QPCT_IXOSC
ID QPCT_IXOSC Reviewed; 353 AA.
AC B7QK46;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Glutaminyl-peptide cyclotransferase {ECO:0000305};
DE EC=2.3.2.5 {ECO:0000269|PubMed:23770496, ECO:0000269|PubMed:24598748};
DE AltName: Full=Glutaminyl cyclase {ECO:0000303|PubMed:23770496};
DE Short=QC {ECO:0000303|PubMed:23770496};
DE AltName: Full=Glutaminyl-tRNA cyclotransferase {ECO:0000305};
DE Flags: Precursor;
GN Name=Qptc {ECO:0000250|UniProtKB:Q16769};
GN ORFNames=IscW_ISCW023264 {ECO:0000312|EMBL:EEC19218.1};
OS Ixodes scapularis (Black-legged tick) (Deer tick).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Acari;
OC Parasitiformes; Ixodida; Ixodoidea; Ixodidae; Ixodinae; Ixodes.
OX NCBI_TaxID=6945 {ECO:0000312|Proteomes:UP000001555};
RN [1] {ECO:0000312|Proteomes:UP000001555}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Wikel {ECO:0000312|Proteomes:UP000001555};
RG Ixodes scapularis Genome Project Consortium;
RA Caler E., Hannick L.I., Bidwell S., Joardar V., Thiagarajan M., Amedeo P.,
RA Galinsky K.J., Schobel S., Inman J., Hostetler J., Miller J., Hammond M.,
RA Megy K., Lawson D., Kodira C., Sutton G., Meyer J., Hill C.A., Birren B.,
RA Nene V., Collins F., Alarcon-Chaidez F., Wikel S., Strausberg R.;
RT "Annotation of Ixodes scapularis.";
RL Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, INDUCTION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=23770496; DOI=10.1016/j.ibmb.2013.05.011;
RA Adamson S.W., Browning R.E., Chao C.C., Bateman R.C. Jr., Ching W.M.,
RA Karim S.;
RT "Molecular characterization of tick salivary gland glutaminyl cyclase.";
RL Insect Biochem. Mol. Biol. 43:781-793(2013).
RN [3] {ECO:0007744|PDB:4MHN, ECO:0007744|PDB:4MHP, ECO:0007744|PDB:4MHY, ECO:0007744|PDB:4MHZ}
RP X-RAY CRYSTALLOGRAPHY (1.10 ANGSTROMS) OF 28-353 IN APO FORM AND IN COMPLEX
RP WITH ZINC AND INHIBITOR PBD150, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, DISULFIDE BONDS, AND MUTAGENESIS
RP OF ASP-144 AND ASP-238.
RX PubMed=24598748; DOI=10.1107/s1399004713033488;
RA Huang K.F., Hsu H.L., Karim S., Wang A.H.;
RT "Structural and functional analyses of a glutaminyl cyclase from Ixodes
RT scapularis reveal metal-independent catalysis and inhibitor binding.";
RL Acta Crystallogr. D 70:789-801(2014).
CC -!- FUNCTION: Responsible for the biosynthesis of pyroglutamyl peptides
CC (PubMed:23770496, PubMed:24598748). Seems to have a preference for
CC substrates with neutral or hydrophobic amino-acid residues at the
CC second and third positions (PubMed:24598748). Shows activity towards
CC the peptides [Gln-1]-corazonin, [Gln-1]-periviscerokinin and [Gln-1]-
CC sulfakinin (PubMed:24598748). {ECO:0000269|PubMed:23770496,
CC ECO:0000269|PubMed:24598748}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-terminal L-glutaminyl-[peptide] = N-terminal 5-oxo-L-prolyl-
CC [peptide] + NH4(+); Xref=Rhea:RHEA:23652, Rhea:RHEA-COMP:11736,
CC Rhea:RHEA-COMP:11846, ChEBI:CHEBI:28938, ChEBI:CHEBI:64722,
CC ChEBI:CHEBI:87215; EC=2.3.2.5; Evidence={ECO:0000269|PubMed:23770496,
CC ECO:0000269|PubMed:24598748};
CC -!- ACTIVITY REGULATION: Strongly inhibited by PBD150, 1-benzylimidazole
CC and N-omega-acetylhistamine, in a Zn(2+)-independent manner.
CC {ECO:0000269|PubMed:24598748}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=21.8 uM for L-glutaminyl 2-naphthylamide (Gln-beta-NA) (in the
CC presence of Zn(2+), at 25 degrees Celsius)
CC {ECO:0000269|PubMed:24598748};
CC KM=8.8 uM for L-glutaminyl 2-naphthylamide (Gln-beta-NA) (in the
CC absence of Zn(2+), at 25 degrees Celsius)
CC {ECO:0000269|PubMed:24598748};
CC Note=kcat is 8.8 sec(-1) for L-glutaminyl 2-naphthylamide (Gln-beta-
CC NA) in the presence of Zn(2+). kcat is 6.9 sec(-1) for L-glutaminyl
CC 2-naphthylamide (Gln-beta-NA) in the absence of Zn(2+).
