HBP1_RHIAP
ID HBP1_RHIAP Reviewed; 190 AA.
AC O77420;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Female-specific histamine-binding protein 1 {ECO:0000303|PubMed:10360182};
DE Short=FS-HBP1 {ECO:0000303|PubMed:10360182};
DE AltName: Full=EV131 {ECO:0000303|PubMed:16387687, ECO:0000303|PubMed:16387688};
DE AltName: Full=Histacalin {ECO:0000303|PubMed:35350753};
DE AltName: Full=RaHBP1 {ECO:0000303|PubMed:10360182, ECO:0000303|PubMed:11058751};
DE Flags: Precursor;
OS Rhipicephalus appendiculatus (Brown ear tick).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Acari;
OC Parasitiformes; Ixodida; Ixodoidea; Ixodidae; Rhipicephalinae;
OC Rhipicephalus; Rhipicephalus.
OX NCBI_TaxID=34631;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, DEVELOPMENTAL STAGE, AND
RP RECOMBINANT EXPRESSION.
RC TISSUE=Salivary gland;
RX PubMed=10360182; DOI=10.1016/s1097-2765(00)80359-7;
RA Paesen G.C., Adams P.L., Harlos K., Nuttall P.A., Stuart D.I.;
RT "Tick histamine-binding proteins: isolation, cloning, and three-dimensional
RT structure.";
RL Mol. Cell 3:661-671(1999).
RN [2]
RP FUNCTION, BIOASSAY, AND RECOMBINANT EXPRESSION.
RX PubMed=16387687; DOI=10.1196/annals.1352.009;
RA Weston-Davies W., Couillin I., Schnyder S., Schnyder B., Moser R.,
RA Lissina O., Paesen G.C., Nuttall P., Ryffel B.;
RT "Arthropod-derived protein EV131 inhibits histamine action and allergic
RT asthma.";
RL Ann. N. Y. Acad. Sci. 1056:189-196(2005).
RN [3]
RP FUNCTION, BIOASSAY, AND RECOMBINANT EXPRESSION.
RX PubMed=16387688; DOI=10.1196/annals.1352.034;
RA Ryffel B., Couillin I., Maillet I., Schnyder B., Paesen G.C., Nuttall P.,
RA Weston-Davies W.;
RT "Histamine scavenging attenuates endotoxin-induced acute lung injury.";
RL Ann. N. Y. Acad. Sci. 1056:197-205(2005).
RN [4]
RP FUNCTION, BIOASSAY, AND PHARMACEUTICAL.
RX PubMed=35350753; DOI=10.3389/fphar.2022.846683;
RA Alrashdi I., Alsubaiyel A., Chan M., Battell E.E., Ennaceur A., Nunn M.A.,
RA Weston-Davies W., Chazot P.L., Obara I.;
RT "Votucalis, a novel centrally sparing histamine-binding protein, attenuates
RT histaminergic itch and neuropathic pain in mice.";
RL Front. Pharmacol. 13:846683-846683(2022).
RN [5]
RP REVIEW.
RX PubMed=11058751; DOI=10.1016/s0167-4838(00)00168-0;
RA Paesen G.C., Adams P.L., Nuttall P.A., Stuart D.L.;
RT "Tick histamine-binding proteins: lipocalins with a second binding
RT cavity.";
RL Biochim. Biophys. Acta 1482:92-101(2000).
CC -!- FUNCTION: Salivary tick protein that acts by scavenging histamine at
CC the wound site, outcompeting histamine receptors for histamine, thereby
CC overcoming host inflammatory responses (PubMed:10360182). Binds
CC histamine with a high-affinity (Kd=18 nM) (PubMed:10360182). Contains
CC two binding histamine sites (H and L), that appear to bind histamine
CC with differing affinities (By similarity). In vivo, when tested on a
CC mouse asthma model, shows a profound inhibitory effect on allergic
CC asthma. Aerosol administration of this protein prevents airway
CC hyperreactivity and abrogates peribronchial inflammation, eosinophil
CC recruitment, mucus hypersecretion, and interleukins (IL-4 and IL-5)
CC secretion (PubMed:16387687). In addition, when tested on a mouse model
CC of acute respiratory distress syndrome (ARDS), it attenuates endotoxin-
CC induced acute lung injury (PubMed:16387688).
