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Conserved domains on  [gi|32709467|gb|AAP86752|]
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thymidylate synthase [Enterobacteria phage RB61]

Protein Classification

thymidylate synthase( domain architecture ID 10447802)

thymidylate synthase catalyzes the reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) to 2'-deoxythymidine-5'-monophosphate (dTMP) while utilizing 5,10-methylenetetrahydrofolate (mTHF) as the methyl donor and reductant in the reaction, yielding dihydrofolate (DHF) as a by-product

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Thymidylat_synt pfam00303
Thymidylate synthase; This is a family of proteins that are flavin-dependent thymidylate ...
2-282 1.68e-137

Thymidylate synthase; This is a family of proteins that are flavin-dependent thymidylate synthases.


:

Pssm-ID: 459753  Cd Length: 259  Bit Score: 388.32  E-value: 1.68e-137
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467     2 KQYQDLIKDIFENGYETDDRTGTGTIALFGTKLRWDLTKG-FPAVTTKKLAWNACIAELIWFLSGSTNVNDLRliqhdsl 80
Cdd:pfam00303   1 KQYLDLLRDILENGTEKEDRTGTGTLSVFGYQMRFDLSDGeFPLLTTKKVFWKSIIHELLWFLRGDTNIKYLQ------- 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467    81 IQGKTVWDEnYENQakdlgyhSGELGPIYGKQWRDFG-----GVDQIIEVIDRIKKLPNDRRQIVSAWNPAELKYMALPP 155
Cdd:pfam00303  74 ENGVHIWDE-WADE-------NGDLGPVYGFQWRHWGapdggGIDQLAQVIDQLKNNPDSRRIIVSAWNPADLPKMALPP 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467   156 CHMFYQFNVRNGYLDLQWYQRSVDVFLGLPFNIASYATLVHIVAKMCNLIPGDLIFSGGNTHIYMNHVEQCKEILCREPM 235
Cdd:pfam00303 146 CHYLFQFYVDGGKLSCQLYQRSADVFLGVPFNIASYALLTHMIAQVTGLEPGEFVHTIGDAHIYDNHVEQVKEQLTREPR 225
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 32709467   236 DLCELQLKFPDEFDEWDTEsqvfwlsqfakphNFVLNNYESHPPIKG 282
Cdd:pfam00303 226 PLPKLKINRKVSIFDFTFE-------------DFELEGYQPHPKIKA 259
 
Name Accession Description Interval E-value
Thymidylat_synt pfam00303
Thymidylate synthase; This is a family of proteins that are flavin-dependent thymidylate ...
2-282 1.68e-137

Thymidylate synthase; This is a family of proteins that are flavin-dependent thymidylate synthases.


Pssm-ID: 459753  Cd Length: 259  Bit Score: 388.32  E-value: 1.68e-137
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467     2 KQYQDLIKDIFENGYETDDRTGTGTIALFGTKLRWDLTKG-FPAVTTKKLAWNACIAELIWFLSGSTNVNDLRliqhdsl 80
Cdd:pfam00303   1 KQYLDLLRDILENGTEKEDRTGTGTLSVFGYQMRFDLSDGeFPLLTTKKVFWKSIIHELLWFLRGDTNIKYLQ------- 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467    81 IQGKTVWDEnYENQakdlgyhSGELGPIYGKQWRDFG-----GVDQIIEVIDRIKKLPNDRRQIVSAWNPAELKYMALPP 155
Cdd:pfam00303  74 ENGVHIWDE-WADE-------NGDLGPVYGFQWRHWGapdggGIDQLAQVIDQLKNNPDSRRIIVSAWNPADLPKMALPP 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467   156 CHMFYQFNVRNGYLDLQWYQRSVDVFLGLPFNIASYATLVHIVAKMCNLIPGDLIFSGGNTHIYMNHVEQCKEILCREPM 235
Cdd:pfam00303 146 CHYLFQFYVDGGKLSCQLYQRSADVFLGVPFNIASYALLTHMIAQVTGLEPGEFVHTIGDAHIYDNHVEQVKEQLTREPR 225
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 32709467   236 DLCELQLKFPDEFDEWDTEsqvfwlsqfakphNFVLNNYESHPPIKG 282
Cdd:pfam00303 226 PLPKLKINRKVSIFDFTFE-------------DFELEGYQPHPKIKA 259
ThyA COG0207
Thymidylate synthase [Nucleotide transport and metabolism]; Thymidylate synthase is part of ...
1-286 1.41e-135

