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Q9Y5N1 (HRH3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histamine H3 receptor

Short name=H3R
Short name=HH3R
Alternative name(s):
G-protein coupled receptor 97
Gene names
Name:HRH3
Synonyms:GPCR97
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length445 AA.
Sequence statusComplete.
Protein existenceEvidence 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 neither 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 componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-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: Ensembl

drinking behavior

Inferred from electronic annotation. Source: Ensembl

eating behavior

Inferred from electronic annotation. Source: Ensembl

learning

Inferred from electronic annotation. Source: Ensembl

memory

Inferred from electronic annotation. Source: Ensembl

negative regulation of adenylate cyclase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

negative regulation of gamma-aminobutyric acid secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of glutamate secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of serotonin secretion

Inferred from electronic annotation. Source: Ensembl

neurotransmitter secretion

Traceable author statement Ref.1. Source: ProtInc

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of norepinephrine secretion

Inferred from electronic annotation. Source: Ensembl

response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentintegral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

myelin sheath

Inferred from electronic annotation. Source: Ensembl

neuron projection

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functiondrug binding

Inferred from electronic annotation. Source: Ensembl

histamine receptor activity

Traceable author statement Ref.1. 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 445445Histamine H3 receptor
PRO_0000069690

Regions

Topological domain1 – 3939Extracellular Potential
Transmembrane40 – 6021Helical; Name=1; Potential
Topological domain61 – 7010Cytoplasmic Potential
Transmembrane71 – 9121Helical; Name=2; Potential
Topological domain92 – 10817Extracellular Potential
Transmembrane109 – 12921Helical; Name=3; Potential
Topological domain130 – 15627Cytoplasmic Potential
Transmembrane157 – 17721Helical; Name=4; Potential
Topological domain178 – 19619Extracellular Potential
Transmembrane197 – 21721Helical; Name=5; Potential
Topological domain218 – 359142Cytoplasmic Potential
Transmembrane360 – 38021Helical; Name=6; Potential
Topological domain381 – 39515Extracellular Potential
Transmembrane396 – 41621Helical; Name=7; Potential
Topological domain417 – 44529Cytoplasmic Potential
Compositional bias20 – 234Poly-Ala
Compositional bias250 – 2567Poly-Pro
Compositional bias292 – 2987Poly-Gly

Amino acid modifications

Glycosylation111N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence85 – 9814Missing in isoform 4.
VSP_001881
Alternative sequence197 – 315119Missing in isoform 5.
VSP_001882
Alternative sequence227 – 342116Missing in isoform 6.
VSP_001883
Alternative sequence234 – 26330Missing in isoform 7.
VSP_001884
Alternative sequence274 – 35380Missing in isoform 3.
VSP_001885
Alternative sequence4451K → KKMKKKTCL in isoform 2.
VSP_001886
Natural variant2801A → V in one Shy-Drager syndrome patient; rare variant with unknown pathological significance. Ref.4
VAR_012235

Experimental info

Sequence conflict191E → D Ref.1
Sequence conflict191E → D Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 16, 2001. Version 2.
Checksum: 2ACF7440FBE95B6C

FASTA44548,671
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 4473760FA5ED7E92
Show »

FASTA45349,633
Isoform 3 (H3S) [UniParc].

Checksum: 4FDD1DE0CB809F9B
Show »

FASTA36540,624
Isoform 4 [UniParc].

Checksum: 33C4BCC070A1DA23
Show »

FASTA43147,133
Isoform 5 [UniParc].

Checksum: 2EDA2E296463E616
Show »

FASTA32636,396
Isoform 6 [UniParc].

Checksum: 94955EC0FA4C9590
Show »

FASTA32936,943
Isoform 7 [UniParc].

Checksum: 5A0505BAD0A13E02
Show »

FASTA41545,607

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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.
RefSeqNP_009163.2. NM_007232.2.
XP_005260323.1. XM_005260266.1.
UniGeneHs.251399.

3D structure databases

ProteinModelPortalQ9Y5N1.
SMRQ9Y5N1. Positions 30-428.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116416. 1 interaction.
STRING9606.ENSP00000342560.

Chemistry

BindingDBQ9Y5N1.
ChEMBLCHEMBL2111378.
DrugBankDB00667. Histamine Phosphate.
GuidetoPHARMACOLOGY264.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ9Y5N1.

Polymorphism databases

DMDM17367264.

Proteomic databases

PaxDbQ9Y5N1.
PRIDEQ9Y5N1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000317393; ENSP00000321482; ENSG00000101180. [Q9Y5N1-2]
ENST00000340177; ENSP00000342560; ENSG00000101180. [Q9Y5N1-1]
GeneID11255.
KEGGhsa:11255.
UCSCuc002ycf.2. human. [Q9Y5N1-1]
uc002ycg.3. human. [Q9Y5N1-3]
uc002yci.3. human. [Q9Y5N1-2]

Organism-specific databases

CTD11255.
GeneCardsGC20M060790.
HGNCHGNC:5184. HRH3.
MIM604525. gene.
neXtProtNX_Q9Y5N1.
PharmGKBPA29458.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG289713.
HOGENOMHOG000048707.
HOVERGENHBG102132.
InParanoidQ9Y5N1.
KOK04151.
OMACWGCWQK.
OrthoDBEOG73804R.
PhylomeDBQ9Y5N1.
TreeFamTF351747.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeQ9Y5N1.
CleanExHS_HRH3.
GenevestigatorQ9Y5N1.

Family and domain databases

Gene3D1.20.1070.10. 2 hits.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR003980. Histamine_H3_rcpt.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR01471. HISTAMINEH3R.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiHistamine_H3_receptor.
GenomeRNAi11255.
NextBio42830.
PROQ9Y5N1.
SOURCESearch...

Entry information

Entry nameHRH3_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries