# NSFL1C

## Overview
The NSFL1C gene encodes the NSFL1 cofactor, commonly referred to as p47, which is a crucial component of the ubiquitin-proteasome system. As a member of the UBX domain protein family, p47 plays a significant role in cellular processes such as protein degradation and membrane fusion by interacting with the AAA ATPase p97/VCP. This interaction is mediated through the UBX domain and is essential for the regulation of protein degradation pathways (Schuberth2008UBX). The p47 protein is characterized by a central SEP domain that facilitates trimerization and a carboxy-terminal UBX domain that binds to p97. Additionally, p47 contains a unique SHP box motif, which is shared with other proteins involved in ER-associated protein degradation, highlighting its role in maintaining protein homeostasis (Blythe2017Ubiquitin).

## Structure


## Function


## Clinical Significance


## Interactions
The NSFL1C gene encodes the p47 protein, which is a member of the UBX domain protein family. p47 interacts with the AAA ATPase p97/VCP, a key player in various cellular processes, including protein degradation and membrane fusion. p47 contains a central SEP domain involved in trimerization and a carboxy-terminal UBX domain, which facilitates its binding to the N domain of p97. This interaction is crucial for p47's role in the ubiquitin-proteasome system, where it may influence protein degradation pathways (Schuberth2008UBX).

p47 also features a second p97-binding site at the carboxy-terminal end of the SEP domain, known as the FxGzGQxb motif or SHP box. This motif is shared with other Cdc48/p97-interacting proteins, such as the Ufd1 subunit of the Ufd1-Npl4 cofactor complex, and members of the Derlin membrane protein family, which are involved in ER-associated protein degradation (Schuberth2008UBX).

The interaction of NSFL1C with p97 is mutually exclusive with the NPLOC4•UFD1L complex, suggesting that NSFL1C may promote protein segregation through different mechanisms. However, NSFL1C cannot replace NPLOC4•UFD1L in certain unfolding assays, indicating distinct substrate or pathway specificity (Blythe2017Ubiquitin).


## References


[1. (Blythe2017Ubiquitin) Emily E. Blythe, Kristine C. Olson, Vincent Chau, and Raymond J. Deshaies. Ubiquitin- and atp-dependent unfoldase activity of p97/vcp•nploc4•ufd1l is enhanced by a mutation that causes multisystem proteinopathy. Proceedings of the National Academy of Sciences, May 2017. URL: http://dx.doi.org/10.1073/pnas.1706205114, doi:10.1073/pnas.1706205114. This article has 143 citations.](https://doi.org/10.1073/pnas.1706205114)

[2. (Schuberth2008UBX) C. Schuberth and A. Buchberger. Ubx domain proteins: major regulators of the aaa atpase cdc48/p97. Cellular and Molecular Life Sciences, 65(15):2360–2371, April 2008. URL: http://dx.doi.org/10.1007/s00018-008-8072-8, doi:10.1007/s00018-008-8072-8. This article has 235 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1007/s00018-008-8072-8)