H3TH domain of Exonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' nuclease; 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. Members of this subgroup include the H3TH (helix-3-turn-helix) domains of EXO1 and other similar eukaryotic 5' nucleases. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. These nucleases have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (Mg2+ or Mn2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one Asp residue from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119590510 173 EKFRYMCILSGCDYLSSLRGIGLAKACKVLRLANnpDIVKVIKKIGHYLKMniTVPEDYINGFIRANNTFLYQLVFD 249
Cdd:cd09908    1 EKFRHMCILSGCDYLPSLPGIGLKKAYKLVRRHR--TIEKVIKALRFDGKK--EVPPDYEEGFQKALLTFLHQRVFD 73

H3TH domain of Exonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' nuclease; 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. Members of this subgroup include the H3TH (helix-3-turn-helix) domains of EXO1 and other similar eukaryotic 5' nucleases. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. These nucleases have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (Mg2+ or Mn2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one Asp residue from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119590510 173 EKFRYMCILSGCDYLSSLRGIGLAKACKVLRLANnpDIVKVIKKIGHYLKMniTVPEDYINGFIRANNTFLYQLVFD 249
Cdd:cd09908    1 EKFRHMCILSGCDYLPSLPGIGLKKAYKLVRRHR--TIEKVIKALRFDGKK--EVPPDYEEGFQKALLTFLHQRVFD 73

Xeroderma pigmentosum G I-region; domain in nucleases

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119590510    98 RSQGVDCLVAPYEADAQLAYLNKAGIVQAIITEDSDLLAFGCKKVILKMDQFGN-GLEIDQARL-GMCRQLG 167
Cdd:smart00484   1 RLMGIPYIVAPYEAEAQCAYLAKSGLVDAIITEDSDLLLFGAPRLYRNLFFSGKkKLEFRIIDLeSVLKELG 72

DNA excision repair protein (rad2); All proteins in this family for which functions are known are flap endonucleases that generate the 3' incision next to DNA damage as part of nucleotide excision repair. This family is related to many other flap endonuclease families including the fen1 family. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119590510    57 QANLLKGKQLLREGKVSEAREcftrSINITHAMAHKVIKAARSQGVDCLVAPYEADAQLAYLNKAGIVQAIITEDSDLLA 136
Cdd:TIGR00600  745 EANLLAEQNSLKAQKQQQKRI----AAEVTGQMILESQELLRLFGIPYIVAPMEAEAQCAILDLLDQTSGTITDDSDIWL 820

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 119590510   137 FGCKKVILKMDQFGNGLEIDQArLGMCRQLGdvFTEEKFRYMCILSGCDYLSSLRGIGLAKACKVL 202
Cdd:TIGR00600  821 FGARHVYKNFFNQNKFVEYYQY-VDIHNQLG--LDRNKLINLAYLLGSDYTEGIPTVGPVSAMEIL 883

FEN-like PIN domains of Flap endonuclease-1 (FEN1)-like and exonuclease-1 (EXO1)-like nucleases, structure-specific, divalent-metal-ion dependent, 5' nucleases; PIN (PilT N terminus) domain of Flap endonuclease-1 (FEN1) and exonuclease-1 (EXO1)-like nucleases: FEN1, EXO1, Mkt1, Gap endonuclease 1 (GEN1) and Xeroderma pigmentosum complementation group G (XPG) nuclease. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119590510   6 LLQFIKEASEPIHVRKYKGQVVAVDTYCWLHKGAIACAEKLAKGEPTDRRRQANLLKGKQLLREGK----VSEARECFTR 81
Cdd:cd00128    1 LWQFIGEAKEPISIESLKGKTVAIDASIWVYQFLTAKREQGGDIGVTNSHLRGLFYRIIKLLSNGIkpifVFDGGPPPLK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119590510  82 SINITHAMAHKVIKAARSQGVDCLVAPYEADAQLAYLNKAGIVQAIITEDSDLLAFGCKKVILKMDQFG-NGLEIDQARL 160
Cdd:cd00128   81 KETITKKMYQECKHLLSLFGIPYVVAPYEAEAQCAYLLKAGIVDAAITEDSDCLLFGAPRVIRNMTFEGpHVEEFDASSI 160

                 ..
gi 119590510 161 GM 162
Cdd:cd00128  161 LE 162

XPG I-region;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119590510  101 GVDCLVAPYEADAQLAYLNKAGIVQAIITEDSDLLAFGCKKVILKMDQFGNG------LEIDQARlgMCRQLGdvFTEEK 174
Cdd:pfam00867   1 GIPYVVAPGEAEAQCAYLQKSGLVDAVISEDSDVLLFGAPRLLRNLTGKSKKkskvpvEEIDLEK--ILKELG--LTREQ 76

                          90
                  ....*....|.
gi 119590510  175 FRYMCILSGCD 185
Cdd:pfam00867  77 LIDLAILLGCD 87

