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Protein

Histamine H3 receptor

Gene

HRH3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  1. drug binding Source: Ensembl
  2. histamine receptor activity Source: ProtInc

GO - Biological processi

  1. brain development Source: Ensembl
  2. drinking behavior Source: Ensembl
  3. eating behavior Source: Ensembl
  4. G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
  5. learning Source: Ensembl
  6. memory Source: Ensembl
  7. negative regulation of adenylate cyclase activity Source: Ensembl
  8. negative regulation of blood pressure Source: Ensembl
  9. negative regulation of gamma-aminobutyric acid secretion Source: Ensembl
  10. negative regulation of glutamate secretion Source: Ensembl
  11. negative regulation of serotonin secretion Source: Ensembl
  12. neurotransmitter secretion Source: ProtInc
  13. positive regulation of cytosolic calcium ion concentration Source: Ensembl
  14. positive regulation of epithelial cell proliferation Source: Ensembl
  15. regulation of norepinephrine secretion Source: Ensembl
  16. response to organic cyclic compound Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_16903. Histamine receptors.
REACT_19231. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Histamine H3 receptor
Short name:
H3R
Short name:
HH3R
Alternative name(s):
G-protein coupled receptor 97
Gene namesi
Name:HRH3
Synonyms:GPCR97
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 20

Organism-specific databases

HGNCiHGNC:5184. HRH3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3939ExtracellularSequence AnalysisAdd
BLAST
Transmembranei40 – 6021Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini61 – 7010CytoplasmicSequence Analysis
Transmembranei71 – 9121Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini92 – 10817ExtracellularSequence AnalysisAdd
BLAST
Transmembranei109 – 12921Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini130 – 15627CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei157 – 17721Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini178 – 19619ExtracellularSequence AnalysisAdd
BLAST
Transmembranei197 – 21721Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini218 – 359142CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei360 – 38021Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini381 – 39515ExtracellularSequence AnalysisAdd
BLAST
Transmembranei396 – 41621Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini417 – 44529CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: ProtInc
  2. myelin sheath Source: Ensembl
  3. neuron projection Source: Ensembl
  4. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29458.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 445445Histamine H3 receptorPRO_0000069690Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi11 – 111N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9Y5N1.
PRIDEiQ9Y5N1.

PTM databases

PhosphoSiteiQ9Y5N1.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiQ9Y5N1.
CleanExiHS_HRH3.
ExpressionAtlasiQ9Y5N1. baseline and differential.
GenevestigatoriQ9Y5N1.

Interactioni

Protein-protein interaction databases

BioGridi116416. 1 interaction.
STRINGi9606.ENSP00000342560.

Structurei

3D structure databases

ProteinModelPortaliQ9Y5N1.
SMRiQ9Y5N1. Positions 27-249, 352-427.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi20 – 234Poly-Ala
Compositional biasi250 – 2567Poly-Pro
Compositional biasi292 – 2987Poly-Gly

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG289713.
GeneTreeiENSGT00780000121874.
HOGENOMiHOG000048707.
HOVERGENiHBG102132.
InParanoidiQ9Y5N1.
KOiK04151.
OMAiSSLEHCW.
OrthoDBiEOG73804R.
PhylomeDBiQ9Y5N1.
TreeFamiTF351747.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR003980. Histamine_H3_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01471. HISTAMINEH3R.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. Align

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q9Y5N1-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MERAPPDGPL NASGALAGEA AAAGGARGFS AAWTAVLAAL MALLIVATVL
60 70 80 90 100
GNALVMLAFV ADSSLRTQNN FFLLNLAISD FLVGAFCIPL YVPYVLTGRW
110 120 130 140 150
TFGRGLCKLW LVVDYLLCTS SAFNIVLISY DRFLSVTRAV SYRAQQGDTR
160 170 180 190 200
RAVRKMLLVW VLAFLLYGPA ILSWEYLSGG SSIPEGHCYA EFFYNWYFLI
210 220 230 240 250
TASTLEFFTP FLSVTFFNLS IYLNIQRRTR LRLDGAREAA GPEPPPEAQP
260 270 280 290 300
SPPPPPGCWG CWQKGHGEAM PLHRYGVGEA AVGAEAGEAT LGGGGGGGSV
310 320 330 340 350
ASPTSSSGSS SRGTERPRSL KRGSKPSASS ASLEKRMKMV SQSFTQRFRL
360 370 380 390 400
SRDRKVAKSL AVIVSIFGLC WAPYTLLMII RAACHGHCVP DYWYETSFWL
410 420 430 440
LWANSAVNPV LYPLCHHSFR RAFTKLLCPQ KLKIQPHSSL EHCWK
Length:445
Mass (Da):48,671
Last modified:November 16, 2001 - v2
Checksum:i2ACF7440FBE95B6C
GO
Isoform 2 (identifier: Q9Y5N1-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:453
Mass (Da):49,633
Checksum:i4473760FA5ED7E92
GO
Isoform 3 (identifier: Q9Y5N1-3) [UniParc]FASTAAdd to Basket