Thymidylate synthase [Nucleotide transport and metabolism]; Thymidylate synthase is part of the Pathway/BioSystem: Thymidylate biosynthesis


Pssm-ID: 439977  Cd Length: 264  Bit Score: 383.69  E-value: 1.41e-135
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467   1 MKQYQDLIKDIFENGYETDDRTGTGTIALFGTKLRWDLTKGFPAVTTKKLAWNACIAELIWFLSGSTNVNDLRliQHdsl 80
Cdd:COG0207   1 MKQYLDLLRHILEEGTWKEDRTGTGTLSVFGYQMRFDLSEGFPLLTTKKVHWKSIIHELLWFLRGDTNIRYLR--EN--- 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467  81 iqGKTVWDENyenqAKDlgyhSGELGPIYGKQWRDF-----GGVDQIIEVIDRIKKLPNDRRQIVSAWNPAELKYMALPP 155
Cdd:COG0207  76 --GVKIWDEW----ADE----NGDLGPVYGKQWRSWptpdgGTIDQIAQVIDQLKTNPDSRRLIVSAWNPAELDEMALPP 145
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467 156 CHMFYQFNVRNGYLDLQWYQRSVDVFLGLPFNIASYATLVHIVAKMCNLIPGDLIFSGGNTHIYMNHVEQCKEILCREPM 235
Cdd:COG0207 146 CHALFQFYVADGKLSCQLYQRSADVFLGVPFNIASYALLTHMVAQVTGLEPGEFVHTIGDAHIYLNHLEQVKEQLSREPR 225
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|...
gi 32709467 236 DLCELQL--KFPDEFDewdtesqvFwlsqfaKPHNFVLNNYESHPPIKGKMAV 286
Cdd:COG0207 226 PLPKLKInpKVKSIFD--------F------TFEDFELEGYDPHPAIKAPVAV 264
thyA PRK01827
thymidylate synthase; Reviewed
1-286 8.43e-123

thymidylate synthase; Reviewed


Pssm-ID: 234984  Cd Length: 264  Bit Score: 351.37  E-value: 8.43e-123
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467    1 MKQYQDLIKDIFENGYETDDRTGTGTIALFGTKLRWDLTKGFPAVTTKKLAWNACIAELIWFLSGSTNVNDLRliQHdsl 80
Cdd:PRK01827   1 MKQYLDLLRKILDEGTKKNDRTGTGTLSVFGAQMRFDLSKGFPLLTTKKVHFKSIIHELLWFLRGDTNIAYLQ--EN--- 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467   81 iqGKTVWDEnyenQAKDlgyhSGELGPIYGKQWRDF-----GGVDQIIEVIDRIKKLPNDRRQIVSAWNPAELKYMALPP 155
Cdd:PRK01827  76 --GVHIWDE----WADE----NGDLGPVYGKQWRSWptpdgRHIDQISKVIEQLKTNPDSRRLIVSAWNPGELDKMALPP 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467  156 CHMFYQFNVRNGYLDLQWYQRSVDVFLGLPFNIASYATLVHIVAKMCNLIPGDLIFSGGNTHIYMNHVEQCKEILCREPM 235
Cdd:PRK01827 146 CHALFQFYVADGKLSCQLYQRSADVFLGVPFNIASYALLTHMIAQQTGLKVGEFVHTIGDAHIYSNHLEQAREQLSREPR 225
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 32709467  236 DLCELQLKfPDEFDEWDTEsqvfwlsqfakPHNFVLNNYESHPPIKGKMAV 286
Cdd:PRK01827 226 PLPKLVIN-PDIKSIFDFE-----------FEDFELEGYDPHPAIKAPVAV 264
thym_sym TIGR03284
thymidylate synthase; Members of this protein family are thymidylate synthase, an enzyme that ...
3-286 3.13e-109

