Literature summary extracted from

Logtenberg, M.E.W.; Jansen, J.H.M.; Raaben, M.; Toebes, M.; Franke, K.; Brandsma, A.M.; Matlung, H.L.; Fauster, A.; Gomez-Eerland, R.; Bakker, N.A.M.; van der Schot, S.; Marijt, K.A.; Verdoes, M.; Haanen, J.B.A.G.; van den Berg, J.H.; Neefjes, J.; van den Berg, T.K.; Brummelkamp, T.R.; Leusen, J.H.W.; Scheeren, F.A.; Schumacher, T.N.
Glutaminyl cyclase is an enzymatic modifier of the CD47-SIRPalpha axis and a target for cancer immunotherapy (2019), Nat. Med., 25, 612-619 .

Application

EC Number	Application	Comment	Organism
2.3.2.5	pharmacology	the glutaminyl-peptide cyclotransferase-like protein (QPCTL) is a target to interfere with the CD47 pathway and thereby augment antibody therapy of cancer	Homo sapiens

Inhibitors

EC Number	Inhibitors	Comment	Organism	Structure
2.3.2.5	SEN177	-	Homo sapiens

Localization

EC Number	Localization	Comment	Organism	GeneOntology No.	Textmining
2.3.2.5	cell surface	-	Homo sapiens	9986	-
2.3.2.5	Golgi apparatus	-	Homo sapiens	5794	-

Natural Substrates/ Products (Substrates)

EC Number	Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
2.3.2.5	L-glutaminyl-peptide	Homo sapiens	-	5-oxoprolyl-peptide + NH3	-	?

Organism

EC Number	Organism	UniProt	Comment	Textmining
2.3.2.5	Homo sapiens	Q9NXS2	-	-

Source Tissue

EC Number	Source Tissue	Comment	Organism	Textmining
2.3.2.5	A-375 cell	-	Homo sapiens	-
2.3.2.5	A-431 cell	-	Homo sapiens	-
2.3.2.5	A-549 cell	-	Homo sapiens	-
2.3.2.5	carcinoma cell	-	Homo sapiens	-
2.3.2.5	colorectal cancer cell	-	Homo sapiens	-
2.3.2.5	DLD-1 cell	-	Homo sapiens	-
2.3.2.5	HAP-1 cell	-	Homo sapiens	-
2.3.2.5	lung cancer cell	-	Homo sapiens	-
2.3.2.5	marrow cell	-	Homo sapiens	-
2.3.2.5	melanoma cell	-	Homo sapiens	-
2.3.2.5	rectal cancer cell	-	Homo sapiens	-
2.3.2.5	RKO cell	-	Homo sapiens	-
2.3.2.5	squamous cell carcinoma cell	-	Homo sapiens	-

Substrates and Products (Substrate)

EC Number	Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
2.3.2.5	L-glutaminyl-peptide	-	Homo sapiens	5-oxoprolyl-peptide + NH3	-	?

Synonyms

EC Number	Synonyms	Comment	Organism
2.3.2.5	glutaminyl-peptide cyclotransferase-like protein	-	Homo sapiens
2.3.2.5	Golgi-resident enzyme	-	Homo sapiens
2.3.2.5	isoQC	-	Homo sapiens
2.3.2.5	QPCTL	-	Homo sapiens

General Information

EC Number	General Information	Comment	Organism
2.3.2.5	malfunction	glutaminyl cyclase inhibitors alter the CD47 protein by inhibiting QPCTL function and the resulting block in pGlu-modified CD47 is nearly complete. The expansion, differentiation, cytokine production and killing capacity of human T cells is compatible with small molecule inhibition of QPCTL. But QPCTL deficiency and QPCTL inhibition enhance tumor cell control by tumor-specific antibodies	Homo sapiens
2.3.2.5	metabolism	the activity of myeloid cells such as macrophages and neutrophils is likewise regulated by a balance between stimulatory and inhibitory signals. In particular, cell surface expression of the CD47 protein creates a 'don't eat me' signal on tumor cells by binding to SIRPalpha expressed on myeloid cells. CD47 is a broadly expressed inhibitory ligand for myeloid cells. The glutaminyl-peptide cyclotransferase-like protein (QPCTL) is a major component of the CD47-SIRPalpha checkpoint. Interference with QPCTL expression leads to a major increase in neutrophil-mediated killing of tumor cells in vivo. Diglutamate formation occurs early in the CD47 protein life cycle and fully depends on QPCTL. Synergy between blockade of CD47 diglutamate formation and tumor opsonization in tumor cell killing by macrophages and neutrophils	Homo sapiens
2.3.2.5	physiological function	the glutaminyl-peptide cyclotransferase-like protein (QPCTL) is a Golgi-resident enzyme that, like its secreted family member QPCT, can catalyze the cyclization of N-terminal glutamine and glutamic acid residues on target proteins into an N-terminal pyroglutamate residue (pGlu). QPCTL is a major component of the CD47-SIRPalpha checkpoint. Diglutamate formation occurs early in the CD47 protein life cycle and fully depends on QPCTL. QPCTL is critical for diglutamate formation on CD47 at the SIRPalpha binding site shortly after biosynthesis. QPCTL is a modulator of CD47-SIRPalpha binding. Genetic and pharmacological interference with QPCTL activity enhances antibody-dependent cellular phagocytosis and cellular cytotoxicity of tumor cells. Interference with QPCTL expression leads to a major increase in neutrophil-mediated killing of tumor cells in vivo	Homo sapiens