VapC-like PIN domain of human nonsense-mediated decay factor Smg5, and other similar eukaryotic homologs; Nonsense-mediated decay (NMD) factors, Smg5 and Smg6 are essential to the post-transcriptional regulatory pathway, NMD, which recognizes and rapidly degrades mRNAs containing premature translation termination codons. 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 112807193  856 PYLIPDTQALCYHLPLIRQLATSGRFIIIIPRTVIDGLDLLKKEQPGARDGIRYLEAEFKKGNRYIRCQKEVGKSfERHK 935
Cdd:cd09884     1 PYLVPDTSALCDHLHLIKQLVQSGKFIVIIPLAVIDGLDELKKESAGAREAIRWLEAEFKKGNRYIRAQKPNEKL-PLPL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112807193  936 LKRQ---DADAWTLYKILDSCRQLTLAQGAGEEDPSGMVTIITGLHLDSPSALSgPMQAALQAAAHASVDVKNVLDFYRQ 1012
Cdd:cd09884    80 LKRPkkkDRDAWRLYQILDCCKYLAQQQGDGEEDGAGMVTLLTGNDLDEKEAFN-KGFSVLGAAHAAGVEIENILDFYSK 158

                  ..
gi 112807193 1013 WK 1014
Cdd:cd09884   159 WK 160

Telomerase activating protein Est1; Est1 is a protein which recruits or activates telomerase at the site of polymerization. Structurally it resembles a TPR-like repeat.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112807193    77 KAEELLWRKVYYEVIQLIKTNKKHIHS----------RSTLECAYRTHLVAGIGFYQHLLLYIQSHyqlelqccidwthv 146
Cdd:pfam10374    1 KVLDLLWRKTHYPIIKWFRKWRKRLDGnskkkkypveFRKLNSKLRKFLKSAQKFYYGLIQRLVSR-------------- 66

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 112807193   147 tdplmgfkkpvSASGKEMDWAQMACHRCLVYLGDLSRYQNEL 188
Cdd:pfam10374   67 -----------EASSSLTALALLSCHRCLIYLGDLHRYRELL 97

VapC-like PIN domain of human nonsense-mediated decay factor Smg5, and other similar eukaryotic homologs; Nonsense-mediated decay (NMD) factors, Smg5 and Smg6 are essential to the post-transcriptional regulatory pathway, NMD, which recognizes and rapidly degrades mRNAs containing premature translation termination codons. 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 112807193  856 PYLIPDTQALCYHLPLIRQLATSGRFIIIIPRTVIDGLDLLKKEQPGARDGIRYLEAEFKKGNRYIRCQKEVGKSfERHK 935
Cdd:cd09884     1 PYLVPDTSALCDHLHLIKQLVQSGKFIVIIPLAVIDGLDELKKESAGAREAIRWLEAEFKKGNRYIRAQKPNEKL-PLPL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112807193  936 LKRQ---DADAWTLYKILDSCRQLTLAQGAGEEDPSGMVTIITGLHLDSPSALSgPMQAALQAAAHASVDVKNVLDFYRQ 1012
Cdd:cd09884    80 LKRPkkkDRDAWRLYQILDCCKYLAQQQGDGEEDGAGMVTLLTGNDLDEKEAFN-KGFSVLGAAHAAGVEIENILDFYSK 158

                  ..
gi 112807193 1013 WK 1014
Cdd:cd09884   159 WK 160

Telomerase activating protein Est1; Est1 is a protein which recruits or activates telomerase at the site of polymerization. Structurally it resembles a TPR-like repeat.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112807193    77 KAEELLWRKVYYEVIQLIKTNKKHIHS----------RSTLECAYRTHLVAGIGFYQHLLLYIQSHyqlelqccidwthv 146
Cdd:pfam10374    1 KVLDLLWRKTHYPIIKWFRKWRKRLDGnskkkkypveFRKLNSKLRKFLKSAQKFYYGLIQRLVSR-------------- 66

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 112807193   147 tdplmgfkkpvSASGKEMDWAQMACHRCLVYLGDLSRYQNEL 188
Cdd:pfam10374   67 -----------EASSSLTALALLSCHRCLIYLGDLHRYRELL 97

PIN domain; Members of this family of bacterial domains are predicted to be RNases (from similarities to 5'-exonucleases).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112807193   858 LIPDTQALCYHLPLIRQLatSGRFIIIIPRTVIDGLDLLKKEQPG--------ARDGIRYLEAEFKKGNRYIRCQKEVGK 929
Cdd:pfam13638    1 YVLDTNVLLHDPDALFNF--GEENDVVIPITVLEELDGLKKGSDEsgrelarlARQANRWLDELLENNGGRLRGQTLDER 78

                           90       100
                   ....*....|....*....|....*..
gi 112807193   930 SFERHKLKRQDAdawtlykILDSCRQL 956
Cdd:pfam13638   79 LPPDPFDKNDNR-------ILAVALYL 98

