Q9H3N8 (HRH4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histamine H4 receptor
Short name=H4R
Short name=HH4R

Alternative name(s):
AXOR35
G-protein coupled receptor 105
GPRv53
Pfi-013
SP9144

Gene names

Name:	HRH4
Synonyms:	GPCR105

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	390 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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). Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	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. Ref.7
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.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	integral to membrane Non-traceable author statement. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Molecular function	histamine receptor activity Non-traceable author statement Ref.1Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 390	390	Histamine H4 receptor		PRO_0000069693
Regions
	Topological domain	1 – 19	19	Extracellular Potential
	Transmembrane	20 – 40	21	Helical; Name=1; Potential
	Topological domain	41 – 52	12	Cytoplasmic Potential
	Transmembrane	53 – 73	21	Helical; Name=2; Potential
	Topological domain	74 – 87	14	Extracellular Potential
	Transmembrane	88 – 108	21	Helical; Name=3; Potential
	Topological domain	109 – 131	23	Cytoplasmic Potential
	Transmembrane	132 – 152	21	Helical; Name=4; Potential
	Topological domain	153 – 172	20	Extracellular Potential
	Transmembrane	173 – 193	21	Helical; Name=5; Potential
	Topological domain	194 – 304	111	Cytoplasmic Potential
	Transmembrane	305 – 325	21	Helical; Name=6; Potential
	Topological domain	326 – 341	16	Extracellular Potential
	Transmembrane	342 – 362	21	Helical; Name=7; Potential
	Topological domain	363 – 390	28	Cytoplasmic Potential
Amino acid modifications
	Lipidation	374	1	S-palmitoyl cysteine Potential
	Glycosylation	5	1	N-linked (GlcNAc...) Potential
	Glycosylation	9	1	N-linked (GlcNAc...) Potential
	Disulfide bond	87 ↔ 164		By similarity
Natural variations
	Natural variant	138	1	A → V. Ref.1 Corresponds to variant rs11665084 [ dbSNP | Ensembl ].		VAR_033477
	Natural variant	206	1	H → R. Ref.1 Corresponds to variant rs11662595 [ dbSNP | Ensembl ].		VAR_033478
Experimental info
	Sequence conflict	253	1	Q → R in BAB13698. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9H3N8 [UniParc]. Last modified June 1, 2001. Version 2. Checksum: C986B8AE7FF912C3	FASTA	390	44,496
	10 20 30 40 50 60 MPDTNSTINL SLSTRVTLAF FMSLVAFAIM LGNALVILAF VVDKNLRHRS SYFFLNLAIS 70 80 90 100 110 120 DFFVGVISIP LYIPHTLFEW DFGKEICVFW LTTDYLLCTA SVYNIVLISY DRYLSVSNAV 130 140 150 160 170 180 SYRTQHTGVL KIVTLMVAVW VLAFLVNGPM ILVSESWKDE GSECEPGFFS EWYILAITSF 190 200 210 220 230 240 LEFVIPVILV AYFNMNIYWS LWKRDHLSRC QSHPGLTAVS SNICGHSFRG RLSSRRSLSA 250 260 270 280 290 300 STEVPASFHS ERQRRKSSLM FSSRTKMNSN TIASKMGSFS QSDSVALHQR EHVELLRARR 310 320 330 340 350 360 LAKSLAILLG VFAVCWAPYS LFTIVLSFYS SATGPKSVWY RIAFWLQWFN SFVNPLLYPL 370 380 390 CHKRFQKAFL KIFCIKKQPL PSQHSRSVSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes." Oda T., Morikawa N., Saito Y., Masuho Y., Matsumoto S. J. Biol. Chem. 275:36781-36786(2000) [PubMed: 10973974] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS VAL-138 AND ARG-206.
[2]	"Molecular cloning and characterization of a new human histamine receptor, HH4R." Nakamura T., Itadani H., Hidaka Y., Ohta M., Tanaka K. Biochem. Biophys. Res. Commun. 279:615-620(2000) [PubMed: 11118334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION. Tissue: Leukocyte.
