QPCTL_HUMAN
ID QPCTL_HUMAN Reviewed; 382 AA.
AC Q9NXS2; Q53HE4; Q96F74;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Glutaminyl-peptide cyclotransferase-like protein;
DE EC=2.3.2.5;
DE AltName: Full=Golgi-resident glutaminyl-peptide cyclotransferase;
DE AltName: Full=isoQC;
DE Short=gQC;
GN Name=QPCTL;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
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 [5]
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS) OF 53-382 IN COMPLEXES WITH
RP SYNTHETIC INHIBITORS PBD150 AND ZINC IONS, FUNCTION, AND CATALYTIC
RP 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 {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:18486145,
CC ECO:0000269|PubMed:21288892};
CC -!- INTERACTION:
CC Q9NXS2-3; Q6UX06: OLFM4; NbExp=3; IntAct=EBI-13336719, EBI-2804156;
CC Q9NXS2-3; Q5BVD1: TTMP; NbExp=3; IntAct=EBI-13336719, EBI-10243654;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:18486145}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:18486145}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NXS2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NXS2-3; Sequence=VSP_054066;
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:21288892). However, a recent
CC study suggests a Zn(2+)-independent catalytic mechanism (By
CC similarity). {ECO:0000250|UniProtKB:B7QK46,
CC ECO:0000269|PubMed:21288892}.
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DR EMBL; AK000091; BAA90938.1; -; mRNA.
DR EMBL; AK172764; BAD18747.1; -; mRNA.
DR EMBL; AK222636; BAD96356.1; -; mRNA.
DR EMBL; AC007191; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC011553; AAH11553.1; -; mRNA.
DR CCDS; CCDS12672.1; -. [Q9NXS2-1]
DR CCDS; CCDS54282.1; -. [Q9NXS2-3]
DR RefSeq; NP_001156849.1; NM_001163377.1. [Q9NXS2-3]
DR RefSeq; NP_060129.2; NM_017659.3. [Q9NXS2-1]
DR PDB; 3PB4; X-ray; 1.13 A; X=53-382.
DR PDB; 3PB6; X-ray; 1.05 A; X=53-382.
DR PDB; 3PB7; X-ray; 1.40 A; X=53-382.
DR PDB; 3PB8; X-ray; 1.13 A; X=53-382.
DR PDB; 3PB9; X-ray; 1.12 A; X=53-382.
DR PDBsum; 3PB4; -.
DR PDBsum; 3PB6; -.
DR PDBsum; 3PB7; -.
DR PDBsum; 3PB8; -.
DR PDBsum; 3PB9; -.
DR AlphaFoldDB; Q9NXS2; -.
DR SMR; Q9NXS2; -.
DR BioGRID; 120171; 65.
DR IntAct; Q9NXS2; 42.
DR MINT; Q9NXS2; -.
DR STRING; 9606.ENSP00000012049; -.
DR BindingDB; Q9NXS2; -.
DR ChEMBL; CHEMBL3638349; -.
DR MEROPS; M28.016; -.
DR iPTMnet; Q9NXS2; -.
DR PhosphoSitePlus; Q9NXS2; -.
DR BioMuta; QPCTL; -.
DR DMDM; 296452875; -.
DR EPD; Q9NXS2; -.
DR jPOST; Q9NXS2; -.
DR MassIVE; Q9NXS2; -.
DR MaxQB; Q9NXS2; -.
DR PaxDb; Q9NXS2; -.
DR PeptideAtlas; Q9NXS2; -.
DR PRIDE; Q9NXS2; -.
DR ProteomicsDB; 83131; -. [Q9NXS2-1]
DR Antibodypedia; 31379; 118 antibodies from 19 providers.
DR DNASU; 54814; -.
DR Ensembl; ENST00000012049.10; ENSP00000012049.4; ENSG00000011478.13. [Q9NXS2-1]
DR Ensembl; ENST00000366382.8; ENSP00000387944.2; ENSG00000011478.13. [Q9NXS2-3]
DR GeneID; 54814; -.
DR KEGG; hsa:54814; -.
DR MANE-Select; ENST00000012049.10; ENSP00000012049.4; NM_017659.4; NP_060129.2.
DR UCSC; uc010ekn.4; human. [Q9NXS2-1]
DR CTD; 54814; -.
DR DisGeNET; 54814; -.
DR GeneCards; QPCTL; -.
DR HGNC; HGNC:25952; QPCTL.
DR HPA; ENSG00000011478; Low tissue specificity.
DR neXtProt; NX_Q9NXS2; -.
DR OpenTargets; ENSG00000011478; -.
DR PharmGKB; PA134922163; -.
DR VEuPathDB; HostDB:ENSG00000011478; -.
DR eggNOG; KOG3946; Eukaryota.
DR GeneTree; ENSGT00390000003107; -.
DR HOGENOM; CLU_045003_3_0_1; -.
DR InParanoid; Q9NXS2; -.
DR OMA; WNAYLRP; -.
DR OrthoDB; 1257754at2759; -.
DR PhylomeDB; Q9NXS2; -.
DR TreeFam; TF315071; -.
DR BRENDA; 2.3.2.5; 2681.