CC {ECO:0000250|UniProtKB:O77421, ECO:0000269|PubMed:10360182,
CC ECO:0000269|PubMed:16387687, ECO:0000269|PubMed:16387688}.
CC -!- SUBUNIT: Monomer. {ECO:0000305|PubMed:10360182}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:10360182}.
CC -!- TISSUE SPECIFICITY: Expressed by salivary glands.
CC {ECO:0000305|PubMed:10360182}.
CC -!- DEVELOPMENTAL STAGE: Early stage of adult feeding.
CC {ECO:0000269|PubMed:10360182}.
CC -!- DOMAIN: Contains 2 sites/pockets that bind histamine with different
CC affinities. Site H (high affinity) is indicated here as binding to
CC histamine 1, and site L (low affinity) is indicated as binding to
CC histamine 2. {ECO:0000250|UniProtKB:O77421}.
CC -!- PHARMACEUTICAL: Is currently under preclinical trials by Akari
CC therapeutics under the name Votucalis to act as an anti-histaminic to
CC treat pruritus/itch and nociception. {ECO:0000269|PubMed:35350753}.
CC -!- SIMILARITY: Belongs to the calycin superfamily. Histamine-binding
CC salivary protein family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U96080; AAC63106.1; -; mRNA.
DR AlphaFoldDB; O77420; -.
DR SMR; O77420; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0043176; F:amine binding; IEA:InterPro.
DR GO; GO:0030682; P:mitigation of host defenses by symbiont; IEA:InterPro.
DR Gene3D; 2.40.128.20; -; 1.
DR InterPro; IPR012674; Calycin.
DR InterPro; IPR002970; Tick_his-bd.
DR Pfam; PF02098; His_binding; 1.
DR PRINTS; PR01220; HISBINDING.
DR SUPFAM; SSF50814; SSF50814; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Pharmaceutical; Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..190
FT /note="Female-specific histamine-binding protein 1"
FT /id="PRO_0000021399"
FT BINDING 54
FT /ligand="histamine"
FT /ligand_id="ChEBI:CHEBI:58432"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O77421"
FT BINDING 57
FT /ligand="histamine"
FT /ligand_id="ChEBI:CHEBI:58432"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O77421"
FT BINDING 60
FT /ligand="histamine"
FT /ligand_id="ChEBI:CHEBI:58432"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O77421"
FT BINDING 100
FT /ligand="histamine"
FT /ligand_id="ChEBI:CHEBI:58432"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O77421"
FT BINDING 118
FT /ligand="histamine"
FT /ligand_id="ChEBI:CHEBI:58432"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O77421"
FT BINDING 153
FT /ligand="histamine"
FT /ligand_id="ChEBI:CHEBI:58432"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O77421"
FT BINDING 155
FT /ligand="histamine"
FT /ligand_id="ChEBI:CHEBI:58432"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O77421"
FT DISULFID 66..187
FT /evidence="ECO:0000250|UniProtKB:O77421"
FT DISULFID 137..166
FT /evidence="ECO:0000250|UniProtKB:O77421"
SQ SEQUENCE 190 AA; 21370 MW; 855BE151A90053B1 CRC64;
MKLLLSLAFV LALSQVKADK PVWADEAANG EHQDAWKHLQ KLVEENYDLI KATYKNDPVW
GNDFTCVGTA AQNLNEDEKN VEAWFMFMNN ADTVYQHTFE KATPDKMYGY NKENAITYQT
EDGQVLTDVL AFSDDNCYVI YALGPDGSGA GYELWATDYT DVPASCLEKF NEYAAGLPVR
DVYTSDCLPE
