Glutaminyl-peptide cyclotransferase
Details
- Name
- Glutaminyl-peptide cyclotransferase
- Kind
- protein
- Synonyms
- 2.3.2.5
- EC
- Glutaminyl cyclase
- Glutaminyl-tRNA cyclotransferase
- Glutamyl cyclase
- QC
- sQC
- Gene Name
- QPCT
- UniProtKB Entry
- Q16769Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0006497|Glutaminyl-peptide cyclotransferase MAGGRHRRVVGTLHLLLLVAALPWASRGVSPSASAWPEEKNYHQPAILNSSALRQIAEGT SISEMWQNDLQPLLIERYPGSPGSYAARQHIMQRIQRLQADWVLEIDTFLSQTPYGYRSF SNIISTLNPTAKRHLVLACHYDSKYFSHWNNRVFVGATDSAVPCAMMLELARALDKKLLS LKTVSDSKPDLSLQLIFFDGEEAFLHWSPQDSLYGSRHLAAKMASTPHPPGARGTSQLHG MDLLVLLDLIGAPNPTFPNFFPNSARWFERLQAIEHELHELGLLKDHSLEGRYFQNYSYG GVIQDDHIPFLRRGVPVLHLIPSPFPEVWHTMDDNEENLDESTIDNLNKILQVFVLEYLH L
- Number of residues
- 361
- Molecular Weight
- 40876.14
- Theoretical pI
- 6.6
- GO Classification
- Processesprotein modification processComponentsextracellular region / ficolin-1-rich granule lumen / specific granule lumen / tertiary granule lumen
- General Function
- Responsible for the biosynthesis of pyroglutamyl peptides. Has a bias against acidic and tryptophan residues adjacent to the N-terminal glutaminyl residue and a lack of importance of chain length after the second residue. Also catalyzes N-terminal pyroglutamate formation. In vitro, catalyzes pyroglutamate formation of N-terminally truncated form of APP amyloid-beta peptides [Glu-3]-amyloid-beta. May be involved in the N-terminal pyroglutamate formation of several amyloid-related plaque-forming peptides
- Specific Function
- glutaminyl-peptide cyclotransferase activity
- Pfam Domain Function
- Peptidase_M28 (PF04389)
- Signal Regions
- 1-28
- Transmembrane Regions
- Not Available
- Cellular Location
- Secreted
- Gene sequence
>lcl|BSEQ0012328|Glutaminyl-peptide cyclotransferase (QPCT) ATGGCAGGCGGAAGACACCGGCGCGTCGTGGGCACCCTCCACCTGCTGCTGCTGGTGGCC GCCCTGCCCTGGGCATCCAGGGGGGTCAGTCCGAGTGCCTCAGCCTGGCCAGAGGAGAAG AATTACCACCAGCCAGCCATTTTGAATTCATCGGCTCTTCGGCAAATTGCAGAAGGCACC AGTATCTCTGAAATGTGGCAAAATGACTTACAGCCATTGCTGATAGAGCGATACCCGGGA TCCCCTGGAAGCTATGCTGCTCGTCAGCACATCATGCAGCGAATTCAGAGGCTTCAGGCT GACTGGGTCTTGGAAATAGACACCTTCTTGAGTCAGACACCCTATGGGTACCGGTCTTTC TCAAATATCATCAGCACCCTCAATCCCACTGCTAAACGACATTTGGTCCTCGCCTGCCAC TATGACTCCAAGTATTTTTCCCACTGGAACAACAGAGTGTTTGTAGGAGCCACTGATTCA GCCGTGCCATGTGCAATGATGTTGGAACTTGCTCGTGCCTTAGACAAGAAACTCCTTTCC TTAAAGACTGTTTCAGACTCCAAGCCAGATTTGTCACTCCAGCTGATCTTCTTTGATGGT GAAGAGGCTTTTCTTCACTGGTCTCCTCAAGATTCTCTCTATGGGTCTCGACACTTAGCT GCAAAGATGGCATCGACCCCGCACCCACCTGGAGCGAGAGGCACCAGCCAACTGCATGGC ATGGATTTATTGGTCTTATTGGATTTGATTGGAGCTCCAAACCCAACGTTTCCCAATTTT TTTCCAAACTCAGCCAGGTGGTTCGAAAGACTTCAAGCAATTGAACATGAACTTCATGAA TTGGGTTTGCTCAAGGATCACTCTTTGGAGGGGCGGTATTTCCAGAATTACAGTTATGGA GGTGTGATTCAGGATGACCATATTCCATTTTTAAGAAGAGGTGTTCCAGTTCTGCATCTG ATACCGTCTCCTTTCCCTGAAGTCTGGCACACCATGGATGACAATGAAGAAAATTTGGAT GAATCAACCATTGACAATCTAAACAAAATCCTACAAGTCTTTGTGTTGGAATATCTTCAT TTGTAA
