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Conserved domains on  [gi|15609119|ref|NP_216498|]
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ribonuclease VapC36 [Mycobacterium tuberculosis H37Rv]

Protein Classification

type II toxin-antitoxin system VapC family toxin( domain architecture ID 10007939)

type II toxin-antitoxin (TA) system VapC family toxin functions as a ribonuclease that is neutralized by its cognate antitoxin VapB; similar to Mycolicibacterium smegmatis ribonuclease VapC

Gene Ontology:  GO:0004540
PubMed:  28279904|21036780

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
VapC COG3742
VapC family ribonuclease, contains PIN domain [Defense mechanisms];
1-127 8.11e-50

VapC family ribonuclease, contains PIN domain [Defense mechanisms];


:

Pssm-ID: 442956  Cd Length: 129  Bit Score: 155.35  E-value: 8.11e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15609119   1 MIVDTSAVVALVQGErPHATLVAAALAGAHSPVMSAPTVAECLIVLTARHGPVARTIFERLRSEIGLSVSSFTAEHAAAT 80
Cdd:COG3742   1 MVVDTSALVAILLGE-PEAEALAAALEAAPPRLISAVTVLEAAIVLARRRGPEARRELDALLAELGIEVVPVDAAQARLA 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 15609119  81 QRAFLRYGKGR-HRAALNFGDCMTYATAQLGHQPLLAVGNDFPQTDLE 127
Cdd:COG3742  80 REAYRRYGKGRgHPARLNFGDCFAYALAKALGAPLLFKGDDFSHTDIE 127
 
Name Accession Description Interval E-value
VapC COG3742
VapC family ribonuclease, contains PIN domain [Defense mechanisms];
1-127 8.11e-50

VapC family ribonuclease, contains PIN domain [Defense mechanisms];


Pssm-ID: 442956  Cd Length: 129  Bit Score: 155.35  E-value: 8.11e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15609119   1 MIVDTSAVVALVQGErPHATLVAAALAGAHSPVMSAPTVAECLIVLTARHGPVARTIFERLRSEIGLSVSSFTAEHAAAT 80
Cdd:COG3742   1 MVVDTSALVAILLGE-PEAEALAAALEAAPPRLISAVTVLEAAIVLARRRGPEARRELDALLAELGIEVVPVDAAQARLA 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 15609119  81 QRAFLRYGKGR-HRAALNFGDCMTYATAQLGHQPLLAVGNDFPQTDLE 127
Cdd:COG3742  80 REAYRRYGKGRgHPARLNFGDCFAYALAKALGAPLLFKGDDFSHTDIE 127
PIN_MtVapC28-VapC30-like cd09871
VapC-like PIN domain of Mycobacterium tuberculosis VapC28 and 30 and related proteins; This ...
 1-127 4.13e-49

VapC-like PIN domain of Mycobacterium tuberculosis VapC28 and 30 and related proteins; This subfamily includes the Virulence associated protein C (VapC)-like PIN (PilT N terminus) domain of Mycobacterium tuberculosis VapC28 and VapC30 toxins. M. tuberculosis VapC28 and VapC30 both cleave tRNA25Ser-TGA and tRNA28Ser-CGA. It belongs to the VapC-like family of the PIN domain nuclease superfamily. VapC is a 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 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.


Pssm-ID: 350219  Cd Length: 128  Bit Score: 153.39  E-value: 4.13e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15609119   1 MIVDTSAVVALVQGErPHATLVAAALAGAHSPVMSAPTVAECLIVLTARHGPVARTIFERLRSEIGLSVSSFTAEHAAAT 80
Cdd:cd09871   1 MVVDTSALVAILLGE-PEAERFLAALAAAPRRLISAATLVEAAIVLERRRGPEARSELDELLAELGIEIVPVDAEQARLA 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 15609119  81 QRAFLRYGKGRHRAALNFGDCMTYATAQLGHQPLLAVGNDFPQTDLE 127
Cdd:cd09871  80 REAYRRFGKGRHPARLNFGDCFAYALAKELGEPLLFKGDDFAHTDIR 126
PIN pfam01850
PIN domain;
1-125 2.70e-15

PIN domain;


Pssm-ID: 426475  Cd Length: 121  Bit Score: 67.05  E-value: 2.70e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15609119     1 MIVDTSAVVALVqGERPHATLVAAALAGAHSPVMSAPTVAECLIVLTARHGPV-ARTIFERLRSEIGLSVSSFTAEHAAA 79
Cdd:pfam01850   1 IVLDTSVLIALL-RGEPLHEAARELLEAAGELVTSAIVLAELLYGLNRRLGLGkAAELVELLLLLSALEVLPIDAELAEE 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 15609119    80 TQRAFLRYGKgrhraaLNFGDCMTYATAQLGHQPLLAVGNDFPQTD 125
Cdd:pfam01850  80 AAELRLKYGK------LGPNDALIAATAKEHGAKLITFDEDFARVA 119
 
Name Accession Description Interval E-value
VapC COG3742
VapC family ribonuclease, contains PIN domain [Defense mechanisms];
1-127 8.11e-50