CC {ECO:0000269|PubMed:24598748};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in salivary gland and midgut.
CC {ECO:0000269|PubMed:23770496}.
CC -!- INDUCTION: Strongly up-regulated in salivary gland during blood-feeding
CC on the host. Peak expression is detected 48 hours after feeding begins.
CC {ECO:0000269|PubMed:23770496}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in reduced
CC enzymatic activity in midgut and salivary gland tissue extracts. Weight
CC gain after feeding is reduced. Females lay very small eggs which fail
CC to hatch into larvae. {ECO:0000269|PubMed:23770496}.
CC -!- SIMILARITY: Belongs to the glutaminyl-peptide cyclotransferase family.
CC {ECO:0000305}.
CC -!- CAUTION: It is unclear whether this protein requires a metal cofactor
CC for catalysis. It was originally proposed to be a Zn(2+)-dependent
CC metalloenzyme based on structural similarities to bacterial
CC aminopeptidases and the observation that it can bind Zn(2+) ions,
CC typically in a 1:1 stoichiometry. However, a recent study suggests a
CC Zn(2+)-independent catalytic mechanism. {ECO:0000269|PubMed:24598748}.
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DR EMBL; ABJB010256078; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; ABJB010817920; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DS957018; EEC19218.1; -; Genomic_DNA.
DR RefSeq; XP_002415553.1; XM_002415508.1.
DR PDB; 4MHN; X-ray; 1.15 A; A=28-353.
DR PDB; 4MHP; X-ray; 1.10 A; A=28-353.
DR PDB; 4MHY; X-ray; 1.38 A; A=28-353.
DR PDB; 4MHZ; X-ray; 1.95 A; A=28-353.
DR PDB; 7D1H; X-ray; 1.69 A; A=25-353.
DR PDB; 7D1N; X-ray; 2.26 A; A=25-353.
DR PDB; 7D1P; X-ray; 2.36 A; A=25-353.
DR PDB; 7D1Y; X-ray; 1.95 A; A=25-353.
DR PDB; 7D21; X-ray; 1.97 A; A=25-353.
DR PDB; 7D23; X-ray; 1.40 A; A=25-353.
DR PDB; 7D2B; X-ray; 1.99 A; A=25-353.
DR PDB; 7D2D; X-ray; 1.80 A; A=25-353.
DR PDB; 7D2I; X-ray; 1.85 A; A=25-353.
DR PDB; 7D2J; X-ray; 1.60 A; A=25-353.
DR PDBsum; 4MHN; -.
DR PDBsum; 4MHP; -.
DR PDBsum; 4MHY; -.
DR PDBsum; 4MHZ; -.
DR PDBsum; 7D1H; -.
DR PDBsum; 7D1N; -.
DR PDBsum; 7D1P; -.
DR PDBsum; 7D1Y; -.
DR PDBsum; 7D21; -.
DR PDBsum; 7D23; -.
DR PDBsum; 7D2B; -.
DR PDBsum; 7D2D; -.
DR PDBsum; 7D2I; -.
DR PDBsum; 7D2J; -.
DR AlphaFoldDB; B7QK46; -.
DR SMR; B7QK46; -.
DR STRING; 6945.B7QK46; -.
DR PRIDE; B7QK46; -.
DR GeneID; 8042451; -.
DR KEGG; isc:IscW_ISCW023264; -.
DR VEuPathDB; VectorBase:ISCI023264; -.
DR VEuPathDB; VectorBase:ISCW023264; -.
DR HOGENOM; CLU_045003_1_0_1; -.
DR InParanoid; B7QK46; -.
DR OMA; CDRVRMP; -.
DR OrthoDB; 1257754at2759; -.
DR PhylomeDB; B7QK46; -.
DR BRENDA; 2.3.2.5; 10611.
DR Proteomes; UP000001555; Unassembled WGS sequence.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016603; F:glutaminyl-peptide cyclotransferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0017186; P:peptidyl-pyroglutamic acid biosynthetic process, using glutaminyl-peptide cyclotransferase; IDA:UniProtKB.
DR CDD; cd03880; M28_QC_like; 1.
DR InterPro; IPR037457; M28_QC.
DR InterPro; IPR007484; Peptidase_M28.
DR InterPro; IPR040234; QC/QCL.
DR PANTHER; PTHR12283; PTHR12283; 1.
