Primary Information
BoMiProt ID	Bomi139
Protein Name	Carboxypeptidase Q
Organism	Bos taurus
Uniprot ID	Q17QK3
Milk Fraction	Whey
Ref Sequence ID	NP_001069716.1
Aminoacid Length	472
Molecular Weight	51679
FASTA Sequence	Download
Gene Name	CPQ
Gene ID	540923
Protein Existence Status	Reviewed: Experimental evidence at transcript level
Secondary Information
Presence in other biological fluids/tissue/cells	highest expression levels found in the nervous and prostatic tissue;
Protein Function	membrane-bound binuclear zinc metallopeptidase ; involved in the neuron-neuron and neuron-glia signaling via the hydrolysis of N-acetylaspartylglutamate (NAAG); facilitate integrin signaling in epithelial cells; associated with the anaphase promoting complex in prostate cancer cells; activate the NF-κB signaling pathway promoting cell proliferation; plays an important role in folate absorption in humans
Biochemical Properties	type II transmembrane proteins having a short N-terminal cytoplasmic tail (amino acids 1 – 18), a single membrane-spanning helix (amino acids 19 – 43) and a large extracellular part (amino acids 44 – 750); extracellular portion of GCPII homodimerizes for hydrolytic activity; require zinc ions for proteolytic activity; potent inhibitors - 2-(phosphonomethyl)pentanedioic acid, 2-(3-mercaptopropyl) pentanedioic acid and zinc- binding group
Significance in milk	belong to the protease system in milk
PTMs	heavily N- and Oglycosylated - ten N-glycosylation sites predicted within the primary sequence of human GCPII
Site(s) of PTM(s) N-glycosylation, O-glycosylation, Phosphorylation
Predicted Disorder Regions	NA
DisProt Annotation
TM Helix Prediction	No TM helices
Significance of PTMs	N-glycosylation is indispensable for GCPII enzymatic activity and stability; glycosylation of the protein is implicated in apical sorting, proteolytic resistance and its association with lipid rafts
Bibliography	1. Barinka, C., Sácha, P., Sklenár, J., Man, P., Bezouska, K., Slusher, B. S., & Konvalinka, J. (2004). Identification of the N-glycosylation sites on glutamate carboxypeptidase II necessary for proteolytic activity. Protein Science : A Publication of the Protein Society, 13(6), 1627–1635. https://doi.org/10.1110/ps.04622104. 2. Schülke, N., Varlamova, O. A., Donovan, G. P., Ma, D., Gardner, J. P., Morrissey, D. M., … Olson, W. C. (2003). The homodimer of prostate-specific membrane antigen is a functional target for cancer therapy. Proceedings of the National Academy of Sciences of the United States of America, 100(22), 12590–12595. https://doi.org/10.1073/pnas.1735443100. 3. Barinka, C., Rinnová, M., Sácha, P., Rojas, C., Majer, P., Slusher, B. S., & Konvalinka, J. (2002). Substrate specificity, inhibition and enzymological analysis of recombinant human glutamate carboxypeptidase II. Journal of Neurochemistry, 80(3), 477–487. https://doi.org/10.1046/j.0022-3042.2001.00715. 4. Kozikowski, A. P., Zhang, J., Nan, F., Petukhov, P. A., Grajkowska, E., Wroblewski, J. T., … Neale, J. H. (2004). Synthesis of urea-based inhibitors as active site probes of glutamate carboxypeptidase II: efficacy as analgesic agents. Journal of Medicinal Chemistry, 47(7), 1729–1738. https://doi.org/10.1021/jm0306226. 5. Jackson, P. F., Cole, D. C., Slusher, B. S., Stetz, S. L., Ross, L. E., Donzanti, B. A., & Trainor, D. A. (1996). Design, synthesis, and biological activity of a potent inhibitor of the neuropeptidase N-acetylated alpha-linked acidic dipeptidase. Journal of Medicinal Chemistry, 39(2), 619–622. https://doi.org/10.1021/jm950801q.