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P35367 (HRH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histamine H1 receptor

Short name=H1R
Short name=HH1R
Gene names
Name:HRH1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length487 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Post-translational modification

Phosphorylation at sites in the second and third cytoplasmic loops independently contribute to agonist-induced receptor downregulation.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Traceable author statement Ref.3. Source: ProtInc

cellular response to histamine

Inferred from sequence or structural similarity. Source: BHF-UCL

eosinophil chemotaxis

Inferred from electronic annotation. Source: InterPro

inflammatory response

Traceable author statement PubMed 10818238. Source: ProtInc

inositol phosphate-mediated signaling

Inferred from sequence or structural similarity. Source: BHF-UCL

memory

Inferred from electronic annotation. Source: Ensembl

phospholipase C-activating G-protein coupled receptor signaling pathway

Traceable author statement Ref.1. Source: ProtInc

positive regulation of inositol trisphosphate biosynthetic process

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of vasoconstriction

Inferred from electronic annotation. Source: InterPro

regulation of synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

regulation of vascular permeability

Inferred from electronic annotation. Source: InterPro

visual learning

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentintegral component of plasma membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionG-protein coupled receptor activity

Traceable author statement Ref.3. Source: ProtInc

histamine receptor activity

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 487487Histamine H1 receptor
PRO_0000069676

Regions

Topological domain1 – 2929Extracellular Potential
Transmembrane30 – 4920Helical; Name=1; Potential
Topological domain50 – 6314Cytoplasmic Potential
Transmembrane64 – 8320Helical; Name=2; Potential
Topological domain84 – 10118Extracellular Potential
Transmembrane102 – 12322Helical; Name=3; Potential
Topological domain124 – 14522Cytoplasmic Potential
Transmembrane146 – 16520Helical; Name=4; Potential
Topological domain166 – 18924Extracellular Potential
Transmembrane190 – 21021Helical; Name=5; Potential
Topological domain211 – 418208Cytoplasmic Potential
Transmembrane419 – 43820Helical; Name=6; Potential
Topological domain439 – 45012Extracellular Potential
Transmembrane451 – 47020Helical; Name=7; Potential
Topological domain471 – 48717Cytoplasmic Potential

Amino acid modifications

Modified residue1401Phosphothreonine Ref.10
Modified residue1421Phosphothreonine Ref.10
Modified residue2791Phosphothreonine Ref.12
Modified residue3961Phosphoserine Ref.10
Modified residue3981Phosphoserine Ref.10
Lipidation4451S-palmitoyl cysteine Potential
Glycosylation51N-linked (GlcNAc...) Potential
Glycosylation181N-linked (GlcNAc...) Potential
Disulfide bond100 ↔ 180 Ref.13

Natural variations

Natural variant191K → N.
Corresponds to variant rs2067466 [ dbSNP | Ensembl ].
VAR_049410
Natural variant2701G → E.
Corresponds to variant rs7651620 [ dbSNP | Ensembl ].
VAR_033476
Natural variant3851D → E in a colorectal cancer sample; somatic mutation. Ref.14
VAR_035761

Experimental info

Sequence conflict3081V → E in AAH60802. Ref.9

Secondary structure

................................ 487
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P35367 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: E5DB418A4C17A985

FASTA48755,784
        10         20         30         40         50         60 
MSLPNSSCLL EDKMCEGNKT TMASPQLMPL VVVLSTICLV TVGLNLLVLY AVRSERKLHT 

        70         80         90        100        110        120 
VGNLYIVSLS VADLIVGAVV MPMNILYLLM SKWSLGRPLC LFWLSMDYVA STASIFSVFI 

       130        140        150        160        170        180 
LCIDRYRSVQ QPLRYLKYRT KTRASATILG AWFLSFLWVI PILGWNHFMQ QTSVRREDKC 

       190        200        210        220        230        240 
ETDFYDVTWF KVMTAIINFY LPTLLMLWFY AKIYKAVRQH CQHRELINRS LPSFSEIKLR 

