QPCT_HUMAN
ID QPCT_HUMAN Reviewed; 361 AA.
AC Q16769; Q16770; Q3KRG6; Q53TR4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Glutaminyl-peptide cyclotransferase;
DE EC=2.3.2.5;
DE AltName: Full=Glutaminyl cyclase;
DE Short=QC;
DE Short=sQC;
DE AltName: Full=Glutaminyl-tRNA cyclotransferase;
DE AltName: Full=Glutamyl cyclase;
DE Short=EC;
DE Flags: Precursor;
GN Name=QPCT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Pituitary;
RX PubMed=7999256; DOI=10.1677/jme.0.0130077;
RA Song I., Chuang C.Z., Bateman R.C. Jr.;
RT "Molecular cloning, sequence analysis and expression of human pituitary
RT glutaminyl cyclase.";
RL J. Mol. Endocrinol. 13:77-86(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-360.
RC TISSUE=Lung, and Pancreas;
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 [6]
RP FUNCTION AS GLUTAMYL CYCLASE.
RX PubMed=15063747; DOI=10.1016/s0014-5793(04)00300-x;
RA Schilling S., Hoffmann T., Manhart S., Hoffmann M., Demuth H.U.;
RT "Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid
RT conditions.";
RL FEBS Lett. 563:191-196(2004).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=18486145; DOI=10.1016/j.jmb.2008.03.078;
RA Cynis H., Rahfeld J.U., Stephan A., Kehlen A., Koch B., Wermann M.,
RA Demuth H.U., Schilling S.;
RT "Isolation of an isoenzyme of human glutaminyl cyclase: retention in the
RT Golgi complex suggests involvement in the protein maturation machinery.";
RL J. Mol. Biol. 379:966-980(2008).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF 33-361 IN COMPLEX WITH ZINC,
RP CATALYTIC ACTIVITY, MUTAGENESIS OF LYS-144; PHE-146; GLU-201; TRP-207;
RP ASP-248; GLN-304; ASP-305; PHE-325 AND TRP-329, AND CHARACTERIZATION OF
RP VARIANT TRP-54.
RX PubMed=16135565; DOI=10.1073/pnas.0504184102;
RA Huang K.-F., Liu Y.-L., Cheng W.-J., Ko T.-P., Wang A.H.-J.;
RT "Crystal structures of human glutaminyl cyclase, an enzyme responsible for
RT protein N-terminal pyroglutamate formation.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:13117-13122(2005).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF 33-361 OF MUTANTS ALA-160;
RP GLY-160; ASP-201; LEU-201; GLN-201; ALA-248; GLN-248; ALA-305; GLU-305 AND
RP LEU-319 IN COMPLEX WITH ZINC, CATALYTIC ACTIVITY, ACTIVE SITE, AND
RP MUTAGENESIS OF SER-160; GLU-201; ASP-248; ASP-305 AND HIS-319.
RX PubMed=18072935; DOI=10.1042/bj20071073;
RA Huang K.F., Wang Y.R., Chang E.C., Chou T.L., Wang A.H.;
RT "A conserved hydrogen-bond network in the catalytic centre of animal
RT glutaminyl cyclases is critical for catalysis.";
RL Biochem. J. 411:181-190(2008).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 38-361 IN COMPLEX WITH ZINC,
RP GLYCOSYLATION AT ASN-49, 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).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 33-361 IN COMPLEX WITH ZINC,
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=21288892; DOI=10.1074/jbc.m110.208595;
RA Huang K.F., Liaw S.S., Huang W.L., Chia C.Y., Lo Y.C., Chen Y.L.,
RA Wang A.H.;
RT "Structures of human Golgi-resident glutaminyl cyclase and its complexes
RT with inhibitors reveal a large loop movement upon inhibitor binding.";
RL J. Biol. Chem. 286:12439-12449(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. Also catalyzes N-terminal pyroglutamate
CC formation. In vitro, catalyzes pyroglutamate formation of N-terminally
CC truncated form of APP amyloid-beta peptides [Glu-3]-amyloid-beta. May
CC be involved in the N-terminal pyroglutamate formation of several
CC amyloid-related plaque-forming peptides. {ECO:0000269|PubMed:15063747,
CC ECO:0000269|PubMed:18486145, ECO:0000269|PubMed:21288892}.
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:16135565,
CC ECO:0000269|PubMed:18072935, ECO:0000269|PubMed:18486145,
CC ECO:0000269|PubMed:21288892};
CC -!- INTERACTION:
CC Q16769; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-2856807, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18486145}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q16769-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16769-2; Sequence=VSP_038487;
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:18072935, PubMed:21288892).