VapC family ribonuclease, contains PIN domain [Defense mechanisms];


Pssm-ID: 442956  Cd Length: 129  Bit Score: 155.35  E-value: 8.11e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15609119   1 MIVDTSAVVALVQGErPHATLVAAALAGAHSPVMSAPTVAECLIVLTARHGPVARTIFERLRSEIGLSVSSFTAEHAAAT 80
Cdd:COG3742   1 MVVDTSALVAILLGE-PEAEALAAALEAAPPRLISAVTVLEAAIVLARRRGPEARRELDALLAELGIEVVPVDAAQARLA 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 15609119  81 QRAFLRYGKGR-HRAALNFGDCMTYATAQLGHQPLLAVGNDFPQTDLE 127
Cdd:COG3742  80 REAYRRYGKGRgHPARLNFGDCFAYALAKALGAPLLFKGDDFSHTDIE 127
PIN_MtVapC28-VapC30-like cd09871
VapC-like PIN domain of Mycobacterium tuberculosis VapC28 and 30 and related proteins; This ...
 1-127 4.13e-49

VapC-like PIN domain of Mycobacterium tuberculosis VapC28 and 30 and related proteins; This subfamily includes the Virulence associated protein C (VapC)-like PIN (PilT N terminus) domain of Mycobacterium tuberculosis VapC28 and VapC30 toxins. M. tuberculosis VapC28 and VapC30 both cleave tRNA25Ser-TGA and tRNA28Ser-CGA. It belongs to the VapC-like family of the PIN domain nuclease superfamily. VapC is a 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 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.


Pssm-ID: 350219  Cd Length: 128  Bit Score: 153.39  E-value: 4.13e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15609119   1 MIVDTSAVVALVQGErPHATLVAAALAGAHSPVMSAPTVAECLIVLTARHGPVARTIFERLRSEIGLSVSSFTAEHAAAT 80
Cdd:cd09871   1 MVVDTSALVAILLGE-PEAERFLAALAAAPRRLISAATLVEAAIVLERRRGPEARSELDELLAELGIEIVPVDAEQARLA 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 15609119  81 QRAFLRYGKGRHRAALNFGDCMTYATAQLGHQPLLAVGNDFPQTDLE 127
Cdd:cd09871  80 REAYRRFGKGRHPARLNFGDCFAYALAKELGEPLLFKGDDFAHTDIR 126
PIN pfam01850
PIN domain;
1-125 2.70e-15

PIN domain;


Pssm-ID: 426475  Cd Length: 121  Bit Score: 67.05  E-value: 2.70e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15609119     1 MIVDTSAVVALVqGERPHATLVAAALAGAHSPVMSAPTVAECLIVLTARHGPV-ARTIFERLRSEIGLSVSSFTAEHAAA 79
Cdd:pfam01850   1 IVLDTSVLIALL-RGEPLHEAARELLEAAGELVTSAIVLAELLYGLNRRLGLGkAAELVELLLLLSALEVLPIDAELAEE 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 15609119    80 TQRAFLRYGKgrhraaLNFGDCMTYATAQLGHQPLLAVGNDFPQTD 125
Cdd:pfam01850  80 AAELRLKYGK------LGPNDALIAATAKEHGAKLITFDEDFARVA 119
PIN_VapC-like cd18682
Uncharacterized subfamily of the VapC (virulence-associated protein C)-like family of the PIN ...
 1-108 2.53e-10

Uncharacterized subfamily of the VapC (virulence-associated protein C)-like family of the PIN domain 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 PIN domain belongs to a large nuclease superfamily. 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. 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.


Pssm-ID: 350249  Cd Length: 118  Bit Score: 53.98  E-value: 2.53e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15609119   1 MIVDTSAVVALVQGErPHATLVAAALAGAhspVMSAPTVAECLIVLTARHGPVArTIFERLrSEIGLSVSSFTAEHAAAT 80
Cdd:cd18682   1 VVLDASALLALLNGE-PGAERVEAALPGA---VISAVNLAEVVAKLADRGVDPE-EIREAL-AALGLEVVPFDEEQALLA 74

                        90       100
                ....*....|....*....|....*...
gi 15609119  81 qrAFLRyGKGRHrAALNFGDCMTYATAQ 108
Cdd:cd18682  75 --ARLR-PLTRP-LGLSLGDRACLALAI 98
COG2402 COG2402
Predicted nucleic acid-binding protein, contains PIN domain [General function prediction only]; ...
 2-121 1.08e-08

Predicted nucleic acid-binding protein, contains PIN domain [General function prediction only];