       250        260        270        280        290        300 
PENPKGDAKK PGKESPWEVL KRKPKDAGGG SVLKSPSQTP KEMKSPVVFS QEDDREVDKL 

       310        320        330        340        350        360 
YCFPLDIVHM QAAAEGSSRD YVAVNRSHGQ LKTDEQGLNT HGASEISEDQ MLGDSQSFSR 

       370        380        390        400        410        420 
TDSDTTTETA PGKGKLRSGS NTGLDYIKFT WKRLRSHSRQ YVSGLHMNRE RKAAKQLGFI 

       430        440        450        460        470        480 
MAAFILCWIP YFIFFMVIAF CKNCCNEHLH MFTIWLGYIN STLNPLIYPL CNENFKKTFK 


RILHIRS 

« Hide

References

« Hide 'large scale' references
[1]"Genomic cloning, heterologous expression and pharmacological characterization of a human histamine H1 receptor."
de Backer M.D., Gommeren W., Moereels H., Nobels G., van Gompel P., Leysen J.E., Luyten W.H.M.L.
Biochem. Biophys. Res. Commun. 197:1601-1608(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Molecular cloning of the human histamine H1 receptor gene."
Fukui K., Fujimoto K., Mizuguchi H., Sakamoto K., Horio Y., Takai S., Yamada K., Ito S.
Biochem. Biophys. Res. Commun. 201:894-901(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Stable expression of human H1-histamine-receptor cDNA in Chinese hamster ovary cells. Pharmacological characterisation of the protein, tissue distribution of messenger RNA and chromosomal localisation of the gene."
Moguilevsky N., Varsalona F., Noyer M., Gillard M., Guillaume J.P., Garcia L., Szpirer C., Szpirer J., Bollen A.
Eur. J. Biochem. 224:489-495(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]Rae J.L., Shepard A.R.
Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Lens epithelium.
[5]"Human-specific amino acid changes found in 103 protein-coding genes."
Kitano T., Liu Y.-H., Ueda S., Saitou N.
Mol. Biol. Evol. 21:936-944(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"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].
Tissue: Lung.
[7]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]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. expand/collapse author list , 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].
[9]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[10]"Two threonine residues and two serine residues in the second and third intracellular loops are both involved in histamine H1 receptor downregulation."
Horio S., Kato T., Ogawa M., Fujimoto K., Fukui H.
FEBS Lett. 573:226-230(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-140; THR-142; SER-396 AND SER-398.
[11]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-279, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"Structure of the human histamine H1 receptor complex with doxepin."
Shimamura T., Shiroishi M., Weyand S., Tsujimoto H., Winter G., Katritch V., Abagyan R., Cherezov V., Liu W., Han G.W., Kobayashi T., Stevens R.C., Iwata S.
Nature 475:65-70(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 20-487 IN COMPLEX WITH ANTAGONIST, DISULFIDE BOND.
[14]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-385.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z34897 mRNA. Translation: CAA84380.1.
X76786 Genomic DNA. Translation: CAA54182.1.
D14436 Genomic DNA. Translation: BAA03319.1.
D28481 mRNA. Translation: BAA05840.1.
AF026261 mRNA. Translation: AAB95156.1.
AB041380 Genomic DNA. Translation: BAA94465.1.
AY136743 mRNA. Translation: AAN01269.1.
AK289412 mRNA. Translation: BAF82101.1.
CH471055 Genomic DNA. Translation: EAW64092.1.
BC060802 mRNA. Translation: AAH60802.1.
PIRJC2495.
RefSeqNP_000852.1. NM_000861.3.
NP_001091681.1. NM_001098211.1.
NP_001091682.1. NM_001098212.1.
NP_001091683.1. NM_001098213.1.
UniGeneHs.1570.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3RZEX-ray3.10A20-487[»]
ProteinModelPortalP35367.
SMRP35367. Positions 28-485.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109505. 1 interaction.
MINTMINT-190077.
STRING9606.ENSP00000347299.