thymidylate synthase; Members of this protein family are thymidylate synthase, an enzyme that produces dTMP from dUMP. In prokaryotes, its gene usually is found close to that for dihydrofolate reductase, and in some systems the two enzymes are found as a fusion protein. This model excludes a set of related proteins (TIGR03283) that appears to replace this family in archaeal methanogens, where tetrahydrofolate is replaced by tetrahydromethanopterin. [Purines, pyrimidines, nucleosides, and nucleotides, 2'-Deoxyribonucleotide metabolism]


Pssm-ID: 213790 [Multi-domain]  Cd Length: 295  Bit Score: 318.23  E-value: 3.13e-109
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467     3 QYQDLIKDIFENGYETDDRTGTGTIALFGTKLRWDLTKGFPAVTTKKLAWNACIAELIWFLSGSTNVNdlRLIQHdsliq 82
Cdd:TIGR03284   1 QYLDLLRDILENGHQKGDRTGTGTISVFGYQMRFDLSKGFPLLTTKKVPFRLIASELLWFLKGDTNIR--YLLDH----- 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467    83 GKTVWDE-NYENQAKDLGYHS------------------------GELGPIYGKQWRDFGG-----VDQIIEVIDRIKKL 132
Cdd:TIGR03284  74 NVNIWDEwAFERWVKSDDYNGpdmtdfghraqddpeeddefadkyGDLGPVYGKQWRSWATpdgetIDQIKNVIEMIKTN 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467   133 PNDRRQIVSAWNPAELKYMALPPCHMFYQFNVRNGYLDLQWYQRSVDVFLGLPFNIASYATLVHIVAKMCNLIPGDLIFS 212
Cdd:TIGR03284 154 PDSRRLIVSAWNPEDVPTMALPPCHTLFQFYVADGKLSCQLYQRSADVFLGVPFNIASYALLTHLIAQETGLEVGEFVHT 233
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 32709467   213 GGNTHIYMNHVEQCKEILCREPMDLCELQLKfPDEFDEWDTESQvfwlsqfakphNFVLNNYESHPPIKGKMAV 286
Cdd:TIGR03284 234 LGDAHLYSNHLEQAKLQLTREPRPLPTLKLN-PDKKDIFDFEYE-----------DIEIEGYDPHPAIKAPVAV 295
TS_Pyrimidine_HMase cd00351
Thymidylate synthase and pyrimidine hydroxymethylase: Thymidylate synthase (TS) and ...
3-227 2.17e-95

Thymidylate synthase and pyrimidine hydroxymethylase: Thymidylate synthase (TS) and deoxycytidylate hydroxymethylase (dCMP-HMase) are homologs that catalyze analogous alkylation of C5 of pyrimidine nucleotides. Both enzymes are involved in the biosynthesis of DNA precursors and are active as homodimers. However, they exhibit distinct pyrimidine base specificities and differ in the details of their catalyzed reactions. TS is biologically ubiquitous and catalyzes the conversion of dUMP and methylene-tetrahydrofolate (CH2THF) to dTMP and dihydrofolate (DHF). It also acts as a regulator of its own expression by binding and inactivating its own RNA. Due to its key role in the de novo pathway for thymidylate synthesis and, hence, DNA synthesis, it is one of the most conserved enzymes across species and phyla. TS is a well-recognized target for anticancer chemotherapy, as well as a valuable new target against infectious diseases. Interestingly, in several protozoa, a single polypeptide chain codes for both, dihydrofolate reductase (DHFR) and thymidylate synthase (TS), forming a bifunctional enzyme (DHFR-TS), possibly through gene fusion at a single evolutionary point. DHFR-TS is also active as a dimer. Virus encoded dCMP-HMase catalyzes the reversible conversion of dCMP and CH2THF to hydroxymethyl-dCMP and THF. This family also includes dUMP hydroxymethylase, which is encoded by several bacteriophages that infect Bacillus subtilis, for their own protection against the host restriction system, and contain hydroxymethyl-dUMP instead of dTMP in their DNA.