Xeroderma pigmentosum G I-region; domain in nucleases

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119590510    98 RSQGVDCLVAPYEADAQLAYLNKAGIVQAIITEDSDLLAFGCKKVILKMDQFGN-GLEIDQARL-GMCRQLG 167
Cdd:smart00484   1 RLMGIPYIVAPYEAEAQCAYLAKSGLVDAIITEDSDLLLFGAPRLYRNLFFSGKkKLEFRIIDLeSVLKELG 72

H3TH domains of Flap endonuclease-1 (FEN1)-like structure specific 5' nucleases; The 5' nucleases within this family are capable of both 5'-3' exonucleolytic activity and cleaving bifurcated or branched DNA, in an endonucleolytic, structure-specific manner, and are involved in DNA replication, repair, and recombination. This family includes the H3TH (helix-3-turn-helix) domains of Flap Endonuclease-1 (FEN1), Exonuclease-1 (EXO1), Mkt1, Gap Endonuclease 1 (GEN1), Xeroderma pigmentosum complementation group G (XPG) nuclease, and other eukaryotic and archaeal homologs. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. With the except of the Mkt1-like proteins, the nucleases within this family have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (i. e., Mg2+, Mn2+, Zn2+, or Co2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one Asp residue from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119590510 173 EKFRYMCILSGCDYLSSLRGIGLAKACKVLRLAnnPDIVKVIKKIGHYLKMNitVPEDYINGFIRANNTFLY 244
Cdd:cd09897    1 EQFIDLCILSGCDYLPGLPGIGPKTALKLIKEY--GSLEKVLKALRDDKKDK--VPVPYDFPYKKARELFLH 68

FEN-like PIN domains of Xeroderma pigmentosum complementation group G (XPG) nuclease, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs; The Xeroderma pigmentosum complementation group G (XPG) nuclease plays a central role in nucleotide excision repair (NER) in cleaving DNA bubble structures or loops. XPG is a member 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119590510   2 GIQGLLQFIKEASEPIHVRKYKGQVVAVDTYCWLHKgAIAcAEKLAKGEPTDR-------RRqanLLKgkqLL------- 67
Cdd:cd09868    1 GVKGLWKLLEPTGRPVSLESLEGKVLAVDASIWLHQ-FVK-GMRDNEGNSVPNahllgffRR---ICK---LLfygikpv 72

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 119590510  68 --REGKVSEA-RECFTRSINITHAMAHKVIKAARSQGVDCLVAPYEADAQLAYLNKAGIVQAIITEDSDLLAFGCKKVI 143
Cdd:cd09868   73 fvFDGPAPALkRRTLARRRSVTDEMYEEIQELLRLFGIPYIVAPMEAEAQCAFLERLGLVDGVITDDSDVFLFGAKRVY 151

FEN-like PIN domains of Mkt1, a global regulator of mRNAs encoding mitochondrial proteins and eukaryotic homologs; The Mkt1 gene product interacts with the Poly(A)-binding protein associated factor, Pbp1, and is present at the 3' end of RNA transcripts during translation. The Mkt1-Pbp1 complex is involved in the post-transcriptional regulation of HO endonuclease expression. Mkt1 and eukaryotic homologs are atypical members of the structure-specific, 5' nuclease family (FEN-like). 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. Although Mkt1 appears to possess both a PIN and H3TH domain, the Mkt1 PIN domain lacks several of the active site residues necessary to bind essential divalent metal ion cofactors (Mg2+/Mn2+) required for nuclease activity in this family. Also, Mkt1 lacks the glycine-rich loop in the H3TH domain which is proposed to facilitate duplex DNA binding.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119590510  51 PTDRRRQANLLKGKQLLREGKVSEARECFTRSINI-THAMAHKVIKAARSQGVDCLVAPYEADAQLAYL--NKAGIVQAI 127
Cdd:cd09858   93 SQSEQAAQKREEAWDLYEKGQADQAVKAFGESGSYrLEDLYRLLQRILKERGVEFLVAPYSAWAQLAYLekHGKQYIDAI 172

                         90       100
                 ....*....|....*....|
gi 119590510 128 ITeDSDLLAFGCKKVILKMD 147
Cdd:cd09858  173 YG-STELLLFGVDKVITSID 191

FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs; Gap Endonuclease 1 (GEN1) is a Holliday junction resolvase reported to symmetrically cleave Holliday junctions and allow religation without additional processing. GEN1 is a member 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119590510   2 GIQGLLQFIKEASEPIHVRKYKGQVVAVDTYCW-----------------------------LHKGAI--------ACAE 44
Cdd:cd09869    1 GVKGLWTILDPVKKRKPLSELRGKTLAVDLSIWiceaqtvlalfetvpkphlrnlffrtvnlLRLGIKpvfvldgdAPEL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119590510  45 KLAkgepTDRRRQAnLLKGKQLLREGKVSEARECFTRSINITHAMAhkvikaaRSQGVDCLVAPYEADAQLAYLNKAGIV 124
Cdd:cd09869   81 KLQ----TIKKRNA-ARFGGAKKKGGSKKRGRSRFSRVLKECEELL-------ELLGVPVVQAPGEAEALCALLNAEGLV 148

