P08908 (5HT1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
5-hydroxytryptamine receptor 1A
Short name=5-HT-1A
Short name=5-HT1A

Alternative name(s):
G-21
Serotonin receptor 1A

Gene names

Name:	HTR1A
Synonyms:	ADRB2RL1, ADRBRL1

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	422 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 inhibit adenylate cyclase activity. Ref.9
Subcellular location	Cell membrane; Multi-pass membrane protein.
Involvement in disease	Periodic fever, menstrual cycle-dependent (PFMC) [MIM:614674]: A condition characterized by recurrent fevers up to 40 degrees Celsius associated with the luteal phase of the menstrual cycle. Women show menstrual cycle-dependent physiologic changes in relation to sex hormone levels. Because ovulation triggers a significant change in the hormonal milieu that is similar to local inflammation, a 0.5 to 1.0 degree Celsius increase in basal body temperature after ovulation is commonly associated with progesterone secretion and is believed to be triggered by the induction of several inflammatory cytokines. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11
Sequence similarities	Belongs to the G-protein coupled receptor 1 family. 5-hydroxytryptamine receptor subfamily. HTR1A sub-subfamily.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	behavior Traceable author statement PubMed 9736659. Source: ProtInc positive regulation of cell proliferation Traceable author statement PubMed 1330092. Source: ProtInc
Cellular_component	integral to plasma membrane Traceable author statement Ref.9. Source: ProtInc
Molecular_function	serotonin receptor activity Traceable author statement PubMed 9736659. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 422	422	5-hydroxytryptamine receptor 1A		PRO_0000068903
Regions
	Topological domain	1 – 36	36	Extracellular By similarity
	Transmembrane	37 – 62	26	Helical; Name=1; By similarity
	Topological domain	63 – 73	11	Cytoplasmic By similarity
	Transmembrane	74 – 98	25	Helical; Name=2; By similarity
	Topological domain	99 – 109	11	Extracellular By similarity
	Transmembrane	110 – 132	23	Helical; Name=3; By similarity
	Topological domain	133 – 152	20	Cytoplasmic By similarity
	Transmembrane	153 – 178	26	Helical; Name=4; By similarity
	Topological domain	179 – 191	13	Extracellular By similarity
	Transmembrane	192 – 217	26	Helical; Name=5; By similarity
	Topological domain	218 – 345	128	Cytoplasmic By similarity
	Transmembrane	346 – 367	22	Helical; Name=6; By similarity
	Topological domain	368 – 378	11	Extracellular By similarity
	Transmembrane	379 – 403	25	Helical; Name=7; By similarity
	Topological domain	404 – 422	19	Cytoplasmic By similarity
Amino acid modifications
	Glycosylation	10	1	N-linked (GlcNAc...) Potential
	Glycosylation	11	1	N-linked (GlcNAc...) Potential
	Glycosylation	24	1	N-linked (GlcNAc...) Potential
	Disulfide bond	109 ↔ 187		By similarity
	Cross-link	334		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.10
Natural variations
	Natural variant	16	1	P → L. Ref.13 Corresponds to variant rs1800041 [ dbSNP | Ensembl ].		VAR_003446
	Natural variant	22	1	G → S. Ref.12 Corresponds to variant rs1799920 [ dbSNP | Ensembl ].		VAR_011826
	Natural variant	28	1	I → V. Ref.12 Corresponds to variant rs1799921 [ dbSNP | Ensembl ].		VAR_011827
	Natural variant	184	1	P → L. Corresponds to variant rs1800043 [ dbSNP | Ensembl ].		VAR_011828
	Natural variant	220	1	R → L. Corresponds to variant rs1800044 [ dbSNP | Ensembl ].		VAR_011829
