline and differential.
GenevisibleiP28222. HS.

Family and domain databases

InterProiIPR002147. 5HT1B_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24247:SF16. PTHR24247:SF16. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00513. 5HT1BRECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry namei5HT1B_HUMAN
AccessioniPrimary (citable) accession number: P28222
Secondary accession number(s): Q4VAY7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: November 30, 2016
This is version 157 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

Miscellaneous

A residue in the 7th transmembrane region (Thr-355 in human, 'Asn-351' in mouse and rat) is important for species-specific sensitivity to various agonists.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 6
    Human chromosome 6: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.