VCP nuclear cofactor family member 1 (VCF1)

VCP nuclear cofactor family member 1 (VCF1, encoded by FAM104A) is a small, nuclear-localized cofactor that regulates the localization and function of the essential AAA+ ATPase p97/VCP. VCF1 binds directly and with high affinity to the N-domain of p97 via a conserved α-helical motif (VRM), and this interaction promotes p97’s nuclear import and its association with chromatin. VCF1 forms multi-component complexes with p97 and other cofactors such as UFD1-NPL4, facilitating the recruitment of p97 to ubiquitylated nuclear substrates targeted for proteasomal degradation. Through this role, VCF1 indirectly influences diverse processes dependent on nuclear p97, including DNA repair, regulation of DNA replication, and control of transcription. VCF1 itself is not an enzyme, receptor, or common drug target, and there are currently no drugs or biomarkers specific for it. It is best classified as an adaptor or cofactor protein within the ubiquitin-proteasome pathway.

Other names

FAM104AProtein VCF1FLJ14775Family with sequence similarity 104 member Aprotein FAM104A

Not applicable (VCF1 is not a direct therapeutic target; no known drugs directly target VCF1 as of current evidence)