CC However, a recent study suggests a Zn(2+)-independent catalytic
CC mechanism (By similarity). {ECO:0000250|UniProtKB:B7QK46,
CC ECO:0000269|PubMed:18072935, ECO:0000269|PubMed:21288892, ECO:0000305}.
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DR EMBL; X71125; CAA50438.1; -; mRNA.
DR EMBL; X67731; CAA47961.1; -; mRNA.
DR EMBL; AK290605; BAF83294.1; -; mRNA.
DR EMBL; AC007391; AAY14804.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00392.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00394.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00396.1; -; Genomic_DNA.
DR EMBL; BC036721; AAH36721.1; -; mRNA.
DR EMBL; BC047756; AAH47756.1; -; mRNA.
DR CCDS; CCDS1790.1; -. [Q16769-1]
DR PIR; I37421; I37421.
DR RefSeq; NP_036545.1; NM_012413.3. [Q16769-1]
DR PDB; 2AFM; X-ray; 1.66 A; A/B=33-361.
DR PDB; 2AFO; X-ray; 2.35 A; A/B=33-361.
DR PDB; 2AFS; X-ray; 2.22 A; A/B=33-361.
DR PDB; 2AFU; X-ray; 2.22 A; A/B=33-361.
DR PDB; 2AFW; X-ray; 1.56 A; A/B=33-361.
DR PDB; 2AFX; X-ray; 1.64 A; A/B=33-361.
DR PDB; 2AFZ; X-ray; 1.68 A; A/B=33-361.
DR PDB; 2ZED; X-ray; 1.70 A; A/B=33-361.
DR PDB; 2ZEE; X-ray; 1.99 A; A/B=33-361.
DR PDB; 2ZEF; X-ray; 1.67 A; A/B=33-361.
DR PDB; 2ZEG; X-ray; 2.08 A; A/B=33-361.
DR PDB; 2ZEH; X-ray; 1.80 A; A/B=33-361.
DR PDB; 2ZEL; X-ray; 1.97 A; A/B=33-361.
DR PDB; 2ZEM; X-ray; 2.18 A; A/B=33-361.
DR PDB; 2ZEN; X-ray; 1.78 A; A/B=33-361.
DR PDB; 2ZEO; X-ray; 1.66 A; A/B=33-361.
DR PDB; 2ZEP; X-ray; 2.10 A; A/B=33-361.
DR PDB; 3PBB; X-ray; 1.95 A; A/B=33-361.
DR PDB; 3PBE; X-ray; 1.95 A; A/B=33-361.
DR PDB; 3SI0; X-ray; 2.10 A; A=38-361.
DR PDB; 4YU9; X-ray; 2.10 A; A/B/C=33-361.
DR PDB; 4YWY; X-ray; 1.95 A; A/B/C=1-361.
DR PDB; 6GBX; X-ray; 1.72 A; A/B/C=33-361.
DR PDB; 6YI1; X-ray; 1.92 A; A/B=35-361.
DR PDB; 6YJY; X-ray; 1.67 A; A/B=35-361.
DR PDB; 7CM0; X-ray; 2.20 A; A/B/C/D=35-361.
DR PDB; 7COZ; X-ray; 1.85 A; A/B/C=35-361.
DR PDB; 7CP0; X-ray; 1.70 A; A/B/C=35-361.
DR PDB; 7D8E; X-ray; 2.00 A; A/B/C=33-361.
DR PDBsum; 2AFM; -.
DR PDBsum; 2AFO; -.
DR PDBsum; 2AFS; -.
DR PDBsum; 2AFU; -.
DR PDBsum; 2AFW; -.
DR PDBsum; 2AFX; -.
DR PDBsum; 2AFZ; -.
DR PDBsum; 2ZED; -.
DR PDBsum; 2ZEE; -.
DR PDBsum; 2ZEF; -.
DR PDBsum; 2ZEG; -.
DR PDBsum; 2ZEH; -.
DR PDBsum; 2ZEL; -.
DR PDBsum; 2ZEM; -.
DR PDBsum; 2ZEN; -.
DR PDBsum; 2ZEO; -.
DR PDBsum; 2ZEP; -.
DR PDBsum; 3PBB; -.
DR PDBsum; 3PBE; -.
DR PDBsum; 3SI0; -.
DR PDBsum; 4YU9; -.
DR PDBsum; 4YWY; -.
DR PDBsum; 6GBX; -.
DR PDBsum; 6YI1; -.
DR PDBsum; 6YJY; -.
DR PDBsum; 7CM0; -.
DR PDBsum; 7COZ; -.