DR PathwayCommons; Q9NXS2; -.
DR SignaLink; Q9NXS2; -.
DR BioGRID-ORCS; 54814; 13 hits in 1074 CRISPR screens.
DR ChiTaRS; QPCTL; human.
DR EvolutionaryTrace; Q9NXS2; -.
DR GenomeRNAi; 54814; -.
DR Pharos; Q9NXS2; Tchem.
DR PRO; PR:Q9NXS2; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9NXS2; protein.
DR Bgee; ENSG00000011478; Expressed in stromal cell of endometrium and 92 other tissues.
DR ExpressionAtlas; Q9NXS2; baseline and differential.
DR Genevisible; Q9NXS2; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
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; Alternative splicing; Disulfide bond;
KW Golgi apparatus; Membrane; Metal-binding; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..382
FT /note="Glutaminyl-peptide cyclotransferase-like protein"
FT /id="PRO_0000302002"
FT TRANSMEM 35..55
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 225
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q16769"
FT ACT_SITE 269
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q16769"
FT BINDING 186
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q16769"
FT BINDING 226
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q16769"
FT BINDING 351
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q16769"
FT DISULFID 167..191
FT /evidence="ECO:0000250|UniProtKB:Q16769"
FT VAR_SEQ 118..211
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054066"
FT VARIANT 214
FT /note="P -> L (in dbSNP:rs28708996)"
FT /id="VAR_034937"
FT CONFLICT 295
FT /note="I -> T (in Ref. 2; BAD96356)"
FT /evidence="ECO:0000305"
FT CONFLICT 321
FT /note="F -> S (in Ref. 1; BAA90938/BAD18747)"
FT /evidence="ECO:0000305"
FT CONFLICT 334
FT /note="R -> G (in Ref. 2; BAD96356)"
FT /evidence="ECO:0000305"
FT HELIX 78..86
FT /evidence="ECO:0007829|PDB:3PB6"
FT HELIX 90..96
FT /evidence="ECO:0007829|PDB:3PB6"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:3PB6"
FT HELIX 110..125
FT /evidence="ECO:0007829|PDB:3PB6"
FT STRAND 131..141
FT /evidence="ECO:0007829|PDB:3PB6"
FT STRAND 144..155
FT /evidence="ECO:0007829|PDB:3PB6"
FT STRAND 159..168
FT /evidence="ECO:0007829|PDB:3PB6"
FT STRAND 176..179
FT /evidence="ECO:0007829|PDB:3PB9"
FT TURN 184..187
FT /evidence="ECO:0007829|PDB:3PB6"
FT HELIX 188..200
FT /evidence="ECO:0007829|PDB:3PB6"
FT HELIX 202..210
FT /evidence="ECO:0007829|PDB:3PB6"
FT STRAND 214..223
FT /evidence="ECO:0007829|PDB:3PB6"
FT STRAND 228..230
FT /evidence="ECO:0007829|PDB:3PB9"
FT HELIX 238..249
FT /evidence="ECO:0007829|PDB:3PB6"
FT STRAND 253..257
FT /evidence="ECO:0007829|PDB:3PB9"
FT TURN 258..261
FT /evidence="ECO:0007829|PDB:3PB6"
FT STRAND 262..270
FT /evidence="ECO:0007829|PDB:3PB6"
FT STRAND 272..275
FT /evidence="ECO:0007829|PDB:3PB6"
FT HELIX 283..285
FT /evidence="ECO:0007829|PDB:3PB6"
FT HELIX 286..301
FT /evidence="ECO:0007829|PDB:3PB6"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:3PB6"
FT HELIX 329..332
FT /evidence="ECO:0007829|PDB:3PB6"
FT TURN 333..335
FT /evidence="ECO:0007829|PDB:3PB6"
FT STRAND 338..342
FT /evidence="ECO:0007829|PDB:3PB6"
FT TURN 348..351
FT /evidence="ECO:0007829|PDB:3PB6"
FT HELIX 357..359
FT /evidence="ECO:0007829|PDB:3PB6"
FT HELIX 362..380
FT /evidence="ECO:0007829|PDB:3PB6"
SQ SEQUENCE 382 AA; 42924 MW; 2DCA79BED029DD4B CRC64;
MRSGGRGRPR LRLGERGLME PLLPPKRRLL PRVRLLPLLL ALAVGSAFYT IWSGWHRRTE
ELPLGRELRV PLIGSLPEAR LRRVVGQLDP QRLWSTYLRP LLVVRTPGSP GNLQVRKFLE
ATLRSLTAGW HVELDPFTAS TPLGPVDFGN VVATLDPRAA RHLTLACHYD SKLFPPGSTP
FVGATDSAVP CALLLELAQA LDLELSRAKK QAAPVTLQLL FLDGEEALKE WGPKDSLYGS
RHLAQLMESI PHSPGPTRIQ AIELFMLLDL LGAPNPTFYS HFPRTVRWFH RLRSIEKRLH
RLNLLQSHPQ EVMYFQPGEP FGSVEDDHIP FLRRGVPVLH LISTPFPAVW HTPADTEVNL
HPPTVHNLCR ILAVFLAEYL GL
