PIN (PilT N terminus) domain: Superfamily; The PIN (PilT N terminus) domain belongs to a large nuclease superfamily, and 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 active center, consisting of three highly conserved catalytic residues which coordinate metal ions; in some members, additional metal coordinating residues can be found while some others lack several of these key catalytic residues. The PIN active site is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons. The PIN domain superfamily includes: the FEN-like PIN domain family such as the PIN domains of Flap endonuclease-1 (FEN1), exonuclease-1 (EXO1), Mkt1, Gap Endonuclease 1 (GEN1), and Xeroderma pigmentosum complementation group G (XPG) nuclease, 5'-3' exonucleases of DNA polymerase I and bacteriophage T4- and T5-5' nucleases; the VapC-like PIN domain family which includes toxins of prokaryotic toxin/antitoxin operons FitAB and VapBC, as well as eukaryotic ribonucleases such as Smg6, ribosome assembly factor NOB1, exosome subunit Rrp44 endoribonuclease and rRNA-processing protein Fcf1; the LabA-like PIN domain family which includes the PIN domains of Synechococcus elongatus LabA (low-amplitude and bright); the PRORP-Zc3h12a-like PIN domain family which includes the PIN domains of RNase P (PRORP), ribonuclease Zc3h12a; and Bacillus subtilis YacP/Rae1-like PIN domains. It also includes the Mut7-C PIN domain family, which is not represented here as it is a shortened version of the PIN fold and lacks a core strand and helix (H3 and S3). The Mut7-C PIN domain family includes the C-terminus of Caenorhabditis elegans exonuclease Mut-7.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469987  28 IVIDGYALFHRLCFSSNLDLR-YGGDYDSFADVVQKFFESLFACNICPYVVLDGGCDISDKKLTTLKDRAREKIQMAHSL 106
Cdd:cd18676   1 LVIDGNNLCYQLYFDSNLDNSaFGGDYDKYARVVREFFELLSKCNVTPYVILDGGYEDRKLKTVTSRLRAKIKIAKAKTP 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33469987 107 SVGGSGYVCPLLIREVFIQVLIKLRVCFVQCFSEADRDIMTLANHWNCPVLSSDSDFCIFDlkTGFCPLNSFQWR 181
Cdd:cd18676  81 STGGSGSILPLLLKEVFVDVLKELNVKVVQCDFEADDEIAALARKLNCPVLSYDSDFYIFD--VLYIPFSTVQWN 153

FEN-like PIN domain of Drosophila melanogaster asteroid and related proteins; This subfamily includes Drosophila melanogaster asteroid protein which may function in EGF receptor signaling, and may play a role in compound eye morphogenesis. This subfamily belongs to the structure-specific, 5' nuclease family (FEN-like) that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. Canonical members of the FEN-like family possess a PIN domain with a two-helical structure insert (also known as the helical arch, helical clamp or I domain) of variable length (approximately 16 to 800 residues), the helical arch/clamp region is involved in DNA binding. The PIN domain belongs to a large nuclease superfamily. 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, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469987  28 IVIDGYALFHRLCFSSNLDLR-YGGDYDSFADVVQKFFESLFACNICPYVVLDGGCDISDKKLTTLKDRAREKIQMAHSL 106
Cdd:cd18676   1 LVIDGNNLCYQLYFDSNLDNSaFGGDYDKYARVVREFFELLSKCNVTPYVILDGGYEDRKLKTVTSRLRAKIKIAKAKTP 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33469987 107 SVGGSGYVCPLLIREVFIQVLIKLRVCFVQCFSEADRDIMTLANHWNCPVLSSDSDFCIFDlkTGFCPLNSFQWR 181
Cdd:cd18676  81 STGGSGSILPLLLKEVFVDVLKELNVKVVQCDFEADDEIAALARKLNCPVLSYDSDFYIFD--VLYIPFSTVQWN 153

FEN-like PIN domain of Drosophila melanogaster asteroid and related proteins; This subfamily includes Drosophila melanogaster asteroid protein which may function in EGF receptor signaling, and may play a role in compound eye morphogenesis. This subfamily belongs to the structure-specific, 5' nuclease family (FEN-like) that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. Canonical members of the FEN-like family possess a PIN domain with a two-helical structure insert (also known as the helical arch, helical clamp or I domain) of variable length (approximately 16 to 800 residues), the helical arch/clamp region is involved in DNA binding. The PIN domain belongs to a large nuclease superfamily. 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, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469987  28 IVIDGYALFHRLCFSSNLDLR-YGGDYDSFADVVQKFFESLFACNICPYVVLDGGCDISDKKLTTLKDRAREKIQMAHSL 106
Cdd:cd18676   1 LVIDGNNLCYQLYFDSNLDNSaFGGDYDKYARVVREFFELLSKCNVTPYVILDGGYEDRKLKTVTSRLRAKIKIAKAKTP 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33469987 107 SVGGSGYVCPLLIREVFIQVLIKLRVCFVQCFSEADRDIMTLANHWNCPVLSSDSDFCIFDlkTGFCPLNSFQWR 181
Cdd:cd18676  81 STGGSGSILPLLLKEVFVDVLKELNVKVVQCDFEADDEIAALARKLNCPVLSYDSDFYIFD--VLYIPFSTVQWN 153

FEN-like PIN domains of Exonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs; exonuclease-1 (EXO1) is involved in multiple, eukaryotic DNA metabolic pathways, including DNA replication processes (5' flap DNA endonuclease activity and double stranded DNA 5'-exonuclease activity), DNA repair processes (DNA mismatch repair (MMR) and post-replication repair (PRR)), recombination, and telomere integrity. EXO1 functions in the MMS2 error-free branch of the PRR pathway in the maintenance and repair of stalled replication forks. Studies also suggest that EXO1 plays both structural and catalytic roles during MMR-mediated mutation avoidance. These nucleases are members of the structure-specific, 5' nuclease family (FEN-like) that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. Canonical members of the FEN-like family possess a PIN domain with a two-helical structure insert (also known as the helical arch, helical clamp or I domain) of variable length (approximately 16 to 800 residues), and at the C-terminus 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 in this model) and the helical arch/clamp region are involved in DNA binding. The PIN domain belongs to a large nuclease superfamily. 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, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons. EXO1 nucleases also have C-terminal Mlh1- and Msh2-binding domains which allow interaction with MMR and PRR proteins, respectively.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469987   1 MGIRGLMSFVED-----HSNEFftdlklRDTKIVIDGYALFHRLCFSSNLDLRYGGDYDSFADVVQKFFESLFACNICPY 75
Cdd:cd09857   1 MGIQGLLPFLKPiqrpvHISEY------AGKTVAVDAYCWLHRGAYSCAEELALGKPTDKYIDYCMKRVNMLLHHGITPI 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33469987  76 VVLDgGCDISDKKLTTLKDRAR--EKIQMAHSL---------------SVGgsgyVCPLLIREVfIQVLIKLRV-CFVQC 137
Cdd:cd09857  75 LVFD-GAPLPSKAGTEEERRERreEALEKALELlregkksearecfqrAVD----ITPEMAHEL-IKALRKENVeYIVAP 148

                ....*
gi 33469987 138 FsEAD 142
Cdd:cd09857 149 Y-EAD 152