VapC-like PIN domain of yeast exosome subunit Rrp44 endoribonuclease and other eukaryotic homologs; PIN (PilT N terminus) domain of the Saccharomyces cerevisiae exosome subunit Rrp44 (Ribosomal RNA-processing protein 44 or Protein Dis3 homolog) and other similar eukaryotic homologs are included in this family. The eukaryotic exosome is a conserved macromolecular complex responsible for many RNA-processing and RNA-degradation reactions. It is composed of nine core subunits that directly binds Rrp44. The Rrp44 nuclease is the catalytic subunit of the exosome and has endonuclease activity in the PIN domain and an exoribonuclease activity in its RNase II-like region. Rrp44 binding to the exosome is mediated mainly by the PIN domain and by subunits Rrp41-Rrp45, and binding predictions indicate that the PIN domain active site is positioned on the outer surface of the exosome. This subgroup belongs to the VapC (virulence-associated protein C)-like family of the PIN domain nuclease superfamily. VapC is the PIN-domain ribonuclease toxin from prokaryotic VapBC toxin-antitoxin (TA) systems. VapB is a transcription factor-like protein antitoxin acting as an inhibitor. Other members of the VapC-like nuclease family include FitB toxin of the FitAB TA system, eukaryotic ribonucleases such as Smg6, ribosome assembly factor NOB1, exosome subunit Rrp44 endoribonuclease and rRNA-processing protein Fcf1. The structural properties of the PIN (PilT N terminus) 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. Some members of the superfamily lack several of these key catalytic residues. PIN domains within this subgroup contain four of these residues which cluster at the C-terminal end of the beta-sheet and form a negatively charged pocket near the center of the molecule. Recombinant Rrp44 was shown to possess manganese-dependent endonuclease activity in vitro that was abolished by point mutations in these putative metal binding residues of its PIN domain. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039746936   9 KKTRAGGVVKIVREHYLRDDIGCGAPACSACGGAHAGPAlelqprdQASSLCPWPHYLLPDTNVLLHQIDVLEHPAIRNV 88
Cdd:cd09862     1 KKTRRGKVVKVVREHYLRDDIPCGSELCPLCPQTNPKLL-------LLSLLSDAKHYLIPDTNVVLHQIDLLEDPEITNV 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039746936  89 IVLQTVMQEVRNRSAPIYKRIRDVTNNQEKHFYTFTNEHHKETYIEQEQGENANDRNDRAIRVAAKWYNEHLKRvaadSQ 168
Cdd:cd09862    74 IILQTVLEEVRHRSLPLYNRLRALLKDPRKRFYVFSNEFHRETYVEREPGESPNDRNDRAIRKAAKWYQNHLAK----LG 149

                         170       180
                  ....*....|....*....|....*....
gi 1039746936 169 LQVILITNDRKNKEKAVQEGIPAFTCEEY 197
Cdd:cd09862   150 IPVVLLTDDADNREKAEEEGILALTVREY 178

VapC-like PIN domain of yeast exosome subunit Rrp44 endoribonuclease and other eukaryotic homologs; PIN (PilT N terminus) domain of the Saccharomyces cerevisiae exosome subunit Rrp44 (Ribosomal RNA-processing protein 44 or Protein Dis3 homolog) and other similar eukaryotic homologs are included in this family. The eukaryotic exosome is a conserved macromolecular complex responsible for many RNA-processing and RNA-degradation reactions. It is composed of nine core subunits that directly binds Rrp44. The Rrp44 nuclease is the catalytic subunit of the exosome and has endonuclease activity in the PIN domain and an exoribonuclease activity in its RNase II-like region. Rrp44 binding to the exosome is mediated mainly by the PIN domain and by subunits Rrp41-Rrp45, and binding predictions indicate that the PIN domain active site is positioned on the outer surface of the exosome. This subgroup belongs to the VapC (virulence-associated protein C)-like family of the PIN domain nuclease superfamily. VapC is the PIN-domain ribonuclease toxin from prokaryotic VapBC toxin-antitoxin (TA) systems. VapB is a transcription factor-like protein antitoxin acting as an inhibitor. Other members of the VapC-like nuclease family include FitB toxin of the FitAB TA system, eukaryotic ribonucleases such as Smg6, ribosome assembly factor NOB1, exosome subunit Rrp44 endoribonuclease and rRNA-processing protein Fcf1. The structural properties of the PIN (PilT N terminus) 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. Some members of the superfamily lack several of these key catalytic residues. PIN domains within this subgroup contain four of these residues which cluster at the C-terminal end of the beta-sheet and form a negatively charged pocket near the center of the molecule. Recombinant Rrp44 was shown to possess manganese-dependent endonuclease activity in vitro that was abolished by point mutations in these putative metal binding residues of its PIN domain. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039746936   9 KKTRAGGVVKIVREHYLRDDIGCGAPACSACGGAHAGPAlelqprdQASSLCPWPHYLLPDTNVLLHQIDVLEHPAIRNV 88
Cdd:cd09862     1 KKTRRGKVVKVVREHYLRDDIPCGSELCPLCPQTNPKLL-------LLSLLSDAKHYLIPDTNVVLHQIDLLEDPEITNV 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039746936  89 IVLQTVMQEVRNRSAPIYKRIRDVTNNQEKHFYTFTNEHHKETYIEQEQGENANDRNDRAIRVAAKWYNEHLKRvaadSQ 168
Cdd:cd09862    74 IILQTVLEEVRHRSLPLYNRLRALLKDPRKRFYVFSNEFHRETYVEREPGESPNDRNDRAIRKAAKWYQNHLAK----LG 149

