Family with sequence similarity 111 member A (FAM111A) (FAM111A)

Family with sequence similarity 111 member A (FAM111A) is an intracellular serine protease that plays essential roles in facilitating DNA replication through protein obstacles such as trapped topoisomerase I-DNA complexes and DNA-protein crosslinks and in restricting replication of certain viruses. FAM111A localizes to nascent DNA at replication forks via a PCNA-interacting peptide (PIP) box and contains a C-terminal trypsin/chymotrypsin-like serine protease domain critical for its activity. Dimerization through its SPD α-helix is required for maximal protease activity and DNA replication functions. Missense mutations in FAM111A cause rare genetic disorders with developmental defects (e.g., Kenny–Caffey syndrome, osteocraniostenosis) due to gain-of-function effects that hyperactivate the enzyme, leading to suppression of DNA replication, transcription, and pro-apoptotic signaling. FAM111A is also implicated in host antiviral defense through interaction with and restriction of viral protein complexes. No drugs are currently known to directly modulate FAM111A, but loss or excess protease activity is associated with disease, making it a potential, though challenging, therapeutic target [1][3][4][5].

Other names

Serine protease FAM111AKIAA1895FLJ22794GCLEBKCS2FAM111 trypsin-like peptidase A

Not applicable, since no direct FAM111A-targeting drugs are known. Theoretically, a serine protease inhibitor could inhibit its enzymatic activity; in vitro inhibition by AEBSF (a generic serine protease inhibitor) has been demonstrated [4]