DR PDBsum; 7CP0; -.
DR PDBsum; 7D8E; -.
DR AlphaFoldDB; Q16769; -.
DR SMR; Q16769; -.
DR BioGRID; 117329; 44.
DR IntAct; Q16769; 25.
DR MINT; Q16769; -.
DR STRING; 9606.ENSP00000344829; -.
DR BindingDB; Q16769; -.
DR ChEMBL; CHEMBL4508; -.
DR DrugBank; DB04581; 1-benzylimidazole.
DR DrugBank; DB04636; Glutamine t-butyl ester.
DR DrugBank; DB04622; N-acetylhistamine.
DR GuidetoPHARMACOLOGY; 2411; -.
DR MEROPS; M28.974; -.
DR GlyGen; Q16769; 2 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q16769; -.
DR PhosphoSitePlus; Q16769; -.
DR BioMuta; QPCT; -.
DR DMDM; 2498824; -.
DR CPTAC; CPTAC-1301; -.
DR jPOST; Q16769; -.
DR MassIVE; Q16769; -.
DR PaxDb; Q16769; -.
DR PeptideAtlas; Q16769; -.
DR PRIDE; Q16769; -.
DR ProteomicsDB; 61056; -. [Q16769-1]
DR ProteomicsDB; 61057; -. [Q16769-2]
DR TopDownProteomics; Q16769-2; -. [Q16769-2]
DR Antibodypedia; 1981; 226 antibodies from 29 providers.
DR DNASU; 25797; -.
DR Ensembl; ENST00000338415.8; ENSP00000344829.3; ENSG00000115828.17. [Q16769-1]
DR GeneID; 25797; -.
DR KEGG; hsa:25797; -.
DR MANE-Select; ENST00000338415.8; ENSP00000344829.3; NM_012413.4; NP_036545.1.
DR UCSC; uc002rqg.4; human. [Q16769-1]
DR CTD; 25797; -.
DR DisGeNET; 25797; -.
DR GeneCards; QPCT; -.
DR HGNC; HGNC:9753; QPCT.
DR HPA; ENSG00000115828; Tissue enhanced (adrenal gland, epididymis).
DR MIM; 607065; gene.
DR neXtProt; NX_Q16769; -.
DR OpenTargets; ENSG00000115828; -.
DR PharmGKB; PA34095; -.
DR VEuPathDB; HostDB:ENSG00000115828; -.
DR eggNOG; KOG3946; Eukaryota.
DR GeneTree; ENSGT00390000003107; -.
DR HOGENOM; CLU_045003_1_0_1; -.
DR InParanoid; Q16769; -.
DR OMA; AFTAEWM; -.
DR OrthoDB; 1257754at2759; -.
DR PhylomeDB; Q16769; -.
DR TreeFam; TF315071; -.
DR BioCyc; MetaCyc:HS03941-MON; -.
DR BRENDA; 2.3.2.5; 2681.
DR PathwayCommons; Q16769; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q16769; -.
DR BioGRID-ORCS; 25797; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; QPCT; human.
DR EvolutionaryTrace; Q16769; -.
DR GeneWiki; QPCT; -.
DR GenomeRNAi; 25797; -.
DR Pharos; Q16769; Tchem.
DR PRO; PR:Q16769; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q16769; protein.
DR Bgee; ENSG00000115828; Expressed in right adrenal gland cortex and 170 other tissues.
DR ExpressionAtlas; Q16769; baseline and differential.
DR Genevisible; Q16769; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
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 GO; GO:0036211; P:protein modification process; TAS:ProtInc.