                         170       180
                  ....*....|....*....|....*....
gi 1039746936 169 LQVILITNDRKNKEKAVQEGIPAFTCEEY 197
Cdd:cd09862   150 IPVVLLTDDADNREKAEEEGILALTVREY 178

This domain is the catalytic domain of ribonuclease II;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1039746936  467 REDLRHLCVCSVDPPGCTDIDDALHCRELSNGNLEVGVHIADVSHFIRPGNALDQESARRGTTVYLCEK 535
Cdd:smart00955   1 RVDLRDLPLFTIDPEDAKDIDDAVSVEKLDNGGYRLGVHIADVSHYVKPGSALDREARKRGTSVYLPDR 69

VacB and RNase II family 3'-5' exoribonucleases; This model is defined to identify a pair of paralogous 3-prime exoribonucleases in E. coli, plus the set of proteins apparently orthologous to one or the other in other eubacteria. VacB was characterized originally as required for the expression of virulence genes, but is now recognized as the exoribonuclease RNase R (Rnr). Its paralog in E. coli and H. influenzae is designated exoribonuclease II (Rnb). Both are involved in the degradation of mRNA, and consequently have strong pleiotropic effects that may be difficult to disentangle. Both these proteins share domain-level similarity (RNB, S1) with a considerable number of other proteins, and full-length similarity scoring below the trusted cutoff to proteins associated with various phenotypes but uncertain biochemistry; it may be that these latter proteins are also 3-prime exoribonucleases. [Transcription, Degradation of RNA]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039746936 375 PADKRIPR---IRIETRQASALEGRRIIVAIDGWPRNSRYPNGHFVKNLGDVGEKETETEVLLLEHDVPHQpFSQAVLSF 451
Cdd:TIGR00358 100 PDDPRIYLdiiVPKASVKNELAEGDKVVVELTEYPLRRNLFYGEITQILGNNDDPLIPWWVTLARHEIPFE-FPDGVEQQ 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039746936 452 LPRMPWSITEEDMKNREDLRHLCVCSVDPPGCTDIDDALHCRELSNGNLEVGVHIADVSHFIRPGNALDQESARRGTTVY 531
Cdd:TIGR00358 179 AAKLQFDVDEQAKKYREDLTDLAFVTIDGADAKDLDDAVYVKKLPDGGWKLYVAIADVSYYVAENSPLDKEAKHRGFSVY 258

                         170
                  ....*....|....
gi 1039746936 532 LcekltcPDQALPL 545
Cdd:TIGR00358 259 L------PGFVIPM 266

Large family of predicted nucleotide-binding domains; From similarities to 5'-exonucleases, these domains are predicted to be RNases. PINc domains in nematode SMG-5 and yeast NMD4p are predicted to be involved in RNAi.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039746936   64 HYLLPDTNVLLHQI--DVLEHPAI--RNVIVLQTVMQEVRNRSAPIYKRIRDVTNNQEKHFYTFTNEHHKETYIEQEQGE 139
Cdd:smart00670   1 MKVVLDTNVLIDGLirDALEKLLEkkGEVYIPQTVLEELEYLALRSLKKLEELALEGKIILKVLKEERIEEEILERLSLK 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1039746936  140 NANDRNDRAIRVAAKWYNEhlkrvaadsqlqVILITNDRKNKE 182
Cdd:smart00670  81 LELLPNDALILATAKELGN------------VVLVTNDRDLRR 111

