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Protein

5-hydroxytryptamine receptor 6

Gene

HTR6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611).By similarity1 Publication

GO - Molecular functioni

  1. histamine receptor activity Source: ProtInc
  2. serotonin receptor activity Source: InterPro

GO - Biological processi

  1. cerebral cortex cell migration Source: UniProtKB
  2. G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
  3. learning Source: Ensembl
  4. long-term synaptic potentiation Source: Ensembl
  5. negative regulation of acetylcholine secretion, neurotransmission Source: Ensembl
  6. negative regulation of gamma-aminobutyric acid secretion Source: Ensembl
  7. negative regulation of glutamate secretion Source: Ensembl
  8. positive regulation of dopamine secretion Source: Ensembl
  9. positive regulation of gamma-aminobutyric acid secretion Source: Ensembl
  10. positive regulation of TOR signaling Source: UniProtKB
  11. response to drug Source: Ensembl
  12. response to estradiol Source: Ensembl
  13. synaptic transmission Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_17064. Serotonin receptors.
REACT_19327. G alpha (s) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
5-hydroxytryptamine receptor 6
Short name:
5-HT-6
Short name:
5-HT6
Alternative name(s):
Serotonin receptor 6
Gene namesi
Name:HTR6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:5301. HTR6.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3434ExtracellularBy similarityAdd
BLAST
Transmembranei35 – 5723Helical; Name=1By similarityAdd
BLAST
Topological domaini58 – 647CytoplasmicBy similarity
Transmembranei65 – 8521Helical; Name=2By similarityAdd
BLAST
Topological domaini86 – 10015ExtracellularBy similarityAdd
BLAST
Transmembranei101 – 12222Helical; Name=3By similarityAdd
BLAST
Topological domaini123 – 14422CytoplasmicBy similarityAdd
BLAST
Transmembranei145 – 16622Helical; Name=4By similarityAdd
BLAST
Topological domaini167 – 18418ExtracellularBy similarityAdd
BLAST
Transmembranei185 – 20824Helical; Name=5By similarityAdd
BLAST
Topological domaini209 – 26557CytoplasmicBy similarityAdd
BLAST
Transmembranei266 – 29025Helical; Name=6By similarityAdd
BLAST
Topological domaini291 – 2955ExtracellularBy similarity
Transmembranei296 – 32025Helical; Name=7By similarityAdd
BLAST
Topological domaini321 – 440120CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  1. cilium Source: Ensembl
  2. dendrite Source: Ensembl
  3. integral component of plasma membrane Source: ProtInc
  4. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29560.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 4404405-hydroxytryptamine receptor 6PRO_0000068974Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi99 ↔ 180PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP50406.
PRIDEiP50406.

PTM databases

PhosphoSiteiP50406.

Expressioni

Tissue specificityi

Expressed in several human brain regions, most prominently in the caudate nucleus.

Gene expression databases

BgeeiP50406.
CleanExiHS_HTR6.
GenevestigatoriP50406.

Interactioni

Subunit structurei

Interacts with MTOR, RPTOR and NF1 (PubMed:23027611). Interacts with CDK5 (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
FYNP062417EBI-1182222,EBI-515315

Protein-protein interaction databases

BioGridi109594. 1 interaction.
IntActiP50406. 1 interaction.
MINTiMINT-7214563.
STRINGi9606.ENSP00000289753.

Structurei

3D structure databases

ProteinModelPortaliP50406.
SMRiP50406. Positions 33-332.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG299437.
GeneTreeiENSGT00760000118774.
HOGENOMiHOG000241520.
HOVERGENiHBG106962.
InParanoidiP50406.
KOiK04162.
OMAiCLLWTAF.
OrthoDBiEOG7XH6Q0.
PhylomeDBiP50406.
TreeFamiTF351753.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P50406-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MVPEPGPTAN STPAWGAGPP SAPGGSGWVA AALCVVIALT AAANSLLIAL
60 70 80 90 100
ICTQPALRNT SNFFLVSLFT SDLMVGLVVM PPAMLNALYG RWVLARGLCL
110 120 130 140 150
LWTAFDVMCC SASILNLCLI SLDRYLLILS PLRYKLRMTP LRALALVLGA
160 170 180 190 200
WSLAALASFL PLLLGWHELG HARPPVPGQC RLLASLPFVL VASGLTFFLP
210 220 230 240 250
SGAICFTYCR ILLAARKQAV QVASLTTGMA SQASETLQVP RTPRPGVESA
260 270 280 290 300
DSRRLATKHS RKALKASLTL GILLGMFFVT WLPFFVANIV QAVCDCISPG
310 320 330 340 350
LFDVLTWLGY CNSTMNPIIY PLFMRDFKRA LGRFLPCPRC PRERQASLAS
360 370 380 390 400
PSLRTSHSGP RPGLSLQQVL PLPLPPDSDS DSDAGSGGSS GLRLTAQLLL
410 420 430 440
PGEATQDPPL PTRAAAAVNF FNIDPAEPEL RPHPLGIPTN
Length:440
Mass (Da):46,954
Last modified:October 1, 1996 - v1
Checksum:iC888F47650C1D2EF
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti247 – 2471V → M in CAA88929. (PubMed:7656980)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L41147 mRNA. Translation: AAA92622.1.
AY429105 mRNA. Translation: AAR07900.1.
AL031727 Genomic DNA. Translation: CAI19020.1.
CH471134 Genomic DNA. Translation: EAW94896.1.
BC074995 mRNA. Translation: AAH74995.1.
BC074996 mRNA. Translation: AAH74996.1.
Z49119 mRNA. Translation: CAA88929.1.
CCDSiCCDS197.1.
PIRiJC5520.
RefSeqiNP_000862.1. NM_000871.2.
UniGeneiHs.22180.