- Chromosome Location
- 2
- Locus
- 2p22.2
- External Identifiers
Resource Link UniProtKB ID Q16769 UniProtKB Entry Name QPCT_HUMAN GenBank Gene ID X71125 GeneCard ID QPCT GenAtlas ID QPCT HGNC ID HGNC:9753 PDB ID(s) 2AFM, 2AFO, 2AFS, 2AFU, 2AFW, 2AFX, 2AFZ, 2ZED, 2ZEE, 2ZEF, 2ZEG, 2ZEH, 2ZEL, 2ZEM, 2ZEN, 2ZEO, 2ZEP, 3PBB, 3PBE, 3SI0, 4YU9, 4YWY, 6GBX, 6YI1, 6YJY, 7CM0, 7COZ, 7CP0, 7D8E, 8HY3, 8XGB, 8XGT, 8XGY KEGG ID hsa:25797 IUPHAR/Guide To Pharmacology ID 2411 NCBI Gene ID 25797 - General References
- Song I, Chuang CZ, Bateman RC Jr: Molecular cloning, sequence analysis and expression of human pituitary glutaminyl cyclase. J Mol Endocrinol. 1994 Aug;13(1):77-86. [Article]
- Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
- Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- Schilling S, Hoffmann T, Manhart S, Hoffmann M, Demuth HU: Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions. FEBS Lett. 2004 Apr 9;563(1-3):191-6. [Article]
- Cynis H, Rahfeld JU, Stephan A, Kehlen A, Koch B, Wermann M, Demuth HU, Schilling S: Isolation of an isoenzyme of human glutaminyl cyclase: retention in the Golgi complex suggests involvement in the protein maturation machinery. J Mol Biol. 2008 Jun 20;379(5):966-80. doi: 10.1016/j.jmb.2008.03.078. Epub 2008 Apr 15. [Article]
- Huang KF, Liu YL, Cheng WJ, Ko TP, Wang AH: Crystal structures of human glutaminyl cyclase, an enzyme responsible for protein N-terminal pyroglutamate formation. Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13117-22. Epub 2005 Aug 31. [Article]
- Huang KF, Wang YR, Chang EC, Chou TL, Wang AH: A conserved hydrogen-bond network in the catalytic centre of animal glutaminyl cyclases is critical for catalysis. Biochem J. 2008 Apr 1;411(1):181-90. [Article]
- Ruiz-Carrillo D, Koch B, Parthier C, Wermann M, Dambe T, Buchholz M, Ludwig HH, Heiser U, Rahfeld JU, Stubbs MT, Schilling S, Demuth HU: Structures of glycosylated mammalian glutaminyl cyclases reveal conformational variability near the active center. Biochemistry. 2011 Jul 19;50(28):6280-8. doi: 10.1021/bi200249h. Epub 2011 Jun 27. [Article]
- Huang KF, Liaw SS, Huang WL, Chia CY, Lo YC, Chen YL, Wang AH: Structures of human Golgi-resident glutaminyl cyclase and its complexes with inhibitors reveal a large loop movement upon inhibitor binding. J Biol Chem. 2011 Apr 8;286(14):12439-49. doi: 10.1074/jbc.M110.208595. Epub 2011 Feb 1. [Article]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details 1-benzylimidazole experimental unknown target Details N-acetylhistamine experimental unknown target Details Glutamine t-butyl ester experimental unknown target Details Varoglutamstat investigational yes target inhibitor Details