Pssm-ID: 238211  Cd Length: 215  Bit Score: 279.93  E-value: 2.17e-95
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467   3 QYQDLIKDIFENGY-ETDDRTGTGTIALFGTKLRWDLTKGFPAVTTKKLAWNACIAELIWFLSGSTNVNDLRLiqhdsli 81
Cdd:cd00351   1 QYLDLWRKILEEGYrKTDDRTGTGTRSLFGAQLRFDLSEGFPLLTTKKVPWKSAIEELLWFLRGDTNAERLKE------- 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467  82 QGKTVWDENyenqakdlGYHSGELGPIYGKQWRDFG----GVDQIIEVIDRIKKLPNDRRQIVSAWNPAELKYMALPPCH 157
Cdd:cd00351  74 YGVSIWDEW--------ASKEGDLGYTYGFQWRHWGapgqGVDQIEKVIEKLKNNPDSRRAIISAWNPADLDLMALPPCH 145
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467 158 MFYQFNVRNGYLDLQWYQRSVDVFLGLPFNIASYATLVHIVAKMCNLIPGDLIFSGGNTHIYMNHVEQCK 227
Cdd:cd00351 146 TLIQFYVRNGKLSLTLYQRSNDAFLGVPFNIASYALLTEMIARVTGLEPGEFIHTIGDAHIYENHLEQVK 215
 
Name Accession Description Interval E-value
Thymidylat_synt pfam00303
Thymidylate synthase; This is a family of proteins that are flavin-dependent thymidylate ...
2-282 1.68e-137

Thymidylate synthase; This is a family of proteins that are flavin-dependent thymidylate synthases.


Pssm-ID: 459753  Cd Length: 259  Bit Score: 388.32  E-value: 1.68e-137
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467     2 KQYQDLIKDIFENGYETDDRTGTGTIALFGTKLRWDLTKG-FPAVTTKKLAWNACIAELIWFLSGSTNVNDLRliqhdsl 80
Cdd:pfam00303   1 KQYLDLLRDILENGTEKEDRTGTGTLSVFGYQMRFDLSDGeFPLLTTKKVFWKSIIHELLWFLRGDTNIKYLQ------- 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467    81 IQGKTVWDEnYENQakdlgyhSGELGPIYGKQWRDFG-----GVDQIIEVIDRIKKLPNDRRQIVSAWNPAELKYMALPP 155
Cdd:pfam00303  74 ENGVHIWDE-WADE-------NGDLGPVYGFQWRHWGapdggGIDQLAQVIDQLKNNPDSRRIIVSAWNPADLPKMALPP 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467   156 CHMFYQFNVRNGYLDLQWYQRSVDVFLGLPFNIASYATLVHIVAKMCNLIPGDLIFSGGNTHIYMNHVEQCKEILCREPM 235
Cdd:pfam00303 146 CHYLFQFYVDGGKLSCQLYQRSADVFLGVPFNIASYALLTHMIAQVTGLEPGEFVHTIGDAHIYDNHVEQVKEQLTREPR 225
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 32709467   236 DLCELQLKFPDEFDEWDTEsqvfwlsqfakphNFVLNNYESHPPIKG 282
Cdd:pfam00303 226 PLPKLKINRKVSIFDFTFE-------------DFELEGYQPHPKIKA 259
ThyA COG0207
Thymidylate synthase [Nucleotide transport and metabolism]; Thymidylate synthase is part of ...
1-286 1.41e-135

Thymidylate synthase [Nucleotide transport and metabolism]; Thymidylate synthase is part of the Pathway/BioSystem: Thymidylate biosynthesis


