NAGPA explained

N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase is an enzyme that in humans is encoded by the NAGPA gene.^{[1] [2] [3]}

Hydrolases are transported to lysosomes after binding to mannose 6-phosphate receptors in the trans-Golgi network. This gene encodes the enzyme that catalyzes the second step in the formation of the mannose 6-phosphate recognition marker on lysosomal hydrolases. Commonly known as 'uncovering enzyme' or UCE, this enzyme removes N-acetyl-D-glucosamine (GlcNAc) residues from GlcNAc-alpha-P-mannose moieties and thereby produces the recognition marker. This reaction most likely occurs in the trans-Golgi network. This enzyme functions as a homotetramer of two disulfide-linked homodimers. In addition to having an N-terminal signal peptide, the protein's C-terminus contains multiple signals for trafficking it between lysosomes, the plasma membrane, and trans-Golgi network.^[3]

To date, the only disorder in humans associated with this gene is Persistent Neurodevelopmental Stuttering (PNdS).^[4]

Further reading

• Lee JK, Pierce M . Purification and characterization of human serum N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase. . Arch. Biochem. Biophys. . 319 . 2 . 413–25 . 1995 . 7786023 . 10.1006/abbi.1995.1312 .
• Andersson B, Wentland MA, Ricafrente JY, etal . A "double adaptor" method for improved shotgun library construction. . Anal. Biochem. . 236 . 1 . 107–13 . 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Page T, Zhao KW, Tao L, Miller AL . Purification and characterization of human lymphoblast N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase. . Glycobiology . 6 . 6 . 619–26 . 1997 . 8922957 . 10.1093/glycob/6.6.619 . free .
• Yu W, Andersson B, Worley KC, etal . Large-scale concatenation cDNA sequencing. . Genome Res. . 7 . 4 . 353–8 . 1997 . 9110174 . 10.1101/gr.7.4.353. 139146 .
• Rohrer J, Kornfeld R . Rosalind Kornfeld. Lysosomal hydrolase mannose 6-phosphate uncovering enzyme resides in the trans-Golgi network. . Mol. Biol. Cell . 12 . 6 . 1623–31 . 2001 . 11408573 . 10.1091/mbc.12.6.1623. 37329 .
• Lee WS, Rohrer J, Kornfeld R, Kornfeld S . Rosalind Kornfeld. Stuart Kornfeld. Multiple signals regulate trafficking of the mannose 6-phosphate-uncovering enzyme. . J. Biol. Chem. . 277 . 5 . 3544–51 . 2002 . 11723124 . 10.1074/jbc.M108531200 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Nair P, Schaub BE, Huang K, etal . Characterization of the TGN exit signal of the human mannose 6-phosphate uncovering enzyme. . J. Cell Sci. . 118 . Pt 13 . 2949–56 . 2005 . 15976452 . 10.1242/jcs.02434 . free .

Notes and References

1. Kornfeld R, Bao M, Brewer K, Noll C, Canfield W . Rosalind Kornfeld. Molecular cloning and functional expression of two splice forms of human N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase . J Biol Chem . 274 . 46 . 32778–85 . Jan 2000 . 10551838 . 10.1074/jbc.274.46.32778 . free .
2. Do H, Lee WS, Ghosh P, Hollowell T, Canfield W, Kornfeld S . Human mannose 6-phosphate-uncovering enzyme is synthesized as a proenzyme that is activated by the endoprotease furin . J Biol Chem . 277 . 33 . 29737–44 . Aug 2002 . 12058031 . 10.1074/jbc.M202369200 . free .
3. Web site: Entrez Gene: NAGPA N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase.
4. Analysis of mannose 6-phosphate uncovering enzyme mutations associated with persistent stuttering. 2011. 21956109. Lee. W. S.. Kang. C.. Drayna. D.. Kornfeld. S.. The Journal of Biological Chemistry. 286. 46. 39786–93. 10.1074/jbc.M111.295899. 3220557. free.