ID 5HT1E_HUMAN Reviewed; 365 AA. AC P28566; E1P503; Q9P1Y1; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-1992, sequence version 1. DT 27-SEP-2017, entry version 164. DE RecName: Full=5-hydroxytryptamine receptor 1E; DE Short=5-HT-1E; DE Short=5-HT1E; DE AltName: Full=S31; DE AltName: Full=Serotonin receptor 1E; GN Name=HTR1E; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION. RC TISSUE=Brain; RX PubMed=1608964; DOI=10.1073/pnas.89.12.5517; RA McAllister G., Charlesworth A., Snodin C., Beer M.S., Noble A.J., RA Middlemiss D.N., Iversen L.L., Whiting P.; RT "Molecular cloning of a serotonin receptor from human brain (5HT1E): a RT fifth 5HT1-like subtype."; RL Proc. Natl. Acad. Sci. U.S.A. 89:5517-5521(1992). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=1733778; DOI=10.1016/0014-5793(92)80379-U; RA Levy F.O., Gudermann T., Birnbaumer M., Kaumann A.J., Birnbaumer L.; RT "Molecular cloning of a human gene (S31) encoding a novel serotonin RT receptor mediating inhibition of adenylyl cyclase."; RL FEBS Lett. 296:201-206(1992). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=1513320; RA Zgombick J.M., Schechter L.E., Macchi M., Hartig P.R., Branchek T.A., RA Weinshank R.L.; RT "Human gene S31 encodes the pharmacologically defined serotonin 5- RT hydroxytryptamine1E receptor."; RL Mol. Pharmacol. 42:180-185(1992). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.; RT "cDNA clones of human proteins involved in signal transduction RT sequenced by the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-363. RX PubMed=15014171; DOI=10.1093/molbev/msh100; RA Kitano T., Liu Y.-H., Ueda S., Saitou N.; RT "Human-specific amino acid changes found in 103 protein-coding RT genes."; RL Mol. Biol. Evol. 21:936-944(2004). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=14744596; DOI=10.1016/j.ejphar.2003.11.019; RA Bai F., Yin T., Johnstone E.M., Su C., Varga G., Little S.P., RA Nelson D.L.; RT "Molecular cloning and pharmacological characterization of the guinea RT pig 5-HT1E receptor."; RL Eur. J. Pharmacol. 484:127-139(2004). RN [10] RP REVIEW. RX PubMed=18476671; DOI=10.1021/cr078224o; RA Nichols D.E., Nichols C.D.; RT "Serotonin receptors."; RL Chem. Rev. 108:1614-1641(2008). RN [11] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=21422162; DOI=10.1124/jpet.111.179606; RA Klein M.T., Dukat M., Glennon R.A., Teitler M.; RT "Toward selective drug development for the human 5-hydroxytryptamine RT 1E receptor: a comparison of 5-hydroxytryptamine 1E and 1F receptor RT structure-affinity relationships."; RL J. Pharmacol. Exp. Ther. 337:860-867(2011). RN [12] RP REVIEW. RX PubMed=20945968; RA Pytliak M., Vargova V., Mechirova V., Felsoci M.; RT "Serotonin receptors - from molecular biology to clinical RT applications."; RL Physiol. Res. 60:15-25(2011). RN [13] RP VARIANT PHE-262. RX PubMed=10391209; DOI=10.1038/10290; RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RT "Characterization of single-nucleotide polymorphisms in coding regions RT of human genes."; RL Nat. Genet. 22:231-238(1999). RN [14] RP ERRATUM. RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RL Nat. Genet. 23:373-373(1999). CC -!