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 27-MAR-2024, entry version 186. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7XTB; EM; 3.30 A; R=2-440. DR PDB; 7YS6; EM; 3.00 A; A=24-345. DR PDB; 8JLZ; EM; 3.09 A; R=1-440. DR PDBsum; 7XTB; -. DR PDBsum; 7YS6; -. DR PDBsum; 8JLZ; -. DR AlphaFoldDB; P50406; -. DR EMDB; EMD-34073; -. DR EMDB; EMD-36409; -. DR SMR; P50406; -. DR BioGRID; 109594; 53. 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; 9606-ENSP00000289753; -. DR PeptideAtlas; P50406; -. DR ProteomicsDB; 56219; -. DR Antibodypedia; 15009; 124 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 AGR; HGNC:5301; -. 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; FCPIWLC; -. DR OrthoDB; 2900736at2759; -. 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 SignaLink; P50406; -. DR SIGNOR; P50406; -. DR BioGRID-ORCS; 3362; 5 hits in 1149 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 59 other cell types or tissues. DR GO; GO:0005929; C:cilium; IEA:Ensembl. DR GO; GO:0030425; C:dendrite; 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 Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR002232; 5HT6_rcpt. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR24247; 5-HYDROXYTRYPTAMINE RECEPTOR; 1. DR PANTHER; PTHR24247:SF202; 5-HYDROXYTRYPTAMINE RECEPTOR 6; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR01102; 5HT6RECEPTR. DR PRINTS; PR00237; GPCRRHODOPSN. DR SMART; SM01381; 7TM_GPCR_Srsx; 1. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; P50406; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor; KW Membrane; 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" FT HELIX 32..53 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 55..57 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 60..62 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 63..78 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 80..89 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 96..98 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 99..128 FT /evidence="ECO:0007829|PDB:7YS6" FT STRAND 131..133 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 134..137 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 140..159 FT /evidence="ECO:0007829|PDB:7YS6" FT TURN 160..163 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 166..169 FT /evidence="ECO:0007829|PDB:7XTB" FT STRAND 177..179 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 186..196 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 198..223 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 265..293 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 299..315 FT /evidence="ECO:0007829|PDB:7YS6" FT TURN 317..320 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 321..323 FT /evidence="ECO:0007829|PDB:7YS6" FT HELIX 325..334 FT /evidence="ECO:0007829|PDB:7YS6" 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 //