VapC-like PIN domain of yeast exosome subunit Rrp44 endoribonuclease and other eukaryotic homologs; PIN (PilT N terminus) domain of the Saccharomyces cerevisiae exosome subunit Rrp44 (Ribosomal RNA-processing protein 44 or Protein Dis3 homolog) and other similar eukaryotic homologs are included in this family. The eukaryotic exosome is a conserved macromolecular complex responsible for many RNA-processing and RNA-degradation reactions. It is composed of nine core subunits that directly binds Rrp44. The Rrp44 nuclease is the catalytic subunit of the exosome and has endonuclease activity in the PIN domain and an exoribonuclease activity in its RNase II-like region. Rrp44 binding to the exosome is mediated mainly by the PIN domain and by subunits Rrp41-Rrp45, and binding predictions indicate that the PIN domain active site is positioned on the outer surface of the exosome. This subgroup belongs to the VapC (virulence-associated protein C)-like family of the PIN domain nuclease superfamily. VapC is the PIN-domain ribonuclease toxin from prokaryotic VapBC toxin-antitoxin (TA) systems. VapB is a transcription factor-like protein antitoxin acting as an inhibitor. Other members of the VapC-like nuclease family include FitB toxin of the FitAB TA system, eukaryotic ribonucleases such as Smg6, ribosome assembly factor NOB1, exosome subunit Rrp44 endoribonuclease and rRNA-processing protein Fcf1. The structural properties of the PIN (PilT N terminus) 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. Some members of the superfamily lack several of these key catalytic residues. PIN domains within this subgroup contain four of these residues which cluster at the C-terminal end of the beta-sheet and form a negatively charged pocket near the center of the molecule. Recombinant Rrp44 was shown to possess manganese-dependent endonuclease activity in vitro that was abolished by point mutations in these putative metal binding residues of its PIN domain. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039746936   9 KKTRAGGVVKIVREHYLRDDIGCGAPACSACGGAHAGPAlelqprdQASSLCPWPHYLLPDTNVLLHQIDVLEHPAIRNV 88
Cdd:cd09862     1 KKTRRGKVVKVVREHYLRDDIPCGSELCPLCPQTNPKLL-------LLSLLSDAKHYLIPDTNVVLHQIDLLEDPEITNV 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039746936  89 IVLQTVMQEVRNRSAPIYKRIRDVTNNQEKHFYTFTNEHHKETYIEQEQGENANDRNDRAIRVAAKWYNEHLKRvaadSQ 168
Cdd:cd09862    74 IILQTVLEEVRHRSLPLYNRLRALLKDPRKRFYVFSNEFHRETYVEREPGESPNDRNDRAIRKAAKWYQNHLAK----LG 149

                         170       180
                  ....*....|....*....|....*....
gi 1039746936 169 LQVILITNDRKNKEKAVQEGIPAFTCEEY 197
Cdd:cd09862   150 IPVVLLTDDADNREKAEEEGILALTVREY 178

This domain is the catalytic domain of ribonuclease II;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1039746936  467 REDLRHLCVCSVDPPGCTDIDDALHCRELSNGNLEVGVHIADVSHFIRPGNALDQESARRGTTVYLCEK 535
Cdd:smart00955   1 RVDLRDLPLFTIDPEDAKDIDDAVSVEKLDNGGYRLGVHIADVSHYVKPGSALDREARKRGTSVYLPDR 69

Dis3-like cold-shock domain 2 (CSD2); This domain has an OB fold and is found in the Dis3l2 protein. This domain along with CSD1 binds to RNA.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1039746936 372 LFTPADKRIPRIRIETRQA--------SALEGRRIIVAIDGWPRNSRYPNGHFVKNLGDVGEKETETEVLLLEHD 438
Cdd:pfam17849   3 LFVPRDKRIPRIRIPTKSApeeflenpEDLEGKLFVVKIDDWPENSRYPLGHIVKVLGEIGDIETETEAILLENG 77