DR Pfam; PF04389; Peptidase_M28; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Disulfide bond; Glycoprotein; Metal-binding;
KW Reference proteome; Secreted; Signal; Transferase; Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..353
FT /note="Glutaminyl-peptide cyclotransferase"
FT /id="PRO_5010827006"
FT ACT_SITE 183
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q16769"
FT ACT_SITE 238
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:24598748"
FT BINDING 144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24598748,
FT ECO:0007744|PDB:4MHN, ECO:0007744|PDB:4MHY"
FT BINDING 184
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24598748,
FT ECO:0007744|PDB:4MHN, ECO:0007744|PDB:4MHY"
FT BINDING 322
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24598748,
FT ECO:0007744|PDB:4MHN, ECO:0007744|PDB:4MHY"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 96..109
FT /evidence="ECO:0000269|PubMed:24598748,
FT ECO:0007744|PDB:4MHN, ECO:0007744|PDB:4MHP,
FT ECO:0007744|PDB:4MHY, ECO:0007744|PDB:4MHZ"
FT DISULFID 120..218
FT /evidence="ECO:0000269|PubMed:24598748,
FT ECO:0007744|PDB:4MHN, ECO:0007744|PDB:4MHP,
FT ECO:0007744|PDB:4MHY, ECO:0007744|PDB:4MHZ"
FT DISULFID 127..149
FT /evidence="ECO:0000250|UniProtKB:Q16769"
FT MUTAGEN 144
FT /note="D->A: Significantly impairs catalytic activity."
FT /evidence="ECO:0000269|PubMed:24598748"
FT MUTAGEN 238
FT /note="D->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:24598748"
FT HELIX 39..45
FT /evidence="ECO:0007829|PDB:4MHP"
FT HELIX 50..61
FT /evidence="ECO:0007829|PDB:4MHP"
FT HELIX 72..86
FT /evidence="ECO:0007829|PDB:4MHP"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:4MHP"
FT STRAND 91..101
FT /evidence="ECO:0007829|PDB:4MHP"
FT STRAND 104..115
FT /evidence="ECO:0007829|PDB:4MHP"
FT STRAND 119..128
FT /evidence="ECO:0007829|PDB:4MHP"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:7D1N"
FT TURN 142..145
FT /evidence="ECO:0007829|PDB:4MHP"
FT HELIX 146..158
FT /evidence="ECO:0007829|PDB:4MHP"
FT HELIX 160..167
FT /evidence="ECO:0007829|PDB:4MHP"
FT STRAND 172..181
FT /evidence="ECO:0007829|PDB:4MHP"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:4MHP"
FT STRAND 191..194
FT /evidence="ECO:0007829|PDB:4MHP"
FT HELIX 196..207
FT /evidence="ECO:0007829|PDB:4MHP"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:4MHP"
FT STRAND 215..217
FT /evidence="ECO:0007829|PDB:4MHP"
FT HELIX 227..230
FT /evidence="ECO:0007829|PDB:4MHP"
FT STRAND 231..237
FT /evidence="ECO:0007829|PDB:4MHP"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:4MHP"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:4MHP"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:4MHP"
FT HELIX 255..270
FT /evidence="ECO:0007829|PDB:4MHP"
FT STRAND 286..290
FT /evidence="ECO:0007829|PDB:4MHP"
FT HELIX 300..303
FT /evidence="ECO:0007829|PDB:4MHP"
FT TURN 304..306
FT /evidence="ECO:0007829|PDB:4MHP"
FT STRAND 309..312
FT /evidence="ECO:0007829|PDB:4MHP"
FT TURN 319..322
FT /evidence="ECO:0007829|PDB:4MHP"
FT HELIX 328..330
FT /evidence="ECO:0007829|PDB:4MHP"
FT HELIX 333..351
FT /evidence="ECO:0007829|PDB:4MHP"
SQ SEQUENCE 353 AA; 40700 MW; F1B384798A1E6E86 CRC64;
MLFPVLLLLK LVIGALIIDA SALSWHDLKW PRDLRPLAHH DLLYMGQISE EDRGDFNATL
RNFLVPRVVG SQKHREVREF IVRSLKDLDW DVEEDCFDGQ TPHGIKPFCN VIATLNPSAC
HRLVLACHYD SLLHKEGTFI GATDSAVPCA QLLYLARSLN GKLQNQKTRG DGLTLQLVFF
DGEEAFERWS SHDSLYGSRH LAQKWHEDRT SAERLESCLE RSEIANQIDR MEVMVLLDLL
GAENPRFYSY FGETQPVYRR LVNIESRLND AGLMELPRRR RRTNYFSNSS TVGFIEDDHI
PFLKRSVPIV HIIPSPFPDV WHTLDDNEQN LHHPTISNLN KIFKAFVSEY LQL