Pssm-ID: 441958  Cd Length: 135  Bit Score: 50.28  E-value: 1.08e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15609119   2 IVDTSAVVALV-QGERPHA---TLVAAALAGAHSPVMSAPTVAECLIVLTARHGP-VARTIFERLRSEIGLSVSSFTAEH 76
Cdd:COG2402   3 FVDTGALIALFnRRDQYHEaavELLESLLEGELPLVTTDYVLTETLTLLSRRLGReAAVKFLDRLRESGGLEIVPLTEED 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 15609119  77 AAATQRAFLRYGKGRhraaLNFGDCMTYATAQ-LGHQPLLAVGNDF 121
Cdd:COG2402  83 FERALELFEKYADKP----LSLTDASSVALMErLGIDEILTFDRDF 124
PIN_VapC-like cd09854
VapC-like PIN domains of VapC and Smg6 ribonucleases, ribosome assembly factor NOB1, ...
 2-121 9.08e-05

VapC-like PIN domains of VapC and Smg6 ribonucleases, ribosome assembly factor NOB1, rRNA-processing protein Fcf1, Archaeoglobus fulgidus AF0591 protein, and homologs; PIN (PilT N terminus) domains of such ribonucleases as the 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, are included in VapC-like this family. Also included are the PIN domains of the Pyrobaculum aerophilum Pea0151 and Archaeoglobus fulgidus AF0591 proteins and other similar archaeal homologs. The PIN domain belongs to a large nuclease superfamily. 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.


Pssm-ID: 350205  Cd Length: 129  Bit Score: 39.57  E-value: 9.08e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15609119   2 IVDTSAVVALVQGERPHATLVA-AALAGAHSPVMSAPTV-AECLIVLTARHG-PVARTIFERLRSEIGLSVSSFTAEHAA 78
Cdd:cd09854   1 VLDTNVLIALLSSEPESEAAKElLALLLGDSELVIPPLVlAELLRLLARERGaRRALEILELLRALEVVEEEPALAEIAL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 15609119  79 atqraflRYGKGRHRAALNFGDCMTYATAQ-LGHQPLLAVGNDF 121
Cdd:cd09854  81 -------EVLALGLERGLDFGDALILALAKeLGGAVLVTNDRDF 117
PIN_VapC-FitB-like cd09875
VapC-like PIN domain of ribonucleases (toxins), VapC and FitB, of prokaryotic toxin/antitoxin ...
 2-121 2.79e-04

VapC-like PIN domain of ribonucleases (toxins), VapC and FitB, of prokaryotic toxin/antitoxin operons, Pyrococcus horikoshii protein PH0500, and other similar bacterial and archaeal homologs; PIN (PilT N terminus) domain-containing proteins of prokaryotic toxin/antitoxin (TA) operons, such as, Mycobacterium tuberculosis VapC of the VapBC (virulence associated proteins) TA operon, and Neisseria gonorrhoeae FitB of the FitAB (fast intracellular trafficking) TA operon, as well as, the archaeal Pyrococcus horikoshii protein PH0500 are included in this family. Toxins of TA operons are believed to be involved in growth inhibition by regulating translation and are nearly always co-expressed with an antitoxin, a cognate protein inhibitor, forming an inert protein complex. Disassociation of the complex activates the ribonuclease activity of the toxin. In N. gonorrhoeae, FitA and FitB form a heterodimer: FitA is the DNA binding subunit and FitB contains a ribonuclease activity that is blocked by the presence of FitA. A tetramer of FitAB heterodimers binds DNA from the fitAB upstream promoter region with high affinity. This results in both sequestration of FitAB and repression of fitAB transcription. It is thought that FitAB release from the DNA and subsequent dissociation both slows N. gonorrhoeae replication and transcytosis by an as yet undefined mechanism. The toxin M. tuberculosis VapC is a structural homolog of N. gonorrhoeae FitB, but their antitoxin partners, VapB and FitA, respectively, differ structurally. The M. tuberculosis VapC-5 is proposed to be both an endoribonuclease and an exoribonuclease that can act on free RNA in a similar manner to the endo and exonuclease Flap endonuclease-1 (FEN1). VapC-like toxins are structural homologs of FEN1-like PIN domains, but lack the extensive arch/clamp region and the H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region, seen in FEN1-like PIN domains. PIN domains within this group typically contain three or four conserved acidic residues that cluster at the C-terminal end of the beta-sheet and form a negatively charged pocket near the center of the molecule. These putative active site residues are thought to bind Mg2+ and/or Mn2+ ions and be essential for single-stranded ribonuclease activity. VapC-like PIN domains are single domain proteins that form dimers and dimerization configures the active sites in a groove along the long-axis of the structure.


Pssm-ID: 350223  Cd Length: 130  Bit Score: 38.32  E-value: 2.79e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15609119   2 IVDTSAVVALVQGErPHATLVAAALAGAHSPV-MSAPTVAECLIVLTARHGPVARTIFERLRSEIGL--SVSSFT----A 74
Cdd:cd09875   1 LLDTSVLIWLLDND-PKSHLRSLADRIERGKVyVSIVSRWELAIGVNINKLRLNYAFADLENLLADLaiPVLPLTpriaD 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 15609119  75 EHAAATQRAFLRygkGRHRAALnfgDCMTYATAQLGHQPLLAVGNDF 121
Cdd:cd09875  80 EYLEACRNLPLR---GRHRSPF---DRMIAAQALQHGFTVAHRDEDF 120
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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