HRH3
Histamine H3 receptor
Also known as: GPCR97, HRH3_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9Y5N1
- Gene
- HRH3
- Ensembl
- ENSG00000101180
- Chromosome
- 20
- Canonical length
- 445 aa
- Protein class
- FDA approved drug targets, G-protein coupled receptors, Predicted membrane proteins
OverviewNCBI Gene
Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H1, H2, H3 and H4. This gene encodes one of the histamine receptors (H3) which belongs to the family 1 of G protein-coupled receptors. It is an integral membrane protein and can regulate neurotransmitter release. This receptor can also increase voltage-dependent calcium current in smooth muscles and innervates the blood vessels and the heart in cardiovascular system. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
445 residues, UniProt reviewed canonical sequence.
>Q9Y5N1|HRH3
1 MERAPPDGPL NASGALAGEA AAAGGARGFS AAWTAVLAAL MALLIVATVL GNALVMLAFV
61 ADSSLRTQNN FFLLNLAISD FLVGAFCIPL YVPYVLTGRW TFGRGLCKLW LVVDYLLCTS
121 SAFNIVLISY DRFLSVTRAV SYRAQQGDTR RAVRKMLLVW VLAFLLYGPA ILSWEYLSGG
181 SSIPEGHCYA EFFYNWYFLI TASTLEFFTP FLSVTFFNLS IYLNIQRRTR LRLDGAREAA
241 GPEPPPEAQP SPPPPPGCWG CWQKGHGEAM PLHRYGVGEA AVGAEAGEAT LGGGGGGGSV
301 ASPTSSSGSS SRGTERPRSL KRGSKPSASS ASLEKRMKMV SQSFTQRFRL SRDRKVAKSL
361 AVIVSIFGLC WAPYTLLMII RAACHGHCVP DYWYETSFWL LWANSAVNPV LYPLCHHSFR
421 RAFTKLLCPQ KLKIQPHSSL EHCWKLocalizationUniProt · AlphaFold · HPA
Whether an antibody against HRH3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 7
- Mean surface accessibility (rSASA)
- 0.41
- Highest tissue expression
- 52 nTPM
Expression across tissuesHPA
Tissue
- basal ganglia: 52 nTPM
- cerebellum: 37 nTPM
- hypothalamus: 35 nTPM
- cerebral cortex: 26 nTPM
- amygdala: 13 nTPM
- hippocampal formation: 10 nTPM
Single-cell type
- brain inhibitory neurons: 45 nCPM
- other brain neurons: 30 nCPM
- retinal ganglion cells: 16 nCPM
- brain excitatory neurons: 11 nCPM
- retinal amacrine cells: 7.6 nCPM
- bergmann glia: 4.3 nCPM
Immune cell
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
- MAIT T-cell: 0 nTPM
Brain region
- thalamus: 141 nTPM
- basal ganglia: 120 nTPM
- hypothalamus: 81 nTPM
- midbrain: 70 nTPM
- amygdala: 59 nTPM
- cerebral cortex: 57 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.69
- gnomAD pLI
- 0.04
- gnomAD missense Z
- 2.27
- DepMap mean gene effect
- -0.08
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- adenylate cyclase-activating G protein-coupled receptor signaling pathway
- adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway
- chemical synaptic transmission
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
- neurotransmitter secretion
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of HRH3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads HRH3 as an antibody target. Whether an autoantibody or antibody against HRH3 could matter depends on whether native HRH3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
HRH3 is annotated at the cell surface, where native HRH3 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label HRH3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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