This entry represents the AN1-type zinc finger domain, which has a dimetal (zinc)-bound α/β fold. This domain was first identified as a zinc finger at the C terminus of AN1 Q91889 a ubiquitin-like protein in Xenopus laevis [ PUBMED:8390387 … expand

This entry represents the AN1-type zinc finger domain, which has a dimetal (zinc)-bound α/β fold. This domain was first identified as a zinc finger at the C terminus of AN1 Q91889 a ubiquitin-like protein in Xenopus laevis [ PUBMED:8390387 ]. The AN1-type zinc finger contains six conserved cysteines and two histidines that could potentially coordinate 2 zinc atoms.

Certain stress-associated proteins (SAP) contain AN1 domain, often in combination with A20 zinc finger domains (SAP8) or C2H2 domains (SAP16) [ PUBMED:17033811 ]. 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 NFkappaB activation pathway and to interact with components of the immune response like RIP, IKKgamma and TRAF6. The interact of Znf216 with IKK-gamma and RIP is mediated by the A20 zinc-finger domain, while its interaction with TRAF6 is mediated by the AN1 zinc-finger domain; therefore, both zinc-finger domains are involved in regulating the immune response [ PUBMED:14754897 ]. The AN1 zinc finger domain is also found in proteins containing a ubiquitin-like domain, which are involved in the ubiquitination pathway [ PUBMED:8390387 ]. Proteins containing an AN1-type zinc finger include:

• Ascidian posterior end mark 6 (pem-6) protein [ PUBMED:9441682 ].
• Human AWP1 protein (associated with PRK1), which is expressed during early embryogenesis [ PUBMED:11054541 ].
• Human immunoglobulin mu binding protein 2 (SMUBP-2), mutations in which cause muscular atrophy with respiratory distress type 1 [ PUBMED:12547203 ].

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [ PUBMED:10529348 PUBMED:15963892 PUBMED:15718139 PUBMED:17210253 PUBMED:12665246 ]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few [ PUBMED:11179890 ]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.