Histamine H4 receptor
Also known as: GPCR105, HRH4
Function
G protein-coupled receptor primarily expressed in immune cells such as mast cells, eosinophils, basophils, dendritic cells and neutrophils that plays a key role in immune and inflammatory responses. Mediates chemotaxis of immune cells to sites of inflammation or injury by responding to histamine. Activation by histamine also influences the release of proinflammatory cytokines such as TNF, CCL4, IL6 and IFN-gamma. Ligand binding induces a conformation change that triggers signaling via G(i)/GNAI1 leading to decreased intracellular cAMP levels by inhibiting adenylate cyclase activity. In addition, plays a role in the control of renal reabsorption processes, particularly albumin uptake (By similarity).
Classification
- Family (Pfam)
- PF00001 7tm_1
- InterPro
- GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, Histamine_H4_rcpt
- Functional cluster
- Membrane Transporters & GPCRs
Experimental structures · PDB · 15
- 7YFC EM 3.00A
- 7YFD EM 3.10A
- 8HN8 EM 3.00A
- 8HOC EM 3.00A
- 8JXT EM 3.07A
- 8JXV EM 3.21A
- 8JXW EM 3.01A
- 8JXX EM 3.06A
- 8YN9 EM 2.30A
- 8YNA EM 2.63A
- 9JED EM 2.58A
- 9JG1 EM 3.62A
- … and 3 more
A predicted model is available from AlphaFold.
Gene Ontology · 12
- GO:0030425 dendrite
- GO:0005886 plasma membrane
- GO:0045202 synapse
- GO:0004969 histamine receptor activity
- GO:0030594 neurotransmitter receptor activity
- GO:0007197 adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway
- GO:0007193 adenylate cyclase-inhibiting 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:0006954 inflammatory response
- GO:0007204 positive regulation of cytosolic calcium ion concentration
- GO:0043408 regulation of MAPK cascade
Drugs targeting this protein · 3
- ADRIFORANT antagonist
- TOREFORANT antagonist
- UR-63325 antagonist
Related proteins · sequence + function similarity
- Histamine H4 receptor 0.98
- Histamine H4 receptor 0.97
- Histamine H1 receptor 0.84
- Histamine H1 receptor 0.83
- Histamine H1 receptor 0.82
- Histamine H1 receptor 0.82
- Histamine H1 receptor 0.81
- Muscarinic acetylcholine receptor M5 0.81
- Muscarinic acetylcholine receptor M3 0.81
- Histamine H1 receptor 0.81
- Muscarinic acetylcholine receptor M5 0.81
- Histamine H1 receptor 0.81
Co-cited proteins · studied together in the literature
- Tetraspanin-4 1 shared papers
- Histamine H3 receptor 1 shared papers
- Histamine H2 receptor 1 shared papers
Literature · 14 cited papers
- Structural basis of ligand recognition and activation of the histamine receptor family. Nat. Commun. · 2024
- Identification of TSPAN4 as Novel Histamine H4 Receptor Interactor. Biomolecules · 2021
- Histamine H4 receptor regulates IL-6 and INF-gamma secretion in native monocytes from healthy subjects and patients with allergic rhinitis. Clin. Transl. Allergy · 2019
- The histamine H4 receptor modulates the differentiation process of human monocyte-derived M1 macrophages and the release of CCL4/MIP-1beta from fully differentiated M1 macrophages. Inflamm. Res. · 2018
- Human basophil chemotaxis and activation are regulated via the histamine H4 receptor. Allergy · 2016
- Cloning and characterization of dominant negative splice variants of the human histamine H4 receptor. Biochem. J. · 2008
- DNA sequence and analysis of human chromosome 18. Nature · 2005
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Identification of a histamine H4 receptor on human eosinophils --role in eosinophil chemotaxis. J. Recept. Signal Transduct. · 2002
- Cloning and characterization of a novel human histamine receptor. J. Pharmacol. Exp. Ther. · 2001
- Cloning, expression, and pharmacological characterization of a novel human histamine receptor. Mol. Pharmacol. · 2001
- Cloning and pharmacological characterization of a fourth histamine receptor (H4) expressed in bone marrow. Mol. Pharmacol. · 2001
- … and 2 more in the literature graph