                        170       180
                 ....*....|....*....|....*.
gi 119590510 125 QAIITEDSDLLAFGCKKVI--LKMDQ 148
Cdd:cd09869  149 DGCITNDGDAFLYGARTVYrnFSLNT 174

FEN-like PIN domains of Flap endonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs; Flap endonuclease-1 (FEN1) is involved in multiple DNA metabolic pathways, including DNA replication processes (5' flap DNA endonuclease activity and double stranded DNA 5'-exonuclease activity) and DNA repair processes (long-patch base excision repair) in eukaryotes and archaea. Interaction between FEN1 and PCNA (Proliferating cell nuclear antigen) is an essential prerequisite to FEN1's DNA replication functionality and stimulates FEN1 nuclease activity by 10-50 fold. FEN1 belongs to the FEN1-EXO1-like subfamily of structure-specific, 5' nucleases (FEN-like family). 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. FEN1 has a C-terminal extension containing residues forming the consensus PIP-box - Qxx(M/L/I)xxF(Y/F) which serves to anchor FEN1 to PCNA.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119590510  55 RRQANLLKGKQLLREGKVSEARECFTRSINITHAMAHKVIKAARSQGVDCLVAPYEADAQLAYLNKAGIVQAIITEDSDL 134
Cdd:cd09867   95 RREEAEEKLEEALEEGDLEEARKYAKRTVRVTKEMVEEAKKLLDLMGIPYVQAPSEGEAQAAYLVKKGDVYAVASQDYDS 174

                 ....*....
gi 119590510 135 LAFGCKKVI 143
Cdd:cd09867  175 LLFGAPRLV 183

H3TH domains of structure-specific 5' nucleases (or flap endonuclease-1-like) involved in DNA replication, repair, and recombination; The 5' nucleases of this superfamily are capable of both 5'-3' exonucleolytic activity and cleaving bifurcated or branched DNA, in an endonucleolytic, structure-specific manner, and are involved in DNA replication, repair, and recombination. The superfamily includes the H3TH (helix-3-turn-helix) domains of Flap Endonuclease-1 (FEN1), Exonuclease-1 (EXO1), Mkt1, Gap Endonuclease 1 (GEN1) and Xeroderma pigmentosum complementation group G (XPG) nuclease. Also included are the H3TH domains of the 5'-3' exonucleases of DNA polymerase I and single domain protein homologs, as well as, the bacteriophage T4 RNase H, T5-5'nuclease, and other homologs. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the C-terminal region of the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. Typically, the nucleases within this superfamily have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (i. e., Mg2+, Mn2+, Zn2+, or Co2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one or two Asp residues from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119590510 173 EKFRYMCILSGCDYL--SSLRGIG----LAKACKVLRLANNPDIVKVIKKIghyLKMNITVPEDYINGFIRA 238
Cdd:cd00080    1 EQFIDLCALVGCDYSdnPGVPGIGpktaAKLALKYGSLEGILENLDELKGK---KREKLEEPKEYAFLSRKL 69

FEN-like PIN domains of structure-specific 5' nucleases (or Flap endonuclease-1-like) involved in DNA replication, repair, and recombination; Structure-specific 5' nucleases are capable of both 5'-3' exonucleolytic activity and cleaving bifurcated or branched DNA, in an endonucleolytic, structure-specific manner. The family includes the PIN (PilT N terminus) domains of Flap endonuclease-1 (FEN1), exonuclease-1 (EXO1), Mkt1, Gap Endonuclease 1 (GEN1), and Xeroderma pigmentosum complementation group G (XPG) nuclease. Also included are the PIN domains of the 5'-3' exonucleases of DNA polymerase I and single domain protein homologs, as well as, the bacteriophage T4- and T5-5' nucleases, and other homologs. Canonical members of this 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119590510  43 AEKLAKGEPTDRRRQANLLKGKQllrEGKVSEARECFTRSINITHAMAHKVIKAARSQ-GVDCLVAPYEADAQLAYLNKA 121
Cdd:cd09853   54 KPKAKKGNRDKRRERRAREEDRK---KGQLKEHKEFDKRLIELGPEYLIRLFELLKHFmGIPVMDAPGEAEDEIAYLVKK 130

                         90       100       110
                 ....*....|....*....|....*....|.
gi 119590510 122 ----GIVQAIITEDSDLLAFG--CKKVILKM 146
Cdd:cd09853  131 hkhlGTVHLIISTDGDFLLLGtdHPYIPRNL 161

Helix-hairpin-helix class 2 (Pol1 family) motifs;

                           10        20        30
                   ....*....|....*....|....*....|...
gi 119590510   173 EKFRYMCILSG--CDYLSSLRGIGLAKACKVLR 203
Cdd:smart00279   2 EQFIDYAILVGdySDNIPGVKGIGPKTALKLLR 34