P50406 (5HT6R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
5-hydroxytryptamine receptor 6
Short name=5-HT-6
Short name=5-HT6

Alternative name(s):
Serotonin receptor 6

Gene names

Name:

HTR6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	440 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in several human brain regions, most prominently in the caudate nucleus.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Traceable author statement Ref.1. Source: ProtInc brain development Inferred from electronic annotation. Source: Compara learning Inferred from electronic annotation. Source: Compara long-term synaptic potentiation Inferred from electronic annotation. Source: Compara negative regulation of acetylcholine secretion Inferred from electronic annotation. Source: Compara negative regulation of gamma-aminobutyric acid secretion Inferred from electronic annotation. Source: Compara negative regulation of glutamate secretion Inferred from electronic annotation. Source: Compara positive regulation of dopamine secretion Inferred from electronic annotation. Source: Compara positive regulation of gamma-aminobutyric acid secretion Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement Ref.1. Source: ProtInc
Cellular_component	dendrite Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	histamine receptor activity Traceable author statement Ref.1. Source: ProtInc serotonin receptor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FYN	P06241	7	EBI-1182222,EBI-515315

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 440	440	5-hydroxytryptamine receptor 6		PRO_0000068974
Regions
	Topological domain	1 – 34	34	Extracellular By similarity
	Transmembrane	35 – 57	23	Helical; Name=1; By similarity
	Topological domain	58 – 64	7	Cytoplasmic By similarity
	Transmembrane	65 – 85	21	Helical; Name=2; By similarity
	Topological domain	86 – 100	15	Extracellular By similarity
	Transmembrane	101 – 122	22	Helical; Name=3; By similarity
	Topological domain	123 – 144	22	Cytoplasmic By similarity
	Transmembrane	145 – 166	22	Helical; Name=4; By similarity
	Topological domain	167 – 184	18	Extracellular By similarity
	Transmembrane	185 – 208	24	Helical; Name=5; By similarity
	Topological domain	209 – 265	57	Cytoplasmic By similarity
	Transmembrane	266 – 290	25	Helical; Name=6; By similarity
	Topological domain	291 – 295	5	Extracellular By similarity
	Transmembrane	296 – 320	25	Helical; Name=7; By similarity
	Topological domain	321 – 440	120	Cytoplasmic By similarity
Amino acid modifications
	Disulfide bond	99 ↔ 180		By similarity
Experimental info
	Sequence conflict	247	1	V → M in CAA88929. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P50406 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: C888F47650C1D2EF	FASTA	440	46,954
	10 20 30 40 50 60 MVPEPGPTAN STPAWGAGPP SAPGGSGWVA AALCVVIALT AAANSLLIAL ICTQPALRNT 70 80 90 100 110 120 SNFFLVSLFT SDLMVGLVVM PPAMLNALYG RWVLARGLCL LWTAFDVMCC SASILNLCLI 130 140 150 160 170 180 SLDRYLLILS PLRYKLRMTP LRALALVLGA WSLAALASFL PLLLGWHELG HARPPVPGQC 190 200 210 220 230 240 RLLASLPFVL VASGLTFFLP SGAICFTYCR ILLAARKQAV QVASLTTGMA SQASETLQVP 250 260 270 280 290 300 RTPRPGVESA DSRRLATKHS RKALKASLTL GILLGMFFVT WLPFFVANIV QAVCDCISPG 310 320 330 340 350 360 LFDVLTWLGY CNSTMNPIIY PLFMRDFKRA LGRFLPCPRC PRERQASLAS PSLRTSHSGP 370 380 390 400 410 420 RPGLSLQQVL PLPLPPDSDS DSDAGSGGSS GLRLTAQLLL PGEATQDPPL PTRAAAAVNF 430 440 FNIDPAEPEL RPHPLGIPTN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00032009.
PIR	JC5520.
RefSeq	NP_000862.1. NM_000871.1.
UniGene	Hs.22180.
3D structure databases
ProteinModelPortal	P50406.
ModBase	Search...
Protein-protein interaction databases
IntAct	P50406. 1 interaction.
STRING	9606.ENSP00000289753.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P50406.
Polymorphism databases
DMDM	1703010.
Proteomic databases
PaxDb	P50406.
PRIDE	P50406.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000289753; ENSP00000289753; ENSG00000158748.
GeneID	3362.
KEGG	hsa:3362.
UCSC	uc001bcl.3. human.
Organism-specific databases
CTD	3362.
GeneCards	GC01P019991.
HGNC	HGNC:5301. HTR6.
MIM	601109. gene.
neXtProt	NX_P50406.
PharmGKB	PA29560.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG299437.
HOGENOM	HOG000241520.
HOVERGEN	HBG106962.
InParanoid	P50406.
KO	K04162.
OMA	KLRMTPP.
OrthoDB	EOG47WNPD.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	P50406.
CleanEx	HS_HTR6.
Genevestigator	P50406.
GermOnline	ENSG00000158748. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P50406.
ChEMBL	CHEMBL3371.
DrugBank	DB00889. Granisetron. DB00904. Ondansetron. DB06144. Sertindole.
GenomeRNAi	3362.
NextBio	13308.
SOURCE	Search...

Entry information

Entry name

5HT6R_HUMAN

Accession

Primary (citable) accession number: P50406
Secondary accession number(s): Q13640, Q5TGZ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.