cl14812

PIN (PilT N terminus) domain: Superfamily; PIN_SF The PIN (PilT N terminus) domain belongs to a large nuclease superfamily with representatives from eukaryota, eubacteria, and archaea. PIN domains were originally named for their sequence similarity to the N-terminal domain of an annotated pili biogenesis protein, PilT, a domain fusion between a PIN-domain and a PilT ATPase domain. The structural properties of the PIN domain indicate its putative active center, consisting of invariant acidic amino acid residues (putative metal-binding residues) is geometrically similar in the active center of structure-specific 5' nucleases (also known as Flap endonuclease-1-like), PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons. Seen here, are two major divisions in the PIN domain superfamily. The first major division, the structure-specific 5' nuclease family, is represented by FEN1, the 5'-3' exonuclease of DNA polymerase I, and T4 RNase H nuclease PIN domains. These 5' nucleases are involved in DNA replication, repair, and recombination. They are capable of both 5'-3' exonucleolytic activity and cleaving bifurcated DNA, in an endonucleolytic, structure-specific manner. Unique to FEN1-like nucleases, the PIN domain has a helical arch/clamp region (I domain) of variable length (approximately 16 to 800 residues) and, inserted within the C-terminal region of the PIN domain, a H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region. Both the H3TH domain (not included here) and the helical arch/clamp region are involved in DNA binding. With the exception of Mkt1, these nucleases have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (Mg2+, Mn2+, Zn2+, or Co2+). The second major division of the PIN domain superfamily, the VapC-Smg6 family, includes such eukaryotic ribonucleases as, Smg6, an essential factor in nonsense-mediated mRNA decay; Rrp44, the catalytic subunit of the exosome; and Nob1, a ribosome assembly factor critical in pre-rRNA processing. A large percentage of members in this family are bacterial ribonuclease toxins of TA operons such as Mycobacterium tuberculosis VapC and Neisseria gonorrhoeae FitB, as well as, archaeal homologs, Pyrobaculum aerophilum Pea0151 and P. aerophilum Pae2754. Also included are the eukaryotic Fcf1/ Utp24 (FAF1-copurifying factor 1/U three-associated protein 24) and Utp23-like proteins. Components of the small subunit processome, Fcf1/Utp24 and Utp23 are essential proteins involved in pre-rRNA processing and 40S ribosomal subunit assembly.