5HT6R_HUMAN
ID 5HT6R_HUMAN Reviewed; 440 AA.
AC P50406; Q13640; Q5TGZ1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=5-hydroxytryptamine receptor 6;
DE Short=5-HT-6;
DE Short=5-HT6;
DE AltName: Full=Serotonin receptor 6;
GN Name=HTR6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Corpus striatum;
RX PubMed=8522988; DOI=10.1046/j.1471-4159.1996.66010047.x;
RA Kohen R., Metcalf M.A., Khan N., Druck T., Huebner K., Lachowicz J.E.,
RA Sibley D.R., Roth B., Hamblin M.W.;
RT "Cloning, characterization, and chromosomal localization of a human 5-HT6
RT serotonin receptor.";
RL J. Neurochem. 66:47-56(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 215-280.
RC TISSUE=Corpus striatum;
RX PubMed=7656980; DOI=10.1016/0014-5793(95)00828-w;
RA Ullmer C., Schmuck K., Kalkman H.O., Luebbert H.;
RT "Expression of serotonin receptor mRNAs in blood vessels.";
RL FEBS Lett. 370:215-221(1995).
RN [7]
RP FUNCTION, AND INTERACTION WITH MTOR; RPTOR AND NF1.
RX PubMed=23027611; DOI=10.1002/emmm.201201410;
RA Meffre J., Chaumont-Dubel S., Mannoury la Cour C., Loiseau F., Watson D.J.,
RA Dekeyne A., Seveno M., Rivet J.M., Gaven F., Deleris P., Herve D.,
RA Fone K.C., Bockaert J., Millan M.J., Marin P.;
RT "5-HT(6) receptor recruitment of mTOR as a mechanism for perturbed
RT cognition in schizophrenia.";
RL EMBO Mol. Med. 4:1043-1056(2012).
CC -!- FUNCTION: This is one of the several different receptors for 5-
CC hydroxytryptamine (serotonin), a biogenic hormone that functions as a
CC neurotransmitter, a hormone, and a mitogen. The activity of this
CC receptor is mediated by G proteins that stimulate adenylate cyclase. It
CC has a high affinity for tricyclic psychotropic drugs (By similarity).
CC Controls pyramidal neurons migration during corticogenesis, through the
CC regulation of CDK5 activity (By similarity). Is an activator of TOR
CC signaling (PubMed:23027611). {ECO:0000250|UniProtKB:P31388,
CC ECO:0000250|UniProtKB:Q9R1C8, ECO:0000269|PubMed:23027611}.
CC -!- SUBUNIT: Interacts with MTOR, RPTOR and NF1 (PubMed:23027611).
CC Interacts with CDK5 (By similarity). {ECO:0000250|UniProtKB:Q9R1C8,
CC ECO:0000269|PubMed:23027611}.
CC -!- INTERACTION:
CC P50406; P06241: FYN; NbExp=7; IntAct=EBI-1182222, EBI-515315;
CC P50406; P46821: MAP1B; NbExp=4; IntAct=EBI-1182222, EBI-764611;
CC P50406; P51513: NOVA1; NbExp=9; IntAct=EBI-1182222, EBI-726123;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in several human brain regions, most
CC prominently in the caudate nucleus.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; L41147; AAA92622.1; -; mRNA.
DR EMBL; AY429105; AAR07900.1; -; mRNA.
DR EMBL; AL031727; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471134; EAW94896.1; -; Genomic_DNA.
DR EMBL; BC074995; AAH74995.1; -; mRNA.
DR EMBL; BC074996; AAH74996.1; -; mRNA.
DR EMBL; Z49119; CAA88929.1; -; mRNA.
DR CCDS; CCDS197.1; -.
DR PIR; JC5520; JC5520.
DR RefSeq; NP_000862.1; NM_000871.2.
DR AlphaFoldDB; P50406; -.
DR SMR; P50406; -.
DR BioGRID; 109594; 52.
DR IntAct; P50406; 31.
DR MINT; P50406; -.
DR STRING; 9606.ENSP00000289753; -.
DR BindingDB; P50406; -.
DR ChEMBL; CHEMBL3371; -.
DR DrugBank; DB00321; Amitriptyline.
DR DrugBank; DB00543; Amoxapine.
DR DrugBank; DB01238; Aripiprazole.
DR DrugBank; DB14185; Aripiprazole lauroxil.
DR DrugBank; DB06216; Asenapine.
DR DrugBank; DB00477; Chlorpromazine.
DR DrugBank; DB01239; Chlorprothixene.
DR DrugBank; DB00363; Clozapine.
DR DrugBank; DB00924; Cyclobenzaprine.
DR DrugBank; DB11273; Dihydroergocornine.
DR DrugBank; DB13345; Dihydroergocristine.
DR DrugBank; DB01488; Dimethyltryptamine.
DR DrugBank; DB01142; Doxepin.
DR DrugBank; DB01049; Ergoloid mesylate.
DR DrugBank; DB12141; Gilteritinib.
DR DrugBank; DB00502; Haloperidol.
DR DrugBank; DB04946; Iloperidone.
DR DrugBank; DB00458; Imipramine.