- FUNCTION: G-protein coupled receptor for 5-hydroxytryptamine CC (serotonin). Also functions as a receptor for various alkaloids CC and psychoactive substances. Ligand binding causes a conformation CC change that triggers signaling via guanine nucleotide-binding CC proteins (G proteins) and modulates the activity of down-stream CC effectors, such as adenylate cyclase. Signaling inhibits adenylate CC cyclase activity. {ECO:0000269|PubMed:14744596, CC ECO:0000269|PubMed:1513320, ECO:0000269|PubMed:1608964, CC ECO:0000269|PubMed:1733778, ECO:0000269|PubMed:21422162}. CC -!- INTERACTION: CC P50222:MEOX2; NbExp=3; IntAct=EBI-1043151, EBI-748397; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14744596, CC ECO:0000269|PubMed:1513320, ECO:0000269|PubMed:1608964, CC ECO:0000269|PubMed:1733778, ECO:0000269|PubMed:21422162}; Multi- CC pass membrane protein {ECO:0000269|PubMed:14744596, CC ECO:0000269|PubMed:1513320, ECO:0000269|PubMed:1608964, CC ECO:0000269|PubMed:1733778, ECO:0000269|PubMed:21422162}. CC -!- TISSUE SPECIFICITY: Detected in brain. CC {ECO:0000269|PubMed:14744596}. 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; M91467; AAA58353.1; -; mRNA. DR EMBL; Z11166; CAA77558.1; -; Genomic_DNA. DR EMBL; M92826; AAA58355.1; -; Genomic_DNA. DR EMBL; AF498980; AAM21127.1; -; mRNA. DR EMBL; AL157777; CAC10582.1; -; Genomic_DNA. DR EMBL; CH471051; EAW48616.1; -; Genomic_DNA. DR EMBL; CH471051; EAW48617.1; -; Genomic_DNA. DR EMBL; BC069751; AAH69751.1; -; mRNA. DR EMBL; AB041373; BAA94458.1; -; Genomic_DNA. DR CCDS; CCDS5006.1; -. DR PIR; S20579; A45260. DR RefSeq; NP_000856.1; NM_000865.2. DR RefSeq; XP_011534091.1; XM_011535789.2. DR UniGene; Hs.1611; -. DR ProteinModelPortal; P28566; -. DR BioGrid; 109586; 8. DR IntAct; P28566; 3. DR STRING; 9606.ENSP00000307766; -. DR BindingDB; P28566; -. DR ChEMBL; CHEMBL2182; -. DR DrugBank; DB01238; Aripiprazole. DR DrugBank; DB00363; Clozapine. DR DrugBank; DB00216; Eletriptan. DR DrugBank; DB01049; Ergoloid mesylate. DR DrugBank; DB01221; Ketamine. DR DrugBank; DB00408; Loxapine. DR DrugBank; DB00247; Methysergide. DR DrugBank; DB00334; Olanzapine. DR DrugBank; DB01224; Quetiapine. DR DrugBank; DB13025; Tiapride. DR DrugBank; DB00246; Ziprasidone. DR GuidetoPHARMACOLOGY; 4; -. DR iPTMnet; P28566; -. DR PhosphoSitePlus; P28566; -. DR BioMuta; HTR1E; -. DR DMDM; 112822; -. DR PaxDb; P28566; -. DR PRIDE; P28566; -. DR Ensembl; ENST00000305344; ENSP00000307766; ENSG00000168830. DR GeneID; 3354; -. DR KEGG; hsa:3354; -. DR UCSC; uc003pli.4; human. DR CTD; 3354; -. DR DisGeNET; 3354; -. DR EuPathDB; HostDB:ENSG00000168830.7; -. DR GeneCards; HTR1E; -. DR HGNC; HGNC:5291; HTR1E. DR HPA; HPA004931; -. DR MIM; 182132; gene. DR neXtProt; NX_P28566; -. DR OpenTargets; ENSG00000168830; -. DR PharmGKB; PA29552; -. DR eggNOG; KOG3656; Eukaryota. DR eggNOG; ENOG410XRW9; LUCA. DR GeneTree; ENSGT00760000118795; -. DR HOGENOM; HOG000239242; -. DR HOVERGEN; HBG106962; -. DR InParanoid; P28566; -. DR KO; K04153; -. DR OMA; PLSITYI; -. DR OrthoDB; EOG091G06VI; -. DR PhylomeDB; P28566; -. DR TreeFam; TF316350; -. DR Reactome; R-HSA-390666; Serotonin receptors. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR ChiTaRS; HTR1E; human. DR GeneWiki; 5-HT1E_receptor; -. DR GenomeRNAi; 3354; -. DR PRO; PR:P28566; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; ENSG00000168830; -. DR CleanEx; HS_HTR1E; -. DR Genevisible; P28566; HS. DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0004930; F:G-protein coupled receptor activity; TAS:ProtInc. DR GO; GO:0004993; F:G-protein coupled serotonin receptor activity; IDA:MGI. DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central. DR GO; GO:0051378; F:serotonin binding; IDA:MGI. DR GO; GO:0007193; P:adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc. DR GO; GO:0007186; P:G-protein coupled receptor signaling pathway; TAS:ProtInc. DR GO; GO:0007187; P:G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; TAS:ProtInc. DR GO; GO:0030815; P:negative regulation of cAMP metabolic process; IEA:InterPro. DR CDD; cd15335; 7tmA_5-HT1E; 1. DR InterPro; IPR027425; 5HT1E_rcpt. DR InterPro; IPR002231; 5HT_rcpt. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR24247:SF135; PTHR24247:SF135; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR01101; 5HTRECEPTOR. 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; Complete proteome; Disulfide bond; KW G-protein coupled receptor; Glycoprotein; Membrane; Polymorphism; KW Receptor; Reference proteome; Transducer; Transmembrane; KW Transmembrane helix. FT CHAIN 1 365 5-hydroxytryptamine receptor 1E. FT /FTId=PRO_0000068933. FT TOPO_DOM 1 22 Extracellular. {ECO:0000250}. FT TRANSMEM 23 47 Helical; Name=1. {ECO:0000250}. FT TOPO_DOM 48 59 Cytoplasmic. {ECO:0000250}. FT TRANSMEM 60 82 Helical; Name=2. {ECO:0000250}. FT TOPO_DOM 83 96 Extracellular. {ECO:0000250}. FT TRANSMEM 97 118 Helical; Name=3. {ECO:0000250}. FT TOPO_DOM 119 138 Cytoplasmic. {ECO:0000250}. FT TRANSMEM 139 159 Helical; Name=4. {ECO:0000250}. FT TOPO_DOM 160 179 Extracellular. {ECO:0000250}. FT TRANSMEM 180 202 Helical; Name=5. {ECO:0000250}. FT TOPO_DOM 203 291 Cytoplasmic. {ECO:0000250}. FT TRANSMEM 292 314 Helical; Name=6. {ECO:0000250}. FT TOPO_DOM 315 324 Extracellular. {ECO:0000250}. FT TRANSMEM 325 347 Helical; Name=7. {ECO:0000250}. FT TOPO_DOM 348 365 Cytoplasmic. {ECO:0000250}. FT REGION 98 107 Agonist binding. {ECO:0000250}. FT REGION 304 308 Agonist binding. {ECO:0000250}. FT MOTIF 119 121 DRY motif; important for ligand-induced FT conformation changes. {ECO:0000250}. FT MOTIF 340 344 NPxxY motif; important for ligand-induced FT conformation changes and signaling. FT {ECO:0000250}. FT CARBOHYD 2 2 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 5 5 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 95 173 {ECO:0000255|PROSITE-ProRule:PRU00521}. FT VARIANT 208 208 A -> T (in dbSNP:rs3828741). FT /FTId=VAR_022061. FT VARIANT 262 262 S -> F (in dbSNP:rs6303). FT {ECO:0000269|PubMed:10391209}. FT /FTId=VAR_014165. SQ SEQUENCE 365 AA; 41682 MW; 4C31DD783A3F7483 CRC64; MNITNCTTEA SMAIRPKTIT EKMLICMTLV VITTLTTLLN LAVIMAIGTT KKLHQPANYL ICSLAVTDLL VAVLVMPLSI IYIVMDRWKL GYFLCEVWLS VDMTCCTCSI LHLCVIALDR YWAITNAIEY ARKRTAKRAA LMILTVWTIS IFISMPPLFW RSHRRLSPPP SQCTIQHDHV IYTIYSTLGA FYIPLTLILI LYYRIYHAAK SLYQKRGSSR HLSNRSTDSQ NSFASCKLTQ TFCVSDFSTS DPTTEFEKFH ASIRIPPFDN DLDHPGERQQ ISSTRERKAA RILGLILGAF ILSWLPFFIK ELIVGLSIYT VSSEVADFLT WLGYVNSLIN PLLYTSFNED FKLAFKKLIR CREHT //