UniProtKB - Q9H3N8 (HRH4_HUMAN)
Protein
Histamine H4 receptor
Gene
HRH4
Organism
Homo sapiens (Human)
Status
Functioni
The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist).1 Publication
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.
GO - Molecular functioni
- G protein-coupled acetylcholine receptor activity Source: GO_Central
- G protein-coupled receptor activity Source: GO_Central
- G protein-coupled serotonin receptor activity Source: GO_Central
- histamine receptor activity Source: UniProtKB
- neurotransmitter receptor activity Source: GO_Central
GO - Biological processi
- adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway Source: GO_Central
- chemical synaptic transmission Source: GO_Central
- G protein-coupled receptor signaling pathway Source: Reactome
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: GO_Central
- inflammatory response Source: GO_Central
- positive regulation of cytosolic calcium ion concentration Source: InterPro
- regulation of MAPK cascade Source: InterPro
Keywordsi
Molecular function | G-protein coupled receptor, Receptor, Transducer |
Enzyme and pathway databases
PathwayCommonsi | Q9H3N8 |
Reactomei | R-HSA-390650, Histamine receptors R-HSA-418594, G alpha (i) signalling events |
SIGNORi | Q9H3N8 |
Names & Taxonomyi
Protein namesi | Recommended name: Histamine H4 receptorShort name: H4R Short name: HH4R Alternative name(s): AXOR35 G-protein coupled receptor 105 GPRv53 Pfi-013 SP9144 |
Gene namesi | Name:HRH4 Synonyms:GPCR105 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:17383, HRH4 |
MIMi | 606792, gene |
neXtProti | NX_Q9H3N8 |
VEuPathDBi | HostDB:ENSG00000134489.6 |
Subcellular locationi
Plasma membrane
Plasma Membrane
- integral component of plasma membrane Source: GO_Central
- plasma membrane Source: Reactome
Other locations
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 19 | ExtracellularSequence analysisAdd BLAST | 19 | |
Transmembranei | 20 – 40 | Helical; Name=1Sequence analysisAdd BLAST | 21 | |
Topological domaini | 41 – 52 | CytoplasmicSequence analysisAdd BLAST | 12 | |
Transmembranei | 53 – 73 | Helical; Name=2Sequence analysisAdd BLAST | 21 | |
Topological domaini | 74 – 87 | ExtracellularSequence analysisAdd BLAST | 14 | |
Transmembranei | 88 – 108 | Helical; Name=3Sequence analysisAdd BLAST | 21 | |
Topological domaini | 109 – 131 | CytoplasmicSequence analysisAdd BLAST | 23 | |
Transmembranei | 132 – 152 | Helical; Name=4Sequence analysisAdd BLAST | 21 | |
Topological domaini | 153 – 172 | ExtracellularSequence analysisAdd BLAST | 20 | |
Transmembranei | 173 – 193 | Helical; Name=5Sequence analysisAdd BLAST | 21 | |
Topological domaini | 194 – 304 | CytoplasmicSequence analysisAdd BLAST | 111 | |
Transmembranei | 305 – 325 | Helical; Name=6Sequence analysisAdd BLAST | 21 | |
Topological domaini | 326 – 341 | ExtracellularSequence analysisAdd BLAST | 16 | |
Transmembranei | 342 – 362 | Helical; Name=7Sequence analysisAdd BLAST | 21 | |
Topological domaini | 363 – 390 | CytoplasmicSequence analysisAdd BLAST | 28 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 59340 |
OpenTargetsi | ENSG00000134489 |
PharmGKBi | PA134982275 |
Miscellaneous databases
Pharosi | Q9H3N8, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3759 |
DrugBanki | DB00321, Amitriptyline DB00543, Amoxapine DB01238, Aripiprazole DB00477, Chlorpromazine DB00363, Clozapine DB01142, Doxepin DB05381, Histamine DB00408, Loxapine DB06148, Mianserin DB01620, Pheniramine DB05032, REV131 |
DrugCentrali | Q9H3N8 |
GuidetoPHARMACOLOGYi | 265 |
Genetic variation databases
BioMutai | HRH4 |
DMDMi | 14194819 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000069693 | 1 – 390 | Histamine H4 receptorAdd BLAST | 390 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 5 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 9 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 87 ↔ 164 | PROSITE-ProRule annotation |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
jPOSTi | Q9H3N8 |
PaxDbi | Q9H3N8 |
PeptideAtlasi | Q9H3N8 |
PRIDEi | Q9H3N8 |
ProteomicsDBi | 80734 [Q9H3N8-1] 80735 [Q9H3N8-2] |
PTM databases
GlyGeni | Q9H3N8, 2 sites |
iPTMneti | Q9H3N8 |
PhosphoSitePlusi | Q9H3N8 |
Expressioni
Tissue specificityi
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. 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.1 Publication
Inductioni
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.