Rrp44-like cold shock domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039746936 228 FSEHLPLSKLQQGIKSGSYLQGTFRASRENYLEATVWIhgdKEEEKEILIQGIKHLNRAVHEDIVAVELLPRSQWVAPSS 307
Cdd:pfam17216   4 FPEYYSTARVMGGLKNGVLYQGNIQISEYNFLEGSVSL---PRFSKPVLIVGQKNLNRAFNGDQVIVELLPQSEWKAPSS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1039746936 308 VVLDDE------------GQNEDDVE--------KDEERELLLKTAV---SEKMLRPTGRVVGIIKRN 352
Cdd:pfam17216  81 IVLDSEhfdvndnpdieaGDDDDNNEsssnttviSDKQRRLLAKDAMiaqRSKKIQPTAKVVYIQRRS 148

Large family of predicted nucleotide-binding domains; From similarities to 5'-exonucleases, these domains are predicted to be RNases. PINc domains in nematode SMG-5 and yeast NMD4p are predicted to be involved in RNAi.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039746936   64 HYLLPDTNVLLHQI--DVLEHPAI--RNVIVLQTVMQEVRNRSAPIYKRIRDVTNNQEKHFYTFTNEHHKETYIEQEQGE 139
Cdd:smart00670   1 MKVVLDTNVLIDGLirDALEKLLEkkGEVYIPQTVLEELEYLALRSLKKLEELALEGKIILKVLKEERIEEEILERLSLK 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1039746936  140 NANDRNDRAIRVAAKWYNEhlkrvaadsqlqVILITNDRKNKE 182
Cdd:smart00670  81 LELLPNDALILATAKELGN------------VVLVTNDRDLRR 111

exoribonuclease II; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039746936 432 VLLLEHDVPHQPFSQAVlsflprmPWSITEEDMKnREDLRHLCVCSVDPPGCTDIDDALHCRELSNGNLEVGVHIADVSH 511
Cdd:PRK05054  163 VTLARHNLEREAPAGGV-------AWEMLDEGLE-REDLTALDFVTIDSASTEDMDDALYVEKLPDGGLQLTVAIADPTA 234

                          90       100
                  ....*....|....*....|.
gi 1039746936 512 FIRPGNALDQESARRGTTVYL 532
Cdd:PRK05054  235 YIAEGSKLDKAARQRAFTNYL 255

VapC-like PIN domain of Saccharomyces cerevisiae Swt1p, human SWT1 and related proteins; Saccharomyces cerevisiae mRNA-processing endoribonuclease Swt1p plays an important role in quality control of nuclear mRNPs in eukaryotes. Human transcriptional protein SWT1 (RNA endoribonuclease homolog, also known as HsSwt1, C1orf26, and chromosome 1 open reading frame 26) is an RNA endonuclease that participates in quality control of nuclear mRNPs and can associate with the nuclear pore complex (NPC). This subfamily belongs to the Smg5 and Smg6-like PIN domain family. Smg5 and Smg6 are essential factors in NMD, a post-transcriptional regulatory pathway that recognizes and rapidly degrades mRNAs containing premature translation termination codons. In vivo, the Smg6 PIN domain elicits degradation of bound mRNAs, as well as, metal-ion dependent, degradation of single-stranded RNA, in vitro. The PIN (PilT N terminus) 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 (also known as Flap endonuclease-1-like), PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons. Point mutation studies of the conserved aspartate residues in the catalytic center of the Smg6 PIN domain revealed that Smg6 is the endonuclease involved in human NMD. However, Smg5 lacks several of these key catalytic residues and does not degrade single-stranded RNA, in vivo.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039746936  69 DTNVLLHQIDVL-------EHPAIRNVIVLQ-TVMQEV-----RNRSAPIYKRIRDVTN--NQEkhfytFTNEH------ 127
Cdd:cd18727     3 DTNVLISHLDLLkqlvedvEKLSLPVVIVIPwVVLQELdglkkSKRKSSLGWLARRASTwlLEK-----LRSKHprvrgq 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1039746936 128 -HKETYIEQEQGENandRNDRAIRVAAKWYNEHLkrvaadsQLQVILITNDrKN-KEKAVQEGIPAFTCEE 196
Cdd:cd18727    78 aLSETLRASGDPGE---SNDDAILDCCLYFQEKY-------GAPVVLLSND-KNlCNKALINGIPTISPEE 137