Reviewed, UniProtKB/Swiss-Prot Q9Y5N1 (HRH3_HUMAN)

Names and origin

Protein names

Recommended name:
Histamine H3 receptor
Short name=HH3R
Short name=H3R

Alternative name(s):
G-protein coupled receptor 97

Gene names

Name:	HRH3
Synonyms:	GPCR97

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	445 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 niether modified adenylate cyclase activity nor induced intracellular calcium mobilization.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Expressed predominantly in the CNS, with the greatest expression in the thalamus and caudate nucleus. The various isoforms are mainly coexpressed in brain, but their relative expression level varies in a region-specific manner. Isoform 3 and isoform 7 are highly expressed in the thalamus, caudate nucleus and cerebellum while isoform 5 and isoform 6 show a poor expression. Isoform 5 and isoform 6 show a high expression in the amygdala, substantia nigra, cerebral cortex and hypothalamus. Isoform 7 is not found in hypothalamus or substantia nigra.
Miscellaneous	Does not bind to cimetidine and tripolidine. Shows modest affinity for thioperamide, imetit, N-alpha-methylhistamine and R--alpha-methylhistamine. Isoform 4 is unable to bind to iodoproxyfan while isoforms 1 and 3 bind it with high affinity.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	G-protein signaling, coupled to cyclic nucleotide second messenger Ref.1 Traceable author statement. Source: ProtInc neurotransmitter secretion Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	histamine receptor activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q9Y5N1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9Y5N1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     445-445: K → KKMKKKTCL

Isoform 3 (identifier: Q9Y5N1-3)

Also known as: H3S;

The sequence of this isoform differs from the canonical sequence as follows:
     274-353: Missing.

Isoform 4 (identifier: Q9Y5N1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     85-98: Missing.

Isoform 5 (identifier: Q9Y5N1-5)

The sequence of this isoform differs from the canonical sequence as follows:
     197-315: Missing.

Isoform 6 (identifier: Q9Y5N1-6)

The sequence of this isoform differs from the canonical sequence as follows:
     227-342: Missing.

Isoform 7 (identifier: Q9Y5N1-7)