[3]	"Cloning of a novel histamine receptor." Jones P.G., Wu S., Betty M. Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Cloning and pharmacological characterization of a fourth histamine receptor (H4) expressed in bone marrow." Liu C., Ma X.-J., Jiang X., Wilson S.J., Hofstra C.L., Blevitt J., Pyati J., Li X., Chai W., Carruthers N., Lovenberg T.W. Mol. Pharmacol. 59:420-426(2001) [PubMed: 11179434] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION. Tissue: Bone marrow.
[5]	"Cloning and characterization of a novel human histamine receptor." Morse K.L., Behan J., Laz T.M., West R.E. Jr., Greenfeder S.A., Anthes J.C., Umland S., Wan Y., Hipkin R.W., Gonsiorek W., Shin N., Gustafson E.L., Qiao X., Wang S., Hedrick J.A., Greene J., Bayne M., Monsma F.J. Jr. J. Pharmacol. Exp. Ther. 296:1058-1066(2001) [PubMed: 11181941] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION. Tissue: Eosinophil.
[6]	"Cloning, expression, and pharmacological characterization of a novel human histamine receptor." Zhu Y., Michalovich D., Wu H.-L., Tan K.B., Dytko G.M., Mannan I.J., Boyce R., Alston J., Tierney L.A., Li X., Herrity N.C., Vawter L., Sarau H.M., Ames R.S., Davenport C.M., Hieble P., Wilson S., Bergsma D.J., Fitzgerald L.R. Mol. Pharmacol. 59:434-441(2001) [PubMed: 11179436] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]	"Identification of a histamine H4 receptor on human eosinophils --role in eosinophil chemotaxis." O'Reilly M.A., Alpert R., Jenkinson S., Gladue R.P., Foo S., Trim S., Peter B., Trevethick M., Fidock M. J. Recept. Signal Transduct. 22:431-448(2002) [PubMed: 12503632] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
[8]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Puhl H.L. III, Ikeda S.R., Aronstam R.S. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]	NHLBI resequencing and genotyping service (RS&G) Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[10]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. AY136745 mRNA. Translation: AAN01271.1. EF444982 Genomic DNA. Translation: ACA05997.1. CH471088 Genomic DNA. Translation: EAX01189.1. BC069136 mRNA. Translation: AAH69136.1. BC112348 mRNA. Translation: AAI12349.1.
IPI	IPI00023596.
PIR	JC7566.
RefSeq	NP_001137300.1. NM_001143828.1. NP_001153638.1. NM_001160166.1. NP_067637.2. NM_021624.3.
UniGene	Hs.287388.
3D structure databases
ProteinModelPortal	Q9H3N8.
SMR	Q9H3N8. Positions 9-376.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9H3N8.
Protein family/group databases
GPCRDB	Search...
Polymorphism databases
DMDM	14194819.
Proteomic databases
PRIDE	Q9H3N8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000256906; ENSP00000256906; ENSG00000134489.
GeneID	59340.
KEGG	hsa:59340.
UCSC	uc002kvi.1. human.
Organism-specific databases
CTD	59340.
GeneCards	GC18P022040.
H-InvDB	HIX0039701.
HGNC	HGNC:17383. HRH4.
HPA	HPA035009.
MIM	606792. gene.
neXtProt	NX_Q9H3N8.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG04156.
GeneTree	ENSGT00560000076730.
HOGENOM	HBG713567.
HOVERGEN	HBG102132.
InParanoid	Q9H3N8.
OMA	DFFVGVI.
OrthoDB	EOG47M1Z2.
PhylomeDB	Q9H3N8.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q9H3N8.
Bgee	Q9H3N8.
CleanEx	HS_HRH4.
Genevestigator	Q9H3N8.
GermOnline	ENSG00000134489. Homo sapiens.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_supfam. IPR008102. Histamine_H4_recept. [Graphical view]
KO	K04152.
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR01726. HISTAMINEH4R.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00363. Clozapine.
NextBio	65224.
SOURCE	Search...

Entry information

Entry name

HRH4_HUMAN

Accession

Primary (citable) accession number: Q9H3N8
Secondary accession number(s): B0YJ19, Q4G0I6, Q9GZQ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	June 1, 2001
Last modified:	January 25, 2012
This is version 105 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.