Chemistry

BindingDBP35367.
ChEMBLCHEMBL231.
DrugBankDB01615. Aceprometazine.
DB00637. Astemizole.
DB00719. Azatadine.
DB00972. Azelastine.
DB00767. Benzquinamide.
DB04890. Bepotastine.
DB01237. Bromodiphenhydramine.
DB00835. Brompheniramine.
DB00354. Buclizine.
DB00748. Carbinoxamine.
DB00341. Cetirizine.
DB04837. Chlophedianol.
DB01114. Chlorpheniramine.
DB01239. Chlorprothixene.
DB00568. Cinnarizine.
DB00283. Clemastine.
DB00363. Clozapine.
DB01176. Cyclizine.
DB00434. Cyproheptadine.
DB01151. Desipramine.
DB00967. Desloratadine.
DB00405. Dexbrompheniramine.
DB00985. Dimenhydrinate.
DB01075. Diphenhydramine.
DB01146. Diphenylpyraline.
DB01142. Doxepin.
DB00366. Doxylamine.
DB01084. Emedastine.
DB00751. Epinastine.
DB00950. Fexofenadine.
DB04841. Flunarizine.
DB00667. Histamine Phosphate.
DB00557. Hydroxyzine.
DB00920. Ketotifen.
DB01106. Levocabastine.
DB00455. Loratadine.
DB00934. Maprotiline.
DB00737. Meclizine.
DB01071. Mequitazine.
DB00902. Methdilazine.
DB01403. Methotrimeprazine.
DB06148. Mianserin.
DB00370. Mirtazapine.
DB00716. Nedocromil.
DB00334. Olanzapine.
DB00768. Olopatadine.
DB01173. Orphenadrine.
DB00885. Pemirolast.
DB01619. Phenindamine.
DB01620. Pheniramine.
DB00433. Prochlorperazine.
DB00420. Promazine.
DB01069. Promethazine.
DB00777. Propiomazine.
DB01224. Quetiapine.
DB00734. Risperidone.
DB00342. Terfenadine.
DB00372. Thiethylperazine.
DB00656. Trazodone.
DB01246. Trimeprazine.
DB00792. Tripelennamine.
DB00427. Triprolidine.
DB00246. Ziprasidone.
GuidetoPHARMACOLOGY262.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP35367.

Polymorphism databases

DMDM547645.

Proteomic databases

PaxDbP35367.
PRIDEP35367.

Protocols and materials databases

DNASU3269.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000397056; ENSP00000380247; ENSG00000196639.
ENST00000431010; ENSP00000397028; ENSG00000196639.
ENST00000438284; ENSP00000406705; ENSG00000196639.
GeneID3269.
KEGGhsa:3269.
UCSCuc003bwb.4. human.

Organism-specific databases

CTD3269.
GeneCardsGC03P011113.
HGNCHGNC:5182. HRH1.
HPAHPA029740.
MIM600167. gene.
neXtProtNX_P35367.
PharmGKBPA29456.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG318797.
HOGENOMHOG000273869.
HOVERGENHBG101103.
InParanoidP35367.
KOK04149.
OMAEDKMCEG.
OrthoDBEOG70CR7W.
PhylomeDBP35367.
TreeFamTF333432.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeP35367.
CleanExHS_HRH1.
GenevestigatorP35367.

Family and domain databases

Gene3D1.20.1070.10. 2 hits.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000921. Histamine_H1_rcpt.
[Graphical view]
PANTHERPTHR24249:SF56. PTHR24249:SF56. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR00530. HISTAMINEH1R.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHRH1. human.
GeneWikiHistamine_H1_receptor.
GenomeRNAi3269.
NextBio12981.
PROP35367.
SOURCESearch...

Entry information

Entry nameHRH1_HUMAN
AccessionPrimary (citable) accession number: P35367
Secondary accession number(s): A8K047, Q6P9E5
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: April 16, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries