NP_CIMLE
ID NP_CIMLE Reviewed; 302 AA.
AC O76745;
DT 03-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Nitrophorin Cim l NP {ECO:0000305};
DE Short=NP {ECO:0000305};
DE AltName: Full=Salivary nitrophorin {ECO:0000303|PubMed:16417223, ECO:0000303|PubMed:9716517};
DE AltName: Full=cNP {ECO:0000303|PubMed:15637157, ECO:0000303|PubMed:22305681};
DE AltName: Allergen=Cim l NP {ECO:0000305};
DE Flags: Precursor;
OS Cimex lectularius (Bed bug) (Acanthia lectularia).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Paraneoptera; Hemiptera; Heteroptera; Panheteroptera;
OC Cimicomorpha; Cimicidae; Cimex.
OX NCBI_TaxID=79782 {ECO:0000312|EMBL:AAC28738.1};
RN [1] {ECO:0000312|EMBL:AAC28738.1}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 139-147; 179-195; 229-245
RP AND 275-286, IDENTIFICATION BY MASS SPECTROMETRY, COFACTOR, TISSUE
RP SPECIFICITY, AND PTM.
RC TISSUE=Salivary gland {ECO:0000303|PubMed:9716517};
RX PubMed=9716517; DOI=10.1242/jeb.201.18.2659;
RA Valenzuela J.G., Ribeiro J.M.C.;
RT "Purification and cloning of the salivary nitrophorin from the hemipteran
RT Cimex lectularius.";
RL J. Exp. Biol. 201:2659-2664(1998).
RN [2]
RP TISSUE SPECIFICITY, AND ALLERGEN.
RX PubMed=16417223; DOI=10.1038/sj.jid.5700012;
RA Leverkus M., Jochim R.C., Schaed S., Broecker E.B., Andersen J.F.,
RA Valenzuela J.G., Trautmann A.;
RT "Bullous allergic hypersensitivity to bed bug bites mediated by IgE against
RT salivary nitrophorin.";
RL J. Invest. Dermatol. 126:91-96(2006).
RN [3]
RP ALLERGEN.
RX PubMed=22305681; DOI=10.1016/j.jaci.2012.01.034;
RA Price J.B., Divjan A., Montfort W.R., Stansfield K.H., Freyer G.A.,
RA Perzanowski M.S.;
RT "IgE against bed bug (Cimex lectularius) allergens is common among adults
RT bitten by bed bugs.";
RL J. Allergy Clin. Immunol. 129:863-865(2012).
RN [4] {ECO:0007744|PDB:1NTF, ECO:0007744|PDB:1Y21}
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 21-302 IN COMPLEX WITH HEME AND
RP NITRIC OXIDE, COFACTOR, REACTION MECHANISM, AND EPR SPECTROSCOPY.
RX PubMed=15637157; DOI=10.1073/pnas.0406549102;
RA Weichsel A., Maes E.M., Andersen J.F., Valenzuela J.G., Shokhireva T.K.,
RA Walker F.A., Montfort W.R.;
RT "Heme-assisted S-nitrosation of a proximal thiolate in a nitric oxide
RT transport protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:594-599(2005).
RN [5] {ECO:0007744|PDB:2IMQ}
RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 21-302 IN COMPLEX WITH HEME.
RA Weichsel A., Badgandi H., Montfort W.R.;
RT "Crystal Structure of Cimex Nitrophorin.";
RL Submitted (JUN-2013) to the PDB data bank.
CC -!- FUNCTION: Heme-based protein that delivers nitric oxide gas (NO) to the
CC victim while feeding, resulting in vasodilation (Probable). In place of
CC heme, the heme-binding cysteine can also reversibly bind NO when it is
CC present in high concentrations (PubMed:15637157).
CC {ECO:0000269|PubMed:15637157, ECO:0000305}.
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000269|PubMed:15637157, ECO:0000305|PubMed:9716517};
CC Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.
CC {ECO:0000305|PubMed:15637157};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:16417223,
CC ECO:0000305|PubMed:22305681, ECO:0000305|PubMed:9716517}.
CC -!- TISSUE SPECIFICITY: Expressed in salivary glands.
CC {ECO:0000269|PubMed:16417223, ECO:0000269|PubMed:9716517}.
CC -!- PTM: The N-terminus is blocked. {ECO:0000269|PubMed:9716517}.
CC -!- ALLERGEN: Causes an allergic reaction in human. Binds to IgE of
CC patients allergic to bed bugs (PubMed:16417223, PubMed:22305681). Binds
CC to IgE in 30% of the 30 adult New York City (NYC) residents tested who
CC had been bitten by the bed bug and had a visible response to it (an
CC itchy raised bump) (PubMed:22305681). {ECO:0000269|PubMed:16417223,
CC ECO:0000269|PubMed:22305681}.
CC -!- MISCELLANEOUS: Has some sequence similarity to inositol phosphatases,
CC but no inositol trisphosphate phosphatase activity is detected.
CC {ECO:0000269|PubMed:9716517}.
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DR EMBL; AF079803; AAC28738.1; -; mRNA.
DR RefSeq; NP_001303633.1; NM_001316704.1.
DR PDB; 1NTF; X-ray; 1.80 A; A=21-302.
DR PDB; 1SI6; X-ray; 1.45 A; X=21-302.
DR PDB; 1Y21; X-ray; 1.75 A; A=21-302.
DR PDB; 1YJH; X-ray; 1.65 A; A=21-302.
DR PDB; 2IMQ; X-ray; 1.30 A; X=21-302.
DR PDB; 4L1Y; X-ray; 1.55 A; A=23-302.
DR PDB; 4L1Z; X-ray; 1.65 A; A=23-302.
DR PDB; 4L20; X-ray; 1.68 A; A=23-302.
DR PDB; 4L21; X-ray; 1.65 A; A=23-302.
DR PDBsum; 1NTF; -.
DR PDBsum; 1SI6; -.
DR PDBsum; 1Y21; -.
DR PDBsum; 1YJH; -.
DR PDBsum; 2IMQ; -.
DR PDBsum; 4L1Y; -.
DR PDBsum; 4L1Z; -.
DR PDBsum; 4L20; -.
DR PDBsum; 4L21; -.
DR AlphaFoldDB; O76745; -.
DR SMR; O76745; -.
DR Allergome; 2915; Cim l NP.
DR EnsemblMetazoa; NM_001316704.1; NP_001303633.1; LOC106662976.
DR GeneID; 106662976; -.
DR KEGG; clec:106662976; -.
DR VEuPathDB; VectorBase:CLEC004331; -.
DR EvolutionaryTrace; O76745; -.
DR Proteomes; UP000494040; Unplaced.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0016791; F:phosphatase activity; IEA:InterPro.
DR GO; GO:0030185; P:nitric oxide transport; IDA:UniProtKB.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IEA:InterPro.
DR GO; GO:0044552; P:vasodilation in another organism; IC:UniProtKB.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR000300; IPPc.
DR SMART; SM00128; IPPc; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allergen; Direct protein sequencing; Heme; Iron;
KW Metal-binding; Reference proteome; Secreted; Signal; Transport; Vasoactive;
KW Vasodilator.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..302
FT /note="Nitrophorin Cim l NP"
FT /evidence="ECO:0000255"
FT /id="PRO_5004159790"
FT BINDING 80
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="proximal binding residue"
FT /evidence="ECO:0000269|PubMed:15637157,
FT ECO:0007744|PDB:1NTF, ECO:0007744|PDB:2IMQ"
FT CONFLICT 139
FT /note="V -> N (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 25..37
FT /evidence="ECO:0007829|PDB:2IMQ"
FT TURN 46..50
FT /evidence="ECO:0007829|PDB:2IMQ"
FT STRAND 58..67
FT /evidence="ECO:0007829|PDB:2IMQ"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:2IMQ"
FT HELIX 77..90
FT /evidence="ECO:0007829|PDB:2IMQ"
FT STRAND 93..100
FT /evidence="ECO:0007829|PDB:2IMQ"
FT STRAND 102..111
FT /evidence="ECO:0007829|PDB:2IMQ"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:2IMQ"
FT TURN 117..119
FT /evidence="ECO:0007829|PDB:2IMQ"
FT STRAND 123..128
FT /evidence="ECO:0007829|PDB:2IMQ"
FT STRAND 135..144
FT /evidence="ECO:0007829|PDB:2IMQ"
FT STRAND 147..155
FT /evidence="ECO:0007829|PDB:2IMQ"
FT STRAND 165..169
FT /evidence="ECO:0007829|PDB:2IMQ"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:2IMQ"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:2IMQ"
FT STRAND 184..191
FT /evidence="ECO:0007829|PDB:2IMQ"
FT HELIX 200..208
FT /evidence="ECO:0007829|PDB:2IMQ"
FT HELIX 212..216
FT /evidence="ECO:0007829|PDB:2IMQ"
FT HELIX 221..226
FT /evidence="ECO:0007829|PDB:2IMQ"
FT TURN 227..232
FT /evidence="ECO:0007829|PDB:1NTF"
FT STRAND 263..268
FT /evidence="ECO:0007829|PDB:2IMQ"
FT STRAND 270..272
FT /evidence="ECO:0007829|PDB:2IMQ"
FT STRAND 275..282
FT /evidence="ECO:0007829|PDB:2IMQ"
FT STRAND 288..291
FT /evidence="ECO:0007829|PDB:2IMQ"
FT STRAND 294..301
FT /evidence="ECO:0007829|PDB:2IMQ"
SQ SEQUENCE 302 AA; 33624 MW; B83471EAE2E39290 CRC64;
MKLLLSAGAA LAFVLGLCAA GSPPAQLSVH TVSWNSGHER APTNLEELLG LNSGETPDVI
AVAVQGFGFQ TDKPQQGPAC VKNFQSLLTS KGYTKLKNTI TETMGLTVYC LEKHLDQNTL
KNETIIVTVD DQKKSGGIVT SFTIYNKRFS FTTSRMSDED VTSTNTKYAY DTRLDYSKKD
DPSDFLFWIG DLNVRVETNA THAKSLVDQN NIDGLMAFDQ LKKAKEQKLF DGWTEPQVTF
KPTYKFKPNT DEYDLSATPS WTDRALYKSG TGKTIQPLSY NSLTNYKQTE HRPVLAKFRV
TL
