|Protein Name||Carboxypeptidase Q|
|Ref Sequence Id||NP_001069716.1|
|Amino Acid Lenth||472|
|Protein Existence Status||Reviewed: Experimental evidence at transcript level|
|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|
|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.