DR DrugBank; DB00408; Loxapine.
DR DrugBank; DB04829; Lysergic acid diethylamide.
DR DrugBank; DB06148; Mianserin.
DR DrugBank; DB00334; Olanzapine.
DR DrugBank; DB00715; Paroxetine.
DR DrugBank; DB05993; PRX-07034.
DR DrugBank; DB01224; Quetiapine.
DR DrugBank; DB06144; Sertindole.
DR DrugBank; DB09304; Setiptiline.
DR DrugBank; DB05042; SGS518.
DR DrugBank; DB06140; SUVN-502.
DR DrugBank; DB13025; Tiapride.
DR DrugBank; DB00246; Ziprasidone.
DR DrugBank; DB09225; Zotepine.
DR DrugCentral; P50406; -.
DR GuidetoPHARMACOLOGY; 11; -.
DR iPTMnet; P50406; -.
DR PhosphoSitePlus; P50406; -.
DR BioMuta; HTR6; -.
DR DMDM; 1703010; -.
DR MassIVE; P50406; -.
DR PaxDb; P50406; -.
DR PeptideAtlas; P50406; -.
DR PRIDE; P50406; -.
DR ProteomicsDB; 56219; -.
DR Antibodypedia; 15009; 113 antibodies from 28 providers.
DR DNASU; 3362; -.
DR Ensembl; ENST00000289753.2; ENSP00000289753.1; ENSG00000158748.4.
DR GeneID; 3362; -.
DR KEGG; hsa:3362; -.
DR MANE-Select; ENST00000289753.2; ENSP00000289753.1; NM_000871.3; NP_000862.1.
DR UCSC; uc001bcl.5; human.
DR CTD; 3362; -.
DR DisGeNET; 3362; -.
DR GeneCards; HTR6; -.
DR HGNC; HGNC:5301; HTR6.
DR HPA; ENSG00000158748; Tissue enriched (brain).
DR MIM; 601109; gene.
DR neXtProt; NX_P50406; -.
DR OpenTargets; ENSG00000158748; -.
DR PharmGKB; PA29560; -.
DR VEuPathDB; HostDB:ENSG00000158748; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01010000222287; -.
DR HOGENOM; CLU_009579_11_0_1; -.
DR InParanoid; P50406; -.
DR OMA; RFLPCPH; -.
DR OrthoDB; 1173208at2759; -.
DR PhylomeDB; P50406; -.
DR TreeFam; TF351753; -.
DR PathwayCommons; P50406; -.
DR Reactome; R-HSA-390666; Serotonin receptors.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P50406; -.
DR SIGNOR; P50406; -.
DR BioGRID-ORCS; 3362; 4 hits in 1067 CRISPR screens.
DR GeneWiki; 5-HT6_receptor; -.
DR GenomeRNAi; 3362; -.
DR Pharos; P50406; Tchem.
DR PRO; PR:P50406; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P50406; protein.
DR Bgee; ENSG00000158748; Expressed in type B pancreatic cell and 58 other tissues.
DR Genevisible; P50406; HS.
DR GO; GO:0005929; C:cilium; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IBA:GO_Central.
DR GO; GO:0004969; F:histamine receptor activity; TAS:ProtInc.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0021795; P:cerebral cortex cell migration; ISS:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; IBA:GO_Central.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IDA:UniProtKB.
DR CDD; cd15054; 7tmA_5-HT6; 1.
DR InterPro; IPR002232; 5HT6_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; G-protein coupled receptor; Membrane;
KW Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..440
FT /note="5-hydroxytryptamine receptor 6"
FT /id="PRO_0000068974"
FT TOPO_DOM 1..34
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 35..57
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 58..64
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 65..85
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 86..100
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 101..122
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 123..144
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 145..166
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 167..184
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 185..208
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 209..265
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 266..290
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 291..295
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 296..320
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 321..440
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 346..392
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 348..363
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 99..180
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT CONFLICT 247
FT /note="V -> M (in Ref. 6; CAA88929)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 440 AA; 46954 MW; C888F47650C1D2EF CRC64;
MVPEPGPTAN STPAWGAGPP SAPGGSGWVA AALCVVIALT AAANSLLIAL ICTQPALRNT
SNFFLVSLFT SDLMVGLVVM PPAMLNALYG RWVLARGLCL LWTAFDVMCC SASILNLCLI
SLDRYLLILS PLRYKLRMTP LRALALVLGA WSLAALASFL PLLLGWHELG HARPPVPGQC
RLLASLPFVL VASGLTFFLP SGAICFTYCR ILLAARKQAV QVASLTTGMA SQASETLQVP
RTPRPGVESA DSRRLATKHS RKALKASLTL GILLGMFFVT WLPFFVANIV QAVCDCISPG
LFDVLTWLGY CNSTMNPIIY PLFMRDFKRA LGRFLPCPRC PRERQASLAS PSLRTSHSGP
RPGLSLQQVL PLPLPPDSDS DSDAGSGGSS GLRLTAQLLL PGEATQDPPL PTRAAAAVNF
FNIDPAEPEL RPHPLGIPTN