VapC-like PIN domain of human nonsense-mediated decay factor Smg5, and other similar eukaryotic homologs; Nonsense-mediated decay (NMD) factors, Smg5 and Smg6 are essential to the post-transcriptional regulatory pathway, NMD, which recognizes and rapidly degrades mRNAs containing premature translation termination codons. 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 112807193  856 PYLIPDTQALCYHLPLIRQLATSGRFIIIIPRTVIDGLDLLKKEQPGARDGIRYLEAEFKKGNRYIRCQKEVGKSfERHK 935
Cdd:cd09884     1 PYLVPDTSALCDHLHLIKQLVQSGKFIVIIPLAVIDGLDELKKESAGAREAIRWLEAEFKKGNRYIRAQKPNEKL-PLPL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112807193  936 LKRQ---DADAWTLYKILDSCRQLTLAQGAGEEDPSGMVTIITGLHLDSPSALSgPMQAALQAAAHASVDVKNVLDFYRQ 1012
Cdd:cd09884    80 LKRPkkkDRDAWRLYQILDCCKYLAQQQGDGEEDGAGMVTLLTGNDLDEKEAFN-KGFSVLGAAHAAGVEIENILDFYSK 158

                  ..
gi 112807193 1013 WK 1014
Cdd:cd09884   159 WK 160

VapC-like PIN domain of nonsense-mediated decay (NMD) factors, Smg5 and Smg6, and related proteins; PIN (PilT N terminus) domain of nonsense-mediated decay (NMD) factors, Smg5 and Smg6, and homologs are included in this 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 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. Many of the bacterial homologs in this group have an N-terminal PIN domain and a C-terminal PhoH-like ATPase domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112807193  859 IPDTQALCYHLPLIRQLATSGRFIIIIPRTVIDGLDLLKKEQ----PGARDGIRYLEAEFKKGNRYIRCQKEVGKSFERH 934
Cdd:cd09880     1 VFDTNILLSHLDVLKLLVESGKWTVVIPLIVITELDGLKKNPdplgPKARSALRYIEACLKKHSRWLRVQTSKGNYLADL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 112807193  935 K-----------LKRQDADAWTLYKILDSCRQLTLAqgageEDPSGMVTIITG 976
Cdd:cd09880    81 TirseqlsdaseLRRRNNDDRILECALWQQKHFVDR-----EDGDGKVVLVTN 128

VapC-like PIN domain of human telomerase-binding protein EST1, Smg6, and other similar eukaryotic homologs; Nonsense-mediated decay (NMD) factors, Smg5 and Smg6 are essential to the post-transcriptional regulatory pathway, NMD, which recognizes and rapidly degrades mRNAs containing premature translation termination codons. In vivo, the Smg6 PIN (PilT N terminus) domain elicits degradation of bound mRNAs, as well as, metal ion dependent, degradation of single-stranded RNA, in vitro. 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 (also known as Flap endonuclease-1-like), PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons. PIN domains within this subgroup contain four highly conserved acidic residues (putative metal-binding, active site residues) which cluster at the C-terminal end of the beta-sheet and form a negatively charged pocket near the center of the molecule. 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. Eukaryotic Smg6 PIN domains are present at the C-terminal end of the telomerase activating proteins, EST1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112807193  857 YLIPDTQALCYHLPLIRQLATSGRFIIIIPRTVIDGLDLLKKEQP---------------GARDGIRYLEAEFKKGNRYI 921
Cdd:cd09885     7 YLVPDTNCFIDHLELIEKLVESRKFTVLVPLIVVNELDGLAKGSEsdsyadeahaeevqaKARKAVKFLEEQFEARNPYV 86

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 112807193  922 RCQKEVGKSFERHKLKRQDaDAWTLY-----KILDSCRQL 956
Cdd:cd09885    87 RALTSKGTLLDTIAFRSED-INDGDGgnnddLILSCCLNL 125

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 112807193    857 YLIPDTQALCYHL--PLIRQLAtSGRFIIIIPRTVIDGLDLLKkeqpgaRDGIRYLEAEFKKGNRYIRCQKEVGksFERH 934
Cdd:smart00670    2 KVVLDTNVLIDGLirDALEKLL-EKKGEVYIPQTVLEELEYLA------LRSLKKLEELALEGKIILKVLKEER--IEEE 72

                            90       100
                    ....*....|....*....|....*
gi 112807193    935 KLKRQDADAWTLY---KILDSCRQL 956
Cdd:smart00670   73 ILERLSLKLELLPndaLILATAKEL 97

Est1 DNA/RNA binding domain; Est1 is a protein which recruits or activates telomerase at the site of polymerization. This is the DNA/RNA binding domain of EST1.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112807193   652 AEGLLPAVKVFLDWLRTNPDLiIVCAQSSQSLWNRLSVLLNLLPASAELqdsglalcsevQGLLEGCELPDlpASLLLPE 731
Cdd:pfam10373  200 ATRYLPALRVYLCWLKSNPSV-LEFEDKDEKLVDSLSDLWNELLSSTLL-----------NSSFDVEKRPK--RDYLLEE 265

                           90
                   ....*....|....
gi 112807193   732 DMALRNLPPLRAAH 745
Cdd:pfam10373  266 DVELKGFSPLGYRL 279