	Natural variant	273	1	G → D. Ref.13 Corresponds to variant rs1800042 [ dbSNP | Ensembl ].		VAR_011830
Experimental info
	Sequence conflict	152 – 154	3	RAA → PR in AAA36440. Ref.1
	Sequence conflict	152 – 154	3	RAA → PR in CAA31908. Ref.1
	Sequence conflict	172	1	M → I in AAA36440. Ref.1
	Sequence conflict	172	1	M → I in CAA31908. Ref.1
	Sequence conflict	200 – 202	3	TFG → RPR no nucleotide entry Ref.8
	Sequence conflict	228	1	K → R no nucleotide entry Ref.8
	Sequence conflict	244	1	A → AA no nucleotide entry Ref.8
	Sequence conflict	355	1	I → T no nucleotide entry Ref.8
	Sequence conflict	363 – 365	3	IVA → MRP no nucleotide entry Ref.8
	Sequence conflict	418	1	K → N in AAA36440. Ref.1
	Sequence conflict	418	1	K → N in CAA31908. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P08908 [UniParc]. Last modified April 1, 1993. Version 3. Checksum: 762664FCF62CFD8F	FASTA	422	46,107
	10 20 30 40 50 60 MDVLSPGQGN NTTSPPAPFE TGGNTTGISD VTVSYQVITS LLLGTLIFCA VLGNACVVAA 70 80 90 100 110 120 IALERSLQNV ANYLIGSLAV TDLMVSVLVL PMAALYQVLN KWTLGQVTCD LFIALDVLCC 130 140 150 160 170 180 TSSILHLCAI ALDRYWAITD PIDYVNKRTP RRAAALISLT WLIGFLISIP PMLGWRTPED 190 200 210 220 230 240 RSDPDACTIS KDHGYTIYST FGAFYIPLLL MLVLYGRIFR AARFRIRKTV KKVEKTGADT 250 260 270 280 290 300 RHGASPAPQP KKSVNGESGS RNWRLGVESK AGGALCANGA VRQGDDGAAL EVIEVHRVGN 310 320 330 340 350 360 SKEHLPLPSE AGPTPCAPAS FERKNERNAE AKRKMALARE RKTVKTLGII MGTFILCWLP 370 380 390 400 410 420 FFIVALVLPF CESSCHMPTL LGAIINWLGY SNSLLNPVIY AYFNKDFQNA FKKIIKCKFC RQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins." Kobilka B.K., Frielle T., Collins S., Yang-Feng T.L., Kobilka T.S., Francke U., Lefkowitz R.J., Caron M.G. Nature 329:75-79(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Nucleotide and deduced amino acid sequence of the human serotonin 5-HT1a receptor gene." Saltzman A.G., Morse B., Felder S. Submitted (FEB-1991) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	Levy F.O., Gudermann T., Birnbaumer M., Kaumann A.J., Birnbaumer L. Submitted (MAY-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Human-specific amino acid changes found in 103 protein-coding genes." Kitano T., Liu Y.-H., Ueda S., Saitou N. Mol. Biol. Evol. 21:936-944(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Puhl H.L. III, Ikeda S.R., Aronstam R.S. Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"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].
[7]	"A polymerase chain reaction mediated by a single primer: cloning of genomic sequences adjacent to a serotonin receptor protein coding region." Parks C.L., Chang L.S., Shenk T. Nucleic Acids Res. 19:7155-7160(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
[8]	"Expression of 5HT1a receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-hydroxytryptamine." Aune T.M., McGrath K.M., Sarr T., Bombara M.P., Kelley K.A. J. Immunol. 151:1175-1183(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 200-365.
[9]	"The genomic clone G-21 which resembles a beta-adrenergic receptor sequence encodes the 5-HT1A receptor." Fargin A., Raymond J.R., Lohse M.L., Kobilka B.K., Caron M.G., Lefkowitz R.J. Nature 335:358-360(1988) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"The proteomic reactor facilitates the analysis of affinity-purified proteins by mass spectrometry: application for identifying ubiquitinated proteins in human cells." Vasilescu J., Zweitzig D.R., Denis N.J., Smith J.C., Ethier M., Haines D.S., Figeys D. J. Proteome Res. 6:298-305(2007) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-334, MASS SPECTROMETRY. Tissue: Lung adenocarcinoma.