Gene expression databases
Bgeei | ENSG00000134489, Expressed in leukocyte and 46 other tissues |
Genevisiblei | Q9H3N8, HS |
Organism-specific databases
HPAi | ENSG00000134489, Tissue enriched (blood) |
Interactioni
Protein-protein interaction databases
STRINGi | 9606.ENSP00000256906 |
Chemistry databases
BindingDBi | Q9H3N8 |
Miscellaneous databases
RNActi | Q9H3N8, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3656, Eukaryota |
GeneTreei | ENSGT00940000162118 |
HOGENOMi | CLU_009579_11_2_1 |
InParanoidi | Q9H3N8 |
OMAi | VSYRTQH |
OrthoDBi | 614573at2759 |
PhylomeDBi | Q9H3N8 |
TreeFami | TF351747 |
Family and domain databases
InterProi | View protein in InterPro IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM IPR008102, Histamine_H4_rcpt |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR00237, GPCRRHODOPSN PR01726, HISTAMINEH4R |
PROSITEi | View protein in PROSITE PS00237, G_PROTEIN_RECEP_F1_1, 1 hit PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q9H3N8-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MPDTNSTINL SLSTRVTLAF FMSLVAFAIM LGNALVILAF VVDKNLRHRS
60 70 80 90 100
SYFFLNLAIS DFFVGVISIP LYIPHTLFEW DFGKEICVFW LTTDYLLCTA
110 120 130 140 150
SVYNIVLISY DRYLSVSNAV SYRTQHTGVL KIVTLMVAVW VLAFLVNGPM
160 170 180 190 200
ILVSESWKDE GSECEPGFFS EWYILAITSF LEFVIPVILV AYFNMNIYWS
210 220 230 240 250
LWKRDHLSRC QSHPGLTAVS SNICGHSFRG RLSSRRSLSA STEVPASFHS
260 270 280 290 300
ERQRRKSSLM FSSRTKMNSN TIASKMGSFS QSDSVALHQR EHVELLRARR
310 320 330 340 350
LAKSLAILLG VFAVCWAPYS LFTIVLSFYS SATGPKSVWY RIAFWLQWFN
360 370 380 390
SFVNPLLYPL CHKRFQKAFL KIFCIKKQPL PSQHSRSVSS
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 253 | Q → R in BAB13698 (PubMed:10973974).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_033477 | 138 | A → V1 PublicationCorresponds to variant dbSNP:rs11665084Ensembl. | 1 | |
Natural variantiVAR_033478 | 206 | H → R1 PublicationCorresponds to variant dbSNP:rs11662595Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_042737 | 65 – 152 | Missing in isoform 2. 1 PublicationAdd BLAST | 88 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB044934 mRNA Translation: BAB13698.1 AB045370 mRNA Translation: BAB20091.1 AF307973 mRNA Translation: AAG32052.1 AF312230 mRNA Translation: AAK12081.1 AF329449 mRNA Translation: AAK43542.1 AF325356 mRNA Translation: AAL01684.1 AJ298292 mRNA Translation: CAC83493.1 DQ835186 mRNA Translation: ABI54174.1 AY136745 mRNA Translation: AAN01271.1 EF444982 Genomic DNA Translation: ACA05997.1 AC007922 Genomic DNA No translation available. CH471088 Genomic DNA Translation: EAX01189.1 BC069136 mRNA Translation: AAH69136.1 BC112348 mRNA Translation: AAI12349.1 |
CCDSi | CCDS11887.1 [Q9H3N8-1] CCDS45841.1 [Q9H3N8-2] |
PIRi | JC7566 |
RefSeqi | NP_001137300.1, NM_001143828.1 [Q9H3N8-2] NP_001153638.1, NM_001160166.1 NP_067637.2, NM_021624.3 [Q9H3N8-1] |
Genome annotation databases
Ensembli | ENST00000256906; ENSP00000256906; ENSG00000134489 [Q9H3N8-1] ENST00000426880; ENSP00000402526; ENSG00000134489 [Q9H3N8-2] |
GeneIDi | 59340 |
KEGGi | hsa:59340 |
UCSCi | uc002kvi.3, human [Q9H3N8-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB044934 mRNA Translation: BAB13698.1 AB045370 mRNA Translation: BAB20091.1 AF307973 mRNA Translation: AAG32052.1 AF312230 mRNA Translation: AAK12081.1 AF329449 mRNA Translation: AAK43542.1 AF325356 mRNA Translation: AAL01684.1 AJ298292 mRNA Translation: CAC83493.1 DQ835186 mRNA Translation: ABI54174.1 AY136745 mRNA Translation: AAN01271.1 EF444982 Genomic DNA Translation: ACA05997.1 AC007922 Genomic DNA No translation available. CH471088 Genomic DNA Translation: EAX01189.1 BC069136 mRNA Translation: AAH69136.1 BC112348 mRNA Translation: AAI12349.1 |
CCDSi | CCDS11887.1 [Q9H3N8-1] CCDS45841.1 [Q9H3N8-2] |
PIRi | JC7566 |
RefSeqi | NP_001137300.1, NM_001143828.1 [Q9H3N8-2] NP_001153638.1, NM_001160166.1 NP_067637.2, NM_021624.3 [Q9H3N8-1] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
STRINGi | 9606.ENSP00000256906 |
Chemistry databases
BindingDBi | Q9H3N8 |
ChEMBLi | CHEMBL3759 |
DrugBanki | DB00321, Amitriptyline DB00543, Amoxapine DB01238, Aripiprazole DB00477, Chlorpromazine DB00363, Clozapine DB01142, Doxepin DB05381, Histamine DB00408, Loxapine DB06148, Mianserin DB01620, Pheniramine DB05032, REV131 |
DrugCentrali | Q9H3N8 |
GuidetoPHARMACOLOGYi | 265 |
Protein family/group databases
GPCRDBi | Search... |
PTM databases
GlyGeni | Q9H3N8, 2 sites |
iPTMneti | Q9H3N8 |
PhosphoSitePlusi | Q9H3N8 |
Genetic variation databases
BioMutai | HRH4 |
DMDMi | 14194819 |
Proteomic databases
jPOSTi | Q9H3N8 |
PaxDbi | Q9H3N8 |
PeptideAtlasi | Q9H3N8 |
PRIDEi | Q9H3N8 |
ProteomicsDBi | 80734 [Q9H3N8-1] 80735 [Q9H3N8-2] |
Protocols and materials databases
Antibodypediai | 7806, 282 antibodies |
Genome annotation databases
Ensembli | ENST00000256906; ENSP00000256906; ENSG00000134489 [Q9H3N8-1] ENST00000426880; ENSP00000402526; ENSG00000134489 [Q9H3N8-2] |
GeneIDi | 59340 |
KEGGi | hsa:59340 |
UCSCi | uc002kvi.3, human [Q9H3N8-1] |
Organism-specific databases
CTDi | 59340 |
DisGeNETi | 59340 |
GeneCardsi | HRH4 |
HGNCi | HGNC:17383, HRH4 |
HPAi | ENSG00000134489, Tissue enriched (blood) |
MIMi | 606792, gene |
neXtProti | NX_Q9H3N8 |
OpenTargetsi | ENSG00000134489 |
PharmGKBi | PA134982275 |
VEuPathDBi | HostDB:ENSG00000134489.6 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3656, Eukaryota |
GeneTreei | ENSGT00940000162118 |
HOGENOMi | CLU_009579_11_2_1 |
InParanoidi | Q9H3N8 |
OMAi | VSYRTQH |
OrthoDBi | 614573at2759 |
PhylomeDBi | Q9H3N8 |
TreeFami | TF351747 |
Enzyme and pathway databases
PathwayCommonsi | Q9H3N8 |
Reactomei | R-HSA-390650, Histamine receptors R-HSA-418594, G alpha (i) signalling events |
SIGNORi | Q9H3N8 |
Miscellaneous databases
BioGRID-ORCSi | 59340, 7 hits in 872 CRISPR screens |
GeneWikii | Histamine_H4_receptor |
GenomeRNAii | 59340 |
Pharosi | Q9H3N8, Tchem |
PROi | PR:Q9H3N8 |
RNActi | Q9H3N8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000134489, Expressed in leukocyte and 46 other tissues |
Genevisiblei | Q9H3N8, HS |
Family and domain databases
InterProi | View protein in InterPro IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM IPR008102, Histamine_H4_rcpt |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR00237, GPCRRHODOPSN PR01726, HISTAMINEH4R |
PROSITEi | View protein in PROSITE PS00237, G_PROTEIN_RECEP_F1_1, 1 hit PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HRH4_HUMAN | |
Accessioni | Q9H3N8Primary (citable) accession number: Q9H3N8 Secondary accession number(s): B0YJ19 Q9GZQ0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 1, 2001 |
Last sequence update: | June 1, 2001 | |
Last modified: | February 10, 2021 | |
This is version 175 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- 7-transmembrane G-linked receptors
List of 7-transmembrane G-linked receptor entries - Human chromosome 18
Human chromosome 18: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families