The sequence of this isoform differs from the canonical sequence as follows:
     234-263: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 445	445	Histamine H3 receptor		PRO_0000069690
Regions
	Topological domain	1 – 39	39	Extracellular Potential
	Transmembrane	40 – 60	21	1 Potential
	Topological domain	61 – 70	10	Cytoplasmic Potential
	Transmembrane	71 – 91	21	2 Potential
	Topological domain	92 – 108	17	Extracellular Potential
	Transmembrane	109 – 129	21	3 Potential
	Topological domain	130 – 156	27	Cytoplasmic Potential
	Transmembrane	157 – 177	21	4 Potential
	Topological domain	178 – 196	19	Extracellular Potential
	Transmembrane	197 – 217	21	5 Potential
	Topological domain	218 – 359	142	Cytoplasmic Potential
	Transmembrane	360 – 380	21	6 Potential
	Topological domain	381 – 395	15	Extracellular Potential
	Transmembrane	396 – 416	21	7 Potential
	Topological domain	417 – 445	29	Cytoplasmic Potential
	Compositional bias	20 – 23	4	Poly-Ala
	Compositional bias	250 – 256	7	Poly-Pro
	Compositional bias	292 – 298	7	Poly-Gly
Amino acid modifications
	Glycosylation	11	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	85 – 98	14	Missing in isoform 4.		VSP_001881
	Alternative sequence	197 – 315	119	Missing in isoform 5.		VSP_001882
	Alternative sequence	227 – 342	116	Missing in isoform 6.		VSP_001883
	Alternative sequence	234 – 263	30	Missing in isoform 7.		VSP_001884
	Alternative sequence	274 – 353	80	Missing in isoform 3.		VSP_001885
	Alternative sequence	445	1	K → KKMKKKTCL in isoform 2.		VSP_001886
	Natural variant	280	1	A → V in one Shy-Drager syndrome patient; rare variant with unknown pathological significance. Ref.4		VAR_012235
Experimental info
	Sequence conflict	19	1	E → D Ref.1
	Sequence conflict	19	1	E → D Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 16, 2001. Version 2. Checksum: 2ACF7440FBE95B6C	FASTA	445	48,671
	10 20 30 40 50 60 MERAPPDGPL NASGALAGEA AAAGGARGFS AAWTAVLAAL MALLIVATVL GNALVMLAFV 70 80 90 100 110 120 ADSSLRTQNN FFLLNLAISD FLVGAFCIPL YVPYVLTGRW TFGRGLCKLW LVVDYLLCTS 130 140 150 160 170 180 SAFNIVLISY DRFLSVTRAV SYRAQQGDTR RAVRKMLLVW VLAFLLYGPA ILSWEYLSGG 190 200 210 220 230 240 SSIPEGHCYA EFFYNWYFLI TASTLEFFTP FLSVTFFNLS IYLNIQRRTR LRLDGAREAA 250 260 270 280 290 300 GPEPPPEAQP SPPPPPGCWG CWQKGHGEAM PLHRYGVGEA AVGAEAGEAT LGGGGGGGSV 310 320 330 340 350 360 ASPTSSSGSS SRGTERPRSL KRGSKPSASS ASLEKRMKMV SQSFTQRFRL SRDRKVAKSL 370 380 390 400 410 420 AVIVSIFGLC WAPYTLLMII RAACHGHCVP DYWYETSFWL LWANSAVNPV LYPLCHHSFR 430 440 RAFTKLLCPQ KLKIQPHSSL EHCWK
	Isoform 2. Checksum: 4473760FA5ED7E92	FASTA	453	49,633
	10 20 30 40 50 60 MERAPPDGPL NASGALAGEA AAAGGARGFS AAWTAVLAAL MALLIVATVL GNALVMLAFV 70 80 90 100 110 120 ADSSLRTQNN FFLLNLAISD FLVGAFCIPL YVPYVLTGRW TFGRGLCKLW LVVDYLLCTS 130 140 150 160 170 180 SAFNIVLISY DRFLSVTRAV SYRAQQGDTR RAVRKMLLVW VLAFLLYGPA ILSWEYLSGG 190 200 210 220 230 240 SSIPEGHCYA EFFYNWYFLI TASTLEFFTP FLSVTFFNLS IYLNIQRRTR LRLDGAREAA 250 260 270 280 290 300 GPEPPPEAQP SPPPPPGCWG CWQKGHGEAM PLHRYGVGEA AVGAEAGEAT LGGGGGGGSV 310 320 330 340 350 360 ASPTSSSGSS SRGTERPRSL KRGSKPSASS ASLEKRMKMV SQSFTQRFRL SRDRKVAKSL 370 380 390 400 410 420 AVIVSIFGLC WAPYTLLMII RAACHGHCVP DYWYETSFWL LWANSAVNPV LYPLCHHSFR 430 440 450 RAFTKLLCPQ KLKIQPHSSL EHCWKKMKKK TCL
	Isoform 3 (H3S). Checksum: 4FDD1DE0CB809F9B	FASTA	365	40,624
