The Zinc Finger, AN1-Type Domain 1 (ZFAND1) is a protein coding gene that plays a significant role in various biological processes. This domain is part of the larger family of zinc finger proteins, which are characterized by their finger-like DNA binding domains. Zinc finger proteins are the largest family of transcription factors in the human genome and are involved in gene regulation, protein degradation, and immune response regulation .
The AN1-type zinc finger domain has a dimetal (zinc)-bound alpha/beta fold. It contains six conserved cysteines and two histidines that coordinate two zinc atoms. This domain was first identified at the C terminus of AN1, a ubiquitin-like protein in Xenopus laevis . The AN1-type zinc finger domain is often found in combination with other domains, such as the A20 zinc finger domain, and is involved in various cellular processes, including the regulation of the NF-kappaB activation pathway and interactions with components of the immune response .
Proteins containing the AN1-type zinc finger domain are involved in the ubiquitination pathway, which is crucial for protein degradation. For example, the human protein Znf216 has an A20 zinc-finger at the N terminus and an AN1 zinc-finger at the C terminus, acting to negatively regulate the NF-kappaB activation pathway and interact with immune response components like RIP, IKKgamma, and TRAF6 . The AN1-type zinc finger domain is also found in proteins involved in muscle atrophy and apoptosis .
Mutations in genes encoding AN1-type zinc finger domains have been associated with various diseases. For instance, mutations in the human immunoglobulin mu binding protein 2 (SMUBP-2), which contains an AN1-type zinc finger domain, cause muscular atrophy with respiratory distress type 1 . Additionally, the ZFAND1 gene is associated with conditions such as spastic paraplegia 53, autosomal recessive, and cataract 39, multiple types .