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..28
FT /evidence="ECO:0000255"
FT CHAIN 29..361
FT /note="Glutaminyl-peptide cyclotransferase"
FT /id="PRO_0000022195"
FT ACT_SITE 201
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:18072935"
FT ACT_SITE 248
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:18072935"
FT BINDING 159
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16135565,
FT ECO:0000269|PubMed:18072935, ECO:0000269|PubMed:21288892,
FT ECO:0000269|PubMed:21671571, ECO:0007744|PDB:2AFM,
FT ECO:0007744|PDB:2AFO, ECO:0007744|PDB:2AFS,
FT ECO:0007744|PDB:2AFU, ECO:0007744|PDB:2AFW,
FT ECO:0007744|PDB:2AFX, ECO:0007744|PDB:2AFZ,
FT ECO:0007744|PDB:2ZED, ECO:0007744|PDB:2ZEE,
FT ECO:0007744|PDB:2ZEF, ECO:0007744|PDB:2ZEG,
FT ECO:0007744|PDB:2ZEH, ECO:0007744|PDB:2ZEL,
FT ECO:0007744|PDB:2ZEM, ECO:0007744|PDB:2ZEN,
FT ECO:0007744|PDB:2ZEO, ECO:0007744|PDB:2ZEP,
FT ECO:0007744|PDB:3PBB, ECO:0007744|PDB:3PBE,
FT ECO:0007744|PDB:3SI0, ECO:0007744|PDB:4YU9,
FT ECO:0007744|PDB:4YWY"
FT BINDING 202
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16135565,
FT ECO:0000269|PubMed:18072935, ECO:0000269|PubMed:21288892,
FT ECO:0000269|PubMed:21671571, ECO:0007744|PDB:2AFM,
FT ECO:0007744|PDB:2AFO, ECO:0007744|PDB:2AFS,
FT ECO:0007744|PDB:2AFU, ECO:0007744|PDB:2AFW,
FT ECO:0007744|PDB:2AFX, ECO:0007744|PDB:2AFZ,
FT ECO:0007744|PDB:2ZED, ECO:0007744|PDB:2ZEE,
FT ECO:0007744|PDB:2ZEF, ECO:0007744|PDB:2ZEG,
FT ECO:0007744|PDB:2ZEH, ECO:0007744|PDB:2ZEL,
FT ECO:0007744|PDB:2ZEM, ECO:0007744|PDB:2ZEN,
FT ECO:0007744|PDB:2ZEO, ECO:0007744|PDB:2ZEP,
FT ECO:0007744|PDB:3PBB, ECO:0007744|PDB:3PBE,
FT ECO:0007744|PDB:3SI0, ECO:0007744|PDB:4YU9,
FT ECO:0007744|PDB:4YWY"
FT BINDING 330
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16135565,
FT ECO:0000269|PubMed:18072935, ECO:0000269|PubMed:21288892,
FT ECO:0000269|PubMed:21671571, ECO:0007744|PDB:2AFM,
FT ECO:0007744|PDB:2AFO, ECO:0007744|PDB:2AFS,
FT ECO:0007744|PDB:2AFU, ECO:0007744|PDB:2AFW,
FT ECO:0007744|PDB:2AFX, ECO:0007744|PDB:2AFZ,
FT ECO:0007744|PDB:2ZED, ECO:0007744|PDB:2ZEE,
FT ECO:0007744|PDB:2ZEF, ECO:0007744|PDB:2ZEG,
FT ECO:0007744|PDB:2ZEH, ECO:0007744|PDB:2ZEL,
FT ECO:0007744|PDB:2ZEM, ECO:0007744|PDB:2ZEN,
FT ECO:0007744|PDB:2ZEO, ECO:0007744|PDB:2ZEP,
FT ECO:0007744|PDB:3PBB, ECO:0007744|PDB:3PBE,
FT ECO:0007744|PDB:3SI0, ECO:0007744|PDB:4YU9,
FT ECO:0007744|PDB:4YWY"
FT CARBOHYD 49
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21671571"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 139..164
FT /evidence="ECO:0000269|PubMed:21671571"
FT VAR_SEQ 41..89
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_038487"
FT VARIANT 54
FT /note="R -> W (lowers activity by approximately 30%;
FT dbSNP:rs2255991)"
FT /evidence="ECO:0000269|PubMed:16135565"
FT /id="VAR_053956"
FT VARIANT 71
FT /note="Q -> R (in dbSNP:rs895245310)"
FT /id="VAR_005569"
FT VARIANT 360
FT /note="H -> P (in dbSNP:rs4670696)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_053957"
FT MUTAGEN 144
FT /note="K->A: Lowers activity by approximately 40%."
FT /evidence="ECO:0000269|PubMed:16135565"
FT MUTAGEN 146
FT /note="F->A: Lowers activity by approximately 30%."
FT /evidence="ECO:0000269|PubMed:16135565"
FT MUTAGEN 160
FT /note="S->A: Reduces activity by about 50%."
FT /evidence="ECO:0000269|PubMed:18072935"
FT MUTAGEN 160
FT /note="S->G: Reduces activity by 96%."
FT /evidence="ECO:0000269|PubMed:18072935"
FT MUTAGEN 201
FT /note="E->D: Reduces activity by about 98%."
FT /evidence="ECO:0000269|PubMed:16135565,
FT ECO:0000269|PubMed:18072935"
FT MUTAGEN 201
FT /note="E->L,Q: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:16135565,
FT ECO:0000269|PubMed:18072935"
FT MUTAGEN 207
FT /note="W->L: Greatly lowers activity."
