Histamine H2 receptor

Function

G protein-coupled receptor for histamine, primarily mediating gastric acid secretion. Predominantly expressed in the gastric mucosa, couples to G(s) G alpha proteins upon histamine binding, leading to activation of adenylate cyclase and increased intracellular cyclic AMP (cAMP) levels. This signaling cascade stimulates parietal cells to secrete hydrochloric acid, playing a key role in digestive physiology. Also expressed in other tissues, including the heart and central nervous system, where it may contribute to cardiac stimulation and modulate neurotransmitter release (By similarity).

Classification

Family (Pfam)

PF00001 7tm_1

InterPro

GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, Histamine_H2_rcpt

Functional cluster

G Protein-Coupled Receptors

Experimental structures · PDB · 6

• 7UL3 EM 3.00A
• 8POK EM 3.40A
• 8YN3 EM 2.56A
• 8YN4 EM 2.97A
• 8YUT EM 2.70A
• 9IXJ EM 2.92A

A predicted model is available from AlphaFold.

Gene Ontology · 11

• GO:0030425 dendrite
• GO:0005886 plasma membrane
• GO:0045202 synapse
• GO:0004969 histamine receptor activity
• GO:0030594 neurotransmitter receptor activity
• GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
• GO:0007268 chemical synaptic transmission
• GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• GO:0001696 gastric acid secretion
• GO:0006955 immune response
• GO:0045907 positive regulation of vasoconstriction

Drugs targeting this protein · 12

• BETAZOLE HYDROCHLORIDE agonist
• METHANTHELINE BROMIDE antagonist
• CIMETIDINE HYDROCHLORIDE antagonist
• TOLAZOLINE HYDROCHLORIDE agonist
• LAFUTIDINE antagonist
• EBROTIDINE antagonist
• RANITIDINE antagonist
• RANITIDINE HYDROCHLORIDE antagonist
• RANITIDINE BISMUTH CITRATE antagonist
• CIMETIDINE antagonist
• NIZATIDINE antagonist
• FAMOTIDINE antagonist

Related proteins · sequence + function similarity

• Histamine H2 receptor 1.00
• Histamine H2 receptor 1.00
• Histamine H2 receptor 1.00
• Histamine H2 receptor 0.99
• Histamine H2 receptor 0.99
• Histamine H2 receptor 0.99
• Histamine H2 receptor 0.96
• Beta-2 adrenergic receptor 0.92
• Beta-2 adrenergic receptor 0.92
• Beta-2 adrenergic receptor 0.92
• Beta-2 adrenergic receptor 0.92
• Beta-2 adrenergic receptor 0.92

Co-cited proteins · studied together in the literature

• Histamine H4 receptor 1 shared papers
• Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 1 shared papers

Literature · 11 cited papers

• Structural basis of ligand recognition and activation of the histamine receptor family. Nat. Commun. · 2024
• Molecular Determinant Underlying Selective Coupling of Primary G-Protein by Class A GPCRs. Adv. Sci. · 2024
• Cryo-EM structure of cell-free synthesized human histamine 2 receptor/Gs complex in nanodisc environment. Nat. Commun. · 2024
• Human protein factory for converting the transcriptome into an in vitro-expressed proteome. Nat. Methods · 2008
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Human-specific amino acid changes found in 103 protein-coding genes. Mol. Biol. Evol. · 2004
• Human histamine H2 receptor gene: multiple transcription initiation and tissue-specific expression. FEBS Lett. · 1999
• Novel insights into histamine H2 receptor biology. Am. J. Physiol. · 1997
• Allelic variations of the human histamine H2 receptor gene. NeuroReport · 1996
• Identification of the promoter region of the human histamine H2-receptor gene. Biochem. Biophys. Res. Commun. · 1995
• Molecular cloning of the human histamine H2 receptor. Biochem. Biophys. Res. Commun. · 1991