Also known as: H3S

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

Show »
Length:365
Mass (Da):40,624
Checksum:i4FDD1DE0CB809F9B
GO
Isoform 4 (identifier: Q9Y5N1-4) [UniParc]FASTAAdd to Basket

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

Show »
Length:431
Mass (Da):47,133
Checksum:i33C4BCC070A1DA23
GO
Isoform 5 (identifier: Q9Y5N1-5) [UniParc]FASTAAdd to Basket

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

Show »
Length:326
Mass (Da):36,396
Checksum:i2EDA2E296463E616
GO
Isoform 6 (identifier: Q9Y5N1-6) [UniParc]FASTAAdd to Basket

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

Show »
Length:329
Mass (Da):36,943
Checksum:i94955EC0FA4C9590
GO
Isoform 7 (identifier: Q9Y5N1-7) [UniParc]FASTAAdd to Basket

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

Show »
Length:415
Mass (Da):45,607
Checksum:i5A0505BAD0A13E02
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti19 – 191E → D(PubMed:10347254)Curated
Sequence conflicti19 – 191E → D1 PublicationCurated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti280 – 2801A → V in one Shy-Drager syndrome patient; rare variant with unknown pathological significance. 1 Publication
VAR_012235

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei85 – 9814Missing in isoform 4. CuratedVSP_001881Add
BLAST
Alternative sequencei197 – 315119Missing in isoform 5. CuratedVSP_001882Add
BLAST
Alternative sequencei227 – 342116Missing in isoform 6. CuratedVSP_001883Add
BLAST
Alternative sequencei234 – 26330Missing in isoform 7. CuratedVSP_001884Add
BLAST
Alternative sequencei274 – 35380Missing in isoform 3. 1 PublicationVSP_001885Add
BLAST
Alternative sequencei445 – 4451K → KKMKKKTCL in isoform 2. 1 PublicationVSP_001886

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13493.1. [Q9Y5N1-1]
RefSeqiNP_009163.2. NM_007232.2. [Q9Y5N1-1]
XP_005260323.1. XM_005260266.1. [Q9Y5N1-2]
UniGeneiHs.251399.

Genome annotation databases

EnsembliENST00000340177; ENSP00000342560; ENSG00000101180. [Q9Y5N1-1]
GeneIDi11255.
KEGGihsa:11255.
UCSCiuc002ycf.2. human. [Q9Y5N1-1]
uc002ycg.3. human. [Q9Y5N1-3]
uc002yci.3. human. [Q9Y5N1-2]

Polymorphism databases

DMDMi17367264.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13493.1. [Q9Y5N1-1]
RefSeqiNP_009163.2. NM_007232.2. [Q9Y5N1-1]
XP_005260323.1. XM_005260266.1. [Q9Y5N1-2]
UniGeneiHs.251399.

3D structure databases

ProteinModelPortaliQ9Y5N1.
SMRiQ9Y5N1. Positions 27-249, 352-427.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116416. 1 interaction.
STRINGi9606.ENSP00000342560.

Chemistry

BindingDBiQ9Y5N1.
ChEMBLiCHEMBL2111378.
DrugBankiDB06698. Betahistine.
DB00667. Histamine Phosphate.
DB00370. Mirtazapine.
GuidetoPHARMACOLOGYi264.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiQ9Y5N1.

Polymorphism databases

DMDMi17367264.

Proteomic databases

PaxDbiQ9Y5N1.
PRIDEiQ9Y5N1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340177; ENSP00000342560; ENSG00000101180. [Q9Y5N1-1]
GeneIDi11255.
KEGGihsa:11255.
UCSCiuc002ycf.2. human. [Q9Y5N1-1]
uc002ycg.3. human. [Q9Y5N1-3]
uc002yci.3. human. [Q9Y5N1-2]

Organism-specific databases

CTDi11255.
GeneCardsiGC20M060790.
HGNCiHGNC:5184. HRH3.
MIMi604525. gene.
neXtProtiNX_Q9Y5N1.
PharmGKBiPA29458.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG289713.
GeneTreeiENSGT00780000121874.
HOGENOMiHOG000048707.
HOVERGENiHBG102132.
InParanoidiQ9Y5N1.
KOiK04151.
OMAiSSLEHCW.
OrthoDBiEOG73804R.
PhylomeDBiQ9Y5N1.
TreeFamiTF351747.

Enzyme and pathway databases

ReactomeiREACT_16903. Histamine receptors.
REACT_19231. G alpha (i) signalling events.

Miscellaneous databases

ChiTaRSiHRH3. human.
GeneWikiiHistamine_H3_receptor.
GenomeRNAii11255.
NextBioi42830.
PROiQ9Y5N1.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y5N1.
CleanExiHS_HRH3.
ExpressionAtlasiQ9Y5N1. baseline and differential.
GenevestigatoriQ9Y5N1.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR003980. Histamine_H3_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01471. HISTAMINEH3R.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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).

Entry informationi

Entry nameiHRH3_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5N1
Secondary accession number(s): Q4QRI7, Q9GZX2, Q9H4K8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: November 16, 2001
Last modified: February 4, 2015
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.