	10 20 30 40 50 60 MERAPPDGPL NASGALAGEA AAAGGARGFS AAWTAVLAAL MALLIVATVL GNALVMLAFV 70 80 90 100 110 120 ADSSLRTQNN FFLLNLAISD FLVGAFCIPL YVPYVLTGRW TFGRGLCKLW LVVDYLLCTS 130 140 150 160 170 180 SAFNIVLISY DRFLSVTRAV SYRAQQGDTR RAVRKMLLVW VLAFLLYGPA ILSWEYLSGG 190 200 210 220 230 240 SSIPEGHCYA EFFYNWYFLI TASTLEFFTP FLSVTFFNLS IYLNIQRRTR LRLDGAREAA 250 260 270 280 290 300 GPEPPPEAQP SPPPPPGCWG CWQKGHGEAM PLHRKVAKSL AVIVSIFGLC WAPYTLLMII 310 320 330 340 350 360 RAACHGHCVP DYWYETSFWL LWANSAVNPV LYPLCHHSFR RAFTKLLCPQ KLKIQPHSSL EHCWK
	Isoform 4. Checksum: 33C4BCC070A1DA23	FASTA	431	47,133
	10 20 30 40 50 60 MERAPPDGPL NASGALAGEA AAAGGARGFS AAWTAVLAAL MALLIVATVL GNALVMLAFV 70 80 90 100 110 120 ADSSLRTQNN FFLLNLAISD FLVGRWTFGR GLCKLWLVVD YLLCTSSAFN IVLISYDRFL 130 140 150 160 170 180 SVTRAVSYRA QQGDTRRAVR KMLLVWVLAF LLYGPAILSW EYLSGGSSIP EGHCYAEFFY 190 200 210 220 230 240 NWYFLITAST LEFFTPFLSV TFFNLSIYLN IQRRTRLRLD GAREAAGPEP PPEAQPSPPP 250 260 270 280 290 300 PPGCWGCWQK GHGEAMPLHR YGVGEAAVGA EAGEATLGGG GGGGSVASPT SSSGSSSRGT 310 320 330 340 350 360 ERPRSLKRGS KPSASSASLE KRMKMVSQSF TQRFRLSRDR KVAKSLAVIV SIFGLCWAPY 370 380 390 400 410 420 TLLMIIRAAC HGHCVPDYWY ETSFWLLWAN SAVNPVLYPL CHHSFRRAFT KLLCPQKLKI 430 QPHSSLEHCW K
	Isoform 5. Checksum: 2EDA2E296463E616	FASTA	326	36,396
	10 20 30 40 50 60 MERAPPDGPL NASGALAGEA AAAGGARGFS AAWTAVLAAL MALLIVATVL GNALVMLAFV 70 80 90 100 110 120 ADSSLRTQNN FFLLNLAISD FLVGAFCIPL YVPYVLTGRW TFGRGLCKLW LVVDYLLCTS 130 140 150 160 170 180 SAFNIVLISY DRFLSVTRAV SYRAQQGDTR RAVRKMLLVW VLAFLLYGPA ILSWEYLSGG 190 200 210 220 230 240 SSIPEGHCYA EFFYNWRPRS LKRGSKPSAS SASLEKRMKM VSQSFTQRFR LSRDRKVAKS 250 260 270 280 290 300 LAVIVSIFGL CWAPYTLLMI IRAACHGHCV PDYWYETSFW LLWANSAVNP VLYPLCHHSF 310 320 RRAFTKLLCP QKLKIQPHSS LEHCWK
	Isoform 6. Checksum: 94955EC0FA4C9590	FASTA	329	36,943
	10 20 30 40 50 60 MERAPPDGPL NASGALAGEA AAAGGARGFS AAWTAVLAAL MALLIVATVL GNALVMLAFV 70 80 90 100 110 120 ADSSLRTQNN FFLLNLAISD FLVGAFCIPL YVPYVLTGRW TFGRGLCKLW LVVDYLLCTS 130 140 150 160 170 180 SAFNIVLISY DRFLSVTRAV SYRAQQGDTR RAVRKMLLVW VLAFLLYGPA ILSWEYLSGG 190 200 210 220 230 240 SSIPEGHCYA EFFYNWYFLI TASTLEFFTP FLSVTFFNLS IYLNIQSFTQ RFRLSRDRKV 250 260 270 280 290 300 AKSLAVIVSI FGLCWAPYTL LMIIRAACHG HCVPDYWYET SFWLLWANSA VNPVLYPLCH 310 320 HSFRRAFTKL LCPQKLKIQP HSSLEHCWK
	Isoform 7. Checksum: 5A0505BAD0A13E02	FASTA	415	45,607
	10 20 30 40 50 60 MERAPPDGPL NASGALAGEA AAAGGARGFS AAWTAVLAAL MALLIVATVL GNALVMLAFV 70 80 90 100 110 120 ADSSLRTQNN FFLLNLAISD FLVGAFCIPL YVPYVLTGRW TFGRGLCKLW LVVDYLLCTS 130 140 150 160 170 180 SAFNIVLISY DRFLSVTRAV SYRAQQGDTR RAVRKMLLVW VLAFLLYGPA ILSWEYLSGG 190 200 210 220 230 240 SSIPEGHCYA EFFYNWYFLI TASTLEFFTP FLSVTFFNLS IYLNIQRRTR LRLKGHGEAM 250 260 270 280 290 300 PLHRYGVGEA AVGAEAGEAT LGGGGGGGSV ASPTSSSGSS SRGTERPRSL KRGSKPSASS 310 320 330 340 350 360 ASLEKRMKMV SQSFTQRFRL SRDRKVAKSL AVIVSIFGLC WAPYTLLMII RAACHGHCVP 370 380 390 400 410 DYWYETSFWL LWANSAVNPV LYPLCHHSFR RAFTKLLCPQ KLKIQPHSSL EHCWK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and functional expression of the human histamine H3 receptor." Lovenberg T.W., Roland B.L., Wilson S.J., Jiang X., Pyati J., Huvar A., Jackson M.R., Erlander M.G. Mol. Pharmacol. 55:1101-1107(1999) [PubMed: 10347254] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Thalamus.
[2]	"Molecular cloning and characterization of a new human histamine receptor, HH4R." Nakamura T., Itadani H., Hidaka Y., Ohta M., Tanaka K. Biochem. Biophys. Res. Commun. 279:615-620(2000) [PubMed: 11118334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CHARACTERIZATION.
[3]	"Genomic organization and characterization of splice variants of the human histamine H3 receptor." Coge F., Guenin S.-P., Audinot V., Renouard-Try A., Beauverger P., Macia C., Ouvry C., Nagel N., Rique H., Boutin J.A., Galizzi J.-P. Biochem. J. 355:279-288(2001) [PubMed: 11284713] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 3; 4; 5; 6 AND 7). Tissue: Thalamus.
[4]	"Structure of the human histamine H3 receptor gene (HRH3) and identification of naturally occurring variations." Wiedemann P., Boenisch H., Oerters F., Bruess M. J. Neural Transm. 109:443-453(2002) [PubMed: 11956964] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-280. Tissue: Blood.
[5]	"Cloning and functional expression of the human histamine H3S receptor." Ullmer C., Zirwes E., Lubbert H. Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[6]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF140538 mRNA. Translation: AAD38151.1. AB045369 mRNA. Translation: BAB20090.1. AB019000 mRNA. Translation: BAB17030.1. AJ296652 Genomic DNA. Translation: CAC51025.1. AJ278250 Genomic DNA. Translation: CAC39434.1. AF363791 mRNA. Translation: AAK50040.1. AL078633 Genomic DNA. Translation: CAC04014.1. BC096840 mRNA. Translation: AAH96840.1.
IPI	IPI00027012. IPI00217217. IPI00217218. IPI00217219. IPI00217220. IPI00217221. IPI00217222.
RefSeq	NP_009163.2.
UniGene	Hs.251399
3D structure databases
SMR	Q9Y5N1. Positions 35-428.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9Y5N1.
Protein family/group databases
GPCRDB	Search...
Proteomic databases
PRIDE	Q9Y5N1.
Genome annotation databases
Ensembl	ENST00000317393; ENSP00000321482; ENSG00000101180; Homo sapiens. [Genome view] ENST00000340177; ENSP00000342560; ENSG00000101180; Homo sapiens. [Genome view]
GeneID	11255.
KEGG	hsa:11255.
UCSC	uc002ycf.1. human. uc002yci.1. human.
Organism-specific databases
CTD	11255.
GeneCards	GC20M060223.
H-InvDB	HIX0040487.
HGNC	HGNC:5184. HRH3.
MIM	604525. gene.
PharmGKB	PA29458.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG14930.
HOGENOM	HBG713567.
HOVERGEN	HBG102132.
InParanoid	Q9Y5N1.
OMA	HRYGVGE.
OrthoDB	EOG9P5NVX.
PhylomeDB	Q9Y5N1.
Enzyme and pathway databases
Reactome	REACT_14797. Signaling by GPCR.
Gene expression databases
ArrayExpress	Q9Y5N1.
Bgee	Q9Y5N1.
CleanEx	HS_HRH3.
Genevestigator	Q9Y5N1.
GermOnline	ENSG00000101180. Homo sapiens.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_supfam. IPR003980. Histamine_H3_recept. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR01471. HISTAMINEH3R.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00667. Histamine Phosphate.
NextBio	42830.
SOURCE	Search...

Entry information

Entry name

HRH3_HUMAN

Accession

Primary (citable) accession number: Q9Y5N1
Secondary accession number(s): Q4QRI7, Q9GZX2, Q9H4K8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 16, 2001
Last sequence update:	November 16, 2001
Last modified:	March 2, 2010
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.