Title : Cytoplasmic O-GlcNAc modification of the head
domain and the KSP repeat motif of the neurofilament protein neurofilament-H
Abstract :
- Neurofilaments, the major intermediate filaments in large myelinated neurons, are essential for specifying proper axonal caliber
- Mammalian neurofilaments are obligate heteropolymers assembled from three polypeptides , neurofilament (NF)-H , NF-M , and NF-L , each of which undergoes phosphorylation at multiple sites
- NF-M and NF-L are known to be modified by O-linked N-acetylglucosamine (O-GlcNAc) (Dong, D. L.-Y., Xu, Z.-S., Chevrier, M. R., Cotter, R. J., Cleveland, D. W., and Hart , G. W. (1993) J. Biol
- Chem
- 268, 16679-16687)
- Here we further report that NF-H is extensively modified by O-GlcNAc at Thr53, Ser54, and Ser56 in the head domain and, somewhat surprisingly, at multiple sites within the Lys-Ser-Pro repeat motif in the tail domain , a region in assembled neurofilaments known to be nearly stoichiometrically phosphorylated on each of the approximately 50 KSP repeats
- Beyond the earlier identified sites on NF-M and NF-L , O-GlcNAc sites on Thr19 and Ser34 of NF-M and Ser34 and Ser48 of NF-L are also determined here, all of which are localized in head domain sequences critical for filament assembly
- The proximity of O-GlcNAc and phosphorylation sites in both head and tail domains of each subunit indicates that these modifications may influence one another and play a role in filament assembly and network formation
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. domain, , -, Cytoplasmic O-GlcNAc modification, domain
- 0. modification, , -, Cytoplasmic O-GlcNAc modification, domain
- 0. motif, , -, Cytoplasmic O-GlcNAc modification, -
- 3. modified, , NF-L, O-GlcNAc, -
- 3. modified, , NF-L, O-linked N-acetylglucosamine, -
- 3. modified, , NF-M, O-GlcNAc, -
- 3. modified, , NF-M, O-linked N-acetylglucosamine, -
- 6. modified, , NF-H, O-GlcNAc, -
- 6. motif, , -, a region, region
- 6. motif, , -, the tail domain, domain
- 7. localized, , -, all, sequences
- 7. sites, , -, Ser34, Thr19 and Ser34
- 7. sites, , -, Ser48, Ser34 and Ser48
- 7. sites, , -, Thr19, Thr19 and Ser34
Output(Part-Of) (sent_index,
protein,
site):
- 2. neurofilament (NF)-H, polypeptides
- 7. NF-L, Ser34 and Ser48
- 7. NF-L, Thr19 and Ser34
- 7. NF-L, sites
- 7. NF-M, Ser34 and Ser48
- 7. NF-M, Thr19 and Ser34
- 7. NF-M, sites
- 8. subunit, domains
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):
- 7. NF-L, Ser34, Thr19 and Ser34
- 7. NF-L, Ser48, Ser34 and Ser48
- 7. NF-L, Thr19, Thr19 and Ser34