QPCT_MOUSE
ID QPCT_MOUSE Reviewed; 362 AA.
AC Q9CYK2; Q8BH20; Q8VE07;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Glutaminyl-peptide cyclotransferase;
DE EC=2.3.2.5;
DE AltName: Full=Glutaminyl cyclase;
DE Short=QC;
DE AltName: Full=Glutaminyl-tRNA cyclotransferase;
DE Flags: Precursor;
GN Name=Qpct;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina, Embryo, and Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=Czech II; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 36-362 IN COMPLEX WITH ZINC,
RP GLYCOSYLATION AT ASN-50, AND DISULFIDE BOND.
RX PubMed=21671571; DOI=10.1021/bi200249h;
RA Ruiz-Carrillo D., Koch B., Parthier C., Wermann M., Dambe T., Buchholz M.,
RA Ludwig H.H., Heiser U., Rahfeld J.U., Stubbs M.T., Schilling S.,
RA Demuth H.U.;
RT "Structures of glycosylated mammalian glutaminyl cyclases reveal
RT conformational variability near the active center.";
RL Biochemistry 50:6280-6288(2011).
CC -!- FUNCTION: Responsible for the biosynthesis of pyroglutamyl peptides.
CC Has a bias against acidic and tryptophan residues adjacent to the N-
CC terminal glutaminyl residue and a lack of importance of chain length
CC after the second residue (By similarity). {ECO:0000250}.
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;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9CYK2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CYK2-2; Sequence=VSP_013911;
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 (PubMed:21671571). However, a recent
CC study suggests a Zn(2+)-independent catalytic mechanism (By
CC similarity). {ECO:0000250|UniProtKB:B7QK46,
CC ECO:0000269|PubMed:21671571}.
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DR EMBL; AK037197; BAC29748.1; -; mRNA.
DR EMBL; AK045974; BAC32556.1; -; mRNA.
DR EMBL; AK017598; BAB30831.1; -; mRNA.
DR EMBL; BC020023; AAH20023.1; -; mRNA.
DR CCDS; CCDS28983.1; -. [Q9CYK2-1]
DR CCDS; CCDS89158.1; -. [Q9CYK2-2]
DR RefSeq; NP_001303658.1; NM_001316729.1.
DR RefSeq; NP_081731.1; NM_027455.3.
DR PDB; 3SI1; X-ray; 2.90 A; A=36-362.
DR PDB; 3SI2; X-ray; 1.80 A; A=36-362.
DR PDBsum; 3SI1; -.
DR PDBsum; 3SI2; -.
DR AlphaFoldDB; Q9CYK2; -.
DR SMR; Q9CYK2; -.
DR STRING; 10090.ENSMUSP00000038732; -.
DR BindingDB; Q9CYK2; -.
DR ChEMBL; CHEMBL4105900; -.
DR MEROPS; M28.979; -.
DR GlyGen; Q9CYK2; 2 sites.
DR iPTMnet; Q9CYK2; -.
DR PhosphoSitePlus; Q9CYK2; -.
DR MaxQB; Q9CYK2; -.
DR PaxDb; Q9CYK2; -.
DR PeptideAtlas; Q9CYK2; -.
DR PRIDE; Q9CYK2; -.
DR ProteomicsDB; 300333; -. [Q9CYK2-1]
DR ProteomicsDB; 300334; -. [Q9CYK2-2]
DR DNASU; 70536; -.
DR GeneID; 70536; -.
DR KEGG; mmu:70536; -.
DR UCSC; uc008dpv.1; mouse. [Q9CYK2-1]
DR UCSC; uc008dpw.1; mouse. [Q9CYK2-2]
DR CTD; 25797; -.
DR MGI; MGI:1917786; Qpct.
DR eggNOG; KOG3946; Eukaryota.
DR InParanoid; Q9CYK2; -.
DR OrthoDB; 1257754at2759; -.
DR PhylomeDB; Q9CYK2; -.
DR TreeFam; TF315071; -.
DR BRENDA; 2.3.2.5; 3474.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 70536; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Qpct; mouse.
