Hrh3 histamine receptor H3 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Hrh3provided by RGD
Official Full Name: histamine receptor H3provided by RGD
Primary source: RGD:620630
See related: EnsemblRapid:ENSRNOG00000061153 AllianceGenome:RGD:620630
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Summary: This gene encodes a histamine H3 receptor that belongs to the superfamily of G-protein coupled receptors. This protein functions as a presynaptic autoreceptor on histamine neurons in the brain, and a presynaptic heteroreceptor in nonhistamine-containing neurons in both the central and peripheral nervous systems. It is deemed a great target for the development of therapeutics for numerous disorders, including obesity, epilepsy, and such cognitive diseases as attention deficit hyperactivity disorder and Alzheimer's disease. Several alternatively spliced transcript variants encoding different isoforms, with different brain expression patterns and signaling properties, have been described for this gene. [provided by RefSeq, Jul 2012]
Expression: Biased expression in Brain (RPKM 50.6), Thymus (RPKM 18.3) and 4 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 3q43

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	3	NC_086021.1 (187569174..187575263, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	3	NC_051338.1 (167191551..167196642, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	3	NC_005102.4 (175474310..175479395, complement)

Chromosome 3 - NC_086021.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Histamine H3 Receptor Activation Modulates Glutamate Release in the Corticostriatal Synapse by Acting at CaV2.1 (P/Q-Type) Calcium Channels and GIRK (KIR3) Potassium Channels.
Title: Histamine H(3) Receptor Activation Modulates Glutamate Release in the Corticostriatal Synapse by Acting at Ca(V)2.1 (P/Q-Type) Calcium Channels and GIRK (K(IR)3) Potassium Channels.
Histamine H3 Receptors Expressed in Ventral Horns Modulate Spinal Motor Output.
Title: Histamine H(3) Receptors Expressed in Ventral Horns Modulate Spinal Motor Output.
indicate that histamine H1, H2, and H3 receptors are present in rat olfactory epithelium and may play a physiological role in olfactory transmission.
Title: Expression and localization of histamine H(1), H(2), and H(3) receptors in rat olfactory epithelium.
Results indicate that in rat nucleus accumbens H3Rs do not modulate dopamine uptake or release, but regulate dopamine synthesis by inhibiting cAMP formation and thus PKA activation
Title: Histamine H3 receptor activation inhibits dopamine synthesis but not release or uptake in rat nucleus accumbens.
These data support the hypothesis that H3R could also mediate non-neuronal histamine effects, suggesting its involvement in fluid homeostasis
Title: H3 receptor renal expression in normal and diabetic rats.
H3 and H4 receptors in endothelial cells are potentially important for regulation of blood-brain barrier permeability, including trafficking of immunocompetent cells
Title: Expression of histamine receptor genes Hrh3 and Hrh4 in rat brain endothelial cells.
This study confirmed the ability of cultured astrocytes from different rat brain regions to express histamine H3 receptors.
Title: Identification and pharmacological characterization of the histamine H3 receptor in cultured rat astrocytes.
results indicate that co-stimulation of post-synaptic D1 and H3 receptors may indirectly regulate basal dopamine release in the rat striatum and provide in vivo evidence for a functional interaction between D1 and H3 receptors in the basal ganglia
Title: Histamine H3 receptor activation prevents dopamine D1 receptor-mediated inhibition of dopamine release in the rat striatum: a microdialysis study.
ZEL-H16 is a novel and potent nonimidazole agonist of H3R, which might serve as a pharmacological tool for future investigations or as possible therapeutic agent of H3R.
Title: Identification and characterization of ZEL-H16 as a novel agonist of the histamine H3 receptor.
Finsings show that short, but not long, isoforms fulfill the function of autoreceptor and thereby confirm the hypothesis that H3 receptor isoforms have distinct functional roles in the brain
Title: The histamine autoreceptor is a short isoform of the H₃ receptor.