Pssm-ID: 439977  Cd Length: 264  Bit Score: 383.69  E-value: 1.41e-135
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467   1 MKQYQDLIKDIFENGYETDDRTGTGTIALFGTKLRWDLTKGFPAVTTKKLAWNACIAELIWFLSGSTNVNDLRliQHdsl 80
Cdd:COG0207   1 MKQYLDLLRHILEEGTWKEDRTGTGTLSVFGYQMRFDLSEGFPLLTTKKVHWKSIIHELLWFLRGDTNIRYLR--EN--- 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467  81 iqGKTVWDENyenqAKDlgyhSGELGPIYGKQWRDF-----GGVDQIIEVIDRIKKLPNDRRQIVSAWNPAELKYMALPP 155
Cdd:COG0207  76 --GVKIWDEW----ADE----NGDLGPVYGKQWRSWptpdgGTIDQIAQVIDQLKTNPDSRRLIVSAWNPAELDEMALPP 145
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467 156 CHMFYQFNVRNGYLDLQWYQRSVDVFLGLPFNIASYATLVHIVAKMCNLIPGDLIFSGGNTHIYMNHVEQCKEILCREPM 235
Cdd:COG0207 146 CHALFQFYVADGKLSCQLYQRSADVFLGVPFNIASYALLTHMVAQVTGLEPGEFVHTIGDAHIYLNHLEQVKEQLSREPR 225
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|...
gi 32709467 236 DLCELQL--KFPDEFDewdtesqvFwlsqfaKPHNFVLNNYESHPPIKGKMAV 286
Cdd:COG0207 226 PLPKLKInpKVKSIFD--------F------TFEDFELEGYDPHPAIKAPVAV 264
thyA PRK01827
thymidylate synthase; Reviewed
1-286 8.43e-123

thymidylate synthase; Reviewed


Pssm-ID: 234984  Cd Length: 264  Bit Score: 351.37  E-value: 8.43e-123
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467    1 MKQYQDLIKDIFENGYETDDRTGTGTIALFGTKLRWDLTKGFPAVTTKKLAWNACIAELIWFLSGSTNVNDLRliQHdsl 80
Cdd:PRK01827   1 MKQYLDLLRKILDEGTKKNDRTGTGTLSVFGAQMRFDLSKGFPLLTTKKVHFKSIIHELLWFLRGDTNIAYLQ--EN--- 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467   81 iqGKTVWDEnyenQAKDlgyhSGELGPIYGKQWRDF-----GGVDQIIEVIDRIKKLPNDRRQIVSAWNPAELKYMALPP 155
Cdd:PRK01827  76 --GVHIWDE----WADE----NGDLGPVYGKQWRSWptpdgRHIDQISKVIEQLKTNPDSRRLIVSAWNPGELDKMALPP 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467  156 CHMFYQFNVRNGYLDLQWYQRSVDVFLGLPFNIASYATLVHIVAKMCNLIPGDLIFSGGNTHIYMNHVEQCKEILCREPM 235
Cdd:PRK01827 146 CHALFQFYVADGKLSCQLYQRSADVFLGVPFNIASYALLTHMIAQQTGLKVGEFVHTIGDAHIYSNHLEQAREQLSREPR 225
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 32709467  236 DLCELQLKfPDEFDEWDTEsqvfwlsqfakPHNFVLNNYESHPPIKGKMAV 286
Cdd:PRK01827 226 PLPKLVIN-PDIKSIFDFE-----------FEDFELEGYDPHPAIKAPVAV 264
thym_sym TIGR03284
thymidylate synthase; Members of this protein family are thymidylate synthase, an enzyme that ...
3-286 3.13e-109

thymidylate synthase; Members of this protein family are thymidylate synthase, an enzyme that produces dTMP from dUMP. In prokaryotes, its gene usually is found close to that for dihydrofolate reductase, and in some systems the two enzymes are found as a fusion protein. This model excludes a set of related proteins (TIGR03283) that appears to replace this family in archaeal methanogens, where tetrahydrofolate is replaced by tetrahydromethanopterin. [Purines, pyrimidines, nucleosides, and nucleotides, 2'-Deoxyribonucleotide metabolism]