DR PRO; PR:Q9CYK2; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9CYK2; protein.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016603; F:glutaminyl-peptide cyclotransferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0017186; P:peptidyl-pyroglutamic acid biosynthetic process, using glutaminyl-peptide cyclotransferase; ISS: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; Alternative splicing; Disulfide bond;
KW Glycoprotein; Metal-binding; Reference proteome; Secreted; Signal;
KW Transferase; Zinc.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..362
FT /note="Glutaminyl-peptide cyclotransferase"
FT /id="PRO_0000022196"
FT ACT_SITE 202
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q16769"
FT ACT_SITE 249
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q16769"
FT BINDING 160
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:21671571,
FT ECO:0007744|PDB:3SI1, ECO:0007744|PDB:3SI2"
FT BINDING 203
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:21671571,
FT ECO:0007744|PDB:3SI1, ECO:0007744|PDB:3SI2"
FT BINDING 331
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:21671571,
FT ECO:0007744|PDB:3SI1, ECO:0007744|PDB:3SI2"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 50
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21671571,
FT ECO:0007744|PDB:3SI1, ECO:0007744|PDB:3SI2"
FT DISULFID 140..165
FT /evidence="ECO:0000269|PubMed:21671571,
FT ECO:0007744|PDB:3SI1, ECO:0007744|PDB:3SI2"
FT VAR_SEQ 42..90
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013911"
FT CONFLICT 8
FT /note="R -> L (in Ref. 1; BAC29748/BAC32556/BAB30831)"
FT /evidence="ECO:0000305"
FT CONFLICT 31
FT /note="S -> N (in Ref. 2; AAH20023)"
FT /evidence="ECO:0000305"
FT CONFLICT 35
FT /note="A -> G (in Ref. 2; AAH20023)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="S -> T (in Ref. 1; BAB30831)"
FT /evidence="ECO:0000305"
FT CONFLICT 326
FT /note="F -> S (in Ref. 1; BAB30831)"
FT /evidence="ECO:0000305"
FT HELIX 37..43
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 51..60
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 63..69
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 83..97
FT /evidence="ECO:0007829|PDB:3SI2"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:3SI2"
FT STRAND 103..114
FT /evidence="ECO:0007829|PDB:3SI2"
FT STRAND 117..129
FT /evidence="ECO:0007829|PDB:3SI2"
FT STRAND 132..141
FT /evidence="ECO:0007829|PDB:3SI2"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:3SI1"
FT TURN 158..161
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 162..174
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 176..180
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:3SI2"
FT STRAND 192..200
FT /evidence="ECO:0007829|PDB:3SI2"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:3SI2"
FT STRAND 209..213
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 215..225
FT /evidence="ECO:0007829|PDB:3SI2"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 238..241
FT /evidence="ECO:0007829|PDB:3SI2"
FT STRAND 242..250
FT /evidence="ECO:0007829|PDB:3SI2"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 266..281
FT /evidence="ECO:0007829|PDB:3SI2"
FT STRAND 285..287
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:3SI2"
FT STRAND 298..300
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 309..312
FT /evidence="ECO:0007829|PDB:3SI2"
FT TURN 313..315
FT /evidence="ECO:0007829|PDB:3SI2"
FT STRAND 318..322
FT /evidence="ECO:0007829|PDB:3SI2"
FT TURN 328..331
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 337..339
FT /evidence="ECO:0007829|PDB:3SI2"
FT HELIX 342..360
FT /evidence="ECO:0007829|PDB:3SI2"
SQ SEQUENCE 362 AA; 41119 MW; F23637D4EF6ED1F6 CRC64;
MAGSEDKRVV GTLHLLLLQA TVLSLTAGNL SLVSAAWTQE KNHHQPAHLN SSSLQQVAEG
TSISEMWQND LRPLLIERYP GSPGSYSARQ HIMQRIQRLQ AEWVVEVDTF LSRTPYGYRS
FSNIISTLNP EAKRHLVLAC HYDSKYFPRW DSRVFVGATD SAVPCAMMLE LARALDKKLH
SLKDVSGSKP DLSLRLIFFD GEEAFHHWSP QDSLYGSRHL AQKMASSPHP PGSRGTNQLD
GMDLLVLLDL IGAANPTFPN FFPKTTRWFN RLQAIEKELY ELGLLKDHSL ERKYFQNFGY
GNIIQDDHIP FLRKGVPVLH LIASPFPEVW HTMDDNEENL HASTIDNLNK IIQVFVLEYL
HL
