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Details on Person UniProt:Q9H3N8 HRH4

Class:Id	ReferenceGeneProduct:56508
_chainChangeLog	chain:1-390 added on Sat February 7 2015
_displayName	UniProt:Q9H3N8 HRH4
_timestamp	2026-02-20 22:33:10
chain	chain:1-390
checksum	C986B8AE7FF912C3
comment	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 (PubMed:26948974). Mediates chemotaxis of immune cells to sites of inflammation or injury by responding to histamine (PubMed:26948974). Activation by histamine also influences the release of proinflammatory cytokines such as TNF, CCL4, IL6 and IFN-gamma (PubMed:29600327, PubMed:31583075). Ligand binding induces a conformation change that triggers signaling via G(i)/GNAI1 leading to decreased intracellular cAMP levels by inhibiting adenylate cyclase activity (PubMed:39333117). In addition, plays a role in the control of renal reabsorption processes, particularly albumin uptake (By similarity).SUBUNIT Interacts with TSPAN4. Interacts with GNAI1 (PubMed:39333117).SUBCELLULAR LOCATION Expressed primarily in the bone marrow and eosinophils. Shows preferential distribution in cells of immunological relevance such as T-cells, dendritic cells, monocytes, mast cells, neutrophils and basophils (PubMed:12503632, PubMed:26948974, PubMed:29600327). Also expressed in a wide variety of peripheral tissues, including the heart, kidney, liver, lung, pancreas, skeletal muscle, prostate, small intestine, spleen, testis, colon, fetal liver and lymph node.INDUCTION Expression is either up-regulated or down-regulated upon activation of the lymphoid tissues and this regulation may depend on the presence of IL10/interleukin-10 or IL13/interleukin-13.MISCELLANEOUS Does not bind diphenhydramine, loratadine, ranitidine, cimetidine and chlorpheniramine. Shows modest affinity for dimaprit, impromidine, clobenpropit, thioperamide, burimamide clozapine, immepip and imetit. The order of inhibitory activity was imetit > clobenpropit > burimamide > thioperamide. Clobenpropit behaves as a partial agonist, dimaprit and impromidine show some agonist activity while clozapine behaves as a full agonist. Thioperamide shows inverse agonism (enhances cAMP activity). The order of inhibitory activity of histamine derivatives was Histamine > N-alpha-methylhistamine > R(-)-alpha-methylhistamine > S(+)-alpha-methylhistamine. Both N-alpha-methylhistamine > R(-)-alpha-methylhistamine behave as full agonists.SIMILARITY Belongs to the G-protein coupled receptor 1 family.
description	recommendedName: Histamine H4 receptor shortName: H4R shortName: HH4R alternativeName: AXOR35 alternativeName: G-protein coupled receptor 105 alternativeName: GPRv53 alternativeName: Pfi-013 alternativeName: SP9144
geneName	HRH4 GPCR105
identifier	Q9H3N8
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing Cell membrane Disulfide bond G-protein coupled receptor Glycoprotein Membrane Proteomics identification Receptor Reference proteome Transducer Transmembrane Transmembrane helix
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
name	HRH4
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8990751] ENSEMBL:ENSG00000134489 HRH4 [Homo sapiens]
secondaryIdentifier	HRH4_HUMAN B0YJ19 B2KJ48 Q4G0I6 Q9GZQ0
sequenceLength	390
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:8977443] UniProt:Q9H3N8-1 HRH4 [Homo sapiens] [ReferenceIsoform:8977444] UniProt:Q9H3N8-2 HRH4 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:390910] HRH4 [plasma membrane] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:Q9H3N8 HRH4 (56508)