[11]	"Menstrual cycle-dependent febrile episode mediated by sequence-specific repression of poly(ADP-ribose) polymerase-1 on the transcription of the human serotonin receptor 1A gene." Jiang Y.C., Wu H.M., Cheng K.H., Sunny Sun H. Hum. Mutat. 33:209-217(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PFMC.
[12]	"Two naturally occurring amino acid substitutions in the human 5-HT1A receptor: glycine 22 to serine 22 and isoleucine 28 to valine 28." Nakhai B., Nielsen D.A., Linnoila M., Goldman D. Biochem. Biophys. Res. Commun. 210:530-536(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SER-22 AND VAL-28.
[13]	"Novel mutations in the promoter and coding region of the human 5-HT1A receptor gene and association analysis in schizophrenia." Kawanishi Y., Harada S., Tachikawa H., Okubo T., Shiraishi H. Am. J. Med. Genet. 81:434-439(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LEU-16 AND ASP-273.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M28269 Genomic DNA. Translation: AAA36440.1. X13556 Genomic DNA. Translation: CAA31908.1. X57829 Genomic DNA. Translation: CAA40962.1. M83181 Genomic DNA. Translation: AAA66493.1. AB041403 Genomic DNA. Translation: BAA94488.1. AF498978 mRNA. Translation: AAM21125.1. BC069159 mRNA. Translation: AAH69159.1. Z11168 Genomic DNA. Translation: CAA77560.1.
IPI	IPI00031686.
PIR	I38209.
RefSeq	NP_000515.2. NM_000524.3.
UniGene	Hs.247940.
3D structure databases
ProteinModelPortal	P08908.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000316244.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P08908.
Polymorphism databases
DMDM	231454.
Proteomic databases
PaxDb	P08908.
PRIDE	P08908.
Protocols and materials databases
DNASU	3350.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000323865; ENSP00000316244; ENSG00000178394.
GeneID	3350.
KEGG	hsa:3350.
UCSC	uc011cqt.2. human.
Organism-specific databases
CTD	3350.
GeneCards	GC05M063292.
HGNC	HGNC:5286. HTR1A.
HPA	HPA018073.
MIM	109760. gene. 614674. phenotype.
neXtProt	NX_P08908.
PharmGKB	PA192.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG249628.
HOGENOM	HOG000239242.
HOVERGEN	HBG106962.
InParanoid	P08908.
KO	K04153.
OMA	TGAPCAN.
OrthoDB	EOG4CC41F.
PhylomeDB	P08908.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	P08908.
Bgee	P08908.
CleanEx	HS_HTR1A.
Genevestigator	P08908.
GermOnline	ENSG00000178394. Homo sapiens.
Family and domain databases
InterPro	IPR000610. 5HT1A_rcpt. IPR002231. 5HT_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00512. 5HT1ARECEPTR. PR01101. 5HTRECEPTOR. 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	P08908.
ChEMBL	CHEMBL214.
DrugBank	DB00866. Alprenolol. DB01238. Aripiprazole. DB00490. Buspirone. DB00363. Clozapine. DB00216. Eletriptan. DB01049. Ergoloid mesylate. DB00176. Fluvoxamine. DB00589. Lisuride. DB00247. Methysergide. DB00370. Mirtazapine. DB00960. Pindolol. DB00571. Propranolol. DB01224. Quetiapine. DB01104. Sertraline. DB01079. Tegaserod. DB00656. Trazodone. DB00285. Venlafaxine. DB00246. Ziprasidone.
GenomeRNAi	3350.
NextBio	13248.
SOURCE	Search...

Entry information

Entry name

5HT1A_HUMAN

Accession

Primary (citable) accession number: P08908
Secondary accession number(s): Q6LAE7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	April 1, 1993
Last modified:	May 1, 2013
This is version 133 of the entry and version 3 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.