Pssm-ID: 213790 [Multi-domain]  Cd Length: 295  Bit Score: 318.23  E-value: 3.13e-109
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467     3 QYQDLIKDIFENGYETDDRTGTGTIALFGTKLRWDLTKGFPAVTTKKLAWNACIAELIWFLSGSTNVNdlRLIQHdsliq 82
Cdd:TIGR03284   1 QYLDLLRDILENGHQKGDRTGTGTISVFGYQMRFDLSKGFPLLTTKKVPFRLIASELLWFLKGDTNIR--YLLDH----- 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467    83 GKTVWDE-NYENQAKDLGYHS------------------------GELGPIYGKQWRDFGG-----VDQIIEVIDRIKKL 132
Cdd:TIGR03284  74 NVNIWDEwAFERWVKSDDYNGpdmtdfghraqddpeeddefadkyGDLGPVYGKQWRSWATpdgetIDQIKNVIEMIKTN 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467   133 PNDRRQIVSAWNPAELKYMALPPCHMFYQFNVRNGYLDLQWYQRSVDVFLGLPFNIASYATLVHIVAKMCNLIPGDLIFS 212
Cdd:TIGR03284 154 PDSRRLIVSAWNPEDVPTMALPPCHTLFQFYVADGKLSCQLYQRSADVFLGVPFNIASYALLTHLIAQETGLEVGEFVHT 233
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 32709467   213 GGNTHIYMNHVEQCKEILCREPMDLCELQLKfPDEFDEWDTESQvfwlsqfakphNFVLNNYESHPPIKGKMAV 286
Cdd:TIGR03284 234 LGDAHLYSNHLEQAKLQLTREPRPLPTLKLN-PDKKDIFDFEYE-----------DIEIEGYDPHPAIKAPVAV 295
PTZ00164 PTZ00164
bifunctional dihydrofolate reductase-thymidylate synthase; Provisional
3-286 1.36e-101

bifunctional dihydrofolate reductase-thymidylate synthase; Provisional


Pssm-ID: 240299 [Multi-domain]  Cd Length: 514  Bit Score: 306.21  E-value: 1.36e-101
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467    3 QYQDLIKDIFENGYETDDRTGTGTIALFGTKLRWDLTKGFPAVTTKKLAWNACIAELIWFLSGSTNVNDLrliqhdsLIQ 82
Cdd:PTZ00164 233 QYLDLIADIIKNGNVKEDRTGVGTISKFGYQMRFDLRESFPLLTTKKVFLRGIIEELLWFIRGETNGNLL-------LDK 305
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467   83 GKTVWDEN----YENQAKDLGYHSGELGPIYGKQWRDFG-------------GVDQIIEVIDRIKKLPNDRRQIVSAWNP 145
Cdd:PTZ00164 306 GVRIWEGNgsreFLDSRGLTHREENDLGPVYGFQWRHFGaeykdmhddytgqGVDQLKNIIETIKNNPDDRRLILTAWNP 385
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467  146 AELKYMALPPCHMFYQFNVRNGYLDLQWYQRSVDVFLGLPFNIASYATLVHIVAKMCNLIPGDLIFSGGNTHIYMNHVEQ 225
Cdd:PTZ00164 386 SALDQMALPPCHLLSQFYVNDGKLSCMMYQRSCDMGLGVPFNIASYALLTHMIAQVCGLRPGEFVHFLGDAHVYSNHVDA 465
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 32709467  226 CKEILCREPMDLCELQLKFPDEFDEWDTESqvfwlsqfakphNFVLNNYESHPPIKGKMAV 286
Cdd:PTZ00164 466 LKEQLERVPYPFPTLKLKREVENIEDFTIE------------DIEVIGYVPHPKIKMEMAV 514
TS_Pyrimidine_HMase cd00351
Thymidylate synthase and pyrimidine hydroxymethylase: Thymidylate synthase (TS) and ...
3-227 2.17e-95