Genome annotation databases

EnsembliENST00000289753; ENSP00000289753; ENSG00000158748.
GeneIDi3362.
KEGGihsa:3362.
UCSCiuc001bcl.3. human.

Polymorphism databases

DMDMi1703010.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L41147 mRNA. Translation: AAA92622.1.
AY429105 mRNA. Translation: AAR07900.1.
AL031727 Genomic DNA. Translation: CAI19020.1.
CH471134 Genomic DNA. Translation: EAW94896.1.
BC074995 mRNA. Translation: AAH74995.1.
BC074996 mRNA. Translation: AAH74996.1.
Z49119 mRNA. Translation: CAA88929.1.
CCDSiCCDS197.1.
PIRiJC5520.
RefSeqiNP_000862.1. NM_000871.2.
UniGeneiHs.22180.

3D structure databases

ProteinModelPortaliP50406.
SMRiP50406. Positions 33-332.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109594. 1 interaction.
IntActiP50406. 1 interaction.
MINTiMINT-7214563.
STRINGi9606.ENSP00000289753.

Chemistry

BindingDBiP50406.
ChEMBLiCHEMBL2096904.
DrugBankiDB00321. Amitriptyline.
DB00543. Amoxapine.
DB01238. Aripiprazole.
DB06216. Asenapine.
DB00477. Chlorpromazine.
DB00363. Clozapine.
DB01142. Doxepin.
DB01049. Ergoloid mesylate.
DB04946. Iloperidone.
DB00458. Imipramine.
DB00408. Loxapine.
DB06148. Mianserin.
DB00540. Nortriptyline.
DB00334. Olanzapine.
DB01224. Quetiapine.
DB06144. Sertindole.
DB00246. Ziprasidone.
GuidetoPHARMACOLOGYi11.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiP50406.

Polymorphism databases

DMDMi1703010.

Proteomic databases

PaxDbiP50406.
PRIDEiP50406.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000289753; ENSP00000289753; ENSG00000158748.
GeneIDi3362.
KEGGihsa:3362.
UCSCiuc001bcl.3. human.

Organism-specific databases

CTDi3362.
GeneCardsiGC01P019991.
HGNCiHGNC:5301. HTR6.
MIMi601109. gene.
neXtProtiNX_P50406.
PharmGKBiPA29560.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG299437.
GeneTreeiENSGT00760000118774.
HOGENOMiHOG000241520.
HOVERGENiHBG106962.
InParanoidiP50406.
KOiK04162.
OMAiCLLWTAF.
OrthoDBiEOG7XH6Q0.
PhylomeDBiP50406.
TreeFamiTF351753.

Enzyme and pathway databases

ReactomeiREACT_17064. Serotonin receptors.
REACT_19327. G alpha (s) signalling events.

Miscellaneous databases

GeneWikii5-HT6_receptor.
GenomeRNAii3362.
NextBioi13308.
PROiP50406.
SOURCEiSearch...

Gene expression databases

BgeeiP50406.
CleanExiHS_HTR6.
GenevestigatoriP50406.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor."
    Kohen R., Metcalf M.A., Khan N., Druck T., Huebner K., Lachowicz J.E., Sibley D.R., Roth B., Hamblin M.W.
    J. Neurochem. 66:47-56(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Corpus striatum.
  2. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
    Kopatz S.A., Aronstam R.S., Sharma S.V.
    Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  3. "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.
    , 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].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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: Fetal brain.
  6. "Expression of serotonin receptor mRNAs in blood vessels."
    Ullmer C., Schmuck K., Kalkman H.O., Luebbert H.
    FEBS Lett. 370:215-221(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 215-280.
    Tissue: Corpus striatum.
  7. Cited for: FUNCTION, INTERACTION WITH MTOR; RPTOR AND NF1.

Entry informationi

Entry namei5HT6R_HUMAN
AccessioniPrimary (citable) accession number: P50406
Secondary accession number(s): Q13640, Q5TGZ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: February 4, 2015
This is version 130 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.