Submit: New GeneRIF Correction See all GeneRIFs (34)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AA943666 (e-PCR)
- UniSTS:250159

D3Wox40 (e-PCR)
- UniSTS:518609

NoName (e-PCR)
- UniSTS:495075

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables amine binding	IPI Inferred from Physical Interaction more info	PubMed
enables heterocyclic compound binding	IPI Inferred from Physical Interaction more info	PubMed
enables histamine receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables histamine receptor activity	IEA Inferred from Electronic Annotation more info
enables neurotransmitter receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables organic cyclic compound binding	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	IBA Inferred from Biological aspect of Ancestor more info
involved_in adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cAMP metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in cognition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in drinking behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in eating behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in learning	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in memory	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of adenylate cyclase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of blood pressure	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of gamma-aminobutyric acid secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of glutamate secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of serotonin secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of arachidonate secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cytosolic calcium ion concentration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of norepinephrine secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to forskolin	IDA Inferred from Direct Assay more info	PubMed
involved_in response to organic cyclic compound	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
is_active_in synapse	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: histamine H3 receptor

Names: H3R; HH3R

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001270564.1 → NP_001257493.1 histamine H3 receptor isoform H3B

See identical proteins and their annotated locations for NP_001257493.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) is alternatively spliced at the 3' end compared to variant 1, and encodes a shorter isoform (H3B, also known as H3S or H3(413)) containing 7 transmembrane domains, but missing part of the third intracellular loop compared to isoform H3A. This isoform is thought to function as the histamine autoreceptor (PMID:22356432).

Source sequence(s)

AB015646, AY009371, BC087707, CB735595

UniProtKB/TrEMBL

Q541U0

Related

ENSRNOP00000090011.1, ENSRNOT00000116829.2

Conserved Domains (1) summary

cd15296
Location:48 → 391

7tmA_Histamine_H3R; histamine receptor subtypes H3R and H3R-like, member of the class A family of seven-transmembrane G protein-coupled receptors
NM_001270565.1 → NP_001257494.1 histamine H3 receptor isoform H3C

See identical proteins and their annotated locations for NP_001257494.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) is alternatively spliced at the 3' end compared to variant 1, and encodes a shorter isoform (H3C, also known as H3(397)) containing 7 transmembrane domains, but missing part of the third intracellular loop compared to isoform H3A.

Source sequence(s)

AB015646, BC087707, CB735595

UniProtKB/Swiss-Prot

Q9QYN8

UniProtKB/TrEMBL

Q5PPG3

Conserved Domains (1) summary

cd15296
Location:48 → 375

7tmA_Histamine_H3R; histamine receptor subtypes H3R and H3R-like, member of the class A family of seven-transmembrane G protein-coupled receptors
NM_001270566.1 → NP_001257495.1 histamine H3 receptor isoform H3D

See identical proteins and their annotated locations for NP_001257495.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) is alternatively spliced at the 3' end compared to variant 1, which results in a frame-shift, and a longer isoform (H3D) containing 6 transmembrane domains and a distinct C-terminus compared to isoform H3A.

Source sequence(s)

AB015646, BC087707, DQ112342

UniProtKB/TrEMBL

A0A0G2JU84, Q2VJ18

Conserved Domains (1) summary

pfam00001
Location:51 → 230

7tm_1; 7 transmembrane receptor (rhodopsin family)
NM_001270567.1 → NP_001257496.1 histamine H3 receptor isoform H3E

See identical proteins and their annotated locations for NP_001257496.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) is alternatively spliced at the 3' end compared to variant 1, which results in a frame-shift, and a longer isoform (H3E) containing 6 transmembrane domains and a distinct C-terminus compared to isoform H3A.