Thymidylate synthase and pyrimidine hydroxymethylase: Thymidylate synthase (TS) and deoxycytidylate hydroxymethylase (dCMP-HMase) are homologs that catalyze analogous alkylation of C5 of pyrimidine nucleotides. Both enzymes are involved in the biosynthesis of DNA precursors and are active as homodimers. However, they exhibit distinct pyrimidine base specificities and differ in the details of their catalyzed reactions. TS is biologically ubiquitous and catalyzes the conversion of dUMP and methylene-tetrahydrofolate (CH2THF) to dTMP and dihydrofolate (DHF). It also acts as a regulator of its own expression by binding and inactivating its own RNA. Due to its key role in the de novo pathway for thymidylate synthesis and, hence, DNA synthesis, it is one of the most conserved enzymes across species and phyla. TS is a well-recognized target for anticancer chemotherapy, as well as a valuable new target against infectious diseases. Interestingly, in several protozoa, a single polypeptide chain codes for both, dihydrofolate reductase (DHFR) and thymidylate synthase (TS), forming a bifunctional enzyme (DHFR-TS), possibly through gene fusion at a single evolutionary point. DHFR-TS is also active as a dimer. Virus encoded dCMP-HMase catalyzes the reversible conversion of dCMP and CH2THF to hydroxymethyl-dCMP and THF. This family also includes dUMP hydroxymethylase, which is encoded by several bacteriophages that infect Bacillus subtilis, for their own protection against the host restriction system, and contain hydroxymethyl-dUMP instead of dTMP in their DNA.


Pssm-ID: 238211  Cd Length: 215  Bit Score: 279.93  E-value: 2.17e-95
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467   3 QYQDLIKDIFENGY-ETDDRTGTGTIALFGTKLRWDLTKGFPAVTTKKLAWNACIAELIWFLSGSTNVNDLRLiqhdsli 81
Cdd:cd00351   1 QYLDLWRKILEEGYrKTDDRTGTGTRSLFGAQLRFDLSEGFPLLTTKKVPWKSAIEELLWFLRGDTNAERLKE------- 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467  82 QGKTVWDENyenqakdlGYHSGELGPIYGKQWRDFG----GVDQIIEVIDRIKKLPNDRRQIVSAWNPAELKYMALPPCH 157
Cdd:cd00351  74 YGVSIWDEW--------ASKEGDLGYTYGFQWRHWGapgqGVDQIEKVIEKLKNNPDSRRAIISAWNPADLDLMALPPCH 145
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467 158 MFYQFNVRNGYLDLQWYQRSVDVFLGLPFNIASYATLVHIVAKMCNLIPGDLIFSGGNTHIYMNHVEQCK 227
Cdd:cd00351 146 TLIQFYVRNGKLSLTLYQRSNDAFLGVPFNIASYALLTEMIARVTGLEPGEFIHTIGDAHIYENHLEQVK 215
thyA PRK13821
thymidylate synthase; Provisional
1-286 2.54e-69

