P35367 (HRH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histamine H1 receptor
Short name=H1R
Short name=HH1R

Gene names

Name:

HRH1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	487 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Potential sites of phosphorylation in the third cytoplasmic loop may play an important role in regulating signal transduction through the receptor molecule.
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 Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to histamine Inferred from sequence or structural similarity. Source: BHF-UCL elevation of cytosolic calcium ion concentration Inferred from electronic annotation. Source: InterPro 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 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 cAMP metabolic process Inferred from electronic annotation. Source: InterPro regulation of synaptic transmission Inferred from electronic annotation. Source: InterPro regulation of vascular permeability Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA integral to plasma membrane Inferred from sequence or structural similarity. Source: BHF-UCL nucleus Inferred from direct assay. Source: HPA
Molecular_function	histamine receptor activity Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 487

487

Histamine H1 receptor

PRO_0000069676

Regions

Topological domain

1 – 29

29

Extracellular Potential

Transmembrane

30 – 49

20

Helical; Name=1; Potential

Topological domain

50 – 63

14

Cytoplasmic Potential

Transmembrane

64 – 83

20

Helical; Name=2; Potential

Topological domain

84 – 101

18

Extracellular Potential

Transmembrane

102 – 123

22

Helical; Name=3; Potential

Topological domain

124 – 145

22

Cytoplasmic Potential

Transmembrane

146 – 165

20

Helical; Name=4; Potential

Topological domain

166 – 189

24

Extracellular Potential

Transmembrane

190 – 210

21

Helical; Name=5; Potential

Topological domain

211 – 418

208

Cytoplasmic Potential

Transmembrane

419 – 438

20

Helical; Name=6; Potential

Topological domain

439 – 450

12

Extracellular Potential

Transmembrane

451 – 470

20

Helical; Name=7; Potential

Topological domain

471 – 487

17

Cytoplasmic Potential

Amino acid modifications

Modified residue

279

1

Phosphothreonine Ref.11

Lipidation

445

1

S-palmitoyl cysteine Potential

Glycosylation

5

1

N-linked (GlcNAc...) Potential

Glycosylation

18

1

N-linked (GlcNAc...) Potential

Disulfide bond

100 ↔ 180

Ref.12

Natural variations

Natural variant

19

1

K → N.
Corresponds to variant rs2067466 [ dbSNP | Ensembl ].

VAR_049410

Natural variant

270

1

G → E.
Corresponds to variant rs7651620 [ dbSNP | Ensembl ].

VAR_033476

Natural variant

385

1

D → E in a colorectal cancer sample; somatic mutation. Ref.13

VAR_035761

Experimental info

Sequence conflict

308

1

V → E in AAH60802. Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

487

Helix Strand Turn

Details...

Helix

29 – 31

3

Helix

33 – 54

22

Helix

61 – 63

3

Helix

64 – 78

15

Helix

80 – 89

10

Beta strand

90 – 92

3

Helix

96 – 130

35

Turn

135 – 138

4

Helix

141 – 155

15

Helix

156 – 158

3

Helix

159 – 163

5

Beta strand

177 – 180

4

Helix

188 – 198

11

Helix

200 – 216

17

Helix

408 – 441

34

Turn

447 – 449

3

Helix

450 – 471

22

Helix

473 – 483

11

Sequences

	Sequence		Length	Mass (Da)
	P35367 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: E5DB418A4C17A985	FASTA	487	55,784
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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]	"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.
[11]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"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.
[13]	"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. , 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.

IPI

IPI00018147.

PIR

JC2495.

RefSeq

NP_000852.1. NM_000861.3.
NP_001091681.1. NM_001098211.1.
NP_001091682.1. NM_001098212.1.
NP_001091683.1. NM_001098213.1.

UniGene

Hs.1570.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3RZE	X-ray	3.10	A	20-487	[»]

ProteinModelPortal

P35367.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000347299.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P35367.

Polymorphism databases

DMDM

547645.

Proteomic databases

PaxDb

P35367.

PRIDE

P35367.

Protocols and materials databases

DNASU

3269.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000397056; ENSP00000380247; ENSG00000196639.
ENST00000431010; ENSP00000397028; ENSG00000196639.
ENST00000438284; ENSP00000406705; ENSG00000196639.

GeneID

3269.

KEGG

hsa:3269.

UCSC

uc003bwb.4. human.

Organism-specific databases

CTD

3269.

GeneCards

GC03P011113.

HGNC

HGNC:5182. HRH1.

HPA

HPA029740.

MIM

600167. gene.

neXtProt

NX_P35367.

PharmGKB

PA29456.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG318797.

HOGENOM

HOG000273869.

HOVERGEN

HBG101103.

InParanoid

P35367.

KO

K04149.

OMA

IAFCKNC.

OrthoDB

EOG4P2Q2Z.

PhylomeDB

P35367.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

Bgee

P35367.

CleanEx

HS_HRH1.

Genevestigator

P35367.

GermOnline

ENSG00000196639. Homo sapiens.

Family and domain databases

InterPro

IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000921. Histamine_H1_rcpt.
[Graphical view]

PANTHER

PTHR24249:SF56. PTHR24249:SF56. 1 hit.

Pfam

PF00001. 7tm_1. 1 hit.
[Graphical view]

PRINTS

PR00237. GPCRRHODOPSN.
PR00530. HISTAMINEH1R.

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P35367.

ChEMBL

CHEMBL231.

ChiTaRS

HRH1. human.

DrugBank

DB01615. 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.

GenomeRNAi

3269.

NextBio

12981.

SOURCE

Search...

Entry information

Entry name

HRH1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 119 of the entry and version 1 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.