HRH4

Protein identityUniProt · HPA

UniProt accession

Q9H3N8

Gene

HRH4

Ensembl

ENSG00000134489

Chromosome

18

Canonical length

390 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 a family of histamine receptors, which are a subset of the G-protein coupled receptor superfamily. This gene encodes a histamine receptor that is predominantly expressed in haematopoietic cells. The protein is thought to play a role in inflammation and allergy reponses. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

Canonical amino-acid sequenceUniProt

390 residues, UniProt reviewed canonical sequence.

>Q9H3N8|HRH4
     1  MPDTNSTINL SLSTRVTLAF FMSLVAFAIM LGNALVILAF VVDKNLRHRS SYFFLNLAIS
    61  DFFVGVISIP LYIPHTLFEW DFGKEICVFW LTTDYLLCTA SVYNIVLISY DRYLSVSNAV
   121  SYRTQHTGVL KIVTLMVAVW VLAFLVNGPM ILVSESWKDE GSECEPGFFS EWYILAITSF
   181  LEFVIPVILV AYFNMNIYWS LWKRDHLSRC QSHPGLTAVS SNICGHSFRG RLSSRRSLSA
   241  STEVPASFHS ERQRRKSSLM FSSRTKMNSN TIASKMGSFS QSDSVALHQR EHVELLRARR
   301  LAKSLAILLG VFAVCWAPYS LFTIVLSFYS SATGPKSVWY RIAFWLQWFN SFVNPLLYPL
   361  CHKRFQKAFL KIFCIKKQPL PSQHSRSVSS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HRH4 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)

0.37

Highest tissue expression

0.7 nTPM

Expression across tissuesHPA

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)

1.44

gnomAD pLI

0

gnomAD missense Z

0.47

DepMap mean gene effect

-0.01

DepMap dependency class

none

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-inhibiting G protein-coupled acetylcholine receptor signaling pathway
• adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
• chemical synaptic transmission
• G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• inflammatory response
• positive regulation of cytosolic calcium ion concentration
• regulation of MAPK cascade

Molecular functions

• histamine receptor activity
• neurotransmitter receptor activity

Cellular components

• dendrite
• plasma membrane
• synapse

Protein domainsUniProt · Pfam · InterPro

• G protein-coupled receptor, rhodopsin-like
• GPCR, rhodopsin-like, 7TM
• 7 transmembrane receptor (rhodopsin family)
• Histamine H4 receptor

KeywordsUniProt

• Cell membrane
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Membrane
• Receptor
• Transducer
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of HRH4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GNAI1
• TSPAN4