Source sequence(s)

AB015646, BC087707, DQ112343

UniProtKB/TrEMBL

A0A0G2JU84, Q2VJ17

Related

ENSRNOP00000071828.1, ENSRNOT00000077308.3

Conserved Domains (1) summary

pfam00001
Location:51 → 353

7tm_1; 7 transmembrane receptor (rhodopsin family)
NM_001270568.1 → NP_001257497.1 histamine H3 receptor isoform H3F

See identical proteins and their annotated locations for NP_001257497.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) is alternatively spliced at the 3' end compared to variant 1, which results in a frame-shift, and a longer isoform (H3F) containing 6 transmembrane domains and a distinct C-terminus compared to isoform H3A.

Source sequence(s)

AB015646, BC087707

UniProtKB/TrEMBL

A0A0G2JU84

Conserved Domains (1) summary

pfam00001
Location:51 → 337

7tm_1; 7 transmembrane receptor (rhodopsin family)
NM_001270569.1 → NP_001257498.1 histamine H3 receptor isoform 7

Status: REVIEWED

Description

Transcript Variant: This variant (7) is alternatively spliced at the 3' end compared to variant 1, and encodes a shorter isoform (7, also known as H3(410)) containing 7 transmembrane domains, but missing part of the third intracellular loop compared to isoform H3A.

Source sequence(s)

AB015646, AY009371, BC087707, CB735595

UniProtKB/TrEMBL

Q541U0, Q5PPG3

Conserved Domains (1) summary

pfam00001
Location:51 → 377

7tm_1; 7 transmembrane receptor (rhodopsin family)
NM_001270570.1 → NP_001257499.1 histamine H3 receptor isoform 8

See identical proteins and their annotated locations for NP_001257499.1

Status: REVIEWED

Description

Transcript Variant: This variant (8) is alternatively spliced at the 3' end and uses an alternate acceptor splice site at the 3' terminal exon compared to variant 1. The latter causes a frame-shift, and a shorter isoform (8) containing 6 transmembrane domains and missing part of the third intracellular loop compared to isoform H3A.

Source sequence(s)

AB015646, BC087707

UniProtKB/TrEMBL

Q5PPG3

Conserved Domains (1) summary

pfam00001
Location:51 → 337

7tm_1; 7 transmembrane receptor (rhodopsin family)
NM_053506.2 → NP_445958.1 histamine H3 receptor isoform H3A

See identical proteins and their annotated locations for NP_445958.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the predominant transcript, and encodes isoform H3A (also known as H3L or H3(445)), which contains 7 transmembrane domains.

Source sequence(s)

AB015646, BC087707, CB735595

UniProtKB/Swiss-Prot

Q9QYN6, Q9QYN7, Q9QYN8, Q9QYN9

UniProtKB/TrEMBL

A6KMB7

Related

ENSRNOP00000069003.2, ENSRNOT00000086761.3

Conserved Domains (1) summary

cd15296
Location:48 → 423

7tmA_Histamine_H3R; histamine receptor subtypes H3R and H3R-like, member of the class A family of seven-transmembrane G protein-coupled receptors

RNA

NR_073042.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (9, also known as H3T or H3(nf1)) uses an alternate donor splice site at the 5' terminal exon compared to variant 1. It is represented as non-coding because the use of the translational start codon (with a strong Kozak signal), as used in variant 1, renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AB015646, BC087707, CB735595

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCr8

Genomic

NC_086021.1 Reference GRCr8

Range

187569174..187575263 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063284743.1 → XP_063140813.1 histamine H3 receptor isoform X2
XM_063284742.1 → XP_063140812.1 histamine H3 receptor isoform X1
XM_063284745.1 → XP_063140815.1 histamine H3 receptor isoform X1
XM_063284747.1 → XP_063140817.1 histamine H3 receptor isoform X1
XM_063284746.1 → XP_063140816.1 histamine H3 receptor isoform X1
XM_008762548.4 → XP_008760770.1 histamine H3 receptor isoform X1

Conserved Domains (1) summary

pfam00001
Location:186 → 230

7tm_1; 7 transmembrane receptor (rhodopsin family)
XM_063284744.1 → XP_063140814.1 histamine H3 receptor isoform X1