thymidylate synthase; Provisional


Pssm-ID: 184347  Cd Length: 323  Bit Score: 217.32  E-value: 2.54e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467    1 MKQYQDLIKDIFENGYETDDRTGTGTIALFGTKLRWDLTKGFPAVTTKKLAWNACIAELIWFLSGSTNVNDLRLIqhdsl 80
Cdd:PRK13821   1 MKQYLDLVRTILDTGTWQENRTGIRTISIPGAMLRFDLQQGFPAVTTKKLAFKSAIGELVGFLRASRSAADFRAL----- 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467   81 iqGKTVWDENYENQAKDLG--YHSGE--LGPIYGKQWRDFGG-------------------------------------- 118
Cdd:PRK13821  76 --GCKVWDQNANENAQWLAnpYRQGVddLGDVYGVQWRQWPGykvldasadaqiadatsrgfrivarfdedgapkvllyk 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467  119 -VDQIIEVIDRIKKLPNDRRQIVSAWNPAELKYMALPPCHMFYQF--NVRNGYLDLQWYQRSVDVFLGLPFNIASYATLV 195
Cdd:PRK13821 154 aIDQLRQCLDTIMNNPGSRRILFHGWNPAVLDEIALPACHLLYQFlpNVETREISLCLYIRSNDVGLGTPFNLTEGAALL 233
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467  196 HIVAKMCNLIPGDLIFSGGNTHIYMNHVEQCKEILCREPMDLCELQL--KFPDEFDEWDTESQvfWLSQFaKPHNFVLNN 273
Cdd:PRK13821 234 SLVGRLTGYTPRWFTYFIGDAHIYENQLDMLQEQLTREPYESPRLVIsdRVPEYAKTGVYEPE--WLEKI-EPSDFSLVG 310
                        330
                 ....*....|...
gi 32709467  274 YESHPPIKGKMAV 286
Cdd:PRK13821 311 YRHHEPLTAPMAV 323
thy_syn_methano TIGR03283
thymidylate synthase, methanogen type; Thymidylate synthase makes dTMP for DNA synthesis, and ...
109-219 3.52e-17

thymidylate synthase, methanogen type; Thymidylate synthase makes dTMP for DNA synthesis, and is among the most widely distributed of all enzymes. Members of this protein family are encoded within a completed genome sequence if and only if that species is one of the methanogenenic archaea. In these species, tetrahydromethanopterin replaces tetrahydrofolate, The member from Methanobacterium thermoautotrophicum was shown to behave as a thymidylate synthase based on similar side reactions (the exchange of a characteristic proton with water), although the full reaction was not reconstituted. Partial sequence data showed no similarity to known thymidylate synthases simply because the region sequenced was from a distinctive N-terminal region not found in other thymidylate synthases. Members of this protein family appear, therefore, to a novel, tetrahydromethanopterin-dependent thymidylate synthase. [Purines, pyrimidines, nucleosides, and nucleotides, 2'-Deoxyribonucleotide metabolism]


Pssm-ID: 132326  Cd Length: 199  Bit Score: 77.86  E-value: 3.52e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467   109 YGKQWRDFGGVDQIIEVIDRIKKLPNDRRQIVSAWNPAELKYMALPPCHMFYQFNVRNGYLDLQWYQRSVDVFLGLPFNI 188
Cdd:TIGR03283  82 YGNRLRRYFGIDQIDYIIERLNQSPNSRRAIAITWDPPQDIKVDEVPCLQLVQFLIRDNKLYLTAFFRSNDVGGAWVANA 161
                          90       100       110
                  ....*....|....*....|....*....|.
gi 32709467   189 ASYATLVHIVAKMCNLIPGDLIFSGGNTHIY 219
Cdd:TIGR03283 162 IGLRRLQEYVAEKVGVEPGTLTTHAISAHIY 192
thyA PRK00956
thymidylate synthase; Provisional
109-230 2.96e-13

thymidylate synthase; Provisional


Pssm-ID: 179181  Cd Length: 208  Bit Score: 67.32  E-value: 2.96e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32709467  109 YGKQWRD-FGGVDQIIEVIDRIKKLPNDRRQIVSAWNPAELKYMALPPCHMFYQFNVRNGYLDLQWYQRSVDVFLGLPFN 187
Cdd:PRK00956  84 YGERLREyPGEVDQIDYIIEKLKENKNSRRATAVTWNPYIDTKVDEVPCLQLVDFLIRDGKLYLTVLFRSNDAGGAFHAN 163
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 32709467  188 IASYATLVHIVAKMCNLIPGDLIFSGGNTHIYMNHVEQCKEIL 230
Cdd:PRK00956 164 AIGLIKLGEYVAEKVGVELGTYTHHSVSAHIYERDWDYLEKIF 206
 
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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