FT /evidence="ECO:0000269|PubMed:16135565"
FT MUTAGEN 248
FT /note="D->A: Reduces activity by 99%."
FT /evidence="ECO:0000269|PubMed:16135565,
FT ECO:0000269|PubMed:18072935"
FT MUTAGEN 248
FT /note="D->Q: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:16135565,
FT ECO:0000269|PubMed:18072935"
FT MUTAGEN 304
FT /note="Q->L: Lowers activity by approximately 35%."
FT /evidence="ECO:0000269|PubMed:16135565"
FT MUTAGEN 305
FT /note="D->A,E,L: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:16135565,
FT ECO:0000269|PubMed:18072935"
FT MUTAGEN 305
FT /note="D->N: Reduces activity by 99%."
FT /evidence="ECO:0000269|PubMed:16135565,
FT ECO:0000269|PubMed:18072935"
FT MUTAGEN 319
FT /note="H->L: Reduces activity by 87%."
FT /evidence="ECO:0000269|PubMed:18072935"
FT MUTAGEN 325
FT /note="F->A: Greatly lowers activity."
FT /evidence="ECO:0000269|PubMed:16135565"
FT MUTAGEN 329
FT /note="W->A: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:16135565"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:2AFW"
FT HELIX 39..42
FT /evidence="ECO:0007829|PDB:2AFW"
FT HELIX 50..59
FT /evidence="ECO:0007829|PDB:2AFW"
FT HELIX 62..68
FT /evidence="ECO:0007829|PDB:2AFW"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:2AFW"
FT HELIX 82..96
FT /evidence="ECO:0007829|PDB:2AFW"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:2AFW"
FT STRAND 103..111
FT /evidence="ECO:0007829|PDB:2AFW"
FT STRAND 116..128
FT /evidence="ECO:0007829|PDB:2AFW"
FT STRAND 131..140
FT /evidence="ECO:0007829|PDB:2AFW"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:3PBB"
FT TURN 157..160
FT /evidence="ECO:0007829|PDB:2AFW"
FT HELIX 161..173
FT /evidence="ECO:0007829|PDB:2AFW"
FT HELIX 175..179
FT /evidence="ECO:0007829|PDB:2AFW"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:7CP0"
FT STRAND 191..199
FT /evidence="ECO:0007829|PDB:2AFW"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:2AFW"
FT STRAND 209..212
FT /evidence="ECO:0007829|PDB:2AFW"
FT HELIX 214..224
FT /evidence="ECO:0007829|PDB:2AFW"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:2AFW"
FT TURN 237..240
FT /evidence="ECO:0007829|PDB:2AFW"
FT STRAND 241..247
FT /evidence="ECO:0007829|PDB:2AFW"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:2AFW"
FT STRAND 257..259
FT /evidence="ECO:0007829|PDB:3SI0"
FT HELIX 262..264
FT /evidence="ECO:0007829|PDB:2AFW"
FT HELIX 265..280
FT /evidence="ECO:0007829|PDB:2AFW"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:2AFW"
FT HELIX 289..291
FT /evidence="ECO:0007829|PDB:7D8E"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:3PBB"
FT HELIX 308..311
FT /evidence="ECO:0007829|PDB:2AFW"
FT TURN 312..314
FT /evidence="ECO:0007829|PDB:2AFW"
FT STRAND 317..320
FT /evidence="ECO:0007829|PDB:2AFW"
FT TURN 327..330
FT /evidence="ECO:0007829|PDB:2AFW"
FT HELIX 336..338
FT /evidence="ECO:0007829|PDB:2AFM"
FT HELIX 341..359
FT /evidence="ECO:0007829|PDB:2AFW"
SQ SEQUENCE 361 AA; 40877 MW; 32C26041BCF5ED75 CRC64;
MAGGRHRRVV GTLHLLLLVA ALPWASRGVS PSASAWPEEK NYHQPAILNS SALRQIAEGT
SISEMWQNDL QPLLIERYPG SPGSYAARQH IMQRIQRLQA DWVLEIDTFL SQTPYGYRSF
SNIISTLNPT AKRHLVLACH YDSKYFSHWN NRVFVGATDS AVPCAMMLEL ARALDKKLLS
LKTVSDSKPD LSLQLIFFDG EEAFLHWSPQ DSLYGSRHLA AKMASTPHPP GARGTSQLHG
MDLLVLLDLI GAPNPTFPNF FPNSARWFER LQAIEHELHE LGLLKDHSLE GRYFQNYSYG
GVIQDDHIPF LRRGVPVLHL IPSPFPEVWH TMDDNEENLD ESTIDNLNKI LQVFVLEYLH
L
