Zinc finger AN1-type containing protein 5 (ZFAND5)

Zinc finger AN1-type containing protein 5 (ZFAND5) is a cytoplasmic protein characterized by AN1- and A20-type zinc finger domains[1][3][4]. It acts as an **activator of the 26S proteasome**, facilitating the degradation of ubiquitinated proteins and short peptides, and is essential for efficient global protein breakdown, particularly during skeletal muscle atrophy[1][2][3][4]. ZFAND5 binds both ubiquitin and proteasomes, functioning as an adapter or “shuttling factor” that anchors ubiquitinated substrates to the proteasome for degradation[4]. It is not itself a ubiquitin ligase or deubiquitinase and does not act in response to proteotoxic stress but is strongly upregulated during muscle wasting[4]. Additionally, ZFAND5 inhibits NF-κB activation (in response to TNF, IL-1, and TLR4) and sensitizes cells to apoptosis, pointing to roles in inflammation, immunity, and cell death pathways[3]. It is also a potent inhibitory factor for osteoclast differentiation[3]. ZFAND5 is highly expressed in heart and brain and upregulated in muscle during atrophy[1][2][4]. Mice lacking ZFAND5 show resistance to muscle atrophy, underscoring its significance in muscle protein catabolism[1][4].\n\nNo approved drugs directly target ZFAND5, but its modulatory effects on the proteasome and signaling pathways make it a potential therapeutic target for muscle wasting, cancer, and inflammatory conditions[3][4].

Other names

AN1-type zinc finger protein 5ZFAND5ZA20D2ZNF216ZFAND5AZinc finger A20 domain-containing protein 2Zinc finger protein 216zinc finger, A20 domain containing 2zinc finger, AN1-type domain 5

Enhancement of proteasome-mediated degradation of ubiquitinated proteins; Modulation of NF-κB activation; Sensitization to TNF-induced apoptosis